Semaphorin–plexin signalling genes associated with human breast tumourigenesis

Introduction Gene expression profiling has enabled us to demonstrate the heterogeneity of breast cancers. The potential of a tumour to grow and metastasise is partly dependant on its ability to initiate angiogenesis or growth and remodelling of new blood vessels, usually from a pre-existing vascular network, to ensure delivery of oxygen, nutrients, and growth factors to rapidly dividing transformed cells along with access to the systemic circulation. Cell–cell signalling of semaphorin ligands through interaction with their plexin receptors is important for the homeostasis and morphogenesis of many tissues and has been widely studied for a role in neural connectivity, cancer, cell migration and immune responses. This study investigated the role of four semaphorin/plexin signalling genes in human breast cancers in vivo and in vitro. Materials and methods mRNA was extracted from formalin fixed paraffin embedded archival breast invasive ductal carcinoma tissue samples of progressive grades (grades I–III) and compared to tissue from benign tumours. Gene expression profiles were determined by microarray using the Affymetrix GeneChip® Human Genome U133 Plus 2.0 Arrays and validated by Q-PCR using a Corbett RotorGene 6000. Following validation, the gene expression profile of the identified targets was correlated with those of the human breast cancer cell lines MCF-7 and MDA-MD-231. Results The array data revealed that 888 genes were found to be significantly (p ≤ 0.05) differentially expressed between grades I and II tumours and 563 genes between grade III and benign tumours. From these genes, we identified four genes involved in semaphorin–plexin signalling including SEMA4D which has previously been identified as being involved in increased angiogenesis in breast cancers, and three other genes, SEMA4F, PLXNA2 and PLXNA3, which in the literature were associated with tumourigenesis, but not directly in breast tumourigenesis. The microarray analysis revealed that SEMA4D was significantly (P = 0.0347) down-regulated in the grade III tumours compared to benign tumours; SEMA4F, was significantly (P = 0.0159) down-regulated between grades I and II tumours; PLXNA2 was significantly (P = 0.036) down-regulated between grade III and benign tumours and PLXNA3 significantly (P = 0.042) up-regulated between grades I and II tumours. Gene expression of SEMA4D was validated using Q-PCR, demonstrating the same expression profile in both data sets. When the sample set was increased to incorporate more cases, SEMA4D continued to follow the same expression profile, including statistical significance for the differences observed and small standard deviations. In vitro the same pattern was present where expression for SEMA4D was significantly higher in MDA-MB-231 cells when compared to MCF-7 cells. The expression of SEMA4F, PLXNA2 and PLXNA3 could not be validated using Q-PCR, however in vitro analysis of these three genes revealed that both SEMA4F and PLXNA3 followed the microarray trend in expression, although they did not reach significance. In contrast, PLXNA2 demonstrated statistical significance and was in concordance with the literature. Discussion We, and others, have proposed SEMA4D to be a gene with a potentially protective effect in benign tumours that contributes to tumour growth and metastatic suppression. Previous data supports a role for SEMA4F as a tumour suppressor in the peripheral nervous system but our data seems to indicate that the gene is involved in tumour progression in breast cancer. Our in vitro analysis of PLXNA2 revealed that the gene has higher expression in more aggressive breast cancer cell types. Finally, our in vitro analysis on PLXNA3 also suggest that this gene may have some form of growth suppressive role in breast cancer, in addition to a similar role for the gene previously reported in ovarian cancer. From the data obtained in this study, SEMA4D may have a role in more aggressive and potentially metastatic breast tumours. Conclusions Semaphorins and their receptors, the plexins, have been implicated in numerous aspects of neural development, however their expression in many other epithelial tissues suggests that the semaphorin–plexin signalling system also contributes to blood vessel growth and development. These findings warrant further investigation of the role of semaphorins and plexins and their role in normal and tumour-induced angiogenesis in vivo and in vitro. This may represent a new front of attack in anti-angiogenic therapies of breast and other cancers.

Variants in the human potassium channel gene (KCNN3) are associated with migraine in a high risk genetic isolate

