Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.

A pilot study assessing the feasibility of a home-based progressive resistance exercise program and trend toward healing rates for patients with venous leg ulcers

Venous leg ulceration is a serious condition affecting 1 – 3% of the population. Decline in the function of the calf muscle pump is correlated with venous ulceration. Many previous studies have reported an improvement in the function of the calf muscle pump, endurance of the calf muscle and increased range of ankle motion after structured exercise programs. However, there is a paucity of published research that assesses if these improvements result in an improvement in the healing rates of venous ulcers. The primary purpose of this pilot study was to establish the feasibility of a homebased progressive resistance exercise program and examine if there was any clinical significance or trend toward healing. The secondary aims were to examine the benefit of a home-based progressive resistance exercise program on calf muscle pump function and physical parameters. The methodology used was a randomised controlled trial where eleven participants were randomised into an intervention (n = 6) or control group (n = 5). Participants who were randomised to receive a 12-week home-based progressive resistance exercise program were instructed through weekly face-to-face consultations during their wound clinic appointment by the author. Control group participants received standard wound care and compression therapy. Changes in ulcer parameters were measured fortnightly at the clinic (number healed at 12 weeks, percentage change in area and pressure ulcer score healing score). An air plethysmography test was performed at baseline and following the 12 weeks of training to determine changes in calf muscle pump function. Functional measures included maximum number of heel raises (endurance), maximal isometric plantar flexion (strength) and range of ankle motion (ROAM); these tests were conducted at baseline, week 6 and week 12. The sample for the study was drawn from the Princess Alexandra Hospital in Brisbane, Australia. Participants with venous leg ulceration who met the inclusion criteria were recruited. The participants were screened via duplex scanning and ankle brachial pressure index (ABPI) to ensure they did not have any arterial complications. Participants were excluded if there was evidence of cellulitis. Demographic data were obtained from each participant and details regarding medical history, quality of life and geriatric depression scores were collected at baseline. Both the intervention and control group were required to complete a weekly exercise diary to monitor activity levels between groups. To test for the effect of the intervention over time, a repeated measures analysis of variance was conducted on the major outcome variables. Group (intervention versus control) was the between subject factor and time (baseline, week 6, week 12) was the within subject or repeated measures factor. Due to the small sample size, further tests were conducted to check the assumptions of the statistical test to be used. The results showed that Mauchly.s Test, the Sphericity assumptions of repeated measures for ANOVA were met. Further tests of homogeneity of variance assumptions also confirmed that this assumption was met. Data analysis was conducted using the software package SPSS for Windows Release 17.0. The pilot study proved feasible with all of the intervention (n=6) participants continuing with the resistance program for the 12 week duration and no deleterious effects noted. Clinical significance was observed in the intervention group with a 32% greater change in ulcer size (p= 0.26) than the control group, and a 10% (p = 0.74) greater difference between the numbers healed compared to the control group. Statistical significance was observed for the ejection fraction (p = 0.05), residual volume fraction (p = 0.04) and ROAM (p = 0.01), which all improved significantly in the intervention group over time. These results are encouraging, nevertheless, further investigations seem warranted to examine the effect exercise has on the healing rates of venous leg ulcers, with a multistudy site, larger sample size and longer follow up period.

The role of cross-functional teams on the alignment between technology innovation effectiveness and operational effectiveness

Organisations are increasingly investing in complex technological innovations, such as enterprise information systems, with the aim of improving the operation of the business, and in this way gaining competitive advantage. However, the implementation of technological innovations tends to have an excessive focus on either technology innovation effectiveness, or the resulting operational effectiveness. Focusing on either one of them is detrimental to long-term performance. Cross-functional teams have been used by many organisations as a way of involving expertise from different functional areas in the implementation of technologies. The role of boundary spanning actors is discussed as they bring a common language to the cross-functional teams. Multiple regression analysis has been used to identify the structural relationships and provide an explanation for the influence of cross-functional teams, technology innovation effectiveness and operational effectiveness in the continuous improvement of operational performance. The findings indicate that cross functional teams have an indirect influence on continuous improvement of operational performance through the alignment between technology innovation effectiveness and operational effectiveness.

