ATF3 suppresses metastasis of bladder cancer by regulating gelsolin-mediated remodeling of the actin cytoskeleton

Bladder cancer is associated with high recurrence and mortality rates due to metastasis. The elucidation of metastasis suppressors may offer therapeutic opportunities if their mechanisms of action can be elucidated and tractably exploited. In this study, we investigated the clinical and functional significance of the transcription factor activating transcription factor 3 (ATF3) in bladder cancer metastasis. Gene expression analysis revealed that decreased ATF3 was associated with bladder cancer progression and reduced survival of patients with bladder cancer. Correspondingly, ATF3 overexpression in highly metastatic bladder cancer cells decreased migration in vitro and experimental metastasis in vivo. Conversely, ATF3 silencing increased the migration of bladder cancer cells with limited metastatic capability in the absence of any effect on proliferation. In keeping with their increased motility, metastatic bladder cancer cells had increased numbers of actin filaments. Moreover, ATF3 expression correlated with expression of the actin filament severing protein gelsolin (GSN). Mechanistic studies revealed that ATF3 upregulated GSN, whereas ATF3 silencing reduced GSN levels, concomitant with alterations in the actin cytoskeleton. We identified six ATF3 regulatory elements in the first intron of the GSN gene confirmed by chromatin immunoprecipitation analysis. Critically, GSN expression reversed the metastatic capacity of bladder cancer cells with diminished levels of ATF3. Taken together, our results indicate that ATF3 suppresses metastasis of bladder cancer cells, at least in part through the upregulation of GSN-mediated actin remodeling. These findings suggest ATF3 coupled with GSN as prognostic markers for bladder cancer metastasis.

Binding of small mono- and oligomeric integrin ligands to membrane-embedded integrins monitored by surface plasmon-enhanced fluorescence spectroscopy

We recently developed a binding assay format by incorporating native transmembrane receptors into artificial phospholipid bilayers on biosensor devices for surface plasmon resonance spectroscopy. By extending the method to surface plasmon-enhanced fluorescence spectroscopy (SPFS), sensitive recording of the association of even very small ligands is enabled. Herewith, we monitored binding of synthetic mono- and oligomeric RGD-based peptides and peptidomimetics to integrins alphavbeta3 and alphavbeta5, after having confirmed correct orientation and functionality of membrane-embedded integrins. We evaluated integrin binding of RGD multimers linked together via aminohexanoic acid (Ahx) spacers and showed that the dimer revealed higher binding activity than the tetramer, followed by the RGD monomers. The peptidomimetic was also found to be highly active with a slightly higher selectivity toward alphavbeta3. The different compounds were also evaluated in in vitro cell adhesion tests for their capacity to interfere with alphavbeta3-mediated cell attachment to vitronectin. We hereby demonstrated that the different RGD monomers were similarly effective; the RGD dimer and tetramer showed comparable IC50 values, which were, however, significantly higher than those of the monomers. Best cell detachment from vitronectin was achieved by the peptidomimetic. The novel SPFS-binding assay platform proves to be a suitable, reliable, and sensitive method to monitor the binding capacity of small ligands to native transmembrane receptors, here demonstrated for integrins.

Are in vitro estimates of cell diffusivity and cell proliferation rate sensitive to assay geometry?

Cells respond to various biochemical and physical cues during wound–healing and tumour progression. In vitro assays used to study these processes are typically conducted in one particular geometry and it is unclear how the assay geometry affects the capacity of cell populations to spread, or whether the relevant mechanisms, such as cell motility and cell proliferation, are somehow sensitive to the geometry of the assay. In this work we use a circular barrier assay to characterise the spreading of cell populations in two different geometries. Assay 1 describes a tumour–like geometry where a cell population spreads outwards into an open space. Assay 2 describes a wound–like geometry where a cell population spreads inwards to close a void. We use a combination of discrete and continuum mathematical models and automated image processing methods to obtain independent estimates of the effective cell diffusivity, D, and the effective cell proliferation rate, λ. Using our parameterised mathematical model we confirm that our estimates of D and λ accurately predict the time–evolution of the location of the leading edge and the cell density profiles for both assay 1 and assay 2. Our work suggests that the effective cell diffusivity is up to 50% lower for assay 2 compared to assay 1, whereas the effective cell proliferation rate is up to 30% lower for assay 2 compared to assay 1.

