Use of the piggyBac transposon to create HIV-1 gag transgenic insect cell lines for continuous VLP production

Background Insect baculovirus-produced Human immunodeficiency virus type 1 (HIV-1) Gag virus-like-particles (VLPs) stimulate good humoral and cell-mediated immune responses in animals and are thought to be suitable as a vaccine candidate. Drawbacks to this production system include contamination of VLP preparations with baculovirus and the necessity for routine maintenance of infectious baculovirus stock. We used piggyBac transposition as a novel method to create transgenic insect cell lines for continuous VLP production as an alternative to the baculovirus system. Results Transgenic cell lines maintained stable gag transgene integration and expression up to 100 cell passages, and although the level of VLPs produced was low compared to baculovirus-produced VLPs, they appeared similar in size and morphology to baculovirus-expressed VLPs. In a murine immunogenicity study, whereas baculovirus-produced VLPs elicited good CD4 immune responses in mice when used to boost a prime with a DNA vaccine, no boost response was elicited by transgenically produced VLPs. Conclusion Transgenic insect cells are stable and can produce HIV Pr55 Gag VLPs for over 100 passages: this novel result may simplify strategies aimed at making protein subunit vaccines for HIV. Immunogenicity of the Gag VLPs in mice was less than that of baculovirus-produced VLPs, which may be due to lack of baculovirus glycoprotein incorporation in the transgenic cell VLPs. Improved yield and immunogenicity of transgenic cell-produced VLPs may be achieved with the addition of further genetic elements into the piggyBac integron.

International differences in management of physical activity data: Can they explain some of the difference in prevalence estimates?

Background: National physical activity data suggest that there is a considerable difference in physical activity levels of US and Australian adults. Although different surveys (Active Australia and BRFSS) are used, the questions are similar. Different protocols, however, are used to estimate “activity” from the data collected. The primary aim of this study was to assess whether the 2 approaches to the management of PA data could explain some of the difference in prevalence estimates derived from the two national surveys. Methods: Secondary data analysis of the most recent AA survey (N = 2987). Results: 15% of the sample was defined as “active” using Australian criteria but as “inactive” using the BRFSS protocol, even though weekly energy expenditure was commensurate with meeting current guidelines. Younger respondents (age < 45 y) were more likely to be “misclassified” using the BRFSS criteria. Conclusions: The prevalence of activity in Australia and the US appears to be more similar than we had previously thought.

A virtual environment to simulate the experience of psychosis

Psychosis is a mental disorder that affects 1-2% of the population at some point in their lives. One of the main causes of psychosis is the mental illness schizophrenia. Sufferers of this illness often have terrifying symptoms such as hallucinations, delusions, and thought disorder. This project aims to develop a virtual environment to simulate the experience of psychosis, focusing on re-creating auditory and visual hallucinations. A model of a psychiatric ward was created and the psychosis simulation software was written to re-create the auditory and visual hallucinations of one particular patient. The patient was very impressed with the simulation, and commented that it effectively re-created the same emotions that she experienced on a day-to-day basis during her psychotic episodes. It is hoped that this work will result in a useful educational tool about schizophrenia, leading to improved training of clinicians, and fostering improved understanding and empathy toward sufferers of schizophrenia in the community, ultimately improving the quality of life and chances of recovery of patients.

The development of a virtual reality environment to model the experience of schizophrenia

Virtual Reality (VR) techniques are increasingly being used for education about and in the treatment of certain types of mental illness. Research indicates that VR is delivering on its promised potential to provide enhanced training and treatment outcomes through incorporation of this high-end technology. Schizophrenia is a mental disorder affecting 1-2% of the population, and it is estimated 12-16% of hospital beds in Australia are occupied by patients with psychosis. Tragically, there is also an increased risk of suicide associated with this diagnosis. A significant research project being undertaken across the University of Queensland faculties of Health Sciences and EPSA (Engineering, Physical Sciences and Architecture) has constructed a number of virtual environments that reproduce the phenomena experienced by patients who have psychosis. Symptoms of psychosis include delusions, hallucinations and thought disorder. The VR environment will allow behavioral, exposure therapies to be conducted with exactly controlled exposure stimuli and an expected reduction in risk of harm. This paper reports on the current work of the project, previous stages of software development and the final goal to introduce VR to medical consulting rooms.

