Multiple human single-stranded DNA binding proteins function in genome maintenance : structural, biochemical and functional analysis

DNA exists predominantly in a duplex form that is preserved via specific base pairing. This base pairing affords a considerable degree of protection against chemical or physical damage and preserves coding potential. However, there are many situations, e.g. during DNA damage and programmed cellular processes such as DNA replication and transcription, in which the DNA duplex is separated into two singlestranded DNA (ssDNA) strands. This ssDNA is vulnerable to attack by nucleases, binding by inappropriate proteins and chemical attack. It is very important to control the generation of ssDNA and protect it when it forms, and for this reason all cellular organisms and many viruses encode a ssDNA binding protein (SSB). All known SSBs use an oligosaccharide/oligonucleotide binding (OB)-fold domain for DNA binding. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating strand-exchange proteins and helicases, and mediation of protein–protein interactions. Recently two additional human SSBs have been identified that are more closely related to bacterial and archaeal SSBs. Prior to this it was believed that replication protein A, RPA, was the only human equivalent of bacterial SSB. RPA is thought to be required for most aspects of DNA metabolism including DNA replication, recombination and repair. This review will discuss in further detail the biological pathways in which human SSBs function.

hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex

hSSB1 is a newly discovered single-stranded DNA (ssDNA)-binding protein that is essential for efficient DNA double-strand break signalling through ATM. However, the mechanism by which hSSB1 functions to allow efficient signalling is unknown. Here, we show that hSSB1 is recruited rapidly to sites of double-strand DNA breaks (DSBs) in all interphase cells (G1, S and G2) independently of, CtIP, MDC1 and the MRN complex (Rad50, Mre11, NBS1). However expansion of hSSB1 from the DSB site requires the function of MRN. Strikingly, silencing of hSSB1 prevents foci formation as well as recruitment of MRN to sites of DSBs and leads to a subsequent defect in resection of DSBs as evident by defective RPA and ssDNA generation. Our data suggests that hSSB1 functions upstream of MRN to promote its recruitment at DSBs and is required for efficient resection of DSBs. These findings, together with previous work establish essential roles of hSSB1 in controlling ATM activation and activity, and subsequent DSB resection and homologous recombination (HR).

Noise robust voice activity detection using features extracted from the time-domain autocorrelation function

This paper presents a method of voice activity detection (VAD) for high noise scenarios, using a noise robust voiced speech detection feature. The developed method is based on the fusion of two systems. The first system utilises the maximum peak of the normalised time-domain autocorrelation function (MaxPeak). The second zone system uses a novel combination of cross-correlation and zero-crossing rate of the normalised autocorrelation to approximate a measure of signal pitch and periodicity (CrossCorr) that is hypothesised to be noise robust. The score outputs by the two systems are then merged using weighted sum fusion to create the proposed autocorrelation zero-crossing rate (AZR) VAD. Accuracy of AZR was compared to state of the art and standardised VAD methods and was shown to outperform the best performing system with an average relative improvement of 24.8% in half-total error rate (HTER) on the QUT-NOISE-TIMIT database created using real recordings from high-noise environments.

Computed success rates of various carrier phase integer estimation solutions and their comparison with statistical success rates

The success rate of carrier phase ambiguity resolution (AR) is the probability that the ambiguities are successfully fixed to their correct integer values. In existing works, an exact success rate formula for integer bootstrapping estimator has been used as a sharp lower bound for the integer least squares (ILS) success rate. Rigorous computation of success rate for the more general ILS solutions has been considered difficult, because of complexity of the ILS ambiguity pull-in region and computational load of the integration of the multivariate probability density function. Contributions of this work are twofold. First, the pull-in region mathematically expressed as the vertices of a polyhedron is represented by a multi-dimensional grid, at which the cumulative probability can be integrated with the multivariate normal cumulative density function (mvncdf) available in Matlab. The bivariate case is studied where the pull-region is usually defined as a hexagon and the probability is easily obtained using mvncdf at all the grid points within the convex polygon. Second, the paper compares the computed integer rounding and integer bootstrapping success rates, lower and upper bounds of the ILS success rates to the actual ILS AR success rates obtained from a 24 h GPS data set for a 21 km baseline. The results demonstrate that the upper bound probability of the ILS AR probability given in the existing literatures agrees with the actual ILS success rate well, although the success rate computed with integer bootstrapping method is a quite sharp approximation to the actual ILS success rate. The results also show that variations or uncertainty of the unit–weight variance estimates from epoch to epoch will affect the computed success rates from different methods significantly, thus deserving more attentions in order to obtain useful success probability predictions.

