PEGylation of lysine residues reduces the pro-migratory activity of IGF-I

Background: The insulin-like growth factor (IGF) system is composed of ligands and receptors which regulate cell proliferation, survival, differentiation and migration. Some functions are regulated via intracellular signaling cascades, others by involvement of the extracellular milieu, including binding proteins and other extracellular matrix proteins. However, understanding of their functions and the exact nature of these interactions remains incomplete. Methods: IGF-I was PEGylated at its lysine sites - K27, K65 and K68. Binding of PEG-IGF-I to the IGFBPs was analyzed using BIAcore and its ability to activate the IGF-IR was assessed using IGF-IR phosphorylation assay. Furthermore, functional consequences of PEGylating the lysine residues of IGF-I was investigated using cell viability and cell migration assays. In addition, particular downstream signaling pathways regularly implicated in these mechanisms were also dissected using phospho-AKT and phospho-ERK1/2 assays. Results: In this study, IGF-I specifically PEGylated at lysine 27 (PEG-K27), 65 (PEG-K65) or 68 (PEG-K68) were employed. Receptor phosphorylation was only reduced by 2-fold with PEG-K65 and PEG-K68 over all the time points tested, and as observed in two cell types, 3T3 fibroblasts and MCF-7 breast cancer cells. PEGylation at K27 resulted in a much larger effect, with more than 10-fold lower activation for 3T3 fibroblasts and a ~3 fold reduced IGF-IR activation for MCF-7 breast cancer cells over 15 minutes. In addition, all PEG-IGF-I variants demonstrated a ten-fold reduction in the association rate to IGF binding proteins (IGFBPs). Functionally, all PEG variants completely lost their ability to induce cell migration in the presence of IGFBP-3/vitronectin (VN) complexes as compared to IGF-I; in contrast, cell viability was fully preserved. Further investigations into the downstream signaling pathways revealed that the PI3-K/AKT pathway was preferentially affected upon treatment with the PEG-IGF-I variants compared to the MAPK/ERK pathway. Conclusion: PEGylation of IGF-I has an impact on cell migration but not cell viability. General significance: PEG-IGF-I may differentially modulate IGF-I mediated functions that are dependent on its interaction with its receptor as well as key extracellular proteins such as VN and IGFBPs.

Citizen journalism as social networking : reporting the 2007 Australian Federal Election

One of the perceived Achilles heels of online citizen journalism is its perceived inability to conduct investigative and first-hand reporting. A number of projects have recently addressed this problem, with varying success: the U.S.-based Assignment Zero was described as "a highly satisfying failure" (Howe 2007), while the German MyHeimat.de appears to have been thoroughly successful in attracting a strong community of contributors, even to the point of being able to generate print versions of its content, distributed free of charge to households in selected German cities. In Australia, citizen journalism played a prominent part in covering the federal elections held on 24 November 2007; news bloggers and public opinion Websites provided a strong counterpoint to the mainstream media coverage of the election campaign (Bruns et al., 2007). Youdecide2007.org, a collaboration between researchers at Queensland University of Technology and media practitioners at the public service broadcaster SBS, the public opinion site On Line Opinion, and technology company Cisco Systems, was developed as a dedicated space for a specifically hyperlocal coverage of the election campaign in each of Australia's 150 electorates from the urban sprawls of Sydney and Brisbane to the sparsely populated remote regions of outback Australia. YD07 provided training materials for would-be citizen journalists and encouraged them to contribute electorate profiles, interview candidates, and conduct vox-pops with citizens in their local area. The site developed a strong following especially in its home state of Queensland, and its interviewers influenced national public debate by uncovering the sometimes controversial personal views of mainstream and fringe candidates. At the same time, the success of YD07 was limited by external constraints determined by campaign timing and institutional frameworks. As part of a continuing action research cycle, lessons learnt from Youdecide2007.org are going to be translated into further iterations of the project, which will cover the local government elections in the Australian state of Queensland, to be held in March 2008, and developments subsequent to these elections. This paper will present research outcomes from the Youdecide2007.org project. In particular, it will examine the roles of staff contributors and citizen journalists in attracting members, providing information, promoting discussion, and fostering community on the site: early indications from a study of interaction data on the site indicate notably different contribution patterns and effects for staff and citizen participants, which may point towards the possibility of developing more explicit pro-am collaboration models in line with the Pro-Am phenomenon outlined by Leadbeater & Miller (2004). The paper will outline strengths and weaknesses of the Youdecide model and highlight requirements for the successful development of active citizen journalism communities. In doing so, it will also evaluate the feasibility of hyperlocal citizen journalism approaches, and their interrelationship with broader regional, state, and national journalism in both its citizen and industrial forms.

