Immunogenicity and protective efficacy of an anti-Streptococcus pyogenes vaccine candidate in multiple animal species

Streptococcus pyogenes, also known as Group A Streptococcus (GAS) has been associated with a range of diseases from the mild pharyngitis and pyoderma to more severe invasive infections such as streptococcal toxic shock. GAS also causes a number of non-suppurative post-infectious diseases such as rheumatic fever, rheumatic heart disease and glomerulonephritis. The large extent of GAS disease burden necessitates the need for a prophylactic vaccine that could target the diverse GAS emm types circulating globally. Anti-GAS vaccine strategies have focused primarily on the GAS M-protein, an extracellular virulence factor anchored to GAS cell wall. As opposed to the hypervariable N-terminal region, the C-terminal portion of the protein is highly conserved among different GAS emm types and is the focus of a leading GAS vaccine candidate, J8-DT/alum. The vaccine candidate J8-DT/alum was shown to be immunogenic in mice, rabbits and the non-human primates, hamadryas baboons. Similar responses to J8-DT/alum were observed after subcutaneous and intramuscular immunization with J8-DT/alum, in mice and in rabbits. Further assessment of parameters that may influence the immunogenicity of J8-DT demonstrated that the immune responses were identical in male and female mice and the use of alum as an adjuvant in the vaccine formulation significantly increased its immunogenicity, resulting in a long-lived serum IgG response. Contrary to the previous findings, the data in this thesis indicates that a primary immunization with J8-DT/alum (50ƒÊg) followed by a single boost is sufficient to generate a robust immune response in mice. As expected, the IgG response to J8- DT/alum was a Th2 type response consisting predominantly of the isotype IgG1 accompanied by lower levels of IgG2a. Intramuscular vaccination of rabbits with J8-DT/alum demonstrated that an increase in the dose of J8-DT/alum up to 500ƒÊg does not have an impact on the serum IgG titers achieved. Similar to the immune response in mice, immunization with J8-DT/alum in baboons also established that a 60ƒÊg dose compared to either 30ƒÊg or 120ƒÊg was sufficient to generate a robust immune response. Interestingly, mucosal infection of naive baboons with a M1 GAS strain did not induce a J8-specific serum IgG response. As J8-DT/alum mediated protection has been previously reported to be due to the J8- specific antibody formed, the efficacy of J8-DT antibodies was determined in vitro and in vivo. In vitro opsonization and in vivo passive transfer confirmed the protective potential of J8-DT antibodies. A reduction in the bacterial burden after challenge with a bioluminescent M49 GAS strain in mice that were passively administered J8-DT IgG established that protection due to J8-DT was mediated by antibodies. The GAS burden in infected mice was monitored using bioluminescent imaging in addition to traditional CFU assays. Bioluminescent GAS strains including the ‘rheumatogenic’ M1 GAS could not be generated due to limitations with transformation of GAS, however, a M49 GAS strain was utilized during BLI. The M49 serotype is traditionally a ‘nephritogenic’ serotype associated with post-streptococcal glomerulonephritis. Anti- J8-DT antibodies now have been shown to be protective against multiple GAS strains such as M49 and M1. This study evaluated the immunogenicity of J8-DT/alum in different species of experimental animals in preparation for phase I human clinical trials and provided the ground work for the development of a rapid non-invasive assay for evaluation of vaccine candidates.

Perceptions of fairness and allocation systems

This paper explores the conditions of acceptability of differing allocation systems under scarcity and evaluates what makes a price system more or less fair. We find that fairness in an allocation arrangement depend on the institutional settings inherent in the situation, such as information, transparency and competition and the perceived institutional quality e.g., fiscal exchange and institutional trust). Results also indicate that the solution “weak people first” is seen as the fairest approach to an excess demand situation, followed by “first come, first serve”, the price system and an auction system. On the other hand, a random procedure or an allocation through the government is not perceived to be fair. Moreover, economics students seemed to be less sceptical towards the price system than other subjects although we observe that female students are more sceptical than male students.

Urban renewal from the inside out: Spatial and critical literacies in a low socioeconomic school community

This article focuses on how teachers worked to build a meaningful curriculum around changes to a neighborhood and school grounds in a precinct listed for urban renewal. Drawing on a long-term relationship with the principal and one teacher, the researchers planned and designed a collaborative project to involve children as active participants in the redevelopment process, negotiating and redesigning an area between the preschool and the school. The research investigated spatial literacies, that is, ways of thinking about and representing the production of spaces, and critical literacies, in this instance how young people might have a say in remaking part of their school grounds. Data included videotapes of key events, interviews, and an archive of the elementary students' artifacts experimenting with spatial literacies. The project builds on the insights of community members and researchers working for social justice in high-poverty areas internationally that indicate the importance of education, local action, family, and youth involvement in building sustainable and equitable communities.