A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia

Background A number of studies have found associations between dysbindin (DTNBP1) polymorphisms and schizophrenia. Recently we identified a DTNBP1 SNP (rs9370822) that is strongly associated with schizophrenia. Individuals diagnosed with schizophrenia were nearly three times as likely to carry the CC genotype compared to the AA genotype. Methods To investigate the importance of this SNP in the function of DTNBP1, a number of psychiatric conditions including addictive behaviours and anxiety disorders were analysed for association with rs9370822. Results The DTNBP1 polymorphism was significantly associated with post-traumatic stress disorder (PTSD) as well as nicotine and opiate dependence but not alcohol dependence. Individuals suffering PTSD were more than three times as likely to carry the CC genotype compared to the AA genotype. Individuals with nicotine or opiate dependence were more than twice as likely to carry the CC genotype compared to the AA genotype. Conclusions This study provides further support for the importance of DTNBP1 in psychiatric conditions and suggests that there is a common underlying molecular defect involving DTNBP1 that contributes to the development of several anxiety and addictive disorders that are generally recognised as separate clinical conditions. These disorders may actually be different expressions of a single metabolic pathway perturbation. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

Discriminative optimisation of the figure of merit for phonetic spoken term detection

This work proposes to improve spoken term detection (STD) accuracy by optimising the Figure of Merit (FOM). In this article, the index takes the form of phonetic posterior-feature matrix. Accuracy is improved by formulating STD as a discriminative training problem and directly optimising the FOM, through its use as an objective function to train a transformation of the index. The outcome of indexing is then a matrix of enhanced posterior-features that are directly tailored for the STD task. The technique is shown to improve the FOM by up to 13% on held-out data. Additional analysis explores the effect of the technique on phone recognition accuracy, examines the actual values of the learned transform, and demonstrates that using an extended training data set results in further improvement in the FOM.

Human-body shadowing effects on indoor MIMO-OFDM channels at 5.2 GHz

Pedestrian movement is known to cause significant effects on indoor MIMO channels. In this paper, a statistical characterization of the indoor MIMO-OFDM channel subject ot pedestrian movement is reported. The experiment used 4 sending and 4 receiving antennas and 114 sub-carriers at 5.2 GHz. Measurement scenarios varied from zero to ten pedestrians walking randomly between transmitter (tx) and receiver (Rx) arrays. The empirical cumulative distribution function (CDF) of the received fading envelope fits the Ricean distribution with K factors ranging from 7dB to 15 dB, for the 10 pedestrians and vacant scenarios respectively. In general, as the number of pedestrians increase, the CDF slope tends to decrease proportionally. Furthermore, as the number of pedestrians increase, increasing multipath contribution, the dynamic range of channel capacity increases proportionally. These results are consistent with measurement results obtained in controlled scenarios for a fixed narrowband Single-Input Single-Output (SISO) link at 5.2 GHz in previous work. The described empirical characterization provides an insight into the prediction of human-body shadowing effects for indoor MIMO-OFDM channels at 5.2 GHz.

Effects of different practice task constraints on fluctuations of player heart rate in small-sided football games

This paper analyzes effects of different practice task constraints on heart rate (HR) variability during 4v4 smallsided football games. Participants were sixteen football players divided into two age groups (U13, Mean age: 12.4±0.5 yrs; U15: 14.6±0.5). The task consisted of a 4v4 sub-phase without goalkeepers, on a 25x15 m field, of 15 minutes duration with an active recovery period of 6 minutes between each condition. We recorded players’ heart rates using heart rate monitors (Polar Team System, Polar Electro, Kempele, Finland) as scoring mode was manipulated (line goal: scoring by dribbling past an extended line; double goal: scoring in either of two lateral goals; and central goal: scoring only in one goal). Subsequently, %HR reserve was calculated with the Karvonen formula. We performed a time-series analysis of HR for each individual in each condition. Mean data for intra-participant variability showed that autocorrelation function was associated with more short-range dependence processes in the “line goal” condition, compared to other conditions, demonstrating that the “line goal” constraint induced more randomness in HR response. Relative to inter-individual variability, line goal constraints demonstrated lower %CV and %RMSD (U13: 9% and 19%; U15: 10% and 19%) compared with double goal (U13: 12% and 21%; U15: 12% and 21%) and central goal (U13: 14% and 24%; U15: 13% and 24%) task constraints, respectively. Results suggested that line goal constraints imposed more randomness on cardiovascular stimulation of each individual and lower inter-individual variability than double goal and central goal constraints.