The calcium-activated potassium ion channel gene (KCNN3) is located in the vicinity of the familial hemiplegic migraine type 2 locus on chromosome 1q21.3. This gene is expressed in the central nervous system and plays a role in neural excitability. Previous association studies have provided some, although not conclusive, evidence for involvement of this gene in migraine susceptibility. To elucidate KCNN3 involvement in migraine, we performed gene-wide SNP genotyping in a high-risk genetic isolate from Norfolk Island, a population descended from a small number of eighteenth century Isle of Man ‘Bounty Mutineer’ and Tahitian founders. Phenotype information was available for 377 individuals who are related through the single, well-defined Norfolk pedigree (96 were affected: 64 MA, 32 MO). A total of 85 SNPs spanning the KCNN3 gene were genotyped in a sub-sample of 285 related individuals (76 affected), all core members of the extensive Norfolk Island ‘Bounty Mutineer’ genealogy. All genotyping was performed using the Illumina BeadArray platform. The analysis was performed using the statistical program SOLAR v4.0.6 assuming an additive model of allelic effect adjusted for the effects of age and sex. Haplotype analysis was undertaken using the program HAPLOVIEW v4.0. A total of four intronic SNPs in the KCNN3 gene displayed significant association (P < 0.05) with migraine. Two SNPs, rs73532286 and rs6426929, separated by approximately 0.1 kb, displayed complete LD (r 2 = 1.00, D′ = 1.00, D′ 95% CI = 0.96–1.00). In all cases, the minor allele led to a decrease in migraine risk (beta coefficient = 0.286–0.315), suggesting that common gene variants confer an increased risk of migraine in the Norfolk pedigree. This effect may be explained by founder effect in this genetic isolate. This study provides evidence for association of variants in the KCNN3 ion channel gene with migraine susceptibility in the Norfolk genetic isolate with the rarer allelic variants conferring a possible protective role. This the first comprehensive analysis of this potential candidate gene in migraine and also the first study that has utilised the unique Norfolk Island large pedigree isolate to implicate a specific migraine gene. Studies of additional variants in KCNN3 in the Norfolk pedigree are now required (e.g. polyglutamine variants) and further analyses in other population data sets are required to clarify the association of the KCNN3 gene and migraine risk in the general outbred population.

Outdoor worker sun protection project : a comprehensive applied research project to demonstrate the effectiveness of sun protection measures which influence high risk outdoor workers in Queensland to adopt sun safe behaviour practices 2010 – 2013

The QUT Outdoor Worker Sun Protection (OWSP) project undertook a comprehensive applied health promotion project to demonstrate the effectiveness of sun protection measures which influence high risk outdoor workers in Queensland to adopt sun safe behaviours. The three year project (2010-2013) was driven by two key concepts: 1) The hierarchy of control, which is used to address risks in the workplace, advocates for six control measures that need to be considered in order of priority (refer to Section 3.4.2); and 2) the Ottawa Charter which recommends five action means to achieve health promotion (refer to Section 2.1). The project framework was underpinned by a participatory action research approach that valued peoples’ input, took advantage of existing skills and resources, and stimulated innovation (refer to Section 4.2). Fourteen workplaces (small and large) with a majority outdoor workforce were recruited across regional Queensland (Darling Downs, Northwest, Mackay and Cairns) from four industries types: 1) building and construction, 2) rural and farming, 3) local government, and 4) public sector. A workplace champion was identified at each workplace and was supported (through resource provision, regular contact and site visits) over a 14 to 18 month intervention period to make sun safety a priority in their workplace. Employees and employers were independently assessed for pre- and postintervention sun protection behaviours. As part of the intervention, an individualised sun safety action plan was developed in conjunction with each workplace to guide changes across six key strategy areas including: 1) Policy (e.g., adopt sun safety practices during all company events); 2) Structural and environmental (e.g., shade on worksites; eliminate or minimise reflective surfaces); 3) Personal protective equipment (PPE) (e.g., trial different types of sunscreens, or wide-brimmed hats); 4) Education and awareness (e.g., include sun safety in inductions and toolbox talks; send reminder emails or text messages to workers);5) Role modelling (e.g., by managers, supervisors, workplace champions and mentors); and 6) Skin examinations (e.g., allow time off work for skin checks). The participatory action process revealed that there was no “one size fits all” approach to sun safety in the workplace; a comprehensive, tailored approach was fundamental. This included providing workplaces with information, resources, skills, know how, incentives and practical help. For example, workplaces engaged in farming complete differing seasonal tasks across the year and needed to prepare for optimal sun safety of their workers during less labour intensive times. In some construction workplaces, long pants were considered a trip hazard and could not be used as part of a PPE strategy. Culture change was difficult to achieve and workplace champions needed guidance on the steps to facilitate this (e.g., influencing leaders through peer support, mentoring and role modelling). With the assistance of the project team the majority of workplaces were able to successfully implement the sun safety strategies contained within their action plans, up skilling them in the evidence for sun safety, how to overcome barriers, how to negotiate with all relevant parties and assess success. The most important enablers to the implementation of a successful action plan were a pro-active workplace champion, strong employee engagement, supportive management, the use of highly visual educational resources, and external support (provided by the project team through regular contact either directly through phone calls or indirectly through emails and e-newsletters). Identified barriers included a lack of time, the multiple roles of workplace champions, (especially among smaller workplaces), competing issues leading to a lack of priority for sun safety, the culture of outdoor workers, and costs or budgeting constraints. The level of sun safety awareness, knowledge, and sun protective behaviours reported by the workers increased between pre-and post-intervention. Of the nine sun protective behaviours that were assessed, the largest changes reported included a 26% increase in workers who “usually or always” wore a broad-brimmed hat, a 20% increase in the use of natural shade, a 19% increase in workers wearing long-sleeved collared shirts, and a 16% increase in workers wearing long trousers.

