Detection of the protein dimers, multiple monomeric states and hydrated forms of Plasmodium falciparum triosephosphate isomerase in the gas phase

Dimeric and monomeric forms of the enzyme triosephosphate isomerase (TIM) from Plasmodium falciparum (Pf) have been detected under conditions of nanoflow by electrospray mass spectrometry. The dimer (M = 55 663 Da) exhibits a narrow charge state distribution with intense peaks limited to values of 18(+) to 21(+), maximal intensity being observed for charge states 19(+) and 20(+). A monomeric species with a charge state distribution ranging from 11(+) to 16(+) is also observed, which may be assigned to folded dissociated subunits. Complete dimer dissociation results under normal electrospray condition. The effects of solution pH and source temperature have been investigated. The observation of four distinct charge state distributions which may be assigned to a dimer, folded monomer, partially folded monomer and unfolded monomer is reported. Circular dichromism and fluorescence studies of Pf TIM at low pH support the retention of substantial secondary and tertiary structures. Satellite peaks in mass spectra corresponding to hydrated species are also observed and isotope shift upon deuteration is demonstrated. The analysis of all available independent crystal structures of Pf TIM and TIMs from other organisms permits identification of structurally conserved water molecules. Hydration observed in the dimer and folded monomeric forms in the gas phase may correspond to these conserved sites.

Social media in selected Australian federal and state election campaigns, 2010-15

Campaigning in Australian election campaigns at local, state, and federal levels is fundamentally affected by the fact that voting is compulsory in Australia, with citizens who are found to have failed to cast their vote subject to fines. This means that - contrary to the situation in most other nations – elections are decided not by which candidate or party has managed to encourage the largest number of nominal supporters to make the effort to cast their vote, but by some 10-20% of genuine ‘swinging voters’ who change their party preferences from one election to the next. Political campaigning is thus aimed less at existing party supporters (so-called ‘rusted on’ voters whose continued support for the party is essentially taken for granted) than at this genuinely undecided middle of the electorate. Over the past decades, this has resulted in a comparatively timid, vague campaigning style from both major party blocs (the progressive Australian Labor Party [ALP] and the conservative Coalition of the Liberal and National Parties [L/NP]). Election commitments that run the risk of being seen as too partisan and ideological are avoided as they could scare away swinging voters, and recent elections have been fought as much (or more) on the basis of party leaders’ perceived personas as they have on stated policies, even though Australia uses a parliamentary system in which the Prime Minister and state Premiers are elected by their party room rather than directly by voters. At the same time, this perceived lack of distinctiveness in policies between the major parties has also enabled the emergence of new, smaller parties which (under Australia’s Westminster-derived political system) have no hope of gaining a parliamentary majority but could, in a close election, come to hold the balance of power and thus exert disproportionate influence on a government which relies on their support.

May the best Tweeter win : The Twitter strategies of key campaign accounts in the 2012 US election

