Discovery and characterization of IGFBP-mediated endocytosis in the human retinal pigment epithelial cell line ARPE-19

Insulin-like growth factor binding proteins (IGFBPs) are prime regulators of IGF-action in numerous cell types including the retinal pigment epithelium (RPE). The RPE performs several functions essential for vision, including growth factor secretion and waste removal via a phagocytic process mediated in part by vitronectin (Vn). In the course of studying the effects of IGFBPs on IGF-mediated VEGF secretion and Vn-mediated phagocytosis in the RPE cell line ARPE-19, we have discovered that these cells avidly ingest synthetic microspheres (2.0 μm diameter) coated with IGFBPs. Given the novelty of this finding and the established role for endocytosis in mediating IGFBP actions in other cell types, we have explored the potential role of candidate cell surface receptors. Moreover, we have examined the role of key IGFBP structural motifs, by comparing responses to three members of the IGFBP family (IGFBP-3, IGFBP-4 and IGFBP-5) which display overlapping variations in primary structure and glycosylation status. Coating of microspheres (FluoSpheres®, sulfate modified polystyrene filled with a fluorophore) was conducted at 37 °C for 1 h using 20 μg/mL of test protein, followed by extensive washing. Binding of proteins was confirmed using a microBCA assay. The negative control consisted of microspheres treated with 0.1% bovine serum albumin (BSA), and all test samples were post-treated with BSA in an effort to coat any remaining free protein binding sites, which might otherwise encourage non-specific interactions with the cell surface. Serum-starved cultures of ARPE-19 cells were incubated with microspheres for 24 h, using a ratio of approximately 100 microspheres per cell. Uptake of microspheres was quantified using a fluorometer and was confirmed visually by confocal fluorescence microscopy. The ARPE-19 cells displayed little affinity for BSA-treated microspheres, but avidly ingested large quantities of those pre-treated with Vn (ANOVA; p < 0.001). Strong responses were also observed towards recombinant formulations of non-glycosylated IGFBP-3, glycosylated IGFBP-3 and glycosylated IGFBP-5 (all p < 0.001), while glycosylated IGFBP-4 induced a relatively minor response (p < 0.05). The response to IGFBP-3 was unaffected in the presence of excess soluble IGFBP-3, IGF-I or Vn. Likewise, soluble IGFBP-3 did not induce uptake of BSA-treated microspheres. Antibodies to either the transferrin receptor or type 1 IGF-receptor displayed slight inhibitory effects on responses to IGFBPs and Vn. Heparin abolished responses to Vn, IGFBP-5 and non-glycosylated IGFBP-3, but only partially inhibited the response to glycosylated IGFBP-3. Our results demonstrate for the first time IGFBP-mediated endocytosis in ARPE-19 cells and suggest roles for the IGFBP-heparin-binding domain and glycosylation status. These findings have important implications for understanding the mechanisms of IGFBP actions on the RPE, and in particular suggest a role for IGFBP-endocytosis.

Polybrominated diphenyl ether (PBDE) concentrations decrease with age : analysis of pooled human blood serum in the Australian population

Introduction Polybrominated diphenyl ethers (PBDEs) are considered to be a cost effective and efficient way to reduce the possibility of product ignition and inhibit the spread of fire, thereby limiting harm caused by fires. PBDEs are incorporated into a wide variety of manufactured products and are now considered an ubiquitous contaminant found worldwide in biological and environmental samples . In comparison to “traditional” persistent organic pollutants (POPs), the exposure modes of PBDEs in humans are less well defined, although dietary sources, inhalation (air/particulate matter) and dust ingestion have been reported 2-4. Limited investigations of population specific factors such as age or gender and PBDE concentrations report: no conclusive correlation by age in adults ; higher concentrations in children ; similar concentrations in maternal and cord blood ; and no gender differences . After preliminary findings of higher PBDE concentrations in children than in adults in Australia11 we sought to investigate at what age the PBDE concentrations peaked in an effort to focus exposure studies. This investigation involved the collection of blood samples from young age groups and the development of a simple model to predict PBDE concentrations by age in Australia.

Experts vs. Discounters: Consumer Free Riding and Experts Withholding Advice in Markets for Credence Goods

This paper studies the incentives for credence goods experts to invest effort in diagnosis if effort is both costly and unobservable, and if they face competition by discounters who are not able to perform a diagnosis. The unobservability of diagnosis effort and the credence characteristic of the good induce experts to choose incentive compatible tariff structures. This makes them vulnerable to competition by discounters. We explore the conditions under which honestly diagnosing experts survive competition by discounters; we identify situations in which experts misdiagnose consumers in order to prevent them from free-riding on experts' advice; and we discuss policy options to solve the free-riding consumers–cheating experts problem.