Turning points in narratives of research design : research innovation stimulating unique responses to existing challenges for beginning rural teachers

This paper explores methodological turning points in researching narratives of early career resilience mediated by the complexities of remote teaching. Innovative, flexible and discursive research design facilitated exploration of emerging narratives using digital technologies. Data were regularly interrogated with participant-researchers to reveal the undercurrents of imbued meaning. Dialogue with participant-researchers enhanced interpretations of data plots and text-based explanations of narrative turning points, providing valuable insights throughout analysis. Reflections on the affordances and tensions in this process illustrate the significance of innovation but also the complexities associated with online collaboration. Consequently, empowering the participant-researchers throughout the life of the research was critical in understanding their narratives of teaching.

Enhancing student learning in the workplace through developing the leadership capabilities of clinical supervisors in the nursing discipline

The purpose of this project was to build the leadership capacity of clinical supervisors in the nursing discipline by developing, implementing and systematically embedding a leadership model into the structure and practice of student supervision. The University worked in partnership with three major metropolitan hospitals in Queensland to develop a framework and professional development program incorporating leadership and clinical supervision. The Leadership and Clinical Education (LaCE) program consisted of two structured workshops complemented by individual personal development projects undertaken by participants. Participants were supported in these activities with a purpose-built website that provides access to a wide variety of information and other learning resources. Quantitative and qualitative evaluations indicated that the approach was highly valued by participants, as it promoted useful peer dialogue, sharing of experiences and personal development in relation to assisting leadership development and student learning in the workplace. The LaCE program provides an ideal springboard for introducing the development of welltrained leaders into the clinical workplace. The resources developed have the potential to provide ongoing support for clinical supervisors to improve the learning of undergraduate nursing student. The challenge will be to achieve continued innovation within clinical education through sustainable leadership programs.

Determination of battery storage capacity in energy buffer for wind farm

Design of a battery energy storage system (BESS) in a buffer scheme is examined for the purpose of attenuating the effects of unsteady input power from wind farms. The design problem is formulated as maximization of an objective function that measures the economic benefit obtainable from the dispatched power from the wind farm against the cost of the BESS. Solution to the problem results in the determination of the capacity of the BESS to ensure constant dispatched power to the connected grid, while the voltage level across the dc-link of the buffer is kept within preset limits. A computational procedure to determine the BESS capacity and the evaluation of the dc voltage is shown. Illustrative examples using the proposed design method are included.

Achieving superior innovation-based performance outcomes in SMEs through innovation resource–capability complementarity

Firms are increasingly identifying new avenues to enhance their market position. One such effort involves the firms' ability to continuously learn. Learning has the capacity to enable firms to develop and implement more efficient and effective innovation-focused strategies, resulting in the ability to develop and deliver more products in a timelier manner. This study tests the relationship between innovation resource–capability complementarity and innovation-based performance. This study further elaborates that while innovation resource–capability complementarity drives innovation-based performance; their relationship will be enhanced via the firms' possession of superior learning capability. The findings show a significant effect of innovation resource–capability complementarity on innovation-based performance. The results also show that firms that possess superior learning capability are willing to question their operational processes and routines and make adjustments following the feedback obtained from customers and channels; thereby enhancing their abilities to develop more new products and increase their speed in delivering products to the customers.

JK1 (FAM134B) represses cell migration in colon cancer : a functional study of a novel gene

Background JK1 is a novel cancer-related gene with unknown functional role in carcinogenesis. The aim of this study is to investigate the role of JK1 gene in carcinogenesis in an in vitro cell proliferation and migration analysis model. Methods Small hairpin RNAs (shRNA) were designed to knock-down JK1 expression in colon cancer cell line (SW480) using transduction ready lentiviral particles. Cell proliferation and cell migration assays were performed on multiple extracellular matrices to investigate the cellular effects of JK1 in colon cancer cells. A non-cancer colonic epithelial cell line (FHC) was used to compare the expression of JK1 in cancer cell line. Results JK1 knock-down did not affect cellular proliferation or survival in colon cancer. However, the manipulation increased cancer cell migration rates on collagen and fibronectin substrates. Conclusions JK1 was shown for the first time to have a functional role in the pathogenesis of colon cancer. The results imply that JK1 represses the capacity of cancer cells to migrate within their tissue. They also concurred with the previous findings of JK1 activity correlations with clinical and pathological features in colon cancer. The capacity may have utility as a means to prevent cancer cells forming metastases.

