Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia

To gain insight into melanoma pathogenesis, we characterized an insertional mouse mutant, TG3, that is predisposed to develop multiple melanomas. Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence. To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice. We observed aberrant expression of only Grm1. Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice. To confirm the involvement of Grm1 in melanocytic neoplasia, we created an additional transgenic line with Grm1 expression driven by the dopachrome tautomerase promoter. Similar to the original TG3, the Tg(Grm1)EPv line was susceptible to melanoma. In contrast to human melanoma, these transgenic mice had a generalized hyperproliferation of melanocytes with limited transformation to fully malignant metastasis. We detected expression of GRM1 in a number of human melanoma biopsies and cell lines but not in benign nevi and melanocytes. This study provides compelling evidence for the importance of metabotropic glutamate signaling in melanocytic neoplasia.

Exploring the parameter space of a rabbit ventricular action potential model to investigate the effect of variation on action potential and calcium transients

Computational models for cardiomyocyte action potentials (AP) often make use of a large parameter set. This parameter set can contain some elements that are fitted to experimental data independently of any other element, some elements that are derived concurrently with other elements to match experimental data, and some elements that are derived purely from phenomenological fitting to produce the desired AP output. Furthermore, models can make use of several different data sets, not always derived for the same conditions or even the same species. It is consequently uncertain whether the parameter set for a given model is physiologically accurate. Furthermore, it is only recently that the possibility of degeneracy in parameter values in producing a given simulation output has started to be addressed. In this study, we examine the effects of varying two parameters (the L-type calcium current (I(CaL)) and the delayed rectifier potassium current (I(Ks))) in a computational model of a rabbit ventricular cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+)) transient. It will subsequently be determined if there is degeneracy in this model to these parameter values, which will have important implications on the stability of these models to cell-to-cell parameter variation, and also whether the current methodology for generating parameter values is flawed. The accuracy of AP duration (APD) as an indicator of AP shape will also be assessed.

Parameter estimation for a phenomenological model of the cardiac action potential

The action potential (ap) of a cardiac cell is made up of a complex balance of ionic currents which flow across the cell membrane in response to electrical excitation of the cell. Biophysically detailed mathematical models of the ap have grown larger in terms of the variables and parameters required to model new findings in subcellular ionic mechanisms. The fitting of parameters to such models has seen a large degree of parameter and module re-use from earlier models. An alternative method for modelling electrically exciteable cardiac tissue is a phenomenological model, which reconstructs tissue level ap wave behaviour without subcellular details. A new parameter estimation technique to fit the morphology of the ap in a four variable phenomenological model is presented. An approximation of a nonlinear ordinary differential equation model is established that corresponds to the given phenomenological model of the cardiac ap. The parameter estimation problem is converted into a minimisation problem for the unknown parameters. A modified hybrid Nelder–Mead simplex search and particle swarm optimization is then used to solve the minimisation problem for the unknown parameters. The successful fitting of data generated from a well known biophysically detailed model is demonstrated. A successful fit to an experimental ap recording that contains both noise and experimental artefacts is also produced. The parameter estimation method’s ability to fit a complex morphology to a model with substantially more parameters than previously used is established.

Hypothetical model of hydrophilic lubrication in synovial joints

This paper presents a new insight into the mechanism of biolubrication of articulating mammalian joints that includes the function of surface-active phospholipids (SAPLs). SAPLs can be adsorbed on surface of cartilage membranes as a hydrophobic monolayer (H-phobic-M Madel or Hills' Model) or as a newly proposed hydrophilic bilayer (H-philic-B Model). With respect to the synovial joint's frictionless work, three processes are identified namely: monolayer/bilayer phospholipids binding to cartilage with lubricin interaction; influence of induced-pressure on interaction of hyaluronan with phospholipids; and biolubrication arising from two gliding articular hydrophilic surfaces acting as reverse micelle. Lubricin is considered to play critical role as a supplier of phospholipids, which overlay the articular surface of articular cartilage. Hyaluronic acid is considered to play a critical mediating role in the interaction between the hydrophilic part of phospholipids, the articular surface and water (hydration) in facilitating the lubrication process. Tivo models of frictionless lubrication processes, namely hydrophobic (H-phobic-M Model) and our conceptual hydrophilic (H-philic-B Model), are compared. © Institution of Engineers Australia, 2008.