Reducing the risk of posttraumatic stress disorder in children following natural disasters

A significant number of children suffer long term psychological disturbance following exposure to a natural disaster. Evidence suggests that a dose-response relationship exists, so that children and adolescents who experience the most intense or extensive exposure to the risk factors for PTSD are likely to develop the most serious and persistent symptoms. Risk factors include gender, age, personality, extent of exposure to the natural disaster, amount of damage to property and infrastructure, witnessing injury or death of others or perceiving a threat to their own life. Knowing these factors enables various strategies to be put in place to decrease the risk of psychological disturbance following the aftermath of traumatic events. Re-establishing a sense of safety, security and normality is important in the aftermath of a natural disaster, and promoting social connectedness, positive family functioning, and effective coping mechanisms can make children more resilient in the face of catastrophic events. This paper examines the risk and protective factors associated with the development of post traumatic stress disorder (PTSD), and considers how schools can use this knowledge to contribute to the recovery effort, and reduce the prevalence of PTSD amongst pupils in the wake of a natural disaster.

Reconstruction of falsified computer logs for digital forensics investigations

Digital forensics investigations aim to find evidence that helps confirm or disprove a hypothesis about an alleged computer-based crime. However, the ease with which computer-literate criminals can falsify computer event logs makes the prosecutor's job highly challenging. Given a log which is suspected to have been falsified or tampered with, a prosecutor is obliged to provide a convincing explanation for how the log may have been created. Here we focus on showing how a suspect computer event log can be transformed into a hypothesised actual sequence of events, consistent with independent, trusted sources of event orderings. We present two algorithms which allow the effort involved in falsifying logs to be quantified, as a function of the number of `moves' required to transform the suspect log into the hypothesised one, thus allowing a prosecutor to assess the likelihood of a particular falsification scenario. The first algorithm always produces an optimal solution but, for reasons of efficiency, is suitable for short event logs only. To deal with the massive amount of data typically found in computer event logs, we also present a second heuristic algorithm which is considerably more efficient but may not always generate an optimal outcome.

Europe and the Media: Building a new kind of Europe; is mass media the key?

The book is a joint effort of eight academics and journalists, Europe specialists from six countries (Australia, Germany, Poland, Slovenia, the United Kingdom and the United States). They give sometimes divergent views on the future of the so-called “European Project”, for building a common European economy and society, but agree that cultural changes, especially changes experienced through mass media, are rapidly taking place. One of the central interests of the book is the operation of the large media centre located at the European Commission in Brussels – the world’s largest gallery of permanently accredited correspondents. Jacket notes: The Lisbon Treaty of December 2009 is the latest success of the European Union’s drive to restructure and expand; yet questions persist about how democratic this new Europe might be. Will Brussels’ promotion of the “European idea” produce a common European culture and society? The authors consider it might, as a culture of everyday shared experience, though old ways are cherished, citizens forever thinking twice about committing to an uncertain future. The book focuses on mass media , as a prime agent of change, sometimes used deliberately to promote a “European project”; sometimes acting more naturally as a medium for new agendas. It looks at proposed media models for Europe, ranging from not very successful pan-European television, to the potentials of media systems based on national markets, and new media based on digital formats. It also studies the Brussels media service, the centre operated by the European Commission, which is the world’s largest concentration of journalists; and ways that dominant national media may come to serve the interests of communities now extending across frontiers. Europe and the Media notes change especially as encountered by new EU member countries of central and eastern Europe.

Performance Research in Rangeland Communities

In 2003, Bill Dunstone, John McCallum and Paul Makeham began a collaboration with researchers at the Centre for the Management of Arid Environments (CMAE) in Kalgoorlie, Western Australia. CMAE researchers are keen to develop 'people-oriented' strategies for implementing agricultural extension initiatives in their region. Traditional hierarchies of knowledge-transfer have impeded the 'connectedness' between community and researchers that gives meaning and relevance to useful practice (Ison and Russell, 2000). Our aim is to establish a partnership between the Live Events Research Network (LERN) and CMAE, investigating ways to link creative, performance-based research and practice with the scientific methodologies associated with natural resources management. This accords with recent work undertaken by Deborah Mills and Paul Brown, showing how community cultural development strategies enhance the implementation of policy concerned with community wellbeing. Mills and Brown 'adopted a concept of wellbeing which builds on a social and environmental view of health', and considered such themes as ecological sustainability, rural economic revitalisation, community strengthening, health and wellbeing (Mills, 2003). We propose that rangeland communities can creatively manage some of the challenges confronting them through performance-based projects which: - activate the stories through which a community enacts its sense of place; - facilitate live events in which the community enacts ownership of its culture and identity; - directly involve the community in the formulation of research issues