Effect of chute level on mill capacity

IN MANY FACTORIES, the feed chute of the first mill is operated with a high chute level for the purpose of maximising the cane rate through the mill. There is a trend towards trying to control chute level within a small control range near the top of a chute that can result in rapid changes in cane feeding rate to maintain the chute level set point. This paper reviews the theory that predicts higher cane rate with higher chute level and discusses the main weakness in the theory that it does not consider the beneficial effect on capacity of cane falling from the top of the chute to the top surface of the cane mat. An extension to the chute theory model is described that predicts higher capacity with lower chute level because of the effect of the falling cane. The original model and this extended model are believed to be the upper and lower limits to the true effect. The paper reports an experiment that measured the real effect of chute level on capacity and finds that increasing chute level does lead to higher capacity but that the trend is only about one-third as strong as the original theory predicted. The paper questions whether the benefits of slightly greater capacity outweigh the costs of operating with the small control range near the top of the chute.

Examining the predictive value of combining the theory of planned behaviour and the volunteer functions inventory

The functions of the volunteer functions inventory were combined with the constructs of the theory of planned behaviour (i.e., attitudes, subjective norms, and perceived behavioural control) to establish whether a stronger, single explanatory model prevailed. Undertaken in the context of episodic, skilled volunteering by individuals who were retired or approaching retirement (N = 186), the research advances on prior studies which either examined the predictive capacity of each model independently or compared their explanatory value. Using hierarchical regression analysis, the functions of the volunteer functions inventory (when controlling for demographic variables) explained an additional 7.0% of variability in individuals’ willingness to volunteer over and above that accounted for by the theory of planned behaviour. Significant predictors in the final model included attitudes, subjective norms and perceived behavioural control from the theory of planned behaviour and the understanding function from the volunteer functions inventory. It is proposed that the items comprising the understanding function may represent a deeper psychological construct (e.g., self-actualisation) not accounted for by the theory of planned behaviour. The findings highlight the potential benefit of combining these two prominent models in terms of improving understanding of volunteerism and providing a single parsimonious model for raising rates of this important behaviour.

Seeing pedestrians at night : effect of driver age and visual abilities

Purpose To quantify the effects of driver age on night-time pedestrian conspicuity, and to determine whether individual differences in visual performance can predict drivers' ability to recognise pedestrians at night. Methods Participants were 32 visually normal drivers (20 younger: M = 24.4 years ± 6.4 years; 12 older: M = 72.0 years ± 5.0 years). Visual performance was measured in a laboratory-based testing session including visual acuity, contrast sensitivity, motion sensitivity and the useful field of view. Night-time pedestrian recognition distances were recorded while participants drove an instrumented vehicle along a closed road course at night; to increase the workload of drivers, auditory and visual distracter tasks were presented for some of the laps. Pedestrians walked in place, sideways to the oncoming vehicles, and wore either a standard high visibility reflective vest or reflective tape positioned on the movable joints (biological motion). Results Driver age and pedestrian clothing significantly (p < 0.05) affected the distance at which the drivers first responded to the pedestrians. Older drivers recognised pedestrians at approximately half the distance of the younger drivers and pedestrians were recognised more often and at longer distances when they wore a biological motion reflective clothing configuration than when they wore a reflective vest. Motion sensitivity was an independent predictor of pedestrian recognition distance, even when controlling for driver age. Conclusions The night-time pedestrian recognition capacity of older drivers was significantly worse than that of younger drivers. The distance at which drivers first recognised pedestrians at night was best predicted by a test of motion sensitivity.