‘Supersize me’ : on equine obesity

There’s nothing like travel to broaden the mind. As a young man living in Britain during the 1980s I thought I knew about human obesity, but it took a visit to the US to show me what an epidemic looks like. Nowadays I live in Australia, where human obesity is rife. We have plenty of fat horses too (Sillence et al., 2006), but they are noticeable. In fact, it was only recently during a return visit to Britain, that I was finally sold on the concept of an equine obesity epidemic. It seems that in the UK, the fat horse or pony is now so commonplace that it has come to represent the norm in the eyes of many owners. I met clinicians who claim to have forgotten what a fit horse looks like, and heard anecdotes of a responsible owner who kept their animals in a healthy body condition, only to be reported to the RSPCA for ‘cruelty’. Round and shiny have become the order of the day and, as we have learned from the tsunami of human obesity, once a problem reaches a certain scale it can seem unstoppable, despite the attendant risks, costs and consequences.

Variation in risk seeking behavior in a natural experiment following a large negative wealth shock induced by a natural disaster

An ongoing challenge in behavioral economics is to understand the variations observed in risk attitudes as a function of their environmental context. Of particular interest is the effect of wealth on risk attitudes. The research in this area has however faced two constraints: the difficulty to study the causal effects of large changes in wealth, and the causal effects of losses on risk behavior. The present paper address this double limitation by providing evidence of the variation of risk attitude after large losses using a natural disaster (Brisbane floods) as the setting for a natural experiment.

Krüppel-associated box (KRAB)-associated co-repressor (KAP-1) Ser-473 phosphorylation regulates heterochromatin protein 1 (HP1- ) mobilization and DNA repair in heterochromatin

The DNA damage response encompasses a complex series of signaling pathways that function to regulate and facilitate the repair of damaged DNA. Recent studies have shown that the repair of transcriptionally inactive chromatin, named heterochromatin, is dependent upon the phosphorylation of the co-repressor, Krüppel-associated box (KRAB) domain-associated protein (KAP-1), by the ataxia telangiectasia-mutated (ATM) kinase. Co-repressors, such as KAP-1, function to regulate the rigid structure of heterochromatin by recruiting histone-modifying enzymes, such HDAC1/2, SETDB1, and nucleosome-remodeling complexes such as CHD3. Here, we have characterized a phosphorylation site in the HP1-binding domain of KAP-1, Ser-473, which is phosphorylated by the cell cycle checkpoint kinase Chk2. Expression of a nonphosphorylatable S473A mutant conferred cellular sensitivity to DNA-damaging agents and led to defective repair of DNA double-strand breaks in heterochromatin. In addition, cells expressing S473A also displayed defective mobilization of the HP1-β chromodomain protein. The DNA repair defect observed in cells expressing S473A was alleviated by depletion of HP1-β, suggesting that phosphorylation of KAP-1 on Ser-473 promotes the mobilization of HP1-β from heterochromatin and subsequent DNA repair. These results suggest a novel mechanism of KAP-1-mediated chromatin restructuring via Chk2-regulated HP1-β exchange from heterochromatin, promoting DNA repair.

Dichotomy in the design studio 2.0 : adapting to new blended learning environments

In a study aimed at better understanding how students adapt to new blended studio learning environments, all undergraduate and masters of architecture students at a large school of architecture in Australia, learned a semester of architectural design in newly renovated, technology embedded, design studio environments. The renovations addressed the lessons learned from a 2011 pilot study of a second year architectural design studio learned in a high technology embedded prototype digital laboratory. The new design studios were purpose designed for the architecture students and adapted Student-Centred Active Learning Environment for Undergraduate Programs design principles. At the end of the semester, the students completed a questionnaire about their experiences of learning in the new design studio environments. Using a dual method qualitative approach, the questionnaire data were coded and extrapolated using both thematic analysis and grounded theory methodology. The results from these two approaches were compared, contrasted and finally merged, to reveal five distinct emerging themes, which were instrumental in offering resistance or influencing adaptation to, the new blended studio learning environments. This paper reports on the study, discusses the major contributors to resistance and adaptation, and proposes points for consideration when renovating or designing new blended studio learning environments. This research extends the 2011 pilot study by the same authors: ‘Dichotomy in the design studio: Adapting to new blended learning environments’.