Uncertainty and innovation in fashion design

Generally speaking, psychologists have suggested three traditional views of how people cope with uncertainty. They are the certainty maximiser, the intuitive statistician-economist and the knowledge seeker (Smithson, 2008). In times of uncertainty, such as the recent global financial crisis, these coping methods often result in innovation in industry. Richards (2003) identifies innovation as different from creativity in that innovation aims to transform and implement rather than simply explore and invent. An examination of the work of iconic fashion designers, through case study and situational analysis, reveals that coping with uncertainty manifests itself in ways that have resulted in innovations in design, marketing methods, production and consumption. In relation to contemporary fashion, where many garments look the same in style, colour, cut and fit (Finn, 2008), the concept of innovation is an important one. This paper explores the role of uncertainty as a driver of innovation in fashion design. A key aspect of seeking knowledge, as a mechanism to cope with this uncertainty, is a return to basics. This is a problem for contemporary fashion designers who are no longer necessarily makers and therefore do not engage with the basic materials and methods of garment construction. In many cases design in fashion has become digital, communicated to an unseen, unknown production team via scanned image and specification alone. The disconnection between the design and the making of garments, as a result of decades of off-shore manufacturing, has limited the opportunity for this return to basics. The authors argue that the role of the fashion designer has become about the final product and as a result there is a lack of innovation in the process of making: in the form, fit and function of fashion garments. They propose that ‘knowledge seeking’ as a result of uncertainty in the fashion industry, in particular through re-examination of the methods of making, could hold the key to a new era of innovation in fashion design.

Student engagement with an ePortfolio : a case study of pre-service education students

The emergence of ePortfolios is relatively recent in the university sector as a way to engage students in their learning and assessment, and to produce records of their accomplishments. An ePortfolio is an online tool that students can utilise to record, catalogue, retrieve and present reflections and artefacts that support and demonstrate the development of graduate students’ capabilities and professional standards across university courses. The ePortfolio is therefore considered as both process and product. Although ePortfolios show promise as a useful tool and their uptake has grown, they are not yet a mainstream higher education technology. To date, the emphasis has been on investigating their potential to support the multiple purposes of learning, assessment and employability, but less is known about whether and how students engage with ePortfolios in the university setting. This thesis investigates student engagement with an ePortfolio in one university. As the educational designer for the ePortfolio project at the University, I was uniquely positioned as a researching professional to undertake an inquiry into whether students were engaging with the ePortfolio. The participants in this study were a cohort (defined by enrolment in a unit of study) of second and third year education students (n=105) enrolled in a four year Bachelor of Education degree. The students were introduced to the ePortfolio in an introductory lecture and a hands-on workshop in a computer laboratory. They were subsequently required to complete a compulsory assessment task – a critical reflection - using the ePortfolio. Following that, engagement with the ePortfolio was voluntary. A single case study approach arising from an interpretivist paradigm directed the methodological approach and research design for this study. The study investigated the participants’ own accounts of their experiences with the ePortfolio, including how and when they engaged with the ePortfolio and the factors that impacted on their engagement. Data collection methods consisted of an attitude survey, student interviews, document collection, a researcher reflective journal and researcher observations. The findings of the study show that, while the students were encouraged to use the ePortfolio as a learning and employability tool, most students ultimately chose to disengage after completing the assessment task. Only six of the forty-five students (13%) who completed the research survey had used the ePortfolio in a sustained manner. The data obtained from the students during this research has provided insight into reasons why they disengaged from the ePortfolio. The findings add to the understandings and descriptions of student engagement with technology, and more broadly, advance the understanding of ePortfolios. These findings also contribute to the interdisciplinary field of technology implementation. There are three key outcomes from this study, a model of student engagement with technology, a set of criteria for the design of an ePortfolio, and a set of recommendations for effective practice for those implementing ePortfolios. The first, the Model of Student Engagement with Technology (MSET) (Version 2) explored student engagement with technology by highlighting key engagement decision points for students The model was initially conceptualised by building on work of previous research (Version 1), however, following data analysis a new model emerged, MSET (Version 2). The engagement decision points were identified as: • Prior Knowledge and Experience, leading to imagined usefulness and imagined ease of use; • Initial Supported Engagement, leading to supported experience of usefulness and supported ease of use; • Initial Independent Engagement, leading to actual experience of independent usefulness and actual ease of use; and • Ongoing Independent Engagement, leading to ongoing experience of usefulness and ongoing ease of use. The Model of Student Engagement with Technology (MSET) goes beyond numerical figures of usage to demonstrate student engagement with an ePortfolio. The explanatory power of the model is based on the identification of the types of decisions that students make and when they make them during the engagement process. This model presents a greater depth of understanding student engagement than was previously available and has implications for the direction and timing of future implementation, and academic and student development activities. The second key outcome from this study is a set of criteria for the re-conceptualisation of the University ePortfolio. The knowledge gained from this research has resulted in a new set of design criteria that focus on the student actions of writing reflections and adding artefacts. The process of using the ePortfolio is reconceptualised in terms of privileging student learning over administrative compliance. The focus of the ePortfolio is that the writing of critical reflections is the key function, not the selection of capabilities. The third key outcome from this research consists of five recommendations for university practice that have arisen from this study. They are that, sustainable implementation is more often achieved through small steps building on one another; that a clear definition of the purpose of an ePortfolio is crucial for students and staff; that ePortfolio pedagogy should be the driving force not the technology; that the merit of the ePortfolio is fostered in students and staff; and finally, that supporting delayed task performance is crucial. Students do not adopt an ePortfolio just because it is provided. While students must accept responsibility for their own engagement with the ePortfolio, the institution has to accept responsibility for providing the environment, and technical and pedagogical support to foster engagement. Ultimately, an ePortfolio should be considered as a joint venture between student and institution where strong returns on investment can be realised by both. It is acknowledged that the current implementation strategies for the ePortfolio are just the beginning of a much longer process. The real rewards for students, academics and the university lie in the future.