Inhibition of platelet aggregation and 5-HT release by extracts of Australian plants used traditionally as headache treatments

To identify potential migraine therapeutics, extracts of eighteen plants were screened to detect plant constituents affecting ADP induced platelet aggregation and [14C]5-hydroxytryptamine (5-HT) release. Extracts of the seven plants exhibiting significant inhibition of platelet function were reanalysed in the presence of polyvinyl pyrrolidone (PVP) to remove polyphenolic tannins that precipitate proteins. Two of these extracts no longer exhibited inhibition of platelet activity after removal of tannins. However, extracts of Crataegus monogyna, Ipomoea pes-caprae, Eremophila freelingii, Eremophila longifolia, and Asteromyrtus symphyocarpa still potently inhibited ADP induced human platelet [14C]5-HT release in vitro, with levels ranging from 62 to 95% inhibition. I. pes-caprae, and C. monogyna also caused significant inhibition of ADP induced platelet aggregation. All of these plants have been previously used as traditional headache treatments, except for C. monogyna which is used primarily for protective effects on the cardiovascular system. Further studies elucidating the compounds that are responsible for these anti-platelet effects are needed to determine their exact mechanism of action.

Load frequency control in a microgrid : challenges and improvements

A microgrid can span over a large area, especially in rural townships. In such cases, the distributed generators (DGs) must be controlled in a decentralized fashion, based on the locally available measurements. The main concerns are control of system voltage magnitude and frequency, which can either lead to system instability or voltage collapse. In this chapter, the operational challenges of load frequency control in a microgrid are discussed and few methods are proposed to meet these challenges. In particular, issues of power sharing, power quality and system stability are addressed, when the system operates under decentralized control. The main focus of this chapter is to provide solutions to improve the system performance in different situations. The scenarios considered are (a) when the system stability margin is low, (b) when the line impedance has a high R to X ratio, (c) when the system contains unbalanced and/or distorted loads. Also a scheme is proposed in which a microgrid can be frequency isolated from a utility grid while being capable of bidirectional power transfer. In all these cases, the use of angle droop in converter interfaced DGs is adopted. It has been shown that this results in a more responsive control action compared to the traditional frequency based droop control.

Simulation of retrofitted unreinforced concrete masonry unit walls under blast loading

This paper describes an investigation into the effectiveness of using spray-on nano-particle reinforced polymer and aluminium foam as new types of retrofit material to prevent the breaching and collapse of unreinforced concrete masonry walls subjected to blast over a whole range of dynamic and impulsive regimes. Material models from the LSDYNA material library were used to model the behaviors of each of the materials and its interface for retrofitted and unretrofitted masonry walls. Available test data were used to validate the numerical models. Using the validated LS-DYNA numerical models, the pressure-impulse diagrams for retrofitted concrete masonry walls were constructed. The efficiency of using these retrofits to strengthen the unreinforced concrete masonry unit (CMU) walls under various pressures and impulses was investigated using pressure-impulse diagrams. Comparisons were made to find the most efficient retrofits for masonry walls against blasts.

Zeta-potential and morphology of electrospun nano- and microfibers from biopolymers and their blends used as scaffolds in tissue engineering

Electrostatic spinning or electrospinning is a fiber spinning technique driven by a high-voltage electric field that produces fibers with diameters in a submicrometer to nanometer range.1 Nanofibers are typical one-dimensional colloidal objects with an increased tensile strength, whose length can achieve a few kilometers and the specific surface area can be 100 m2 g–1 or higher.2 Nano- and microfibers from biocompatible polymers and biopolymers have received much attention in medical applications3 including biomedical structural elements (scaffolding used in tissue engineering,2,4–6 wound dressing,7 artificial organs and vascular grafts8), drug and vaccine delivery,9–11 protective shields in speciality fabrics, multifunctional membranes, etc. Other applications concern superhydrophobic coatings,12 encapsulation of solid materials,13 filter media for submicron particles in separation industry, composite reinforcement and structures for nano-electronic machines.

Development of school connectedness as a component of an injury prevention program for early adolescents