The relationship between Australians and the overseas graves of the First World War

The purpose of this thesis is to outline the relationship that existed in the past and exists in the present, between Australians and the War Graves and Memorials to the Missing. commemorations of Australians who died during the First World War. Their final resting places are scattered all over the world and provide a tangible record of the sacrifice of men and women in the war, and represent the final result by Official Agencies such as the Imperial, and later, Commonwealth War Graves Commission, and its agency representative, the Office of Australian War Graves, of an attempt to appropriately commemorate them. The study follows the path of history from the event of death of an individual in the First World War, through their burial; temporary grave or memorial commemoration; the permanent commemoration; the family and public reaction to the deaths; how the Official Agencies of related Commonwealth Governments dealt with the dead; and finally, how the Australian dead are represented on the battlefields of the world in the 21st century. Australia.s war dead of the First World War are scattered around the globe in more than 40 countries and are represented in war cemeteries and civil cemeteries; and listed on large „Memorials to the Missing., which commemorate the individuals devoid of a known graves or final resting place.

Steering (towards a post apology Australia) without a rudder

After Kevin Rudd’s Apology to Indigenous Peoples after his election as Prime Minister in 2008 the climate was hopeful with many Aboriginal and Torres Strait Islander women (and non-Indigenous women, too) breathing a sigh of relief that the disastrous effects of White Australia’s government policies had at last been symbolically, publicly and officially acknowledged. There was also, though, skepticism about the ‘real’ change this Apology might have for Indigenous Australians. Many of us wondered if the Apology would make any difference at all in the ‘real’ world, where the gaps between non-Indigenous and Indigenous Australians is still so glaringly apparent in areas such as health, education, housing and employment.

The new middle class meets the creative class : the Master of Business Administration (MBA) and creative innovation in 21st-century China

‘MBA fever’ in China needs to be understood in the wider context of forces driving structural change in China’s relation to the global knowledge economy. The rise of a ‘new middle class’ in China is connected to the new claims for cultural leadership of an emergent ‘creative class’, which generates new issues about the relevance of the MBA in China, in terms of its relevance to Chinese economic circumstances, and its flexibility and capacity to respond to accumulation strategies that emphasise innovation, creativity and entrepreneurship.

When He is a She is a He : the pregnant man and the transgendered mother

The recent successful pregnancy of Thomas Beatie, a transgender FTM, billed by the various media as ‘the pregnant man’, has stirred up considerably diverse public opinion and debate, some supportive and indicative of changing and progressive ideas around sex, gender and sexuality; others condemnatory in their claims that Beatie’s pregnancy is an affront to the laws of Nature and/or God. Desired or derided, the pregnant male body contests the terrain of reproductive embodiment and the orthodoxy of Western systems of gender categorization. This chapter analyses a selection of media and internet responses to the case of the pregnant man, arguing that most disturbing of all it seems, is the body in-between (Kristeva 1982, p.4), the one that visibly defies socially obdurate gender oppositions of male and female, feminine and masculine in its insistence on being, to borrow from Homi Bhabha, a ‘third space of enunciation.’ Banana Yoshimoto’s novella Kitchen, also contests gender boundaries in its characterisation of Eriko, a transgendered male to female, a father, then a mother. In this narrative the in-between, the ambiguous, is not reviled but rather celebrated as a ‘horizon of possibility’ (Halperin, qtd in Jagose 1996 http://www.australianhumanitiesreview.org/archive/Issue-Dec- 1996/jagose.html).

User-created content and everyday cultural practice : lessons from YouTube

This chapter sets out the debates about the changing role of audiences in relation to user-created content as they appear in New Media and Cultural Studies. The discussion moves beyond the simple dichotomies between active producers and passive audiences, and draws on empirical evidence, in order to examine those practices that are most ordinary and widespread. Building on the knowledge of television’s role in facilitating public life, and the everyday, affective practices through which it is experienced and used, I focus on the way in which YouTube operates as a site of community, creativity and cultural citizenship; and as an archive of popular cultural memory.

Review of Apple iPad news applications : new media service

The launch of the Apple iPad on January 2010 has seen considerable interest from the newspaper and publishing industry in developing content and business models for the tablet PC device that can address the limits of both the print and online news and information media products. It is early days in the iPad’s evolution, and we wait to see what competitor devices will emerge in the near future. It is apparent, however, that it has become a significant “niche” product, with considerable potential for mass market expansion over the next few years, possibly at the expense of netbook sales. The scope for the iPad and tablet PCs to become a “fourth screen” for users, alongside the TV, PC and mobile phone, is in early stages of evolution. The study used five criteria to assess iPad apps: • Content: timeliness; archive; personalisation; content depth; advertisements; the use of multimedia; and the extent to which the content was in sync with the provider brand. • Useability: degree of static content; ability to control multimedia; file size; page clutter; resolution; signposts; and customisation. • Interactivity: hyperlinks; ability to contribute content or provide feedback to news items; depth of multimedia; search function; ability to use plug-ins and linking; ability to highlight, rate and/or save items; functions that may facilitate a community of users. • Transactions capabilities: ecommerce functionality; purchase and download process; user privacy and transaction security. • Openness: degree of linking to outside sources; reader contribution processes; anonymity measures; and application code ownership.

