Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1P29S) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1P29S showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

Cyclone intensity categories

The weather forecast centers in Australia and many other countries use a scale of cyclone intensity categories (categories 1-5) in their cyclone advisories, which are considered to be indicative of the cyclone damage potential. However, this scale is mainly based on maximum gust wind speeds. In a recent research project involving computer modeling of cyclonic wind forces on roof claddings and fatigue damage to claddings, it was found that cyclone damage not only depends on the maximum gust wind speed, but also on two other cyclone parameters, namely, the forward speed and radius to maximum winds. This paper describes the computer model used in predicting the cyclone damage to claddings and investigates the damage potential of a cyclone as a function of all the relevant cyclone parameters, based on which it attempts to refine the current scale of cyclone intensity categories.

Cyclic pull-out strength of steel roof and wall cladding systems

When crest-fixed thin steel roof cladding systems are subjected to wind uplift, local pull-through or pull-out failures occur prematurely at their screwed connections. During high wind events such as storms and cyclones these localised failures then lead to severe damage to buildings and their contents. In recent times, the use of thin steel battens/purlins has increased considerably. This has made the pull-out failures more critical in the design of steel cladding systems. Recent research has developed a design formula for the static pull-out strength of steel cladding systems. However, the effects of fluctuating wind uplift loading that occurs during high wind events are not known. Therefore a series of constant amplitude cyclic tests has been undertaken on connections between steel battens made of different thicknesses and steel grades, and screw fasteners with varying diameter and pitch. This paper presents the details of these cyclic tests and the results.

Creating efficiencies in teaching : where are the right resources when you need them?

Early career engineering academics are encouraged to join and contribute to established research groups at the leading edge of their discipline. This is often facilitated by various staff development and support programs. Given that academics are often appointed primarily on the basis of their research skills and outputs, such an approach is justified and is likely to result in advancing the individual academic’s career. It also enhances their capacity to attract competitive research funding, while contributing to the overall research performance of their institution, with further potential for an increased share of government funding. In contrast, there is much less clarity of direction or availability of support mechanisms for those academics in their role as teachers. Following a general induction to teaching and learning at their institution, they would commonly think about preparing some lecture materials, whether for delivery in a face-to-face or on-line modality. Typically they would look for new references and textbooks to act as a guide for preparing the content. They would probably find out how the course has been taught before, and what laboratory facilities and experiments have been used. In all of these and other related tasks, the majority of newly appointed academics are guided strongly by their own experiences as students, rather than any firm knowledge of pedagogical principles. At a time of increased demands on academics’ time, and high expectations of performance and productivity in both research and teaching, it is essential to examine possible actions to support academics in enhancing their teaching performance in effective and efficient ways. Many resources have been produced over the years in engineering schools around the world, with very high intellectual and monetary costs. In Australia, the last few years have seen a surge in the number of ALTC/OLT projects and fellowships addressing a range of engineering education issues and providing many resources. There are concerns however regarding the extent to which these resources are being effectively utilised. Why are academics still re-inventing the wheel and creating their own version of teaching resources and pedagogical practice? Why do they spend so much of their precious time in such an inefficient way? A symposium examining the above issues was conducted at the AAEE2012 conference, and some pointers to possible responses to the above questions were obtained. These are explored in this paper and supplemented by the responses to a survey of a group of engineering education leaders on some of the aspects of these research questions. The outcomes of the workshop and survey results have been analysed in view of the literature and the ALTC/OLT sponsored learning and teaching projects and resources. Other factors are discussed, including how such resources can be found, how their quality might be evaluated, and how assessment may be appropriately incorporated, again using readily available resources. This study found a strong resonance between resources reuse with work on technology acceptance (Davis, 1989), suggesting that technology adoption models could be used to encourage resource sharing. Efficient use of outstanding learning materials is an enabling approach. The paper provides some insights on the factors affecting the re-use of available resources, and makes some recommendations and suggestions on how the issue of resources re-use might be incorporated in the process of applying and completing engineering education projects.

Contemporary challenges in e-learning

Technology is impacting on most elements of organisations today and workforce development professionals have been some of the leading proponents of embracing technologies and the benefits they offer. E-learning has emerged as at least a complementary offering to face-to-face training, and in some cases has totally replaced more traditional forms of workforce development. This chapter explores the use of learning technologies and the benefits and drawbacks of their use. In particular it focuses on further exploring the issue of a perceived lack of interaction in some e-learning offerings; a factor identified as critical to address in order to ensure effective e-learning. The chapter discusses the issues of interaction and social presence to address feelings of isolation and offers some key considerations for those considering integrating technology into workforce development.

