A Systematic Review of kinematic models used in foot & ankle biomechanics

Over the past decade our understanding of foot function has increased significantly[1,2]. Our understanding of foot and ankle biomechanics appears to be directly correlated to advances in models used to assess and quantify kinematic parameters in gait. These advances in models in turn lead to greater detail in the data. However, we must consider that the level of complexity is determined by the question or task being analysed. This systematic review aims to provide a critical appraisal of commonly used marker sets and foot models to assess foot and ankle kinematics in a wide variety of clinical and research purposes.

Defining standards for modelling the biomechanics of the foot and ankle: A systematic review

The complex interaction of the bones of the foot has been explored in detail in recent years, which has led to the acknowledgement in the biomechanics community that the foot can no longer be considered as a single rigid segment. With the advance of motion analysis technology it has become possible to quantify the biomechanics of simplified units or segments that make up the foot. Advances in technology coupled with reducing hardware prices has resulted in the uptake of more advanced tools available for clinical gait analysis. The increased use of these techniques in clinical practice requires defined standards for modelling and reporting of foot and ankle kinematics. This systematic review aims to provide a critical appraisal of commonly used foot and ankle marker sets designed to assess kinematics and thus provide a theoretical background for the development of modelling standards.

Transcriptome Profiling of Sexual Maturation and Mating in the Mediterranean Fruit Fly, Ceratitis capitata

Sexual maturation and mating in insects are generally accompanied by major physiological and behavioural changes. Many of these changes are related to the need to locate a mate and subsequently, in the case of females, to switch from mate searching to oviposition behaviour. The prodigious reproductive capacity of the Mediterranean fruit fly, Ceratitis capitata, is one of the factors that has led to its success as an invasive pest species. To identify the molecular changes related to maturation and mating status in male and female medfly, a microarray-based gene expression approach was used to compare the head transcriptomes of sexually immature, mature virgin, and mated individuals. Attention was focused on the changes in abundance of transcripts related to reproduction, behaviour, sensory perception of chemical stimulus, and immune system processes. Broad transcriptional changes were recorded during female maturation, while post-mating transcriptional changes in females were, by contrast, modest. In male medfly, transcriptional changes were consistent both during maturation and as a consequence of mating. Of particular note was the lack of the mating-induced immune responses that have been recorded for Drosophila melanogaster, that may be due to the different reproductive strategies of these species. This study, in addition to increasing our understanding of the molecular machinery behind maturation and mating in the medfly, has identified important gene targets that might be useful in the future management of this pest.

Syntaxin 6 and Vti1b form a novel SNARE complex, which is upregulated in activated macrophages to facilitate exocytosis of TNF.

A key function of activated macrophages is to secrete proinflammatory cytokines such as TNF; however, the intracellular pathway and machinery responsible for cytokine trafficking and secretion is largely undefined. Here we show that individual SNARE proteins involved in vesicle docking and fusion are regulated at both gene and protein expression upon stimulation with the bacterial cell wall component lipopolysaccharide. Focusing on two intracellular SNARE proteins, Vti1b and syntaxin 6 (Stx6), we show that they are up-regulated in conjunction with increasing cytokine secretion in activated macrophages and that their levels are selectively titrated to accommodate the volume and timing of post-Golgi cytokine trafficking. In macrophages, Vti1b and syntaxin 6 are localized on intracellular membranes and are present on isolated Golgi membranes and on Golgi-derived TNF� vesicles budded in vitro. By immunoprecipitation, we find that Vti1b and syntaxin 6 interact to form a novel intracellular Q-SNARE complex. Functional studies using overexpression of full-length and truncated proteins show that both Vti1b and syntaxin 6 function and have rate-limiting roles in TNF� trafficking and secretion. This study shows how macrophages have uniquely adapted a novel Golgi-associated SNARE complex to accommodate their requirement for increased cytokine secretion.

Performing design analysis: game design creativity and the theatre of the impressed

We report and reflect upon the early stages of a research project that endeavours to establish a culture of critical design thinking in a tertiary game design course. We first discuss the current state of the Australian game industry and consider some perceived issues in game design courses and graduate outcomes. The second sec-tion presents our response to these issues: a project in progress which uses techniques originally exploited by Augusto Boal in his work, Theatre of the Oppressed. We appropriate Boal’s method to promote critical design thinking in a games design class. Finally, we reflect on the project and the ontology of design thinking from the perspective of Bruce Archer’s call to reframe design as a ‘third academic art’.