The 2008 US election has been heralded as the first presidential election of the social media era, but took place at a time when social media were still in a state of comparative infancy; so much so that the most important platform was not Facebook or Twitter, but the purpose-built campaign site my.barackobama.com, which became the central vehicle for the most successful electoral fundraising campaign in American history. By 2012, the social media landscape had changed: Facebook and, to a somewhat lesser extent, Twitter are now well-established as the leading social media platforms in the United States, and were used extensively by the campaign organisations of both candidates. As third-party spaces controlled by independent commercial entities, however, their use necessarily differs from that of home-grown, party-controlled sites: from the point of view of the platform itself, a @BarackObama or @MittRomney is technically no different from any other account, except for the very high follower count and an exceptional volume of @mentions. In spite of the significant social media experience which Democrat and Republican campaign strategists had already accumulated during the 2008 campaign, therefore, the translation of such experience to the use of Facebook and Twitter in their 2012 incarnations still required a substantial amount of new work, experimentation, and evaluation. This chapter examines the Twitter strategies of the leading accounts operated by both campaign headquarters: the ‘personal’ candidate accounts @BarackObama and @MittRomney as well as @JoeBiden and @PaulRyanVP, and the campaign accounts @Obama2012 and @TeamRomney. Drawing on datasets which capture all tweets from and at these accounts during the final months of the campaign (from early September 2012 to the immediate aftermath of the election night), we reconstruct the campaigns’ approaches to using Twitter for electioneering from the quantitative and qualitative patterns of their activities, and explore the resonance which these accounts have found with the wider Twitter userbase. A particular focus of our investigation in this context will be on the tweeting styles of these accounts: the mixture of original messages, @replies, and retweets, and the level and nature of engagement with everyday Twitter followers. We will examine whether the accounts chose to respond (by @replying) to the messages of support or criticism which were directed at them, whether they retweeted any such messages (and whether there was any preferential retweeting of influential or – alternatively – demonstratively ordinary users), and/or whether they were used mainly to broadcast and disseminate prepared campaign messages. Our analysis will highlight any significant differences between the accounts we examine, trace changes in style over the course of the final campaign months, and correlate such stylistic differences with the respective electoral positioning of the candidates. Further, we examine the use of these accounts during moments of heightened attention (such as the presidential and vice-presidential debates, or in the context of controversies such as that caused by the publication of the Romney “47%” video; additional case studies may emerge over the remainder of the campaign) to explore how they were used to present or defend key talking points, and exploit or avert damage from campaign gaffes. A complementary analysis of the messages directed at the campaign accounts (in the form of @replies or retweets) will also provide further evidence for the extent to which these talking points were picked up and disseminated by the wider Twitter population. Finally, we also explore the use of external materials (links to articles, images, videos, and other content on the campaign sites themselves, in the mainstream media, or on other platforms) by the campaign accounts, and the resonance which these materials had with the wider follower base of these accounts. This provides an indication of the integration of Twitter into the overall campaigning process, by highlighting how the platform was used as a means of encouraging the viral spread of campaign propaganda (such as advertising materials) or of directing user attention towards favourable media coverage. By building on comprehensive, large datasets of Twitter activity (as of early October, our combined datasets comprise some 3.8 million tweets) which we process and analyse using custom-designed social media analytics tools, and by using our initial quantitative analysis to guide further qualitative evaluation of Twitter activity around these campaign accounts, we are able to provide an in-depth picture of the use of Twitter in political campaigning during the 2012 US election which will provide detailed new insights social media use in contemporary elections. This analysis will then also be able to serve as a touchstone for the analysis of social media use in subsequent elections, in the USA as well as in other developed nations where Twitter and other social media platforms are utilised in electioneering.

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region.

Validation of a 4DOF manoeuvring model of a high-speed vehicle-passenger trimaran

This paper presents the validation of a manoeuvring model for a novel 127m-vehicle-passenger trimaran via full scale trials. The adopted structure of the model is based on a model previously proposed in the literature with some simplifications. The structure of the model is discussed. Then initial parameter estimates are computed, and the final set of parameters are obtained via adjustments based on engineering judgement and application of a genetic algorithm so as to match the data of the trials. The validity of the model is also assessed with data from a trial different from the one use for the parameter adjustment. The model shows good agreement with the trial data.

Impaired physical function associated with childhood obesity: How should we intervene?

- Background This study examined relationships between adiposity, physical functioning and physical activity. - Methods Obese (N=107) and healthy-weight (N=132) children aged 10-13 years underwent assessments of percent body fat (%BF, dual energy X-ray absorptiometry), knee extensor strength (KE, isokinetic dynamometry), cardiorespiratory fitness (CRF, peak oxygen uptake by cycle ergometry), physical health-related quality of life (HRQOL), worst pain intensity and walking capacity [six-minute walk (6MWT)]. Structural equation modelling was used to assess relationships between variables. - Results Moderate relationships were observed between %BF and 6MWT, KE strength corrected for mass and CRF relative to mass (r -.36 to -.69, P≤.007). Weak relationships were found between: %BF and physical HRQOL (r -.27, P=.008); CRF relative to mass and physical HRQOL (r -.24, P=.003); physical activity and 6MWT (r .17, P=.004). Squared multiple correlations showed that 29.6% variance in physical HRQOL was explained by %BF, pain and CRF relative to mass, while 28% variance in 6MWT was explained by %BF and physical activity. - Conclusions It appears that children with a higher body fat percentage have poorer KE strength, CRF and overall physical functioning. Reducing percent fat appears to be the best target to improve functioning. However, a combined approach to intervention, targeting reductions in body fat percentage, pain and improvements in physical activity and CRF may assist physical functioning.

The micropolitics of management in universities: Challenges and opportunities

In recent decades, there has been a strong call by writers in education for alternative forms of leadership and management that are human centred and that value social cohesion, fairness, and democratic practices. Referred to by names such as transformative leadership (Shields, 2013) and ethical leadership (Starratt, 1996), those promoting these types of leadership argue for the use of “power as a moral force for the common good” (Duignan, 2007, p.12). In this chapter, our interest lies with managers in universities and how they use power in ethical and unethical ways. We consider some macro forces (e.g., globalisation, neo-liberal policies) that have impacted universities, making it difficult for managers to promote socially just and equitable practices. In particular, we examine the influence of managerialism—the application of private sector practices to the public sector—where the role of manager is not to question current practices, but to conform to performance targets, and to ensure compliance (O’Brien & Down, 2002). To come to an understanding of what might constitute ethical practices, we refer to the field of micropolitics as a way to help illuminate current practice and point to more positive ways of working.