Going live : building academic capacity in blended learning using web-conferencing technologies

This paper reports on a current initiative at Queensland University of Technology to provide timely, flexible and sustainable training and support to academic staff in blended learning and associated techno-pedagogies via a web-conferencing classroom and collaboration tool, Elluminate Live!. This technology was first introduced to QUT in 2008 as part of the university‘s ongoing commitment to meeting the learning needs of diverse student cohorts. The centralised Learning Design team, in collaboration with the university‘s department of eLearning Services, was given the task of providing training and support to academic staff in the effective use of the technology for teaching and learning, as part of the team‘s ongoing brief to support and enhance the provision of blended learning throughout the university. The resulting program, ―Learning Design Live‖ (LDL) is informed by Rogers‘ theory of innovation and diffusion (2003) and structured according to Wilson‘s framework for faculty development (2007). This paper discusses the program‘s design and structure, considers the program‘s impact on academic capacity in blended learning within the institution, and reflects on future directions for the program and emerging insights into blended learning and participant engagement for both staff and students.

‘Healthy mobile check-ins’ study: using GIS in smartphones to track use of urban environment by survivors of endometrial cancer

Aims/Objectives Our study aims to test the capacity of a newly developed smartphone innovation to obtain data on social, structural, and spatial determinants of the daily health-related behaviours of women living in urban Brisbane neighbourhoods who have survived endometrial cancer. Methods The women used a mobile web app designed specifically for the project to record GIS/location data on every destination they visited within their local urban neighbourhoods over a two-week period. Additionally, we gathered textual data on the social context/reasons for travel, as well as mode of transport to reach these destinations. The data was transported to SPSS and Google Earth for statistical and spatial analysis. We then met with the women to discuss lifestyle interventions to maximise their use of their local neighbourhoods in ways that could increase their physical activity levels and improve their overall health and well-being. These interventions will be evaluated and translated into a large-scale national study if effective. Results Initial findings about patterns in the group’s use of the local urban environment will be displayed, including daily distances travelled, types of locations visited, walking levels, use of public transport, use of green spaces and use of health-related resources. Any socio-demograpahic differences found between the women will be reported. Qualitative, quantitative, and spatial/mapping data will be displayed Conclusion The benefits and limitations of the mobile website designed to collect a range of data types about human-neighbourhood interactions with implications for intervention design will be discussed.

Assessment of the concentrations of polybrominated diphenyl ether flame retardants in the Australian population : levels in blood

Polybrominated diphenyl ethers (PBDEs), a common class of brominated flame retardants, are a ubiquitous part of our built environment, and for many years have contributed to improved public safety by reducing the flammability of everyday goods. Recently, PBDEs have come under increased international attention because of their potential to impact upon the environment and human health. Some PBDE compounds have been nominated for possible inclusion on the Stockholm Convention on Persistent Organic Pollutants, to which Australia is a Party. Work under the Stockholm Convention has demonstrated the capacity of some PBDEs to persist and accumulate in the environment and to be carried long distances. Much is unknown about the impact of PBDEs on living organisms, however recent studies show that some PBDEs can inhibit growth in colonies of plankton and algae and depress the reproduction of zooplankton. Laboratory mice and rats have also shown liver disturbances and damage to developing nervous systems as a result of exposure to PBDEs. In 2004, the Australian Government Department of the Environment and Water Resources began three studies to examine levels of PBDEs in aquatic sediments, indoor environments and human blood, as knowledge about PBDEs in Australia was very limited. The aim of these studies was to improve this knowledge base so that governments were in a better position to consider appropriate management actions. Due to the high costs for laboratory analysis of PBDEs, the number of samples collected for each study was limited and so caution is required when interpreting the findings. Nevertheless, these studies will provide governments with an indication of how prevalent PBDEs are in the Australian population and the environment and will also contribute to international knowledge about these chemicals. The Department of the Environment and Water Resources will be working closely with othergovernment agencies, industry and the community to investigate any further action that may be required to address PBDEs in Australia.

Incorporating complex train paths to an analysis of absolute capacity

Railways are an important mode of transportation. They are however large and complex and their construction, management and operation is time consuming and costly. Evidently planning the current and future activities is vital. Part of that planning process is an analysis of capacity. To determine what volume of traffic can be achieved over time, a variety of railway capacity analysis techniques have been created. A generic analytical approach that incorporates more complex train paths however has yet to be provided. This article provides such an approach. This article extends a mathematical model for determining the theoretical capacity of a railway network. The main contribution of this paper is the modelling of more complex train paths whereby each section can be visited many times in the course of a train’s journey. Three variant models are formulated and then demonstrated in a case study. This article’s numerical investigations have successively shown the applicability of the proposed models and how they may be used to gain insights into system performance.