The current program of research addresses the need for multi-level programs to target the major increase in injury rates that occurs throughout adolescence. Specifically, it involves the investigation of school connectedness as a protective factor for adolescent injury, and the development of school connectedness as a component of an injury prevention program. To date, school-based risk taking and injury prevention has frequently been limited to addressing adolescents' knowledge and attitudes to risk behaviours, and has largely overlooked the importance of the wider school social context as a protective factor in adolescent development. Additionally, school connectedness has been primarily studied in terms of its impact on student achievement, wellbeing and risk taking behaviour, and research has not yet addressed possible links with injury. Further, school connectedness intervention programs have targeted risk taking behaviours without evaluating their potential impact on injury outcomes. This is the first reported research to develop strategies to increase school connectedness as part of a school-based injury prevention program. The research program was conceptualised as three distinct stages. The development of these research stages was informed by a comprehensive review of the literature on adolescent risk taking, injury and school-based prevention, as well as on school connectedness and its importance in adolescence. A review of the school connectedness literature indicated that students' connectedness is largely influenced by relationships within the school context including with teachers and other school staff, and is therefore a potentially modifiable factor that may be targeted in school-based programs. Overall, the literature shows school connectedness to be a key protective factor in adolescent development. This review established a foundation from which the current program of research was designed. The first stage of the research involved an empirical investigation of the relationship between adolescent risk taking-related injuries and school connectedness. Stage one incorporated two studies. The first involved the development of a measure of adolescent injury, the Extended Adolescent Injury Checklist (E-AIC), for use in the current research as well as in future school-based studies and program evaluation. The results of this study also highlighted the extent of the problem of risk-related injury in adolescence. The second study in Stage one examined the relationship between students' reports of school connectedness, risk taking behaviour and risk taking-related injuries on the E-AIC. The results of this study showed significant relationships between increased school connectedness and reduced reported engagement in transport and violence risk taking, and fewer associated injuries. This study therefore suggested the potential for school-based injury prevention programs to incorporate strategies targeting increased adolescent connectedness to school. The second stage of this research involved the compilation of an evidence base to inform the design of a school connectedness intervention. Stage two also incorporated two studies. The first study in Stage two involved a systematic review of programs that have targeted school connectedness for reduced risk taking and injury. The results of this study revealed that interventions targeting school connectedness can be effective in reducing adolescent risk taking behaviour, and also provided an evidence base for the design of the current school connectedness intervention. The second study in Stage two examined teachers' understanding and perceptions of school connectedness. This qualitative study indicated that teachers consider students' connectedness to be an important factor that relates to their risk taking behaviour; and also provided directions and content for the intervention design stage. The third stage of this research built upon the findings of each of the previous studies, and involved the design, implementation and evaluation of a school connectedness intervention as a component of an adolescent injury prevention program, Skills for Preventing Injury in Youth (SPIY). This connectedness intervention was designed as a professional development workshop for teachers of 13 to 14 year old adolescents, and was developed as a complementary component to the curriculum-based SPIY program. The SPIY connectedness component was implemented and evaluated using process and six-month impact evaluation methodologies. The results of this study revealed that teachers saw value in the program and made use of the strategies presented, and that program school students' self-reported violence risk behaviour was reduced at six-month follow-up. Despite these promising findings, the results of this study did not demonstrate a significant impact of the program on change in students' connectedness to school, relative to comparison schools. The positive impact on self-reported violence risk behaviour was however replicated in additional analyses comparing students participating in the connectedness version of SPIY with students participating in an earlier curriculumonly version of the program. This finding indicated that the connectedness component has additional benefits relating to reduction in violence risks, over and above a curriculum-only version of the program. This research was the first reported to address the relationship between school connectedness and adolescent injury outcomes, and to develop school connectedness as a component of an adolescent injury prevention program. Overall, the results of this program of research have demonstrated the importance of incorporating strategies targeting the wider school social context, including school connectedness, in adolescent injury prevention programs. This research has important implications for future research and practice in adolescent injury prevention.