How to extract and expand randomness : a summary and explanation of existing results

We examine the use of randomness extraction and expansion in key agreement (KA) pro- tocols to generate uniformly random keys in the standard model. Although existing works provide the basic theorems necessary, they lack details or examples of appropriate cryptographic primitives and/or parameter sizes. This has lead to the large amount of min-entropy needed in the (non-uniform) shared secret being overlooked in proposals and efficiency comparisons of KA protocols. We therefore summa- rize existing work in the area and examine the security levels achieved with the use of various extractors and expanders for particular parameter sizes. The tables presented herein show that the shared secret needs a min-entropy of at least 292 bits (and even more with more realistic assumptions) to achieve an overall security level of 80 bits using the extractors and expanders we consider. The tables may be used to �nd the min-entropy required for various security levels and assumptions. We also �nd that when using the short exponent theorems of Gennaro et al., the short exponents may need to be much longer than they suggested.

L'étendue internationale des nouvelles firmes de hautes technologies: le rôle du capital humain et de l'intention stratégique des fondateurs

De récentes recherches ont mis l’accent sur l’importance pour les nouvelles entreprises internationales de l’existence de ressources et de compétences spécifiques. La présente recherche, qui s’inscrit dans ce courant, montre en particulier l’importance du capital humain acquis par les entrepreneurs sur base de leur expérience internationale passée. Mais nous montrons en même temps que ces organisations sont soutenues par une intention délibérée d’internationalisation dès l’origine. Notre recherche empirique est basée sur l’analyse d’un échantillon de 466 nouvelles entreprises de hautes technologies anglaises et allemandes. Nous montrons que ce capital humain est un actif qui facilite la pénétration rapide des marchés étrangers, et plus encore quand l’entreprise nouvelle est accompagnée d’une intention stratégique délibérée d’internationalisation. Des conclusions similaires peuvent être étendues au niveau des ressources que l’entrepreneur consacre à la start-up : plus ces ressources sont importantes, plus le processus d’internationalisation tend à se faire à grande échelle ; et là aussi, l’influence de ces ressources est augmenté par l’intention stratégique d’internationalisation. Dans le cadre des études empiriques sur les born-globals (entreprises qui démarrent sur un marché globalisé), cette recherche fournit une des premières études empiriques reliant l’influence des conditions initiales de création aux probabilités de croissance internationale rapide.

De la reconstruction a l’augmentation du corps humain en medecine restaurative et en cybernetique

Aux confluences historiques et conceptuelles de la modernité, de la technologie, et de l’« humain », les textes de notre corpus négocient et interrogent de façon critique les possibilités matérielles et symboliques de la prothèse, ses aspects phénoménologiques et spéculatifs : du côté subjectiviste et conceptualiste avec une philosophie de la conscience, avec Merleau-Ponty ; et de l’autre avec les épistémologues du corps et historiens de la connaissance Canguilhem et Foucault. Le trope prometteur de la prothèse impacte sur les formations discursives et non-discursives concernant la reconstruction des corps, là où la technologie devient le corrélat de l’identité. La technologie s’humanise au contact de l’homme, et, en révélant une hybridité supérieure, elle phagocyte l’humain du même coup. Ce travail de sociologie des sciences (Latour, 1989), ou encore d’anthropologie des sciences (Hakken, 2001) ou d’anthropologie bioculturelle (Andrieu, 1993; Andrieu, 2006; Andrieu, 2007a) se propose en tant qu’exemple de la contribution potentielle que l’anthropologie biologique et culturelle peut rendre à la médecine reconstructrice et que la médecine reconstructrice peut rendre à la plastique de l’homme ; l’anthropologie biologique nous concerne dans la transformation biologique du corps humain, par l’outil de la technologie, tant dans son histoire de la reconstruction mécanique et plastique, que dans son projet d’augmentation bionique. Nous établirons une continuité archéologique, d’une terminologie foucaldienne, entre les deux pratiques. Nous questionnons les postulats au sujet des relations nature/culture, biologie/contexte social, et nous présentons une approche définitionnelle de la technologie, pierre angulaire de notre travail théorique. Le trope de la technologie, en tant qu’outil adaptatif de la culture au service de la nature, opère un glissement sémantique en se plaçant au service d’une biologie à améliorer. Une des clés de notre recherche sur l’augmentation des fonctions et de l’esthétique du corps humain réside dans la redéfinition même de ces relations ; et dans l’impact de l’interpénétration entre réalité et imaginaire dans la construction de l’objet scientifique, dans la transformation du corps humain. Afin de cerner les enjeux du discours au sujet de l’« autoévolution » des corps, les théories évolutionnistes sont abordées, bien que ne représentant pas notre spécialité. Dans le cadre de l’autoévolution, et de l’augmentation bionique de l’homme, la somation culturelle du corps s’exerce par l’usage des biotechnologies, en rupture épistémologique de la pensée darwinienne, bien que l’acte d’hybridation évolutionnaire soit toujours inscrit dans un dessein de maximisation bionique/génétique du corps humain. Nous explorons les courants de la pensée cybernétique dans leurs actions de transformation biologique du corps humain, de la performativité des mutilations. Ainsi technologie et techniques apparaissent-elles indissociables de la science, et de son constructionnisme social.