The roles of the preproghrelin-derived peptides - ghrelin, desacyl ghrelin and obestatin - in prostate cancer

Prostate cancer is the second most common cause of cancer related deaths in Western men. Despite the significant improvements in current treatment techniques, there is no cure for advanced metastatic, castrate-resistant disease. Early detection and prevention of progression to a castrate-resistant state may provide new strategies to improve survival. A number of growth factors have been shown to act in an autocrine/paracrine manner to modulate prostate cancer tumour growth. Our laboratory has previously shown that ghrelin and its receptors (the functional GHS-R1a and the non-functional GHS-R1b) are expressed in prostate cancer specimens and cell lines. We have shown that ghrelin increases cell proliferation in the PC3 and LNCaP prostate cancer cell lines through activation of ERK1/2, suggesting that ghrelin could regulate prostate cancer cell growth and play a role in the progression of the disease. Ghrelin is a 28 amino-acid peptide hormone, identified to be the natural ligand of the growth hormone secretagogue receptor (GHS-R1a). It is well characterised as a growth hormone releasing and as an orexigenic peptide that stimulates appetite and feeding and regulates energy expenditure and bodyweight. In addition to its orexigenic properties, ghrelin has been shown to play a regulatory role in a number of systems, including the reproductive, immune and cardiovascular systems and may play a role in a number of pathological conditions such as chronic heart failure, anorexia, cachexia, obesity, diabetes and cancer. In cancer, ghrelin and its receptor are expressed in a range of tumours and cancer cell lines and ghrelin has been demonstrated to modulate cell proliferation, apoptosis, migration and invasion in some cell types. The ghrelin gene (GHRL) encodes preproghrelin peptide, which is processed to produce three currently known functional peptides - ghrelin, desacyl ghrelin and obestatin. Prohormone convertases (PCs) have been shown to cleave the preproghrelin peptide into two primary products - the 28 amino acid peptide, ghrelin, and the remaining 117 amino acid C-terminal peptide, C-ghrelin. C-ghrelin can then be further processed to produce the 23 amino acid peptide, obestatin. Ghrelin circulates in two different forms - an octanoylated form (known as ghrelin) and a non-octanoylated form, desacyl ghrelin. The unique post-translational addition of octanoic acid to the serine 3 residue of the propeptide chain to form acylated ghrelin is catalysed by ghrelin O-acyltransferase (GOAT). This modification is necessary for binding of ghrelin to its only known functional receptor, the GHS-R1a. As desacyl ghrelin cannot bind and activate the GHS-R1a, it was initially thought to be an inactive peptide, despite the fact that it circulates at much higher levels than ghrelin. Further research has demonstrated that desacyl ghrelin is biologically active and shares some of the actions of ghrelin, as well as having some opposing and distinct roles. Interestingly, both ghrelin and desacyl ghrelin have been shown to modulate apoptosis, cell differentiation and proliferation in some cell types, and to stimulate cell proliferation through activation of ERK1/2 and PI3K/Akt pathways. The third known peptide product of the ghrelin preprohormone, obestatin, was initially thought to oppose the actions of ghrelin in appetite regulation and food intake and to mediate its effects through the G protein-coupled receptor 39 (GPR39). Subsequent research failed to reproduce the initial findings, however, and the possible anorexigenic effects of obestatin, as well as the identity of its receptor, remain unclear. Obestatin plays some important physiological roles, including roles in improving memory, the inhibition of thirst and anxiety, increased secretion of pancreatic juice, and regulation of cell proliferation, survival, apoptosis and differentiation. Preliminary studies have also shown that obestatin stimulates cell proliferation in some cell types through activation of ERK1/2, Akt and PKC pathways. Overall, however, at the commencement of this PhD project, relatively little was known regarding the functions and mechanisms of action of the preproghrelin-derived functional peptides in modulating prostate cancer cell proliferation. The roles of obestatin, and desacyl ghrelin as potential growth factors had not previously been investigated, and the potential expression and regulation of the preproghrelin processing enzymes, GOAT and prohormone convertases was unknown in prostate cancer cell lines. Therefore, the overall objectives of this study were to: 1. investigate the effects of obestatin on cell proliferation and signaling in prostate cancer cell lines 2. compare the effects of desacyl ghrelin and ghrelin on cell proliferation and signaling in prostate cancer cell lines 3. investigate whether prostate cancer cell lines possess the necessary enzymatic machinery to produce ghrelin and desacyl ghrelin and if these peptides can regulate GOAT expression Our laboratory has previously shown that ghrelin stimulates cell proliferation in the PC3 and LNCaP prostate cancer cell line through activation of the ERK1/2 pathway. In this study it has been demonstrated that treatments with either ghrelin, desacyl ghrelin or obestatin over 72 hours significantly increased cell proliferation in the PC3 prostate cancer cell line but had no significant effect in the RWPE-1 transformed normal prostate cell line. Ghrelin (1000nM) stimulated cell proliferation in the PC3 prostate cancer cell line by 31.66 6.68% (p<0.01) with the WST-1 method, and 13.55 