In vitro and in vivo examination of the cell surface glycoprotein CDCP1

A number of reports have demonstrated the importance of the CUB domaincontaining protein 1 (CDCP1) in facilitating cancer progression in animal models and the potential of this protein as a prognostic marker in several malignancies. CDCP1 facilitates metastasis formation in animal models by negatively regulating anoikis, a type of apoptosis triggered by the loss of attachment signalling from cell-cell contacts or cell-extra cellular matrix (ECM) contacts. Due to the important role CDCP1 plays in cancer progression in model systems, it is considered a potential drug target to prevent the metastatic spread of cancers. CDCP1 is a highly glycosylated 836 amino acid cell surface protein. It has structural features potentially facilitating protein-protein interactions including 14 N-glycosylation sites, three CUB-like domains, 20 cysteine residues likely to be involved in disulfide bond formation and five intracellular tyrosine residues. CDCP1 interacts with a variety of proteins including Src family kinases (SFKs) and protein kinase C ä (PKCä). Efforts to understand the mechanisms regulating these interactions have largely focussed on three CDCP1 tyrosine residues Y734, Y743 and Y762. CDCP1-Y734 is the site where SFKs phosphorylate and bind to CDCP1 and mediate subsequent phosphorylation of CDCP1-Y743 and -Y762 which leads to binding of PKCä at CDCP1-Y762. The resulting trimeric protein complex of SFK•CDCP1•PKCä has been proposed to mediate an anti-apoptotic cell phenotype in vitro, and to promote metastasis in vivo. The effect of mutation of the three tyrosines on interactions of CDCP1 with SFKs and PKCä and the consequences on cell phenotype in vitro and in vivo have not been examined. CDCP1 has a predicted molecular weight of ~90 kDa but is usually detected as a protein which migrates at ~135 kDa by Western blot analysis due to its high degree of glycosylation. A low molecular weight form of CDCP1 (LMWCDCP1) of ~70 kDa has been found in a variety of cancer cell lines. The mechanisms leading to the generation of LMW-CDCP1 in vivo are not well understood but an involvement of proteases in this process has been proposed. Serine proteases including plasmin and trypsin are able to proteolytically process CDCP1. In addition, the recombinant protease domain of the serine protease matriptase is also able to cleave the recombinant extracellular portion of CDCP1. Whether matriptase is able to proteolytically process CDCP1 on the cell surface has not been examined. Importantly, proteolytic processing of CDCP1 by trypsin leads to phosphorylation of its cell surface-retained portion which suggests that this event leads to initiation of an intracellular signalling cascade. This project aimed to further examine the biology of CDCP1 with a main of focus on exploring the roles played by CDCP1 tyrosine residues. To achieve this HeLa cells stably expressing CDCP1 or the CDCP1 tyrosine mutants Y734F, Y743F and Y762F were generated. These cell lines were used to examine: • The roles of the tyrosine residues Y734, Y743 and Y762 in mediating interactions of CDCP1 with binding proteins and to examine the effect of the stable expression on HeLa cell morphology. • The ability of the serine protease matriptase to proteolytically process cell surface CDCP1 and to examine the consequences of this event on HeLa cell phenotype and cell signalling in vitro. • The importance of these residues in processes associated with cancer progression in vitro including adhesion, proliferation and migration. • The role of these residues on metastatic phenotype in vivo and the ability of a function-blocking anti-CDCP1 antibody to inhibit metastasis in the chicken embryo chorioallantoic membrane (CAM) assay. Interestingly, biochemical experiments carried out in this study revealed that