Key change: The role of the creative industries in climate change action

The role of the creative industries – arts and artists – in helping to drive the changes in laws and behaviours that are necessary to tackle climate change, while not superficially obvious, is a deep one. Arts and artists of all kinds, as cultural practitioners, have been closely entwined with social change and social control since time immemorial, in large part because they help shape our understanding of the world, framing ideas, prefiguring change, and opening hearts and minds to new ways of thinking. They have played a major role in campaigns for law reform on many issues, and climate change should be no exception. Indeed, with climate change increasingly being seen as a deeply cultural issue, and its solutions as cultural ones to do with changing the way we understand our world and our place in it, the role of cultural practitioners in helping to address it should also increasingly be seen as central. It is curious, then, how comparatively little artistic engagement with climate change has taken place, how little engagement with the arts the climate movement has attempted, and how little theoretical and critical analysis has been undertaken on the role of the creative arts in climate change action. Through a literature review and a series of interviews with individuals working in relevant fields in Australia, this study examines and evaluates the role of the creative industries in climate change action and places it in a historical and theoretical context. It covers examples of the kind of artistic and activist collaborations that have been undertaken, the different roles in communication, campaigning for law reform, and deep culture change that arts and artists can play, and the risks and dangers inherent in the involvement of artists, both to climate change action and to the artist. It concludes that, despite the risks, a deeper and more thoughtful engagement of and by the creative industries in climate action would not only be useful but is perhaps vital to the success of the endeavours.

"Like a monkey with a miniature cymbal": Cultural practices of repetition in visual social media

Looping media are recurring components of online content, from gifs to Vine videos, in addition to the conceptual repetition of memes and related practices. This paper analyses practices around looping visual media as examples of vernacular creativity, social media literacies, and internet culture, especially for irreverent and playful purposes. Focusing on the LGBTQ digital cultural context as a pilot study, this research examines multi-platform uses of looping media, including personal narratives through Vine videos and animated gifs on Tumblr. In addition to textual analysis of LGBTQ looping visual social media content, the study will further explore the platform context as part of the experience of looped media. The research will address how these factors may also contribute to practices of irreverence and play, both within the specific case of LGBTQ culture and internet culture more generally.

Social Media and Everyday Politics

From selfies and memes to hashtags and parodies, social media are used for mundane and personal expressions of political commentary, engagement, and participation. The coverage of politics reflects the social mediation of everyday life, where individual experiences and thoughts are documented and shared online. In Social Media and Everyday Politics, Tim Highfield examines political talk as everyday occurrences on Twitter, Facebook, blogs, Tumblr, Instagram, and more. He considers the personal and the political, the serious and the silly, and the everyday within the extraordinary, as politics arises from seemingly banal and irreverent topics. The analysis features international examples and evolving practices, from French blogs to Vines from Australia, via the Arab Spring, Occupy, #jesuischarlie, Eurovision, #blacklivesmatter, Everyday Sexism, and #illridewithyou. This timely book will be a valuable resource for students and scholars in media and communications, internet studies, and political science, as well as general readers keen to understand our contemporary media and political contexts.

Identifying safety beliefs among Australian electrical workers

The current study explored underlying beliefs regarding work safety among a sample of experienced Australian electrical workers. A qualitative research methodology using the theory of planned behavior as a framework was employed. A series of interviews and focus groups with licensed electrical workers (N = 46) were analyzed using thematic content analysis. Beliefs were classified as advantages (e.g. personal safety of self and co-workers), disadvantages (e.g., inconvenience to customer/clients and workload), referents (e.g., supervisors, work colleagues, customers), barriers (e.g., time and cost), and facilitators (e.g., training and knowledge, equipment availability) of safety adherence. The belief basis of the theory of planned behavior was a useful framework for exploring workers’ safety beliefs. The identified beliefs can inform future research about the important factors influencing safe work decisions and inform strategies to promote safer workplace decision making within the electrical safety context.