Environmental and pro-social norms : evidence on littering

The paper investigates the relationship between pro-social norms and its implications for improved environmentsl outcomes. This is an area, which has been neglected in the environmental economic literature. We provide empirical evidence to demonstrate a small but significant positive impact between perceived environmental cooperation (reduced public littering) and increased voluntary environmental morale. For this purpose we use European Value Survey (EVS) data for 30 European countries. We also demonstrate that Western European countries are more sensitive to perceived environmental cooperation than the public in Eastern Europe. Interestingly, the results also demonstrate that environmental morale is strongly correlated with several socio-economic and environmental variables. Several robustness tests are conducted to check the validity of the results.

Book review : "Community engagement in contemporary legal education : Pro Bono, Clinical legal education and services learning"

The result of a forum on community engagement held in November 2008 at Bond University, Community Engagement in Contemporary Legal Education is a compilation of papers presented at the forum by academics and professionals throughout Australia. Although found initially to be a topic of legal interest, it was not until the reviewer came across the Council of Australian Law Deans (CALD) “Standards for Australian Law Schools” (adopted 17 November 20093) then the full importance and potential of this book was revealed. Clause 2.2.4 of the CALD Standards recognises the importance of “experiential learning opportunities” for law students and cites examples such as clinical programs, internships, practical experience and pro-bono work. Clause 2.3.3 acknowledges the need to develop professional ethics and again cites pro-bono obligations as an example. Clause 9.6.2 encourages interaction of law schools with the profession and the community and again, pro-bono community service is identified as one method of doing so. Yet nowhere in the document are there any uniform standards or binding obligations that law schools must commit to. In the current climate where the importance of practical experience is continually emphasised and student numbers exceed the number of available paid legal positions, there should be more focus on the details of how these commitments should be converted to be included in a law school’s curriculum.

AIDS and pro-social television : industry, policy and Australian television drama

This thesis examines the intersection of popular cultural representations of HIV and AIDS and the discourses of public health campaigns. Part Two provides a comprehensive record of all HIV related storylines in Australian television drama from the first AIDS episode of The Flying Doctors in 1986 to the ongoing narrative of Pacific Drive, with its core HIV character, in 1996. Textual representations are examined alongside the agency of "cultural technicians" working within the television industry. The framework for this analysis is established in Part One of the thesis, which examines the discursive contexts for speaking about HIV and AIDS established through national health policy and the regulatory and industry framework for broadcasting in Australia. The thesis examines the dominant liberal democratic framework for representation of HIV I AIDS and adopts a Foucauldian understanding of the processes of governmentality to argue that during the period of the 1980s and 1990s a strand of social democratic discourse combined with practices of self management and the management of the Australian population. The actions of committed agents within both domains of popular culture and health education ensured that more challenging expressions of HIV found their way into public culture.

News produsage in a pro-am mediasphere : why citizen journalism matters

The rise to prominence of citizen journalism is usually described as a paradigm shift in the relationship between news organizations and their audiences – ‘citizen’ or ‘amateur’ journalists are positioned as inherently different from, and possibly in competition with, ‘professional’ journalists. Some journalists in the industry have taken up this theme, and are at pains to distinguish their professional, supposedly objective and accountable practices from what they describe as the opinionated and partisan ‘armchair journalism’ of amateurs, while some citizen journalists, in turn, give as good at they get and describe the professionals as lackeys of their corporate masters who (willingly or unwittingly) fall prey to political and commercial spin. In fact, the very terminology we use to describe both sides creates the impression that professionals are not also citizens, and that citizen journalists are incapable of having professional skills and knowledges; in reality, of course, the lines between them are much less clear.