The influence of sensitivity to reward and punishment, propensity for sensation seeking, depression, and anxiety on the risky behaviour of novice drivers : a path model

Young novice drivers are significantly more likely to be killed or injured in car crashes than older, experienced drivers. Graduated driver licensing (GDL), which allows the novice to gain driving experience under less-risky circumstances, has resulted in reduced crash incidence; however, the driver's psychological traits are ignored. This paper explores the relationships between gender, age, anxiety, depression, sensitivity to reward and punishment, sensation-seeking propensity, and risky driving. Participants were 761 young drivers aged 17–24 (M= 19.00, SD= 1.56) with a Provisional (intermediate) driver's licence who completed an online survey comprising socio-demographic questions, the Impulsive Sensation Seeking Scale, Kessler's Psychological Distress Scale, the Sensitivity to Punishment and Sensitivity to Reward Questionnaire, and the Behaviour of Young Novice Drivers Scale. Path analysis revealed depression, reward sensitivity, and sensation-seeking propensity predicted the self-reported risky behaviour of the young novice drivers. Gender was a moderator; and the anxiety level of female drivers also influenced their risky driving. Interventions do not directly consider the role of rewards and sensation seeking, or the young person's mental health. An approach that does take these variables into account may contribute to improved road safety outcomes for both young and older road users.

SAP webflow made configurable: unifying workflow templates into a configurable model

To facilitate the implementation of workflows, enterprise and workflow system vendors typically provide workflow templates for their software. Each of these templates depicts a variant of how the software supports a certain business process, allowing the user to save the effort of creating models and links to system components from scratch by selecting and activating the appropriate template. A combination of the strengths from different templates is however only achievable by manually adapting the templates which is cumbersome. We therefore suggest in this paper to combine different workflow templates into a single configurable workflow template. Using the workflow modeling language of SAP’s WebFlow engine, we show how such a configurable workflow modeling language can be created by identifying the configurable elements in the original language. Requirements imposed on configurations inhibit invalid configurations. Based on a default configuration such configurable templates can be used as easy as the traditional templates. The suggested approach is also applicable to other workflow modeling languages

Library and information science education 2.0 : guiding principles and models of best practice ALTC Fellowship Report