On location : the imagined private interior in public life

This paper reveals the interior landscapes of selected contemporary Australian films, such as The Caterpillar Wish and Bad Boy Bubby, to develop a number of thematic influences on the manner in which domestic and private lives are constructed through filmic imagination. The research uncovers the conditions that contribute to particular scenographic representations of the humble interiors that act as both backdrop and performer to subtle and often troubled narratives. Such readings are informed by the theoretical works of writer Gertrude Stein, among others, who explore the relationships between the scenographic third dimension and the fourth dimensional performance in the representation of narrative space. A further theoretical thread lies in Giuliana Bruno’s work on the tension between private and public filmic space, which is explored through the public outing of intensely private spaces generated through narratives framed by the specificities of found interiors. Beyond the interrogation of qualities of imagined filmic space is the condition whereby locations, once transformed by the event of movie making are consequently forever revised. These altered conditions subsequently reinvest the lives of those who return to the location with layered narratives of occupation. Situationally, the now reconverted interior performs as contributor to subsequent private inhabitation, even if only as imagined space. The possibility here is that the qualities of the original may be superimposed and recontextualised to invest post-produced interiors with the qualities of the other space as imagined. This reading of film space explores new theoretical design scenarios for imagined and everyday interior landscapes.

The voices of the exegesis

In a recent journal article, Luke Jaaniste and I identified an emergent model of exegesis. From a content analysis of submitted exegeses within a local archive, we identified an approach that is quite different from the traditional thesis, but is also distinct from previously identified forms of exegesis, which Milech and Schilo have described as a ‘context model’ (which assumes the voice of academic objectivity and provides an historical or theoretical context for the creative practice) and a ‘commentary’ model’ (which takes the form of a first person reflection on the challenges, insights and achievements of the practice). The model we identified combines these dichotomous forms and assumes a dual orientation–looking outwards to the established field of research, exemplars and theories, and inwards to the methodologies, processes and outcomes of the practice. We went on to argue that this ‘connective’ exegesis offers clear benefits to the researcher in connecting the practice to an established field while allowing the researcher to demonstrate how the methods have led to outcomes that advance the field in some way. And, while it helps the candidate to articulate objective claims for research innovation, it enables them to retain a voiced, personal relationship with their practice. However, it also poses considerable complexities and challenges in the writing. It requires a reconciliation of multi-perspectival subject positions: the disinterested perspective and academic objectivity of an observer/ethnographer/analyst/theorist at times and the invested perspective of the practitioner/ producer at others. The author must also contend with a range of writing styles, speech genres and voices: from the formal, polemical voice of the theorist to the personal, questioning and sometimes emotive voice of reflexivity. Moreover, the connective exegesis requires the researcher to synthesize various perspectives, subject positions, writing styles, and voices into a unified and coherent text. In this paper I consider strategies for writing a hybrid, connective exegesis. I first ground the discussion on polyvocality and alternate textual structures through reference to recent discussions in philosophy and critical theory, and point to examples of emergent approaches to texts and practices in related fields. I then return to the collection of archived exegeses to investigate the strategies that postgraduate candidates have adopted to resolve the problems that arise from a polyvocal, connective exegesis.

Response : letter to the editor by Al-Azri and Al-Maniri

Firstly, the authors would like to thank the editor for the opportunity to respond to Dr Al-Azri’s and Dr Al-Maniri’s letter. Secondly, while the current authors also accept that deterrence-based approaches should act as only one corner-stone of a suite of interventions and public policy initiatives designed to improve road safety, deterrence-based approaches have nonetheless consistently proven to be a valuable resource to improve road safety. Dr Al-Azri and Dr Al-Maniri reinforce their assertion about the limited utility of deterrence by citing drink driving research, and the issue of drink driving is particularly relevant within the current context given that the problem of driving after drinking has historically been addressed through deterrence-based approaches. While the effectiveness of deterrence-based approaches to reduce drink driving will always be dependent upon a range of situational and contextual factors (including police enforcement practices, cultural norms, etc), the utilisation of this approach has proven particularly effective within Queensland, Australia. For example, a relatively recent comprehensive review of Random Breath Testing in Queensland demonstrated that this initiative not only had a deterrent impact upon self-reported intentions to drink and drive, but was also found to have significantly reduced alcohol-related fatalities in the state. However, the authors agree that deterrence-based approaches can be particularly transient and thus require constant “topping up” not least through sustained public reinforcement, which was clearly articulated in the seminal work by Homel.