Exploring the Pro‐Am interface between production and produsage

This conference celebrates the passing of 40 years since the establishment of the Internet (dating this, presumably, to the first connection between two nodes on ARPANET in October 1969). For a gathering of media scholars such as this, however, it may be just as important not only to mark the first testing of the core technologies upon which much of our present‐day Net continues to build, but also to reflect on another recent milestone: the 20th anniversary of what is today arguably the chief interface through which billions around the world access and experience the Internet – the World Wide Web, launched by Tim Berners‐Lee in 1989.

La théorie démocratique et La Physique Théorique

Le présent essai soutient, un peu le long d'une ligne simmelienne, que la théorie démocratique peut produire des théories pratiques et universelles, comme celles développées en physique théorique. Le raisonnement qui sous-tend cet essai est de montrer que la théorie de la «démocratie de base" peut-être vrai par le faite si on la comparer à la Relative Spécifique d’Einstein portant spécifiquement sur les paramètres de symétrie, l'unification, la simplicité et l'utilité. Ces paramètres sont ce qui fait qu’une théorie en physique comme ont la rencontre s’adapte non seulement aux connaissances actuelles, mais aussi de produire des chemins vers l'essai (application). Comme la théorie de la «démocratie de base » peut satisfaire ces mêmes paramètres, il pourrait trancher le débat relatif à la définition de la démocratie. Ceci sera d'abord soutenu pour discuter de ce qui est la théorie de la «démocratie de base» et pourquoi cela diffère des travaux précédents, en deuxième lieu, en expliquant les paramètres choisis (comme pour quoi ceux-ci et pas à d'autres confirment ou échouent les théories) et, troisièmement, en comparant comment la relativité et la théorie de la «démocratie de base » peut correspondre aux paramètres.

Socially adaptable housing new housing model for families living with disability

In Australia as far back as 1993, researchers such as Baladin and Chapmen reported that "18% of the total Australian population and 51% of the population over 60 years of age were identified as having a disability" (2001; p38.2). Statistics such as these are not by any means astonishing, even to members of the general public, and it is widely understood that these are only to increase significantly in our near future. What is particularly surprising however is, in the face of such statistics, the lack of new and creative responses to this demographic shift, particularly by the architecture and construction industries. The common response from a range of sectors seems to be the repetition of a series of models which offer limited, and often undesirable, housing options. It is this against this backdrop, characterized by a lack of original options from mainstream practitioners and relevant government bodies, that the need has arisen to develop alternative models at grass-roots level. This paper reports primarily on the work of one group comprising a not-for-profit organization, a pro-bono design practice group and a local university working together to design a more holistic, emotionally sustainable independent living model of housing for families where a member of the family has a disability. This approach recognizes the limitations of universal design in that it often does not " ... meet all the housing needs that arise for people with moderate to severe disabilities" (Scotts, Margie et al, 2007; p.17). It is hoped that by examining the work of such a collective which is not driven by profit or policy, but rather born with the aim to address first and foremost individual and community need, that better insight can be gained into the real requirements of individuals and families as well as open up a view to new ways of fulfilling them.

Can the contra-lateral limb be used as a control with respect to analyses of bone remodelling?

Bone loss may result from remodelling initiated by implant stress protection. Quantifying remodelling requires bone density distributions which can be obtained from computed tomography scans. Pre-operative scans of large animals however are rarely possible. This study aimed to determine if the contra-lateral bone is a suitable control for the purpose of quantifying bone remodelling. CT scans of 8 pairs of ovine tibia were used to determine the likeness of left and right bones. The deviation between the outer surfaces of the bone pairs was used to quantify geometric similarity. The density differences were determined by dividing the bones into discrete volumes along the shaft of the tibia. Density differences were also determined for fractured and contra-lateral bone pairs to determine the magnitude of implant related remodelling. Left and right ovine tibiae were found to have a high degree of similarity with differences of less than 1.0 mm in the outer surface deviation and density difference of less than 5% in over 90% of the shaft region. The density differences (10–40%) as a result of implant related bone remodelling were greater than left-right differences. Therefore, for the purpose of quantifying bone remodelling in sheep, the contra-lateral tibia may be considered an alternative to a pre-operative control.