This ALTC Teaching Fellowship aimed to establish Guiding Principles for Library and Information Science Education 2.0. The aim was achieved by (i) identifying the current and anticipated skills and knowledge required by successful library and information science (LIS) professionals in the age of web 2.0 (and beyond), (ii) establishing the current state of LIS education in Australia in supporting the development of librarian 2.0, and in doing so, identify models of best practice. The fellowship has contributed to curriculum renewal in the LIS profession. It has helped to ensure that LIS education in Australia continues to meet the changing skills and knowledge requirements of the profession it supports. It has also provided a vehicle through which LIS professionals and LIS educators may find opportunities for greater collaboration and more open communication. This will help bridge the gap between LIS theory and practice and will foster more authentic engagement between LIS education and other parts of the LIS industry in the education of the next generation of professionals. Through this fellowship the LIS discipline has become a role model for other disciplines who will be facing similar issues in the coming years. Eighty-one members of the Australian LIS profession participated in a series of focus groups exploring the current and anticipated skills and knowledge needed by the LIS professional in the web 2.0 world and beyond. Whilst each focus group tended to draw on specific themes of interest to that particular group of people, there was a great deal of common ground. Eight key themes emerged: technology, learning and education, research or evidence-based practice, communication, collaboration and team work, user focus, business savvy and personal traits. It was acknowledged that the need for successful LIS professionals to possess transferable skills and interpersonal attributes was not new. It was noted however that the speed with which things are changing in the web 2.0 world was having a significant impact and that this faster pace is placing a new and unexpected emphasis on the transferable skills and knowledge. It was also acknowledged that all librarians need to possess these skills, knowledge and attributes and not just the one or two role models who lead the way. The most interesting finding however was that web 2.0, library 2.0 and librarian 2.0 represented a ‘watershed’ for the LIS profession. Almost all the focus groups spoke about how they are seeing and experiencing a culture change in the profession. Librarian 2.0 requires a ‘different mindset or attitude’. The Levels of Perspective model by Daniel Kim provides one lens by which to view this finding. The focus group findings suggest that we are witnessing a re-awaking of the Australian LIS profession as it begins to move towards the higher levels of Kim’s model (ie mental models, vision). Thirty-six LIS educators participated in telephone interviews aimed at exploring the current state of LIS education in supporting the development of librarian 2.0. Skills and knowledge of LIS professionals in a web 2.0 world that were identified and discussed by the LIS educators mirrored those highlighted in the focus group discussions with LIS professionals. Similarly it was noted that librarian 2.0 needed a focus less on skills and knowledge and more on attitude. However, whilst LIS professionals felt that there was a paradigm shift within the profession. LIS educators did not speak with one voice on this matter with quite a number of the educators suggesting that this might be ‘overstating it a bit’. This study provides evidence for “disparate viewpoints” (Hallam, 2007) between LIS educators and LIS professionals that can have a significant implications for the future of not just LIS professional education specifically but for the profession generally. Library and information science education 2.0: guiding principles and models of best practice 1 Inviting the LIS academics to discuss how their teaching and learning activities support the development of librarian 2.0 was a core part of the interviews conducted. The strategies used and the challenges faced by LIS educators in developing their teaching and learning approaches to support the formation of librarian 2.0 are identified and discussed. A core part of the fellowship was the identification of best practice examples on how LIS educators were developing librarian 2.0. Twelve best practice examples were identified. Each educator was recorded discussing his or her approach to teaching and learning. Videos of these interviews are available via the Fellowship blog at .The LIS educators involved in making the videos felt uncomfortable with the term ‘best practice’. Many acknowledged that there simply seeking to do the best by their students and that there was always room for improvement. For this reason these videos are offered as examples of “great practice”. The videos are a tool for other educators to use, regardless of discipline, in developing their teaching and learning approaches to supporting web 2.0 professionals. It has been argued that the main purpose of professional education is transformation (Dall’ Alba, 2009; Dall’Alba & Barnacle, 2007). As such professional education should focus not just on skills and knowledge acquisition but also on helping students to develop ways of being the professionals in question (ie LIS professionals, teachers, lawyers, engineers).The aim of this fellowship was to establish Guidelines for Library and Information Science Education 2.0 it has however become apparent that at this point in time it is not yet possible to fulfil this aim. The fellowship has clearly identified skills and knowledge needed by the LIS professional in web 2.0 world (and beyond). It has also identified examples of ‘great practice’ by LIS educators as they endeavour to develop LIS professionals who will be successful in a web 20 world. The fellowship however has also shown that the LIS profession is currently undergoing significant attitudinal and conceptual change. Consequently, before a philosophy of LIS education 2.0 can be expressed, the Australian LIS profession must first explore and articulate what it means to be an LIS professional in the 21st century (ie a world of web 2.0 and beyond). In short, the LIS profession in Australia must take stock not of “what we know and can do” but on “who we are becoming” (Dall’Alba, 2009, p 34).