mutation of certain CDCP1 tyrosine residues impacts on interactions of this protein with binding proteins. For example, binding of SFKs as well as PKCä to CDCP1 was markedly decreased in HeLa-CDCP1-Y734F cells, and binding of PKCä was also reduced in HeLa-CDCP1-Y762F cells. In contrast, HeLa-CDCP1-Y743F cells did not display altered interactions with CDCP1 binding proteins. Importantly, observed differences in interactions of CDCP1 with binding partners impacted on basal phosphorylation of CDCP1. It was found that HeLa-CDCP1, HeLa-CDCP1-Y743F and -Y762F displayed strong basal levels of CDCP1 phosphorylation. In contrast, HeLa-CDCP1-Y734F cells did not display CDCP1 phosphorylation but exhibited constitutive phosphorylation of focal adhesion kinase (FAK) at tyrosine 861. Significantly, subsequent investigations to examine this observation suggested that CDCP1-Y734 and FAK-Y861 are competitive substrates for SFK-mediated phosphorylation. It appeared that SFK-mediated phosphorylation of CDCP1- Y734 and FAK-Y861 is an equilibrium which shifts depending on the level of CDCP1 expression in HeLa cells. This suggests that the level of CDCP1 expression may act as a regulatory mechanism allowing cells to switch from a FAK-Y861 mediated pathway to a CDCP1-Y734 mediated pathway. This is the first time that a link between SFKs, CDCP1 and FAK has been demonstrated. One of the most interesting observations from this work was that CDCP1 altered HeLa cell morphology causing an elongated and fibroblastic-like appearance. Importantly, this morphological change depended on CDCP1- Y734. In addition, it was observed that this change in cell morphology was accompanied by increased phosphorylation of SFK-Y416. This suggests that interactions of SFKs with CDCP1-Y734 increases SFK activity since SFKY416 is critical in regulating kinase activity of these proteins. The essential role of SFKs in mediating CDCP1-induced HeLa cell morphological changes was demonstrated using the SFK-selective inhibitor SU6656. This inhibitor caused reversion of HeLa-CDCP1 cell morphology to an epithelial appearance characteristic of HeLa-vector cells. Significantly, in vitro studies revealed that certain CDCP1-mediated cell phenotypes are mediated by cellular pathways dependent on CDCP1 tyrosine residues whereas others are independent of these sites. For example, CDCP1 expression caused a marked increase in HeLa cell motility that was independent of CDCP1 tyrosine residues. In contrast, CDCP1- induced decrease in HeLa cell proliferation was most prominent in HeLa- CDCP1-Y762F cells, potentially indicating a role for this site in regulating proliferation in HeLa cells. Another cellular event which was identified to require phosphorylation of a particular CDCP1 tyrosine residue is adhesion to fibronectin. It was observed that the CDCP1-mediated strong decrease in adhesion to fibronectin is mostly restored in HeLa-CDCP1-Y743F cells. This suggests a possible role for CDCP1-Y743 in causing a CDCP1-mediated decrease in adhesion. Data from in vivo experiments indicated that HeLa-CDCP1-Y734F cells are more metastic than HeLa-CDCP1 cells in vivo. This indicates that interaction of CDCP1 with SFKs and PKCä may not be required for CDCP1-mediated metastasis formation of HeLa cells in vivo. The metastatic phenotype of these cells may be caused by signalling involving FAK since HeLa-CDCP1- Y734F cells are the only CDCP1 expressing cells displaying constitutive phosphorylation of FAK-Y861. HeLa-CDCP1-Y762F cells displayed a very low metastatic ability which suggests that this CDCP1 tyrosine residue is important in mediating a pro-metastatic phenotype in HeLa cells. More detailed exploration of cellular events occurring downstream of CDCP1-Y734 and -Y762 may provide important insights into the mechanisms altering the metastatic ability of CDCP1 expressing HeLa cells. Complementing