Shifting the Focus. Incorporating knowledge about Aboriginal engineering into main stream content

BACKGROUND OR CONTEXT The concept of 'Aboriginal engineering' has had little exposure in conventional engineering education programs, despite more than 40,000 years of active human engagement with the diverse Australian environment. The work reported in this paper began with the premise that Indigenous Student Support Through Indigenous Perspectives Embedded in Engineering Curricula (Goldfinch, et al 2013) would provide a clear and replicable means of encouraging Aboriginal teenagers to consider a career in engineering. Although that remains a key outcome of this OLT project, the direction taken by the research had led to additional insights and perspectives that have wide implications for engineering education more generally. There has only been passing reference to the achievements of Aboriginal engineering in current texts, and the very absence of such references was a prompt to explore further as our work developed. PURPOSE OR GOAL Project goals focused on curriculum-based change, including development of a model for inclusive teaching spaces, and study units employing key features of the model. As work progressed we found we needed to understand more about the principles and practices informing the development of pre-contact Aboriginal engineering strategies for sustaining life and society within the landscape of this often harsh continent. We also found ourselves being asked 'what engineering did Aboriginal cultures have?' Finding that there are no easy-to- access answers, we began researching the question, while continuing to engage with specific curriculum trials. APPROACH Stakeholders in the project had been identified as engineering educators, potential Aboriginal students and Aboriginal communities local to Universities involved in the project. We realised, early on, that at least one more group was involved - all the non-Aboriginal students in engineering classes. This realisation, coupled with recognition of the need to understand Aboriginal engineering as a set of viable, long term practices, altered the focus of our efforts. Rather than focusing primarily on finding ways to attract Aboriginal engineering students, the shift has been towards evolving ways of including knowledge about Aboriginal practices and principles in relevant engineering content. DISCUSSION This paper introduces the model resulting from the work of this project, explores its potential influence on engineering curriculum development and reports on implementation strategies. The model is a static representation of a dynamic and cyclic approach to engaging with Aboriginal engineering through contact with local communities in regard to building knowledge about the social beliefs underlying Aboriginal engineering principles and practices. Ways to engage engineering educators, students and the wider community are evolving through the continuing work of the project team and will be reported in more detail in the paper. RECOMMENDATIONS/IMPLICATIONS/CONCLUSION While engineering may be considered by some to be agnostic in regard to culture and social issues, the work of this project is drawing attention to the importance of including such issues into curriculum materials at a number of levels of complexity. The paper will introduce and explore the central concepts of the research completed to date, as well as suggesting ways in which engineering educators can extend their knowledge and understanding of Aboriginal engineering principles in the context of their own specialisations.

Where the action isn't, that's where it is

Contribution to ARI Remix. ARI remix is a three-year digital humanities, artist interviews and oral history project collecting and presenting memories of Australian Artist-run culture in Queensland, New South Wales and the Australian Capital Territory between 1980 and 2000. Its focus is fleshing out and illuminating the ephemeral and neglected histories of the many lively and socially engaged artistic scenes along the east coast of Australia during the last two decades of the 20th century.

Structural effects of a dimer interface mutation on catalytic activity of triosephosphate isomerase.The role of conserved residues and complementary mutations

The active site of triosephosphate isomerase (TIM, EC: 5.3.1.1), a dimeric enzyme, lies very close to the subunit interface. Attempts to engineer monomeric enzymes have yielded well-folded proteins with dramatically reduced activity. The role of dimer interface residues in the stability and activity of the Plasmodium falciparum enzyme, PfTIM, has been probed by analysis of mutational effects at residue 74. The PfTIM triple mutant W11F/W168F/Y74W (Y74W*) has been shown to dissociate at low protein concentrations, and exhibits considerably reduced stability in the presence of denaturants, urea and guanidinium chloride. The Y74W* mutant exhibits concentration-dependent activity, with an approximately 22-fold enhancement of kcat over a concentration range of 2.5–40 μm, suggesting that dimerization is obligatory for enzyme activity. The Y74W* mutant shows an approximately 20-fold reduction in activity compared to the control enzyme (PfTIM WT*, W11F/W168F). Careful inspection of the available crystal structures of the enzyme, together with 412 unique protein sequences, revealed the importance of conserved residues in the vicinity of the active site that serve to position the functional K12 residue. The network of key interactions spans the interacting subunits. The Y74W* mutation can perturb orientations of the active site residues, due to steric clashes with proximal aromatic residues in PfTIM. The available crystal structures of the enzyme from Giardia lamblia, which contains a Trp residue at the structurally equivalent position, establishes the need for complementary mutations and maintenance of weak interactions in order to accommodate the bulky side chain and preserve active site integrity.