Systematic evaluation of GoSoapBox in tertiary education : a student response system for improving learning experiences and outcomes

There is currently a wide range of research into the recent introduction of student response systems in higher education and tertiary settings (Banks 2006; Kay and Le Sange, 2009; Beatty and Gerace 2009; Lantz 2010; Sprague and Dahl 2009). However, most of this pedagogical literature has generated ‘how to’ approaches regarding the use of ‘clickers’, keypads, and similar response technologies. There are currently no systematic reviews on the effectiveness of ‘GoSoapBox’ – a more recent, and increasingly popular student response system – for its capacity to enhance critical thinking, and achieve sustained learning outcomes. With rapid developments in teaching and learning technologies across all undergraduate disciplines, there is a need to obtain comprehensive, evidence-based advice on these types of technologies, their uses, and overall efficacy. This paper addresses this current gap in knowledge. Our teaching team, in an undergraduate Sociology and Public Health unit at the Queensland University of Technology (QUT), introduced GoSoapBox as a mechanism for discussing controversial topics, such as sexuality, gender, economics, religion, and politics during lectures, and to take opinion polls on social and cultural issues affecting human health. We also used this new teaching technology to allow students to interact with each other during class – both on both social and academic topics – and to generate discussions and debates during lectures. The paper reports on a data-driven study into how this interactive online tool worked to improve engagement and the quality of academic work produced by students. This paper will firstly, cover the recent literature reviewing student response systems in tertiary settings. Secondly, it will outline the theoretical framework used to generate this pedagogical research. In keeping with the social and collaborative features of Web 2.0 technologies, Bandura’s Social Learning Theory (SLT) will be applied here to investigate the effectiveness of GoSoapBox as an online tool for improving learning experiences and the quality of academic output by students. Bandura has emphasised the Internet as a tool for ‘self-controlled learning’ (Bandura 2001), as it provides the education sector with an opportunity to reconceptualise the relationship between learning and thinking (Glassman & Kang 2011). Thirdly, we describe the methods used to implement the use of GoSoapBox in our lectures and tutorials, and which aspects of the technology we drew on for learning purposes, as well as the methods for obtaining feedback from the students about the effectiveness or otherwise of this tool. Fourthly, we report cover findings from an examination of all student/staff activity on GoSoapBox as well as reports from students about the benefits and limitations of it as a learning aid. We then display a theoretical model that is produced via an iterative analytical process between SLT and our data analysis for use by academics and teachers across the undergraduate curriculum. The model has implications for all teachers considering the use of student response systems to improve the learning experiences of their students. Finally, we consider some of the negative aspects of GoSoapBox as a learning aid.

Identifying Core Functions of Asset Management

It is widely acknowledged that effective asset management requires an interdisciplinary approach, in which synergies should exist between traditional disciplines such as: accounting, engineering, finance, humanities, logistics, and information systems technologies. Asset management is also an important, yet complex business practice. Business process modelling is proposed as an approach to manage the complexity of asset management through the modelling of asset management processes. A sound foundation for the systematic application and analysis of business process modelling in asset management is, however, yet to be developed. Fundamentally, a business process consists of activities (termed functions), events/states, and control flow logic. As both events/states and control flow logic are somewhat dependent on the functions themselves, it is a logical step to first identify the functions within a process. This research addresses the current gap in knowledge by developing a method to identify functions common to various industry types (termed core functions). This lays the foundation to extract such functions, so as to identify both commonalities and variation points in asset management processes. This method describes the use of a manual text mining and a taxonomy approach. An example is presented.

Chronic activation of the low affinity site of β1-adrenoceptors stimulates haemodynamics but exacerbates pressure-overload cardiac remodelling

Background and Purpose The β1-adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L, respectively), which mediate cardiostimulation. While β1H-adrenoceptor can be blocked by all clinically used β-blockers, β1L-adrenoceptor is relatively resistant to blockade. Thus, chronic β1L-adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of β1H-adrenoceptors. Hence, it is important to determine the potential significance of β1L-adrenoceptors in vivo, particularly in pathological situations. Experimental Approach C57Bl/6 male mice were used. Chronic (4 or 8 weeks) β1L-adrenoceptor activation was achieved by treatment, via osmotic mini pumps, with (-)-CGP12177 (10 mg·kg−1·day−1). Cardiac function was assessed by echocardiography and micromanometry. Key Results (-)-CGP12177 treatment of healthy mice increased heart rate and left ventricular (LV) contractility. (-)-CGP12177 treatment of mice subjected to transverse aorta constriction (TAC), during weeks 4–8 or 4–12 after TAC, led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (-)-CGP12177 treatment of mice with TAC also exacerbated the myocardial expression of hypertrophic, fibrogenic and inflammatory genes compared to untreated TAC mice. Washout of (-)-CGP12177 revealed a more pronounced cardiac dysfunction after 12 weeks of TAC. Conclusions and Implications β1L-adrenoceptor activation provides functional support to the heart, in both normal and pathological (pressure overload) situations. Sustained β1L-adrenoceptor activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure.