Postnatal depression in Central Vietnam

Postnatal depression (PND) is a significant global health issue, which not only impacts maternal wellbeing, but also infant development and family structures. Mental health disorders represent approximately 14% of global burden of disease and disability, including low and middle-income countries (LMIC), and PND has direct relevance to the Millennium Development Goals of reducing child mortality, improving maternal health, and creating global partnerships (United Nations, 2012; Guiseppe, Becker & Farmer, 2011). Emerging evidence suggests that PND in LMIC is similar to, or higher than in high-income countries (HIC), however, less than 10% of LMIC have prevalence data available (Fisher, Cabral de Mello, & Izutsu 2009; Lund et al., 2011). Whilst a small number of studies on maternal mental disorders have been published in Vietnam, only one specifically focuses on PND in a hospital-based sample. Also, community based mental health studies and information on mental health in rural areas of Vietnam is still scarce. The purpose of this study was to determine the prevalence of PND, and its associated social determinants in postnatal women in Thua Thien Hue Province, Central Vietnam. In order to identify social determinants relevant to the Central Vietnamese context, two qualitative studies and one community survey were undertaken. Associations between maternal mental health and infant health outcomes were also explored. The study was comprised of three phases. Firstly, iterative, qualitative interviews with Vietnamese health professionals (n = 17) and postpartum women (n = 15) were conducted and analysed using Kleinman's theory of explanatory models to identify narratives surrounding PND in the Vietnamese context (Kleinman, 1978). Secondly, a participatory concept mapping exercise was undertaken with two groups of health professionals (n = 12) to explore perceived risk and protective factors for postnatal mental health. Qualitative phases of the research elucidated narratives surrounding maternal mental health in the Vietnamese context such as son preference, use of traditional medicines, and the popularity of confinement practices such as having one to three months of complete rest. The qualitative research also revealed the construct of depression was not widely recognised. Rather, postpartum changes in mood were conceptualised as a loss of 'vital strength' following childbirth or 'disappointment'. Most women managed postpartum changes in mood within the family although some sought help from traditional medicine practitioners or biomedical doctors. Thirdly, a cross-sectional study of twelve randomly selected communes (six urban, six rural) in Thua Thien Hue Province was then conducted. Overall, 465 women with infants between 4 weeks and six months old participated, and 431 questionnaires were analysed. Women from urban (n = 216) and rural (n = 215) areas participated. All eligible women completed a structured interview about their health, basic demographics, and social circumstances. Maternal depression was measured using the Edinburgh Postnatal Depression Scale (EPDS) as a continuous variable. Multivariate generalised linear regression was conducted using PASW Statistics version 18.0 (2009). When using the conventional EPDS threshold for probable depression (EPDS score ~ 13) 18.1% (n = 78) of women were depressed (Gibson, McKenzie-McHarg, Shakespeare, Price & Gray, 2009). Interestingly, 20.4% of urban women (n = 44) had EPDS scores~ 13, which was a higher proportion than rural women, where 15.8% (n = 34) had EPDS scores ~ 13, although this difference was not statistically significant: t(429) = -0.689, p = 0.491. Whilst qualitative narratives identified infant gender and family composition, and traditional confinement practices as relevant to postnatal mood, these were not statistically significant in multivariate analysis. Rather, poverty, food security, being frightened of your husband or family members, experiences of intimate partner violence and breastfeeding difficulties had strong statistical associations. PND was also associated with having an infant with diarrhoea in the past two weeks, but not infant malnutrition or acute respiratory infections. This study is the first to explore maternal mental health in Central Vietnam, and provides further evidence that PND is a universally experienced phenomenon. The independent social risk factors of depressive symptoms identified such as poverty, food insecurity, experiences of violence and powerlessness, and relationship adversity points to women in a context of social suffering which is relevant throughout the world (Kleinman, Das & Lock, 1997). The culturally specific risk factors explored such as infant gender were not statistically significant when included in a multivariable model. However, they feature prominently in qualitative narratives surrounding PND in Vietnam, both in this study and previous literature. It appears that whilst infant gender may not be associated with PND per se, the reactions of close relatives to the gender of the baby can adversely affect maternal wellbeing. This study used a community based participatory research approach (CBPR) (Israel.2005). This approach encourages the knowledge produced to be used for public health interventions and workforce training in the community in which the research was conducted, and such work has commenced. These results suggest that packages of interventions for LMIC devised to address maternal mental health and infant wellbeing could be applied in Central Vietnam. Such interventions could include training lay workers to follow up postpartum women, and incorporating mental health screening and referral into primary maternal and child health care (Pate! et al., 2011; Rahman, Malik, Sikander & Roberts, 2008). Addressing the underlying social determinants of PND through poverty reduction and violence elimination programs is also recommended.

Converse consumption : the converse blank canvas project

Research background For almost 80 years the Chuck Taylor (or Chuck T's) All Star basketball shoe has been an iconic item of fashion apparel. The Chuck T's were first designed in 1921 by Converse, an American shoe company and over the decades they became a popular item not purely for sports and athletic purposes but rather evolved into the shoe of choice for many subcultural groups as a fashion item. In some circles the Chuck Taylor is still seen as the "coolest" sneaker of all time - one which will never go out of fashion regardless of changing trends. With over 600 millions pairs sold all over the world since its release, the Converse shoe is representative of not only a fashion culture - but also of a consumption culture - that evolved as the driving force behind the massive growth of the Western economic system during the 20th Century. Artisan Gallery (Brisbane), in conjunction with the exhibition Reboot: Function, Fashion and the Sneaker, a history of the sneaker, selected 20 designers to customise and re-design the classic Converse Chuck Taylor All Stars shoe and in doing so highlighted the diversity of forms possible for creative outcomes. As Artisan Gallery Curator Kirsten Fitzpatrick states “We were expecting people to draw and paint on them. Instead, we had shoes... mounted as trophies.." referring to the presentation of "Converse Consumption". The exhibition ran from 21 June – 16 August 2012: Research question The Chuck T’s is one of many overwhelmingly commercially successful designs of the last century. Nowadays we are faced with the significant problems of overconsumption and the stress this causes on the natural ecosystem; and on people as a result. As an active member of the industrial design fraternity – a discipline that sits at the core of this problem - how can I use this opportunity to comment on the significant issue of consumption? An effective way to do this was to associate consumption of goods with consumption of sugar. There are significant similarities between our ceaseless desires to consume products and our fervent need to consume indulgent sweet foods. Artisan Statement Delicious, scrumptious, delectable... your pupils dilate, your blood pressure spikes, your liver goes into overdrive. Immediately, your brain cuts off the adenosine receptors, preventing drowsiness. Your body increases dopamine production, in-turn stimulating the pleasure receptors in your brain. Your body absorbs all the sweetness and turns it into fat – while all the nutrients that you actually require are starting to be destroyed, about to be expelled. And this is only after one bite! After some time though, your body comes crashing back to earth. You become irritable and begin to feel sluggish. Your eyelids seem heavy while your breathing pattern changes. Your body has consumed all the energy and destroyed all available nutrients. You literally begin to shut down. These are the physiological effects of sugar consumption. A perfect analogy for our modern day consumer driven world. Enjoy your dessert! Research contribution “Converse Consumption” contributes to the conversation regarding over-consumption by compelling people to reflect on their consumption behaviour through the reconceptualising of the deconstructed Chuck T’s in an attractive edible form. By doing so the viewer has to deal with the desire to consume the indulgent looking dessert with the contradictory fact that it is comprised of a pair of shoes. The fact that the shoes are Chuck T’s make the effect even more powerful due to their iconic status. These clashing motivations are what make “Converse Consumption” a bizarre yet memorable experience. Significance The exhibition was viewed by an excess of 1000 people and generated exceptional media coverage and public exposure/impact. As Artisan Gallery Curator Kirsten Fitzpatrick states “20 of Brisbane's best designers were given the opportunity to customise their own Converse Sneakers, with The Converse Blank Canvas Project.” And to be selected in this category demonstrates the calibre of importance for design prominence.