An examination of IS conference reviewing practices

There has been considerable interest over the years within the IS research community into how to shape articles for successful publication. Little effort has been made, however, to examine the reviewing criteria that make a difference to publication. We argue that, to provide better guidance to authors, more solid evidence is needed into the factors that contribute to acceptance decisions. This paper examines empirically the outcomes of the reviewing processes of three well-known IS conferences held in 2007. Our analyses reveal four major findings. First, the evaluation criteria that influence the acceptance/rejection decision vary by conference. Second, those differences can be explained in terms of the maturity and breadth of the specific conference of interest. Third, while objective review criteria influence acceptance/rejection decisions, subjective assessment on the part of the program committees may also play a substantial role. Fourth, while high scores on objective criteria are essential for acceptance, they do not guarantee acceptance. On the other hand, low scores on any criterion are likely to result in rejection.

A summary view of government cost recovery policies in Australia and New Zealand relating to the supply of public sector information

Researching administrative history is problematical. A trail of authoritative documents is often hard to find; and useful summaries can be difficult to organise, especially if source material is in paper formats in geographically dispersed locations. In the absence of documents, the reasons for particular decisions and the rationale underpinning particular policies can be confounded as key personnel advance in their professions and retire. The rationale for past decisions may be lost for practical purposes; and if an organisation’s memory of events is diminished, its learning through experience is also diminished. Publishing this document tries to avoid unnecessary duplication of effort by other researchers that need to venture into how policies of charging for public sector information have been justified. The author compiled this work within a somewhat limited time period and the work does not pretend to be a complete or comprehensive analysis of the issues.----- A significant part of the role of government is to provide a framework of legally-enforceable rights and obligations that can support individuals and non-government organisations in their lawful activities. Accordingly, claims that governments should be more ‘business-like’ need careful scrutiny. A significant supply of goods and services occurs as non-market activity where neither benefits nor costs are quantified within conventional accounting systems or in terms of money. Where a government decides to provide information as a service; and information from land registries is archetypical, the transactions occur as a political decision made under a direct or a clearly delegated authority of a parliament with the requisite constitutional powers. This is not a market transaction and the language of the market confuses attempts to describe a number of aspects of how governments allocate resources.----- Cost recovery can be construed as an aspect of taxation that is a sole prerogative of a parliament. The issues are fundamental to political constitutions; but they become more complicated where states cede some taxing powers to a central government as part of a federal system. Nor should the absence of markets be construed necessarily as ‘market failure’ or even ‘government failure’. The absence is often attributable to particular technical, economic and political constraints that preclude the operation of markets. Arguably, greater care is needed in distinguishing between the polity and markets in raising revenues and allocating resources; and that needs to start by removing unhelpful references to ‘business’ in the context of government decision-making.

Contrasting scenarios : embracing speech recognition

The purpose of this chapter is to describe the use of caricatured contrasting scenarios (Bødker, 2000) and how they can be used to consider potential designs for disruptive technologies. The disruptive technology in this case is Automatic Speech Recognition (ASR) software in workplace settings. The particular workplace is the Magistrates Court of the Australian Capital Territory.----- Caricatured contrasting scenarios are ideally suited to exploring how ASR might be implemented in a particular setting because they allow potential implementations to be “sketched” quickly and with little effort. This sketching of potential interactions and the emphasis of both positive and negative outcomes allows the benefits and pitfalls of design decisions to become apparent.----- A brief description of the Court is given, describing the reasons for choosing the Court for this case study. The work of the Court is framed as taking place in two modes: Front of house, where the courtroom itself is, and backstage, where documents are processed and the business of the court is recorded and encoded into various systems.----- Caricatured contrasting scenarios describing the introduction of ASR to the front of house are presented and then analysed. These scenarios show that the introduction of ASR to the court would be highly problematic.----- The final section describes how ASR could be re-imagined in order to make it useful for the court. A final scenario is presented that describes how this re-imagined ASR could be integrated into both the front of house and backstage of the court in a way that could strengthen both processes.

How can we exploit mobile data to customise learning based on a student’s environmental surroundings?