Architecture et révolution : Le Corbusier and the fascist revolution

In a letter to a close friend dated April 1922 Le Corbusier announced that he was to publish his first major book, Architecture et révolution, which would collect “a set ofarticles from L’EN.”1—L’Esprit nouveau, the revue jointly edited by him and painter Amédée Ozenfant, which ran from 1920 to 1925.2 A year later, Le Corbusier sketched a book cover design featuring “LE CORBUSIER - SAUGNIER,” the pseudonymic compound of Pierre Jeanneret and Ozenfant, above a square-framed single-point perspective of a square tunnel vanishing toward the horizon. Occupying the lower half of the frame was the book’s provisional title in large handwritten capital letters, ARCHITECTURE OU RÉVOLUTION, each word on a separate line, the “ou” a laconic inflection of Paul Laffitte’s proposed title, effected by Le Corbusier.3 Laffitte was one of two publishers Le Corbusier was courting between 1921 and 1922.4 An advertisement for the book, with the title finally settled upon, Vers une architecture, 5 was solicited for L’Esprit nouveau number 18. This was the original title conceived with Ozenfant, and had in fact already appeared in two earlier announcements.6 “Architecture ou révolution” was retained as the name of the book’s crucial and final chapter—the culmination of six chapters extracted from essays in L’Esprit nouveau. This chapter contained the most quoted passage in Vers une architecture, used by numerous scholars to adduce Le Corbusier’s political sentiment in 1923 to the extent of becoming axiomatic of his early political thought.7 Interestingly, it is the only chapter that was not published in L’Esprit nouveau, owing to a hiatus in the journal’s production from June 1922 to November 1923.8 An agitprop pamphlet was produced in 1922, after L’Esprit nouveau 11-12, advertising an imminent issue “Architecture ou révolution” with the famous warning: “the housing crisis will lead to the revolution. Worry about housing.”9

Solving tri-diagonal linear systems using field programmable gate arrays

In this paper, we present the outcomes of a project on the exploration of the use of Field Programmable Gate Arrays (FPGAs) as co-processors for scientific computation. We designed a custom circuit for the pipelined solving of multiple tri-diagonal linear systems. The design is well suited for applications that require many independent tri-diagonal system solves, such as finite difference methods for solving PDEs or applications utilising cubic spline interpolation. The selected solver algorithm was the Tri-Diagonal Matrix Algorithm (TDMA or Thomas Algorithm). Our solver supports user specified precision thought the use of a custom floating point VHDL library supporting addition, subtraction, multiplication and division. The variable precision TDMA solver was tested for correctness in simulation mode. The TDMA pipeline was tested successfully in hardware using a simplified solver model. The details of implementation, the limitations, and future work are also discussed.

A novel DRD2 single-nucleotide polymorphism associated with schizophrenia predicts age of onset : HapMap tag-single-nucleotide polymorphism analysis

Background: Dopamine D2 receptor (DRD2) is thought to be critical in regulating the dopaminergic pathway in the brain which is known to be important in the aetiology of schizophrenia. It is therefore not surprising that most antipsychotic medication acts on the Dopamine D2 receptor. DRD2 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and DRD2 polymorphisms have been associated with reduced brain expression. We have previously identified a genetic variant in DRD2, rs6277 to be strongly implicated in schizophrenia susceptibility. Methods: To identity new associations in the DRD2 gene with disease status and clinical severity, we genotyped seven single nucleotide polymorphisms (SNPs) in DRD2 using a multiplex mass spectrometry method. SNPs were chosen using a haplotype block-based gene-tagging approach so the entire DRD2 gene was represented. Results: One polymorphism rs2734839 was found to be significantly associated with schizophrenia as well as late onset age. Individuals carrying the genetic variation were more than twice as likely to have schizophrenia compared to controls. Conclusions: Our results suggest that DRD2 genetic variation is a good indicator for schizophrenia risk and may also be used as a predictor age of onset.

Understanding pre-service teacher conceptual change through slowmation animation

This paper is an exploration of conceptual change. It reports on a study which utilised Hewson and Lemberger’s (2000) Conceptual Status Elements, and explores the unique contribution of Slowmation Animation in the conceptual learning of pre-service science teachers. 15 short animations were created by 55 participants in a single two hour tutorial class as a part of their methods training. Conceptual change was found to occur when their animation topic challenged their understandings of the processes within the scientific concept. The pre-service science teachers reported an enthusiasm for Slowmation Animation as a method for learning how to learn, as well as for highlighting what they thought they knew, but didn’t really know.