The role of immunoglobulins and their transporters in urogenital Chlamydial infections

Chlamydia trachomatis infections of the male and female reproductive tracts are the world's leading sexually transmitted bacterial disease, and can lead to damaging pathology, scarring and infertility. The resolution of chlamydial infection requires the development of adaptive immune responses to infection, and includes cell-mediated and humoral immunity. Whilst cluster of differentiation (CD)4+ T cells are known to be essential in clearance of infection [1], they are also associated with immune cell infiltration, autoimmunity and infertility in the testes [2-3]. Conversely, antibodies are less associated with inflammation, are readily transported into the reproductive tracts, and can offer lumenal neutralization of chlamydiae prior to infection. Antibodies, or immunoglobulins (Ig), play a supportive role in the resolution of chlamydial infections, and this thesis sought to define the function of IgA and IgG, against a variety of chlamydial antigens expressed during the intracellular and extracellular stages of the chlamydial developmental cycle. Transport of IgA and IgG into the mucosal lumen is facilitated by receptor-mediated transcytosis yet the expression profile (under normal conditions and during urogenital chlamydial infection) of the polymeric immunoglobulin receptor (pIgR) and the neonatal Fc receptor (FcRn) remains unknown. The expression profile of pIgR and FcRn in the murine male reproductive tract was found to be polarized to the lower and upper reproductive tract tissues respectively. This demonstrates that the two receptors have a tissue tropism, which must be considered when targeting pathogens that colonize different sites. In contrast, the expression of pIgR and FcRn in the female mouse was found to be distributed in both the upper and lower reproductive tracts. When urogenitally infected with Chlamydia muridarum, both male and female reproductive tracts up-regulated expression of pIgR and down-regulated expression of FcRn. Unsurprisingly, the up-regulation of pIgR increased the concentration of IgA in the lumen. However, down-regulation of FcRn, prevented IgG uptake and led to an increase or pooling of IgG in lumenal secretions. As previous studies have identified the importance of pIgR-mediated delivery of IgA, as well as the potential of IgA to bind and neutralize intracellular pathogens, IgA against a variety of chlamydial antigens was investigated. The protection afforded by IgA against the extracellular antigen major outer membrane protein (MOMP), was found to be dependent on pIgR expression in vitro and in vivo. It was also found that in the absence of pIgR, no protection was afforded to mice previously immunized with MOMP. The protection afforded from polyclonal IgA against the intracellular chlamydial antigens; inclusion membrane protein A (IncA), inclusion membrane proteins (IncMem) and secreted chlamydial protease-like activity factor (CPAF) were produced and investigated in vitro. Antigen-specific intracellular IgA was found to bind to the respective antigen within the infected cell, but did not significantly reduce inclusion formation (p > 0.05). This suggests that whilst IgA specific for the selected antigens was transported by pIgR to the chlamydial inclusion, it was unable to prevent growth. Similarly, immunization of male mice with intracellular chlamydial antigens (IncA or IncMem), followed by depletion CD4+ T cells, and subsequent urogenital C. muridarum challenge, provided minimal pIgR-mediated protection. Wild type male mice immunized with IncA showed a 57 % reduction (p < 0.05), and mice deficient in pIgR showed a 35 % reduction (p < 0.05) in reproductive tract chlamydial burden compared to control antigen, and in the absence of CD4+ T cells. This suggests that pIgR and secretory IgA (SIgA) were playing a protective role (21 % pIgR-mediated) in unison with another antigen-specific immune mechanism (36 %). Interestingly, IgA generated during a primary respiratory C. muridarum infection did not provide a significant amount of protection to secondary urogenital C. muridarum challenge. Together, these data suggest that IgA specific for an extracellular antigen (MOMP) can play a strong protective role in chlamydial infections, and that IgA targeting intracellular antigens is also effective but dependent on pIgR expression in tissues. However, whilst not investigated here, IgA targeting and blocking other intracellular chlamydial antigens, that are more essential for replication or type III secretion, may be more efficacious in subunit vaccines. Recently, studies have demonstrated that IgG can neutralize influenza virus by trafficking IgG-bound virus to lysosomes [4]. We sought to determine if this process could also traffic chlamydial antigens for degradation by lysosomes, despite Chlamydia spp. actively inhibiting fusion with the host endocytic pathway. As observed in pIgR-mediated delivery of anti-IncA IgA, FcRn similarly transported IgG specific for IncA which bound the inclusion membrane. Interestingly, FcRn-mediated delivery of anti-IncA IgG significantly decreased inclusion formation by 36 % (p < 0.01), and induced aberrant inclusion morphology. This suggests that unlike IgA, IgG can facilitate additional host cellular responses which affect the intracellular niche of chlamydial growth. Fluorescence microscopy revealed that IgG also bound the inclusion, but unlike influenza studies, did not induce the recruitment of lysosomes. Notably, anti-IncA IgG recruited sequestosomes to the inclusion membrane, markers of the ubiquitin/proteasome pathway and major histocompatibility complex (MHC) class I loading. To determine if the protection against C. muridarum infection afforded by IncA IgG in vitro translated in vivo, wild type mice and mice deficient in functional FcRn and MHC-I, were immunized, depleted of CD4+, and urogenitally infected with C. muridarum. Unlike in pIgR-deficient mice, the protection afforded from IncA immunization was completely abrogated in mice lacking functional FcRn and MHC-I/CD8+. Thus, both anti-IncA IgA and IgG can bind the inclusion in a pIgR and FcRn-mediated manner, respectively. However, only IgG mediates a higher reduction in chlamydial infection in vitro and in vivo suggesting more than steric blocking of IncA had occurred. Unlike anti-MOMP IgA, which reduced chlamydial infection of epithelial cells and male mouse tissues, IgG was found to enhance infectivity in vitro, and in vivo. Opsonization of EBs with MOMP-IgG enhanced inclusion formation of epithelial cells in a MOMP-IgG dose-dependent and FcRn-dependent manner. When MOMP-IgG opsonized EBs were inoculated into the vagina of female mice, a small but non-significant (p > 0.05) enhancement of cervicovaginal C. muridarum shedding was observed three days post infection in mice with functional FcRn. Interestingly, infection with opsonized EBs reduced the intensity of the peak of infection (day six) but protracted the duration of infection by 60 % in wild type mice only. Infection with EBs opsonized in IgG also significantly increased (p < 0.05) hydrosalpinx formation in the oviducts and induced lymphocyte infiltration uterine horns. As MOMP is an immunodominant antigen, and is widely used in vaccines, the ability of IgG specific to extracellular chlamydial antigens to enhance infection and induce pathology needs to be considered. Together, these data suggest that immunoglobulins play a dichotomous role in chlamydial infections, and are dependent on antigen specificity, FcRn and pIgR expression. FcRn was found to be highly expressed in upper male reproductive tract, whilst pIgR was dominantly expressed in the lower reproductive tract. Conversely, female mice expressed FcRn and pIgR in both the lower and upper reproductive tracts. In response to a normal chlamydial infection, pIgR is up-regulated increasing secretory IgA release, but FcRn is down-regulated preventing IgG uptake. Similarly to other studies [5-6], we demonstrate that IgA and IgG generated during primary chlamydial infections plays a minor role in recall immunity, and that antigen-specific subunit vaccines can offer more protection. We also show that both IgA and IgG can be used to target intracellular chlamydial antigens, but that IgG is more effective. Finally, IgA against the extracellular antigen MOMP can afford protection, whist IgG plays a deleterious role by increasing infectivity and inducing damaging immunopathology. Further investigations with additional antigens or combination subunit vaccines will enhance our understanding the protection afforded by antibodies against intracellular and extracellular pathogenic antigens, and help improve the development of an efficacious chlamydial vaccine.