User-Based intelligent systems are already commonplace in a student’s online digital life. Each time they browse, search, buy, join, comment, play, travel, upload, download, a system collects, analyses and processes data in an effort to customise content and further improve services. This panel session will explore how intelligent systems, particularly those that gather data from mobile devices, can offer new possibilities to assist in the delivery of customised, personal and engaging learning experiences. The value of intelligent systems for education lies in their ability to formulate authentic and complex learner profiles that bring together and systematically integrate a student’s personal world with a formal curriculum framework. As we well know, a mobile device can collect data relating to a student’s interests (gathered from search history, applications and communications), location, surroundings and proximity to others (GPS, Bluetooth). However, what has been less explored is the opportunity for a mobile device to map the movements and activities of a student from moment to moment and over time. This longitudinal data provides a holistic profile of a student, their state and surroundings. Analysing this data may allow us to identify patterns that reveal a student’s learning processes; when and where they work best and for how long. Through revealing a student’s state and surroundings outside of schools hour, this longitudinal data may also highlight opportunities to transform a student’s everyday world into an inventory for learning, punctuating their surroundings with learning recommendations. This would in turn lead to new ways to acknowledge and validate and foster informal learning, making it legitimate within a formal curriculum.

Students’ conceptual knowledge about workplace pedagogies and applications to learning in the workplace

The development of effective workplace pedagogies is integral to work-integrated and work-based learning. The workplace pedagogies that facilitate and support learning include: activities in which individuals engage such as daily work practices, questioning; observing, and listening; interactions with more experienced workers through coaching and modelling; and referencing documented procedures. Each of these dimensions is significant in enhancing processes of workplace learning. Learning can be optimised when these pedagogies are appropriately embedded in the context of and process of participating in normal work activities. Yet learners need to understand the nature of these pedagogies, and how and for what purposes to use these to achieve a range of learning outcomes. This is because it is the worker-learners who play the key roles in the process and outcomes of learning through work. A pilot study was conducted on students’ conceptions of how each of these dimensions of workplace pedagogy help their learning, by providing examples of learning from these sources; and stating their preferences for learning in the workplace. A sample of seventeen students, enrolled in the second year of a Diploma in Nursing course at a Technical and Further Education institution, participated in a survey intended to capture these conceptions and the importance attached to each of them. The findings indicate that these students have basic understanding of how each of seven workplace pedagogic practices can contribute to their learning. They reported relying mostly on daily practices, observing and listening to others, modelling, coaching, and other workers. Their selection of these contributions emphasise significant opportunities for guided learning by others, yet suggest fewer student-initiated interactions, less intensity in interactions, and likelihood that learning is more passive. The data also suggests that these students rely mostly on using academic learning skill, and limited workplace learning skills. It is proposed, therefore, that the knowledge and understandings about workplace learning and pedagogies might be best embedded in the full curriculum and not become add-on shortly before students go on work placement. This approach will allow students to appreciate the significance and use of workplace pedagogies for learning.

Air evacuation in war : the role of RAAF nurses undertaking air evacuation of casualties between 1943-1953

Air transportation of Australian casualties in World War II was initially carried out in air ambulances with an accompanying male medical orderly. By late 1943 with the war effort concentrated in the Pacific, Allied military authorities realised that air transport was needed to move the increasing numbers of casualties over longer distances. The Royal Australian Air Force (RAAF) became responsible for air evacuation of Australian casualties and established a formal medical air evacuation system with trained flight teams early in 1944. Specialised Medical Air Evacuation Transport Units (MAETUs) were established whose sole responsibility was undertaking air evacuations of Australian casualties from the forward operational areas back to definitive medical care. Flight teams consisting of a RAAF nursing sister (registered nurse) and a medical orderly carried out the escort duties. These personnel had been specially trained in Australia for their role. Post-WWII, the RAAF Nursing Service was demobilised with a limited number of nurses being retained for the Interim Air Force. Subsequently, those nurses were offered commissions in the Permanent Air Force. Some of the nurses who remained were air evacuation trained and carried out air evacuations both in Australia and as part of the British Commonwealth Occupation Force in Japan. With the outbreak of the Korean War in June 1950, Australia became responsible for the air evacuation of British Commonwealth casualties from Korea to Japan. With a re-organisation of the Australian forces as part of the British Commonwealth forces, RAAF nurses were posted to undertake air evacuation from Korea and back to Australia from Iwakuni, Japan. By 1952, a specialised casualty staging section was established in Seoul and staffed by RAAF nurses from Iwakuni on a rotation basis. The development of the Australian air evacuation system and the role of the flight nurses are not well documented for the period 1943-1953. The aims of this research are three fold and include documenting the origins and development of the air evacuation system from 1943-1953; analysing and documenting the RAAF nurse’s role and exploring whether any influences or lessons remain valid today. A traditional historical methodology of narrative and then analysis was used to inform the flight nurse’s role within the totality of the social system. Evidence was based on primary data sources mainly held in Defence files, the Australian War Memorial or the National Archives of Australia. Interviews with 12 ex-RAAF nurses from both WWII and the Korean War were conducted to provide information where there were gaps in the primary data and to enable exploration of the flight nurses’ role and their contributions in war of the air evacuation of casualties. Finally, this thesis highlights two lessons that remain valid today. The first is that interoperability of air evacuation systems with other nations is a force multiplier when resources are scarce or limited. Second, the pre-flight assessment of patients was essential and ensured that there were no deaths in-flight.