the in vivo studies, anti-CDCP1 antibodies were employed to assess whether these antibodies are able to inhibit metastasis of CDCP1 and CDCP1 tyrosine mutants expressing HeLa cells. It was found that HeLa- CDCP1-Y734F cells were the only cell line which was markedly reduced in the ability to metastasise. In contrast, the ability of HeLa-CDCP1, HeLa- CDCP1-Y743F and -Y762F cells to metastasise in vivo was not inhibited. These data suggest a possible role of interactions of CDCP1 with SFKs, occurring at CDCP1-Y734, in preventing an anti-metastatic effect of anti- CDCP1 antibodies in vivo. The proposal that SFKs may play a role in regulating anti-metastatic effects of anti-CDCP1 antibodies was supported by another experiment where differences between HeLa-CDCP1 cells and CDCP1 expressing HeLa cells (HeLa-CDCP1-S) from collaborators at the Scripps Research Institute were examined. It was found that HeLa-CDCP1-S cells express different SFKs than CDCP1 expressing HeLa cells generated for this study. This is important since HeLa-CDCP1-S cells can be inhibited in their metastatic ability using anti-CDCP1 antibodies in vivo. Importantly, these data suggest that further examinations of the roles of SFKs in facilitating anti-metastatic effects of anti-CDCP1 antibodies may give insights into how CDCP1 can be blocked to prevent metastasis in vivo. This project also explored the ability of the serine protease matriptase to proteolytically process cell surface localised CDCP1 because it is unknown whether matriptase can cleave cell surface CDCP1 as it has been reported for other proteases such as trypsin and plasmin. Furthermore, the consequences of matriptase-mediated proteolysis on cell phenotype in vitro and cell signalling were examined since recent reports suggested that proteolysis of CDCP1 leads to its phosphorylation and may initiate cell signalling and consequently alter cell phenotype. It was found that matriptase is able to proteolytically process cell surface CDCP1 at low nanomolar concentrations which suggests that cleavage of CDCP1 by matriptase may facilitate the generation of LWM-CDCP1 in vivo. To examine whether matriptase-mediated proteolysis induced cell signalling anti-phospho Erk 1/2 Western blot analysis was performed as this pathway has previously been examined to study signalling in response to proteolytic processing of cell surface proteins. It was found that matriptase-mediated proteolysis in CDCP1 expressing HeLa cells initiated intracellular signalling via Erk 1/2. Interestingly, this increase in phosphorylation of Erk 1/2 was also observed in HeLa-vector cells. This suggested that initiation of cell signalling via Erk 1/2 phosphorylation as a result of matriptase-mediated proteolysis occurs by pathways independent of CDCP1. Subsequent investigations measuring the flux of free calcium ions and by using a protease-activated receptor 2 (PAR2) agonist peptide confirmed this hypothesis. These data suggested that matriptase-mediated proteolysis results in cell signalling via a pathway induced by the activation of PAR2 rather than by CDCP1. This indicates that induction of cell signalling in HeLa cells as a consequence of matriptase-mediated proteolysis occurs via signalling pathways which do not involve phosphorylation of Erk 1/2. Consequently, it appears that future attempts should focus on the examination of cellular pathways other than Erk 1/2 to elucidate cell signalling initiated by matriptase-mediated proteolytic processing of CDCP1. The data presented in this thesis has explored in vitro and in vivo aspects of the biology of CDCP1. The observations summarised above will permit the design of future studies to more precisely determine the role of CDCP1 and its binding partners in processes relevant to cancer progression. This may contribute to further defining CDCP1 as a target for cancer treatment.