5.68% (p<0.05) with the CyQUANT assay. Desacyl ghrelin (1000nM) increased cell proliferation in PC3 cells by 21.73 2.62% (p<0.01) (WST-1), and 15.46 7.05% (p<0.05) (CyQUANT) above untreated control. Obestatin (1000nM) induced a 28.37 7.47% (p<0.01) (WST-1) and 12.14 7.47% (p<0.05) (CyQUANT) significant increase in cell proliferation in the PC3 prostate cancer cell line. Ghrelin and desacyl ghrelin treatments stimulated Akt and ERK phosphorylation across a range of concentrations (p<0.01). Obestatin treatment significantly stimulated Akt, ERK and PKC phosphorylation (p<0.05). Through the use of specific inhibitors, the MAPK inhibitor U0126 and the Akt1/2 kinase inhibitor, it was demonstrated that ghrelin- and obestatin-induced cell proliferation in the PC3 prostate cancer cell line is mediated through activation of ERK1/2 and Akt pathways. Although desacyl ghrelin significantly stimulated Akt and ERK phosphorylation, U0126 failed to prevent desacyl ghrelin-induced cell proliferation suggesting ghrelin and desacyl ghrelin might act through different mechanisms to increase cell proliferation. Ghrelin and desacyl ghrelin have shown a proliferative effect in osteoblasts, pancreatic -cells and cardiomyocytes through activation of ERK1/2 and PI3K/Akt pathways. Here it has been shown that ghrelin and its non-acylated form exert the same function and stimulate cell proliferation in the PC3 prostate cancer cell line through activation of the Akt pathway. Ghrelin-induced proliferation was also mediated through activation of the ERK1/2 pathway, however, desacyl ghrelin seems to stimulate cell proliferation in an ERK1/2-independent manner. As desacyl ghrelin does not bind and activate GHSR1a, the only known functional ghrelin receptor, the finding that both ghrelin and desacyl ghrelin stimulate cell proliferation in the PC3 cell line suggests that these peptides could be acting through the yet unidentified alternative ghrelin receptor in this cell type. Obestatin treatment also stimulated PKC phosphorylation, however, a direct role for this pathway in stimulating cell proliferation could not be proven using available PKC pathway inhibitors, as they caused significant cell death over the extended timeframe of the cell proliferation assays. Obestatin has been shown to stimulate cell proliferation through activation of PKC isoforms in human retinal epithelial cells and in the human gastric cancer cell line KATO-III. We have demonstrated that all of the prostate-derived cell lines examined (PC3, LNCaP, DU145, 22Rv1, RWPE-1 and RWPE-2) expressed GOAT and at least one of the prohormone convertases, which are known to cleave the proghrelin peptide, PC1/3, PC2 and furin, at the mRNA level. These cells, therefore, are likely to possess the necessary machinery to cleave the preproghrelin protein and to produce the mature ghrelin and desacyl ghrelin peptides. In addition to prohormone convertases, the presence of octanoic acid is essential for acylated ghrelin production. In this study octanoic acid supplementation significantly increased cell proliferation in the PC3 prostate cancer cell line by over 20% compared to untreated controls (p<0.01), but surprisingly, not in the DU145, LNCaP or 22Rv1 prostate cancer cell lines or in the RWPE-1 and RWPE-2 prostate-derived cell lines. In addition, we demonstrated that exogenous ghrelin induced a statistically significant two-fold decrease in GOAT mRNA expression in the PC3 cell line (p<0.05), suggesting that ghrelin could pontentially downregulate its own acylation and, therefore, regulate the balance between ghrelin and desacyl ghrelin. This was not observed, however, in the DU145 and LNCaP prostate cancer cell lines. The GOAT-ghrelin system represents a direct link between ingested nutrients and regulation of ghrelin production and the ghrelin/desacyl ghrelin ratio. Regulation of ghrelin acylation is a potentially attractive and desirable tool for the development of better therapies for a number of pathological conditions where ghrelin has been shown to play a key role. The finding that desacyl ghrelin stimulates cell proliferation in the PC3 prostate cancer cell line, and responds to ghrelin in the same way, suggests that this cell line expresses an alternative ghrelin receptor. Although all the cell lines examined expressed both GHS-R1a and GHS-R1b mRNA, it remains uncertain whether these cell lines express the unidentified alternative ghrelin receptor. It is possible that the varied responses seen could be due to the expression of different ghrelin receptors in different cell lines. In addition to GOAT, prohormone convertases and octanoic acid availability may regulate the production of different peptides from the ghrelin preprohormone. The studies presented in this thesis provide significant new information regarding the roles and mechanisms of action of the preproghrelin-derived peptides, ghrelin, desacyl ghrelin and obestatin, in modulating prostate cancer cell line proliferation. A number of key questions remain to be resolved, however, including the identification of the alternative ghrelin/desacyl ghrelin receptor, the identification of the obestatin receptor, a clarification of the signaling mechanisms which mediate cell proliferation in response to obestatin treatment and a better understanding of the regulation at both the gene and post-translational levels of functional peptide generation. Further studies investigating the role of the ghrelin axis using in vivo prostate cancer models may be warranted. Until these issues are determined, the potential for the ghrelin axis, to be recognised as a novel useful target for therapy for cancer or other pathologies will be uncertain.