On being balanced in an unbalanced world

This paper examines the case of a procurement auction for a single project, in which the breakdown of the winning bid into its component items determines the value of payments subsequently made to bidder as the work progresses. Unbalanced bidding, or bid skewing, involves the uneven distribution of mark-up among the component items in such a way as to attempt to derive increased benefit to the unbalancer but without involving any change in the total bid. One form of unbalanced bidding for example, termed Front Loading (FL), is thought to be widespread in practice. This involves overpricing the work items that occur early in the project and underpricing the work items that occur later in the project in order to enhance the bidder's cash flow. Naturally, auctioners attempt to protect themselves from the effects of unbalancing—typically reserving the right to reject a bid that has been detected as unbalanced. As a result, models have been developed to both unbalance bids and detect unbalanced bids but virtually nothing is known of their use, success or otherwise. This is of particular concern for the detection methods as, without testing, there is no way of knowing the extent to which unbalanced bids are remaining undetected or balanced bids are being falsely detected as unbalanced. This paper reports on a simulation study aimed at demonstrating the likely effects of unbalanced bid detection models in a deterministic environment involving FL unbalancing in a Texas DOT detection setting, in which bids are deemed to be unbalanced if an item exceeds a maximum (or fails to reach a minimum) ‘cut-off’ value determined by the Texas method. A proportion of bids are automatically and maximally unbalanced over a long series of simulated contract projects and the profits and detection rates of both the balancers and unbalancers are compared. The results show that, as expected, the balanced bids are often incorrectly detected as unbalanced, with the rate of (mis)detection increasing with the proportion of FL bidders in the auction. It is also shown that, while the profit for balanced bidders remains the same irrespective of the number of FL bidders involved, the FL bidder's profit increases with the greater proportion of FL bidders present in the auction. Sensitivity tests show the results to be generally robust, with (mis)detection rates increasing further when there are fewer bidders in the auction and when more data are averaged to determine the baseline value, but being smaller or larger with increased cut-off values and increased cost and estimate variability depending on the number of FL bidders involved. The FL bidder's expected benefit from unbalancing, on the other hand, increases, when there are fewer bidders in the auction. It also increases when the cut-off rate and discount rate is increased, when there is less variability in the costs and their estimates, and when less data are used in setting the baseline values.

Evolving and expanding : the scope of practice of the infection control practitioner

Infection control practitioners (ICPs) work across the full spectrum of health care settings and carry out a broad range of practice activities. Whilst several studies have reported on the role of the ICP, there has been little investigation of the scope of infection control practice. This knowledge is essential to inform the professional, legal, educational and financial implications of this specialist role. One hundred and thirteen ICPs from a range of health care settings across Queensland were surveyed. Respondents were asked to rate the extent to which they were and should be engaging in the range of practices identified by Gardner, Jones & Olesen (1999). Significant differences were evident between what ICPs said was their actual practice versus what they thought they should be doing. Overall, the respondents consistently reported that they should be engaging in more of the range of infection control activities than they were, particularly with regard to management practices. A number of differences were found according to the context in which the practitioners worked, such as the type and size of facility and their employment status. The results of this study indicate that the scope of infection control practice has clearly moved beyond those practices that are confined by the hospital wall and defined by surveillance activities.

Employee perceptions regarding the effectiveness of occupational road safety initiatives

A range of risk management initiatives have been introduced in organisations in attempt to reduce occupational road incidents. However a discrepancy exists between the initiatives that are frequently implemented in organisations and the initiatives that have demonstrated scientific merit in improving occupational road safety. Given that employees’ beliefs may facilitate or act as a barrier to implementing initiatives, it is important to understand whether initiatives with scientific merit are perceived to be effective by employees. To explore employee perceptions pertaining to occupational road safety initiatives, a questionnaire was administered to 679 employees sourced from four Australian organisations. Participants ranged in age from 18 years to 65 years (M = 42, SD = 11). Participants rated 35 initiatives based on how effective they thought they would be in improving road safety in their organisation. The initiatives perceived by employees to be most effective in managing occupational road risks comprised: making vehicle safety features standard e.g. passenger airbags; practical driver skills training; and investigation of serious vehicle incidents. The initiatives perceived to be least effective in managing occupational road risks comprised: signing a promise card commitment to drive safely; advertising the organisation’s phone number on vehicles for complaints and compliments; and consideration of driving competency in staff selection process. Employee perceptions were analysed at a factor level and at an initiative level. The mean scores for the three extracted factors revealed that employees believed occupational road risks could best be managed by the employer implementing engineering and human resource methods to enhance road safety. Initiatives relating to employer management of identified risk factors were perceived to be more effective than feedback or motivational methods that required employees to accept responsibility for their driving safety. Practitioners can use the findings from this study to make informed decisions about how they select, manage and market occupational safety initiatives.