Integrated Bayesian network frameworks for modelling complex ecological issues

Ecological problems are typically multi faceted and need to be addressed from a scientific and a management perspective. There is a wealth of modelling and simulation software available, each designed to address a particular aspect of the issue of concern. Choosing the appropriate tool, making sense of the disparate outputs, and taking decisions when little or no empirical data is available, are everyday challenges facing the ecologist and environmental manager. Bayesian Networks provide a statistical modelling framework that enables analysis and integration of information in its own right as well as integration of a variety of models addressing different aspects of a common overall problem. There has been increased interest in the use of BNs to model environmental systems and issues of concern. However, the development of more sophisticated BNs, utilising dynamic and object oriented (OO) features, is still at the frontier of ecological research. Such features are particularly appealing in an ecological context, since the underlying facts are often spatial and temporal in nature. This thesis focuses on an integrated BN approach which facilitates OO modelling. Our research devises a new heuristic method, the Iterative Bayesian Network Development Cycle (IBNDC), for the development of BN models within a multi-field and multi-expert context. Expert elicitation is a popular method used to quantify BNs when data is sparse, but expert knowledge is abundant. The resulting BNs need to be substantiated and validated taking this uncertainty into account. Our research demonstrates the application of the IBNDC approach to support these aspects of BN modelling. The complex nature of environmental issues makes them ideal case studies for the proposed integrated approach to modelling. Moreover, they lend themselves to a series of integrated sub-networks describing different scientific components, combining scientific and management perspectives, or pooling similar contributions developed in different locations by different research groups. In southern Africa the two largest free-ranging cheetah (Acinonyx jubatus) populations are in Namibia and Botswana, where the majority of cheetahs are located outside protected areas. Consequently, cheetah conservation in these two countries is focussed primarily on the free-ranging populations as well as the mitigation of conflict between humans and cheetahs. In contrast, in neighbouring South Africa, the majority of cheetahs are found in fenced reserves. Nonetheless, conflict between humans and cheetahs remains an issue here. Conservation effort in South Africa is also focussed on managing the geographically isolated cheetah populations as one large meta-population. Relocation is one option among a suite of tools used to resolve human-cheetah conflict in southern Africa. Successfully relocating captured problem cheetahs, and maintaining a viable free-ranging cheetah population, are two environmental issues in cheetah conservation forming the first case study in this thesis. The second case study involves the initiation of blooms of Lyngbya majuscula, a blue-green algae, in Deception Bay, Australia. L. majuscula is a toxic algal bloom which has severe health, ecological and economic impacts on the community located in the vicinity of this algal bloom. Deception Bay is an important tourist destination with its proximity to Brisbane, Australia’s third largest city. Lyngbya is one of several algae considered to be a Harmful Algal Bloom (HAB). This group of algae includes other widespread blooms such as red tides. The occurrence of Lyngbya blooms is not a local phenomenon, but blooms of this toxic weed occur in coastal waters worldwide. With the increase in frequency and extent of these HAB blooms, it is important to gain a better understanding of the underlying factors contributing to the initiation and sustenance of these blooms. This knowledge will contribute to better management practices and the identification of those management actions which could prevent or diminish the severity of these blooms.

Doing business : knowledges in the internationalised business lecture

This paper investigates the oracy (listening/speaking) genres enacted in an undergraduate entry point unit in the internationalised university of the 21st century, and the kind of knowledges these genres elicit and perform. This paper focuses on a series of lectures in the business studies unit and how anecdotal knowledge from both the lecturer’s and the students’ lived experiences was elicited as grist for the curriculum. The analysis of lecture talk suggests that the lecture today is no longer a monologic display of expert disciplinary knowledge bestowed upon the learner. Rather, it is increasingly a multimedia performance with an underlying ethic of engagement and interactivity. Of particular interest is the way international students’ knowledges were elicited to resource the internationalised curriculum with authenticity and insight. The knowledges thus assembled are analysed through Bernstein’s conceptual distinction between vertical and horizontal knowledge structures. The paper offers suggestions on how to maximise the potential and minimize the risks of this more interactive genre of lecture, with particular regard to enabling the participation of the international student.