Towards visualising people’s ecology of hybrid personal learning environments

Ambient media architecture can provide place-based collaborative learning experiences and pathways for social interactions that would not be otherwise possible. This paper is concerned with ways of enhancing peer-to-peer learning affordances in library spaces; how can the library facilitate the community of library users to learn from each other? We report on the findings of a study that employed a participatory design method where participants were asked to reflect and draw places, social networks, and activities that they use to work (be creative, productive), play (have fun, socialize, be entertained), and learn (acquire new information, knowledge, or skills). The results illustrate how informal learning – learning outside the formal education system – is facilitated by a personal selection of physical and socio-cultural environments, as well as online tools, platforms, and networks. This paper sheds light on participants’ individually curated ecologies of their work, play, and learning related networks and the hybrid (physical and digital) nature of these places. These insights reveal opportunities for ambient media architecture to increase awareness of and connections between people’s hybrid personal learning environments.

Please take out your phones : on the spot solicitation of student feedback in class

The use of mobile devices such as smart phones and tablets in classrooms has been met with mixed sentiments. Some instructors and teachers see them as a distraction and regularly ban their usage. Others who see their potential to enhance learning have started to explore ways to integrate them into their teaching in an attempt to improve student engagement. In this paper we report on a pilot study that forms part of a university-wide project reconceptualising its approach to the student evaluation of learning and teaching. In a progressive decision to embrace mobile technology, the university decided to trial a smart phone app designed for students to check-in to class and leave feedback on the spot. Our preliminary findings from trialling the app indicate that the application establishes a more immediate feedback loop between students and teachers. However, the app’s impact depends on how feedback is shared with students and how the teaching team responds.