The role of idea novelty and relatedness in nascent ventures

The study of venture idea characteristics and the contextual fit between venture ideas and individuals are key research goals in entrepreneurship (Davidsson, 2004). However, to date there has been limited scholarly attention given to these phenomena. Accordingly, this study aims to help fill the gap by investigating the importance of novelty and relatedness of venture ideas in entrepreneurial firms. On the premise that new venture creation is a process and that research should be focused on the early stages of the venturing process, this study primarily focuses its attention on examining how venture idea novelty and relatedness affect the performance in the venture creation process. Different types and degrees of novelty are considered here. Relatedness is shown to be based on individuals’ prior knowledge and resource endowment. Performance in the venture creation process is evaluated according to four possible outcomes: making progress, getting operational, being terminated and achieving positive cash flow. A theoretical model is developed demonstrating the relationship between these variables along with the investment of time and money. Several hypotheses are developed to be tested. Among them, it is hypothesised that novelty hinders short term performance in the venture creation process. On the other hand knowledge and resource relatedness are hypothesised to promote performance. An experimental study was required in order to understand how different types and degrees of novelty and relatedness of venture ideas affect the attractiveness of venture ideas in the eyes of experienced entrepreneurs. Thus, the empirical work in this thesis was based on two separate studies. In the first one, a conjoint analysis experiment was conducted on 32 experienced entrepreneurs in order to ascertain attitudinal preferences regarding venture idea attractiveness based on novelty, relatedness and potential financial gains. This helped to estimate utility values for different levels of different attributes of venture ideas and their relative importance in the attractiveness. The second study was a longitudinal investigation of how venture idea novelty and relatedness affect the performance in the venture creation process. The data for this study is from the Comprehensive Australian Study for Entrepreneurial Emergence (CAUSEE) project that has been established in order to explore the new venture creation process in Australia. CAUSEE collects data from a representative sample of over 30,000 households in Australia using random digit dialling (RDD) telephone interviews. From these cases, data was collected at two points in time during a 12 month period from 493 firms, who are currently involved in the start-up process. Hypotheses were tested and inferences were derived through descriptive statistics, confirmatory factor analysis and structural equation modelling. Results of study 1 indicate that venture idea characteristics have a role in the attractiveness and entrepreneurs prefer to introduce a moderate degree of novelty across all types of venture ideas concerned. Knowledge relatedness is demonstrated to be a more significant factor in attractiveness than resource relatedness. Results of study 2 show that the novelty hinders nascent venture performance. On the other hand, resource relatedness has a positive impact on performance unlike knowledge relatedness which has none. The results of these studies have important implications for potential entrepreneurs, investors, researchers, consultants etc. by developing a better understanding in the venture creation process and its success factors in terms of both theory and practice.

A continuous time model for election timing

We consider a continuous time model for election timing in a Majoritarian Parliamentary System where the government maintains a constitutional right to call an early election. Our model is based on the two-party-preferred data that measure the popularity of the government and the opposition over time. We describe the poll process by a Stochastic Differential Equation (SDE) and use a martingale approach to derive a Partial Differential Equation (PDE) for the government’s expected remaining life in office. A comparison is made between a three-year and a four-year maximum term and we also provide the exercise boundary for calling an election. Impacts on changes in parameters in the SDE, the probability of winning the election and maximum terms on the call exercise boundaries are discussed and analysed. An application of our model to the Australian Federal Election for House of Representatives is also given.

A mathematical model for genetic regulation of the lactose operon

In this paper we construct a mathematical model for the genetic regulatory network of the lactose operon. This mathematical model contains transcription and translation of the lactose permease (LacY) and a reporter gene GFP. The probability of transcription of LacY is determined by 14 binding states out of all 50 possible binding states of the lactose operon based on the quasi-steady-state assumption for the binding reactions, while we calculate the probability of transcription for the reporter gene GFP based on 5 binding states out of 19 possible binding states because the binding site O2 is missing for this reporter gene. We have tested different mechanisms for the transport of thio-methylgalactoside (TMG) and the effect of different Hill coefficients on the simulated LacY expression levels. Using this mathematical model we have realized one of the experimental results with different LacY concentrations, which are induced by different concentrations of TMG.

Observing the relevance of an information systems success model

This paper contributes to the rigor vs. relevance debate in the Information Systems (IS) discipline. Using the Action Research methodology, this study evaluates the relevance of a rigorously validated IS evaluation model in practice. The study captures observations of operational end-users employing a market leading Enterprise System application for procurement and order fulfillment in an organization. The analysis of the observations demonstrates the broad relevance of the measurement instrument. More importantly, the study identifies several improvements and possible confusions in applying the instrument in the practice.

Using the Precede-Proceed Model of Health Program Planning in breast cancer nursing research