A fuzzy TOPSIS based multi criteria performance measurement model for lean supply chain

Increasing global competition, rapid technological changes, advances in manufacturing and information technology and discerning customers are forcing supply chains to adopt improvement practices that enable them to deliver high quality products at a lower cost and in a shorter period of time. A lean initiative is one of the most effective approaches toward achieving this goal. In the lean improvement process, it is critical to measure current and desired performance level in order to clearly evaluate the lean implementation efforts. Many attempts have tried to measure supply chain performance incorporating both quantitative and qualitative measures but failed to provide an effective method of measuring improvements in performances for dynamic lean supply chain situations. Therefore, the necessity of appropriate measurement of lean supply chain performance has become imperative. There are many lean tools available for supply chains; however, effectiveness of a lean tool depends on the type of the product and supply chain. One tool may be highly effective for a supply chain involved in high volume products but may not be effective for low volume products. There is currently no systematic methodology available for selecting appropriate lean strategies based on the type of supply chain and market strategy This thesis develops an effective method to measure the performance of supply chain consisting of both quantitative and qualitative metrics and investigates the effects of product types and lean tool selection on the supply chain performance Supply chain performance matrices and the effects of various lean tools over performance metrics mentioned in the SCOR framework have been investigated. A lean supply chain model based on the SCOR metric framework is then developed where non- lean and lean as well as quantitative and qualitative metrics are incorporated in appropriate metrics. The values of appropriate metrics are converted into triangular fuzzy numbers using similarity rules and heuristic methods. Data have been collected from an apparel manufacturing company for multiple supply chain products and then a fuzzy based method is applied to measure the performance improvements in supply chains. Using the fuzzy TOPSIS method, which chooses an optimum alternative to maximise similarities with positive ideal solutions and to minimise similarities with negative ideal solutions, the performances of lean and non- lean supply chain situations for three different apparel products have been evaluated. To address the research questions related to effective performance evaluation method and the effects of lean tools over different types of supply chains; a conceptual framework and two hypotheses are investigated. Empirical results show that implementation of lean tools have significant effects over performance improvements in terms of time, quality and flexibility. Fuzzy TOPSIS based method developed is able to integrate multiple supply chain matrices onto a single performance measure while lean supply chain model incorporates qualitative and quantitative metrics. It can therefore effectively measure the improvements for supply chain after implementing lean tools. It is demonstrated that product types involved in the supply chain and ability to select right lean tools have significant effect on lean supply chain performance. Future study can conduct multiple case studies in different contexts.