The sound of music : sharing song selections between collocated strangers in public urban places

This paper presents Capital Music, a mobile application enabling real-time sharing of song choices with collocated urban dwellers. Due to the real-time, location-based peer-to-peer approach of the application, a user experience study was performed utilising the Wizard of Oz method. The study provides insight into how sharing non-privacy sensitive but personal data in an anonymous way can influence the user experience of people in public urban places. We discuss the findings in relation to how Capital Music influences the process of “cocooning” in public urban places, the practice of designing anonymous interactions between collocated strangers, and how the sharing of song choices can create a sense of commonality between anonymous users in the urban space. The outcomes of this study are relevant for future location-based social networking applications that aim to create interactions between collocated strangers.

Education on plant and machinery valuation for the real market : Malaysian practicality

The purpose of this paper is to determine and discuss on the plant and machinery valuation syllabus for higher learning education in Malaysia to ensure the practicality of the subject in the real market. There have been limited studies in plant and machinery area, either by scholars or practitioners. Most papers highlighted the methodologies but limited papers discussed on the plant and machinery valuation education. This paper will determine inputs for plant and machinery valuation guidance focussing on the syllabus set up and references for valuers interested in this area of expertise. A qualitative approach via content analysis is conducted to compare international and Malaysian plant and machinery valuation syllabus and suggest improvements for Malaysian syllabus. It is found that there are few higher education institutions in the world that provide plant and machinery valuation courses as part of their property studies syllabus. Further investigation revealed that on the job training is the preferable method for plant and machinery valuation education and based on the valuers experience. The significance of this paper is to increase the level of understanding of plant and machinery valuation criteria and provide suggestions to Malaysian stakeholders with the relevant elements in plant and machinery valuation education syllabus.

The capsid protein of beak and feather disease virus binds to the viral DNA and is responsible for transporting the replication-associated protein into the nucleus

Circoviruses lack an autonomous DNA polymerase and are dependent on the replication machinery of the host cell for de novo DNA synthesis. Accordingly, the viral DNA needs to cross both the plasma membrane and the nuclear envelope before replication can occur. Here we report on the subcellular distribution of the beak and feather disease virus (BFDV) capsid protein (CP) and replication-associated protein (Rep) expressed via recombinant baculoviruses in an insect cell system and test the hypothesis that the CP is responsible for transporting the viral genome, as well as Rep, across the nuclear envelope. The intracellular localization of the BFDV CP was found to be directed by three partially overlapping bipartite nuclear localization signals (NLSs) situated between residues 16 and 56 at the N terminus of the protein. Moreover, a DNA binding region was also mapped to the N terminus of the protein and falls within the region containing the three putative NLSs. The ability of CP to bind DNA, coupled with the karyophilic nature of this protein, strongly suggests that it may be responsible for nuclear targeting of the viral genome. Interestingly, whereas Rep expressed on its own in insect cells is restricted to the cytoplasm, coexpression with CP alters the subcellular localization of Rep to the nucleus, strongly suggesting that an interaction with CP facilitates movement of Rep into the nucleus. Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Robots move : bootstrapping the development of object representations using sensorimotor coordination

This paper is concerned with the unsupervised learning of object representations by fusing visual and motor information. The problem is posed for a mobile robot that develops its representations as it incrementally gathers data. The scenario is problematic as the robot only has limited information at each time step with which it must generate and update its representations. Object representations are refined as multiple instances of sensory data are presented; however, it is uncertain whether two data instances are synonymous with the same object. This process can easily diverge from stability. The premise of the presented work is that a robot's motor information instigates successful generation of visual representations. An understanding of self-motion enables a prediction to be made before performing an action, resulting in a stronger belief of data association. The system is implemented as a data-driven partially observable semi-Markov decision process. Object representations are formed as the process's hidden states and are coordinated with motor commands through state transitions. Experiments show the prediction process is essential in enabling the unsupervised learning method to converge to a solution - improving precision and recall over using sensory data alone.