Functional heterogeneity as a two-dimensional concept : empirical evidence for new venture teams

Previous research on entrepreneurial teams has failed to settle the controversy over whether team heterogeneity helps or hinders new venture performance. Reconciling this inconsistency, this paper suggests a new conceptual approach to disentangle differential effects of team heterogeneity by modeling two separate heterogeneity dimensions, namely knowledge scope and knowledge disparity. Analyzing unique data on functional experiences of the members of 337 start-up teams, we find support for our contention of team heterogeneity as a two-dimensional concept. Results suggest that knowledge disparity negatively relates to both start-ups’ entrepreneurial and innovative performance. In contrast, we find knowledge scope to positively affect entrepreneurial performance, while it shows an inverse U-shaped relationship to innovative start-up performance.

An ecological footprint for an early learning centre : identifying opportunities for early childhood sustainability education through interdisciplinary research

In this study, engineers and educators worked together to adapt and apply the ecological footprint (EF) methodology to an early learning centre in Brisbane, Australia. Results were analysed to determine how environmental impact can be reduced at the study site and more generally across early childhood settings. It was found that food, transport and energy consumption had the largest impact on the centre’s overall footprint. In transport and energy, early childhood centres can reduce their impact through infrastructure and cultural change, in association with changed curriculum strategies. Building design, the type of energy purchased and appliance usage can all be modified to reduce the energy footprint. The transport footprint can be reduced through more families using active and public transport, which can be encouraged by providing information, support and facilities and appropriate siting of new centres. Introducing the concept of ecological footprint in early childhood education may be an effective way to educate children, staff and parents on the links between the food they eat, land usage and environmental impact. This study responds directly to the call in this journal for research focused on early childhood education and for more to be made of interdisciplinary research opportunities.

From classroom resistance to school reform

In the project described in this chapter, a group of educationally disengaged high school students investigated their peers' perspectives of factors related to low aspiration for and access to university. On the basis of their findings, they created an informative DVD to address the student needs.

p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas

Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors.

Practices for teaching moral values in the early years : a call for a pedagogy of participation

Schools have long been seen as institutions for preparing children for life, both academically and as moral agents in society. In order to become capable, moral citizens, children need to be provided with opportunities to learn moral values. However, little is known about how teachers enact social and moral values programs in the classroom. The aim of this paper is to investigate the practices that Australian early years teachers describe as important for teaching moral values. To investigate early years teachers’ understandings of moral pedagogy, 379 Australian teachers with experience teaching children in the early years were invited to participate in an on-line survey. This paper focuses on responses provided to an open-ended question relating to teaching practices for moral values. The responses were analysed using an interpretive methodology. The results indicate that the most prominent approaches to teaching moral values described by this group of Australian early years teachers were engaging children in moral activities. This was closely followed by teaching practices for transmitting moral values. Engaging children in building meaning and participatory learning for moral values were least often described.

New variational Bayesian approaches for statistical data mining : with applications to profiling and differentiating habitual consumption behaviour of customers in the wireless telecommunication industry

This thesis investigates profiling and differentiating customers through the use of statistical data mining techniques. The business application of our work centres on examining individuals’ seldomly studied yet critical consumption behaviour over an extensive time period within the context of the wireless telecommunication industry; consumption behaviour (as oppose to purchasing behaviour) is behaviour that has been performed so frequently that it become habitual and involves minimal intentions or decision making. Key variables investigated are the activity initialised timestamp and cell tower location as well as the activity type and usage quantity (e.g., voice call with duration in seconds); and the research focuses are on customers’ spatial and temporal usage behaviour. The main methodological emphasis is on the development of clustering models based on Gaussian mixture models (GMMs) which are fitted with the use of the recently developed variational Bayesian (VB) method. VB is an efficient deterministic alternative to the popular but computationally demandingMarkov chainMonte Carlo (MCMC) methods. The standard VBGMMalgorithm is extended by allowing component splitting such that it is robust to initial parameter choices and can automatically and efficiently determine the number of components. The new algorithm we propose allows more effective modelling of individuals’ highly heterogeneous and spiky spatial usage behaviour, or more generally human mobility patterns; the term spiky describes data patterns with large areas of low probability mixed with small areas of high probability. Customers are then characterised and segmented based on the fitted GMM which corresponds to how each of them uses the products/services spatially in their daily lives; this is essentially their likely lifestyle and occupational traits. Other significant research contributions include fitting GMMs using VB to circular data i.e., the temporal usage behaviour, and developing clustering algorithms suitable for high dimensional data based on the use of VB-GMM.