Independent cinema in the Chinese film industry

Chinese independent cinema has developed for more than twenty years. Two sorts of independent cinema exist in China. One is underground cinema, which is produced without official approvals and cannot be circulated in China, and the other are the films which are legally produced by small private film companies and circulated in the domestic film market. This sort of ‘within-system’ independent cinema has played a significant role in the development of Chinese cinema in terms of culture, economics and ideology. In contrast to the amount of comment on underground filmmaking in China, the significance of ‘within-system’ independent cinema has been underestimated by most scholars. This thesis is a study of how political management has determined the development of Chinese independent cinema and how Chinese independent cinema has developed during its various historical trajectories. This study takes media economics as the research approach, and its major methods utilise archive analysis and interviews. The thesis begins with a general review of the definition and business of American independent cinema. Then, after a literature review of Chinese independent cinema, it identifies significant gaps in previous studies and reviews issues of traditional definition and suggests a new definition. After several case studies on the changes in the most famous Chinese directors’ careers, the thesis shows that state studios and private film companies are two essential domestic backers for filmmaking in China. After that, the body of the thesis provides an examination of the development of ‘within-system’ independent cinema. Specifically, three factors: government intervention, the majors’ performance (state studios and, later, the conglomerates) and the market conduct of independent cinema at various points in their trajectories are studied. The key findings of the study are as follows: First, most scholars have overlooked the existence and the significance of within-system Chinese independent cinema. Drawing on an American definition of the independent sector, this thesis proposes a definition of the sector in China: namely, any film that has not been financed, produced, and/or distributed by majors. The thesis also notes important contradictions in applying this definition: i.e. film-making is still dependent on policies that frame industry development. The thesis recognises that major tensions apply to filmmaking in China, which significantly differentiates the Chinese independents from those in the US. Second, the development of Chinese independent cinema is the result the rise of the private sector and the decline of the state studio system. As state studios encountered difficulties the private sector moved forward; consequently the environment improved for independent cinema. Third, before 2003, the film industry in China had little commercialisation. The government controlled independent cinema by means of license and censorship. State studios produced main melody films and Hollywood attracted most of the audiences. Many independent filmmakers focused on commercial films, thus contributing to film commercialisation. Fourth, after 2003, the film industry became increasingly fragmented. The government created distribution and exhibition opportunities for main melody films; conglomerates collaborated with Hong Kong players; Hong Kong co-productions and Hollywood occupied the film market; and small private film companies produced main melody films in order to earn meagre profits. The original contribution of the thesis is to advance the study of Chinese independent cinema. The study suggests a reasonable and practical definition of Chinese independent cinema. It shows how the Chinese government authorities have implemented economic measures to gain ideological control in the film industry. Finally, this the first study on Chinese independent cinema applying a synthesis of economic, political and historical perspectives.

PCR bias Toward the wild-type k-ras and p53 sequences: Implications for PCR detection of mutations and cancer diagnosis

PCR-based cancer diagnosis requires detection of rare mutations in k- ras, p53 or other genes. The assumption has been that mutant and wild-type sequences amplify with near equal efficiency, so that they are eventually present in proportions representative of the starting material. Work on factor IX suggests that this assumption is invalid for one case of near- sequence identity. To test the generality of this phenomenon and its relevance to cancer diagnosis, primers distant from point mutations in p53 and k-ras were used to amplify wild-type and mutant sequences from these genes. A substantial bias against PCR amplification of mutants was observed for two regions of the p53 gene and one region of k-ras. For k-ras and p53, bias was observed when the wild-type and mutant sequences were amplified separately or when mixed in equal proportions before PCR. Bias was present with proofreading and non-proofreading polymerase. Mutant and wild-type segments of the factor V, cystic fibrosis transmembrane conductance regulator and prothrombin genes were amplified and did not exhibit PCR bias. Therefore, the assumption of equal PCR efficiency for point mutant and wild-type sequences is invalid in several systems. Quantitative or diagnostic PCR will require validation for each locus, and enrichment strategies may be needed to optimize detection of mutants.

Autopoiesis, language, literacy and the brain

When we attempt to speak about the relationship between language, literacy, and the brain, we find ourselves ill equipped to deal with these conceptually and qualitatively different phenomena. Immediately we must straddle different academic traditions that treat each of these as separate “things”. Broadly speaking, the study of language firstly belongs to the domain of biology, then to anthropology, sociology, and linguistics. At its most functional, a study of literacy education is a study of a particular technology, its diffusion techniques, and the abilities and motivations of people to adopt, or adapt themselves to, this technology. The brain is most commonly studied in the field of neurology, which is also a sub-discipline of biology, biochemistry, and medicine.