Cell death control : the interplay of apoptosis and autophagy in the pathogenicity of sclerotinia sclerotiorum

Programmed cell death is characterized by a cascade of tightly controlled events that culminate in the orchestrated death of the cell. In multicellular organisms autophagy and apoptosis are recognized as two principal means by which these genetically determined cell deaths occur. During plant-microbe interactions cell death programs can mediate both resistant and susceptible events. Via oxalic acid (OA), the necrotrophic phytopathogen Sclerotinia sclerotiorum hijacks host pathways and induces cell death in host plant tissue resulting in hallmark apoptotic features in a time and dose dependent manner. OA-deficient mutants are non-pathogenic and trigger a restricted cell death phenotype in the host that unexpectedly exhibits markers associated with the plant hypersensitive response including callose deposition and a pronounced oxidative burst, suggesting the plant can recognize and in this case respond, defensively. The details of this plant directed restrictive cell death associated with OA deficient mutants is the focus of this work. Using a combination of electron and fluorescence microscopy, chemical effectors and reverse genetics, we show that this restricted cell death is autophagic. Inhibition of autophagy rescued the non-pathogenic mutant phenotype. These findings indicate that autophagy is a defense response in this necrotrophic fungus/plant interaction and suggest a novel function associated with OA; namely, the suppression of autophagy. These data suggest that not all cell deaths are equivalent, and though programmed cell death occurs in both situations, the outcome is predicated on who is in control of the cell death machinery. Based on our data, we suggest that it is not cell death per se that dictates the outcome of certain plant-microbe interactions, but the manner by which cell death occurs that is crucial.

Immigrant wage differentials and the role of self-employment in Australia

Immigration has played an important role in the historical development of Australia. Thus, it is no surprise that a large body of empirical work has developed, which focuses upon how migrants fare in the land of opportunity. Much of the literature is comparatively recent, i.e. the last ten years or so, encouraged by the advent of public availability of Australian crosssection micro data. Several different aspects of migrant welfare have been addressed, with major emphasis being placed upon earnings and unemployment experience. For recent examples see Haig (1980), Stromback (1984), Chiswick and Miller (1985), Tran-Nam and Nevile (1988) and Beggs and Chapman (1988). The present paper contributes to the literature by providing additional empirical evidence on the native/migrant earnings differential. The data utilised are from the rather neglected Australian Bureau of Statistics, ABS Special Supplementary Survey No.4. 1982, otherwise known as the Family Survey. The paper also examines the importance of distinguishing between the wage and salary sector and the self-employment sector when discussing native/migrant differentials. Separate earnings equations for the two labour market groups are estimated and the native/migrant earnings differential is broken down by employment status. This is a novel application in the Australian context and provides some insight into the earnings of the selfemployed, a group that despite its size (around 20 per cent of the labour force) is frequently ignored by economic research. Most previous empirical research fails to examine the effect of employment status on earnings. Stromback (1984) includes a dummy variable representing self-employment status in an earnings equation estimated over a pooled sample of paid and self-employed workers. The variable is found to be highly significant, which leads Stromback to question the efficacy of including the self-employed in the estimation sample. The suggestion is that part of self-employed earnings represent a return to non-human capital investment, i.e. investments in machinery, buildings etc, the structural determinants of earnings differ significantly from those for paid employees. Tran-Nam and Nevile (1988) deal with differences between paid employees and the selfemployed by deleting the latter from their sample. However, deleting the self-employed from the estimation sample may lead to bias in the OLS estimation method (see Heckman 1979). The desirable properties of OLS are dependent upon estimation on a random sample. Thus, the 'Ran-Nam and Nevile results are likely to suffer from bias unless individuals are randomly allocated between self-employment and paid employment. The current analysis extends Tran-Nam and Nevile (1988) by explicitly treating the choice of paid employment versus self-employment as being endogenously determined. This allows an explicit test for the appropriateness of deleting self-employed workers from the sample. Earnings equations that are corrected for sample selection are estimated for both natives and migrants in the paid employee sector. The Heckman (1979) two-step estimator is employed. The paper is divided into five major sections. The next section presents the econometric model incorporating the specification of the earnings generating process together with an explicit model determining an individual's employment status. In Section 111 the data are described. Section IV draws together the main econometric results of the paper. First, the probit estimates of the labour market status equation are documented. This is followed by presentation and discussion of the Heckman two-stage estimates of the earnings specification for both native and migrant Australians. Separate earnings equations are estimated for paid employees and the self-employed. Section V documents estimates of the nativelmigrant earnings differential for both categories of employees. To aid comparison with earlier work, the Oaxaca decomposition of the earnings differential for paid-employees is carried out for both the simple OLS regression results as well as the parameter estimates corrected for sample selection effects. These differentials are interpreted and compared with previous Australian findings. A short section concludes the paper.