Sustainable development as a meta-context for engineering education

At the end of the first decade of the twenty-first century, there is unprecedented awareness of the need for a transformation in development, to meet the needs of the present while also preserving the ability of future generations to meet their own needs. However, within engineering, educators still tend to regard such development as an ‘aspect’ of engineering rather than an overarching meta-context, with ad hoc and highly variable references to topics. Furthermore, within a milieu of interpretations there can appear to be conflicting needs for achieving sustainable development, which can be confusing for students and educators alike. Different articulations of sustainable development can create dilemmas around conflicting needs for designers and researchers, at the level of specific designs and (sub-) disciplinary analysis. Hence sustainability issues need to be addressed at a meta-level using a whole of system approach, so that decisions regarding these dilemmas can be made. With this appreciation, and in light of curriculum renewal challenges that also exist in engineering education, this paper considers how educators might take the next step to move from sustainable development being an interesting ‘aspect’ of the curriculum, to sustainable development as a meta-context for curriculum renewal. It is concluded that capacity building for such strategic considerations is critical in engineering education.

Engineering Design

Engineering Your Future: An Australasian Guide, 2nd Edition, is the ideal textbook for undergraduate students beginning their engineering studies. Building on the success of the popular 1st edition, this new edition continues the strong and practical emphasis on skills that are essential for engineering problem-solving and design. Numerous topical and locally focused examples of projects across the broad range of engineering disciplines help to graphically demonstrate the role and responsibilities of a professional engineer. Themes of sustainability, ethical practice and effective communication are constant throughout the text. In addition, its many exercises and project activities will encourage students to put key engineering principles and skills into practice.

Fatty acid uptake and incorporation into phospholipids in the rat lens

PURPOSE. Phospholipids are a major component of lens fiber cells and influence the activity of membrane proteins. Previous investigations of fatty acid uptake by the lens are limited. The purpose of the present study was thus to determine whether exogenous fatty acids could be taken up by the rat lens and incorporated into molecular phospholipids. METHODS. Lenses were incubated with fluorescently labeled palmitic acid and then analyzed by confocal microscopy. Concurrently, lenses incubated with either fluorescently labeled palmitic acid or the more physiologically relevant (13)C(18)-oleic acid were sectioned into nuclear and cortical regions and analyzed by highly sensitive and structurally selective electrospray ionization tandem mass spectrometry techniques. RESULTS. The detection of fluorescently labeled palmitic acid, even after 16 hours of incubation, was limited to approximately the outer 25% to 30% of the rat lens. Mass spectrometry also revealed the presence of free (13)C(18)-oleic acid in the cortex but not the nucleus. No evidence could be found for incorporation of fluorescently labeled palmitic acid into phospholipids; however, a low level of (13)C(18)-oleic acid incorporation into phosphatidylethanolamine (PE), specifically PE (PE 16:0/(13)C(18) 18:1) was detected in the lens cortex after 16 hours. CONCLUSIONS. These data demonstrate that uptake of exogenous (e.g., dietary fatty acids) by the lens and their incorporation into phospholipids is minimal, most likely occurring only during de novo synthesis in the outermost region of the lens. This finding adds support to the hypothesis that once synthesized there is no active remodeling or turnover of fiber cell phospholipids.

Pulsed wall jet simulation of a stationary thunderstorm downburst, Part A: Physical structure and flow field characterization

A pulsed wall jet has been used to simulate the gust front of a thunderstorm downburst. Flow visualization, wind speed and surface pressure measurements were obtained. The characteristics of the hypothesized ring vortex of a full-scale downburst were reproduced at a scale estimated to be 1:3000.

Wind pressure measurements on a cube subjected to pulsed impinging jet flow

A pulsed impinging jet is used to simulate the gust front of a thunderstorm downburst. This work concentrates on investigating the peak transient loading conditions on a 30 mm cubic model submerged in the simulated downburst flow. The outflow induced pressures are recorded and compared to those from boundary layer and steady wall jet flow. Given that peak winds associated with downburst events are often located in the transient frontal region, the importance of using a non-stationary modelling technique for assessing peak downburst wind loads is highlighted with comparisons.

Numerical simulation of idealised three-dimensional downburst wind fields

Convective downburst wind storms generate the peak annual gust wind speed for many parts of the non-cyclonic world at return periods of importance for ultimate limit state design. Despite this there is little clear understanding of how to appropriately design for these wind events given their significant dissimilarities to boundary layer winds upon which most design is based. To enhance the understanding of wind fields associated with these storms a three-dimensional numerical model was developed to simulate a multitude of idealised downburst scenarios and to investigate their near-ground wind characteristics. Stationary and translating downdraft wind events in still and sheared environments were simulated with baseline results showing good agreement with previous numerical work and full-scale observational data. Significant differences are shown in the normalised peak wind speed velocity profiles depending on the environmental wind conditions in the vicinity of the simulated event. When integrated over the height of mid- to high rise structures, all simulated profiles are shown to produce wind loads smaller than an equivalent 10 m height matched open terrain boundary layer profile. This suggests that for these structures the current design approach is conservative from an ultimate loading standpoint. Investigating the influence of topography on the structure of the simulated near-ground downburst wind fields, it is shown that these features amplify wind speeds in a manner similar to that expected for boundary layer winds, but the extent of amplification is reduced. The level of reduction is shown to be dependent on the depth of the simulated downburst outflow.