Sleepiness : how a biological drive can influence other risky road user behaviours

The Safe System approach to road safety utilises a holistic view of the interactions among vehicles, roads and road users. Yet, the contribution of each of these factors to crashes is vastly different. The role of road users is widely acknowledged as an overwhelming contributor to road crashes. Substantial gains have been made with improvements to vehicle and roads over a number of years. However, improvements of the road user’s behaviour has been (in some cases) less substantial. A road user behaviour that is relatively unregulated is driver sleepiness, which is part of the ‘fatal five’ of risky road user behaviours. The effect of sleepiness is ubiquitous – sleepiness is a state that most, if not all drivers on our roads has experienced, and is habitually exposed to. The quality and quantity of daily sleep is integral to our level of neurobehavioural performance during wakefulness and as such can have a compounding effect on a number of other risky driving behaviours. This paper will discuss the potential influence of sleepiness as an interceding factor for a number of risky driving behaviours. Little effort has been given to increasing awareness of the deleterious and wide ranging effects that sleepiness has on road safety. Given the wide ranging influence of sleepiness, improvements of ‘sleep health’ as a protective factor at the community or individual level could lead to significant reductions in road trauma and increases of general well being. A discussion of potential actions to reduce sleepiness is required if reductions of road trauma are to continue.

The electrochemical corrosion behaviour of quaternary gold alloys when exposed to 3.5% NaCl solution

Lower carat gold alloys, specifically 9 carat gold alloys, containing less than 40 % gold, and alloying additions of silver, copper and zinc, are commonly used in many jewellery applications, to offset high costs and poor mechanical properties associated with pure gold. While gold is considered to be chemically inert, the presence of active alloying additions raises concerns about certain forms of corrosion, particularly selective dissolution of these alloys. The purpose of this study was to systematically study the corrosion behaviour of a series of quaternary gold–silver–copper–zinc alloys using dc potentiodynamic scanning in saline (3.5 % NaCl) environment. Full anodic/cathodic scans were conducted to determine the overall corrosion characteristics of the alloy, followed by selective anodic scans and subsequent morphological and compositional analysis of the alloy surface and corroding media to determine the extent of selective dissolution. Varying degrees of selective dissolution and associated corrosion rates were observed after anodic polarisation in 3.5 % NaCl, depending on the alloy composition. The corrosion behaviour of the alloys was determined by the extent of anodic reactions which induce (1) formation of oxide scales on the alloy surface and or (2) dissolution of Zn and Cu species. In general, the improved corrosion characteristics of alloy #3 was attributed to the composition of Zn/Cu in the alloy and thus favourable microstructure promoting the formation of protective oxide/chloride scales and reducing the extent of Cu and Zn dissolution.

System level tests of transformer differential protection using an IEC 61850 process bus

The IEC 61850 family of standards for substation communication systems were released in the early 2000s, and include IEC 61850-8-1 and IEC 61850-9-2 that enable Ethernet to be used for process-level connections between transmission substation switchyards and control rooms. This paper presents an investigation of process bus protection performance, as the in-service behavior of multi-function process buses is largely unknown. An experimental approach was adopted that used a Real Time Digital Simulator and 'live' substation automation devices. The effect of sampling synchronization error and network traffic on transformer differential protection performance was assessed and compared to conventional hard-wired connections. Ethernet was used for all sampled value measurements, circuit breaker tripping, transformer tap-changer position reports and Precision Time Protocol synchronization of sampled value merging unit sampling. Test results showed that the protection relay under investigation operated correctly with process bus network traffic approaching 100% capacity. The protection system was not adversely affected by synchronizing errors significantly larger than the standards permit, suggesting these requirements may be overly conservative. This 'closed loop' approach, using substation automation hardware, validated the operation of protection relays under extreme conditions. Digital connections using a single shared Ethernet network outperformed conventional hard-wired solutions.