Aim: In this paper we discuss the use of the Precede-Proceed model when investigating health promotion options for breast cancer survivors. Background: Adherence to recommended health behaviors can optimize well-being after cancer treatment. Guided by the Precede-Proceed approach, we studied the behaviors of breast cancer survivors in our health service area. Data sources: The interview data from the cohort of breast cancer survivors are used in this paper to illustrate the use of Precede-Proceed in this nursing research context. Interview data were collected from June to December 2009. We also searched Medline, CINAHL, PsychInfo and PsychExtra up to 2010 for relevant literature in English to interrogate the data from other theoretical perspectives. Discussion: The Precede-Proceed model is theoretically-complex. The deductive analytic process guided by the model usefully explained some of the health behaviors of cancer survivors, although it could not explicate many other findings. A complementary inductive approach to the analysis and subsequent interpretation by way of Uncertainty in Illness Theory and other psychosocial perspectives provided a comprehensive account of the qualitative data that resulted in contextually-relevant recommendations for nursing practice. Implications for nursing: Nursing researchers using Precede-Proceed should maintain theoretical flexibility when interpreting qualitative data. Perspectives not embedded in the model might need to be considered to ensure that the data are analyzed in a contextually-relevant way. Conclusion: Precede-Proceed provides a robust framework for nursing researchers investigating health promotion in cancer survivors; however additional theoretical lenses to those embedded in the model can enhance data interpretation.

Developing sustainable housing through building utilities and transport innovation

Sustainability concerns every citizen. Housing affordability and sustainable solutions are being highlighted in research and practice in many parts of the world. This paper discusses the development of a Commuter Energy and Building Utilities System (CEBUS) in sustainable housing projects as a means of bridging the gap between current median house pricing and target affordable house pricing for low income earners. Similar scales of sustainable housing development cannot be achieved through independent application of current best practice methods in ecologically sustainable development strategies or transit oriented development master plans. This paper presents the initial stage of research on first capital and ongoing utilities and transport cost savings available from these sustainable design methods. It also outlines further research and development of a CEBUS Dynamic Simulation Model and Conceptual Framework for the Australian property development and construction industry.

The Long-Term Irrelevance of Trust in Outsourcing Decisions for New Technologies: Insights from an Agent-Based Model

Significant empirical data from the fields of management and business strategy suggest that it is a good idea for a company to make in-house the components and processes underpinning a new technology. Other evidence suggests exactly the opposite, saying that firms would be better off buying components and processes from outside suppliers. One possible explanation for this lack of convergence is that earlier research in this area has overlooked two important aspects of the problem: reputation and trust. To gain insight into how these variables may impact make-buy decisions throughout the innovation process, the Sporas algorithm for measuring reputation was added to an existing agent-based model of how firms interact with each other throughout the development of new technologies. The model�s results suggest that reputation and trust do not play a significant role in the long-term fortunes of an individual firm as it contends with technological change in the marketplace. Accordingly, this model serves as a cue for management researchers to investigate more thoroughly the temporal limitations and contingencies that determine how the trust between firms may affect the R&D process.

Developing a model of embedding academic numeracy in university programs : a case study from nursing

This is a study of the academic numeracy of nursing students. This study develops a theoretical model for the design and delivery of university courses in academic numeracy. The following objectives are addressed: 1. To investigate nursing students' current knowledge of academic numeracy; 2. To investigate how nursing students’ knowledge and skills in academic numeracy can be enhanced using a developmental psychology framework; and 3. To utilise data derived from meeting objectives 1 and 2 to develop a theoretical model to embed academic numeracy in university programs. This study draws from Valsiner’s Human Development Theory (Valsiner, 1997, 2007). It is a quasi-experimental intervention case study (Faltis, 1997) and takes a multimethod approach using pre- and post-tests; observation notes; and semi-structured teaching sessions to document a series of microgenetic studies of student numeracy. Each microgenetic study is centered on the lived experience of students becoming more numerate. The method for this section is based on Vygotsky’s double stimulation (Valsiner, 2000a; 2007). Data collection includes interviews on students’ past experience with mathematics; their present feelings and experiences and how these present feelings and experiences are transformed. The findings from this study have provided evidence that the course developed for nursing students, underpinned by an appropriate framework, does improve academic numeracy. More specifically, students improved their content knowledge of and confidence in mathematics in areas that were directly related to their degree. The study used Valsiner’s microgenetic approach to development to trace the course as it was being taught and two students’ personal academic numeracy journeys. It highlighted particularly troublesome concepts, then outlined scaffolding and pathways used to develop understanding. This approach to academic numeracy development was summarised into a four-faceted model at the university, program, course and individual level. This model can be applied successfully to similar contexts. Thus the thesis advances both theory and practice in this under-researched and under-theorised area.