The ecological dynamics of 1v1 sub-phases in association football

This paper analyzes effects of different practice task constraints on heart rate (HR) variability during 4v4 smallsided football games. Participants were sixteen football players divided into two age groups (U13, Mean age: 12.4±0.5 yrs; U15: 14.6±0.5). The task consisted of a 4v4 sub-phase without goalkeepers, on a 25x15 m field, of 15 minutes duration with an active recovery period of 6 minutes between each condition. We recorded players’ heart rates using heart rate monitors (Polar Team System, Polar Electro, Kempele, Finland) as scoring mode was manipulated (line goal: scoring by dribbling past an extended line; double goal: scoring in either of two lateral goals; and central goal: scoring only in one goal). Subsequently, %HR reserve was calculated with the Karvonen formula. We performed a time-series analysis of HR for each individual in each condition. Mean data for intra-participant variability showed that autocorrelation function was associated with more short-range dependence processes in the “line goal” condition, compared to other conditions, demonstrating that the “line goal” constraint induced more randomness in HR response. Relative to inter-individual variability, line goal constraints demonstrated lower %CV and %RMSD (U13: 9% and 19%; U15: 10% and 19%) compared with double goal (U13: 12% and 21%; U15: 12% and 21%) and central goal (U13: 14% and 24%; U15: 13% and 24%) task constraints, respectively. Results suggested that line goal constraints imposed more randomness on cardiovascular stimulation of each individual and lower inter-individual variability than double goal and central goal constraints.

Children re-read and re-write their neighborhoods : critical literacies and identity work

This chapter considers the complex literate repertoires of 21st century children in multicultural primary classrooms in Adelaide South Australia. It draws on the curricular and pedagogical work of two experienced primary school teachers who explore culture, race and class, by positioning children as textual producers across a variety of media. In particular we discuss two child-authored texts – A is for Arndale – a local alphabet book co-authored by children aged between eight and ten, and – Cooking Afghani Style - a magazine style film produced by a multi-aged class of children (aged eight to thirteen) recently arrived in Australia. In the process of making these texts, primary children engaged in reading as a cultural practice – re-reading and re-writing their neighbourhoods and identities (both individual and collective). This involved frequent excursions to local key sites, both familiar and unfamiliar to the children. They investigated how diverse children experienced and lived their lives in particular places within changing communities.

Design and implementation of the Exercise for Health trial – a pragmatic exercise intervention for women with breast cancer

Background Exercise for Health was a pragmatic, randomised, controlled trial comparing the effect of an eight-month exercise intervention on function, treatment-related side effects and quality of life following breast cancer, compared with usual care. The intervention commenced six weeks post-surgery, and two modes of delivering the same intervention was compared with usual care. The purpose of this paper is to describe the study design, along with outcomes related to recruitment, retention and representativeness, and intervention participation. Methods: Women newly diagnosed with breast cancer and residing in a major metropolitan city of Queensland, Australia, were eligible to participate. Consenting women were randomised to a face-to-face-delivered exercise group (FtF, n=67), telephone-delivered exercise group (Tel, n=67) or usual care group (UC, n=60) and were assessed pre-intervention (5-weeks post-surgery), mid-intervention (6 months post-surgery) and 10 weeks post-intervention (12 months post-surgery). Each intervention arm entailed 16 sessions with an Exercise Physiologist. Results: Of 318 potentially eligible women, 63% (n=200) agreed to participate, with a 12-month retention rate of 93%. Participants were similar to the Queensland breast cancer population with respect to disease characteristics, and the randomisation procedure was mostly successful at attaining group balance, with the few minor imbalances observed unlikely to influence intervention effects given balance in other related characteristics. Median participation was 14 (min, max: 0, 16) and 13 (min, max: 3, 16) intervention sessions for the FtF and Tel, respectively, with 68% of those in Tel and 82% in FtF participating in at least 75% of sessions. Discussion: Participation in both intervention arms during and following treatment for breast cancer was feasible and acceptable to women. Future work, designed to inform translation into practice, will evaluate the quality of life, clinical, psychosocial and behavioural outcomes associated with each mode of delivery.

Critical literacies in place : teachers who work for just and sustainable communities

This chapter draws upon theories of social justice, critical literacy and place-based pedagogies and two research projects to discuss how teachers are working ethically and creatively towards a sustainable and just society in their place(s).