Receptor tyrosine kinases and their activation in melanoma

Receptor tyrosine kinases (RTKs) and their downstream signalling pathways have long been hypothesized to play key roles in melanoma development. A decade ago, evidence was derived largely from animal models, RTK expression studies and detection of activated RAS isoforms in a small fraction of melanomas. Predictions that overexpression of specific RTKs implied increased kinase activity and that some RTKs would show activating mutations in melanoma were largely untested. However, technological advances including rapid gene sequencing, siRNA methods and phospho-RTK arrays now give a more complete picture. Mutated forms of RTK genes including KIT, ERBB4, the EPH and FGFR families and others are known in melanoma. Additional over- or underexpressed RTKs and also protein tyrosine phosphatases (PTPs) have been reported, and activities measured. Complex interactions between RTKs and PTPs are implicated in the abnormal signalling driving aberrant growth and survival in malignant melanocytes, and indeed in normal melanocytic signalling including the response to ultraviolet radiation. Kinases are considered druggable targets, so characterization of global RTK activity in melanoma should assist the rational development of tyrosine kinase inhibitors for clinical use. © 2011 John Wiley & Sons A/S.

Communication Interception Technology (CIT) and its use in the fight against Transnational Organised Crime (TOC) in Australia : a review of the literature

In recent times, technology has advanced in such a manner that the world can now communicate in means previously never thought possible. Transnational organised crime groups, who have exploited these new technologies as basis for their criminal success, however, have not overlooked this development, growth and globalisation. Law enforcement agencies have been confronted with an unremitting challenge as they endeavour to intercept, monitor and analyse these communications as a means of disrupting the activities of criminal enterprises. The challenge lies in the ability to recognise and change tactics to match an increasingly sophisticated adversary. The use of communication interception technology, such as phone taps or email interception, is a tactic that when used appropriately has the potential to cause serious disruption to criminal enterprises. Despite the research that exists on CIT and TOC, these two bodies of knowledge rarely intersect. This paper builds on current literature, drawing them together to provide a clearer picture of the use of CIT in an enforcement and intelligence capacity. It provides a review of the literature pertaining to TOC, the structure of criminal enterprises and the vulnerability of communication used by these crime groups. Identifying the current contemporary models of policing it reviews intelligence-led policing as the emerging framework for modern policing. Finally, it assesses the literature concerning CIT, its uses within Australia and the limitations and arguments that exist. In doing so, this paper provides practitioners with a clearer picture of the use, barriers and benefits of using CIT in the fight against TOC. It helps to bridge the current gaps in modern policing theory and offers a perspective that can help drive future research.

InterLACE : a new international collaboration for a Life course approach to women's reproductive health and chronic disease events.

Evidence from population-based studies of women increasingly points to the inter-related nature of reproductive health, lifestyle, and chronic disease risk. This paper describes the recently established International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease. InterLACE aims to advance the evidence base for women's health policy beyond associations from disparate studies by means of systematic and culturally sensitive synthesis of longitudinal data. Currently InterLACE draws on individual level data for reproductive health and chronic disease among 200,000 women from over thirteen studies of women's health in seven countries. The rationale for this multi-study research programme is set out in terms of a life course perspective to reproductive health. The research programme will build a comprehensive picture of reproductive health through life in relation to chronic disease risk. Although combining multiple international studies poses methodological challenges, InterLACE represents an invaluable opportunity to strength evidence to guide the development of timely and tailored preventive health strategies.

A grand challenge : reflecting on university science curriculum design, collaborative partnerships and integration of information literacy skills

In 2012, Queensland University of Technology (QUT) committed to the massive project of revitalizing its Bachelor of Science (ST01) degree. Like most universities in Australia, QUT has begun work to align all courses by 2015 to the requirements of the updated Australian Qualifications Framework (AQF) which is regulated by the Tertiary Education Quality and Standards Agency (TEQSA). From the very start of the redesigned degree program, students approach scientific study with an exciting mix of theory and highly topical real world examples through their chosen “grand challenge.” These challenges, Fukushima and nuclear energy for example, are the lenses used to explore science and lead to 21st century learning outcomes for students. For the teaching and learning support staff, our grand challenge is to expose all science students to multidisciplinary content with a strong emphasis on embedding information literacies into the curriculum. With ST01, QUT is taking the initiative to rethink not only content but how units are delivered and even how we work together between the faculty, the library and learning and teaching support. This was the desired outcome but as we move from design to implementation, has this goal been achieved? A main component of the new degree is to ensure scaffolding of information literacy skills throughout the entirety of the three year course. However, with the strong focus on problem-based learning and group work skills, many issues arise both for students and lecturers. A move away from a traditional lecture style is necessary but impacts on academics’ workload and comfort levels. Therefore, academics in collaboration with librarians and other learning support staff must draw on each others’ expertise to work together to ensure pedagogy, assessments and targeted classroom activities are mapped within and between units. This partnership can counteract the tendency of isolated, unsupported academics to concentrate on day-to-day teaching at the expense of consistency between units and big picture objectives. Support staff may have a more holistic view of a course or degree than coordinators of individual units, making communication and truly collaborative planning even more critical. As well, due to staffing time pressures, design and delivery of new curriculum is generally done quickly with no option for the designers to stop and reflect on the experience and outcomes. It is vital we take this unique opportunity to closely examine what QUT has and hasn’t achieved to be able to recommend a better way forward. This presentation will discuss these important issues and stumbling blocks, to provide a set of best practice guidelines for QUT and other institutions. The aim is to help improve collaboration within the university, as well as to maximize students’ ability to put information literacy skills into action. As our students embark on their own grand challenges, we must challenge ourselves to honestly assess our own work.

The ABCs of teaching alphabet knowledge : affordances and challenges of ‘weaving’ visible and invisible pedagogies

As researchers interested in the pursuit of high quality/high equity literacy learning outcomes, we focus on the learning experiences of five early years French students, with a special regard for those who are already considered as being at-risk of educational failure. We narrow the empirical focus to a single lesson on a mechanical concept of print, that is matching lower and upper case alphabet letters. In doing so, we examine a deeply philosophical question: Which pedagogical practices dis/enable what sorts of early years students as literacy learners? We extend Cazden’s (2006) notion of ‘weaving’ knowledge across dimensions of knowing to describe how the case study teacher ‘weaves’ visible and invisible pedagogies over the four movements of a lesson. The findings reveal different pedagogical framings (Bernstein, 1996) have potentially different cognitive and social effects that constitute different kinds of literacy knowledge and oppressive subject positions for at-risk students (Young, 1990).

Sequence and organization of barley yellow dwarf virus genomic RNA

The nucleotide sequence of the genomic RNA of barley yellow dwarf virus, PAV serotype was determined except for the 5′-terminal base, and its genome organization deduced. The 5,677 nucleotide genome contains five large open reading frames (ORFs). The genes for the coat protein (1) and the putative viral RNA-dependent RNA polymerase were identified. The latter shows a striking degree of similarity to that of carnation mottle virus (CarMV). By comparison with corona- and retrovirus RNAs, it is proposed that a translational frameshift is involved in expression of the polymerase. An ORF encoding an Mr 49,797 protein (50K ORF) may be translated by in-frame readthrough of the coat protein stop codon. The coat protein, an overlapping 17K ORF, and a 3′ 6.7K ORF are likely to be expressed via subgenomic mRNAs. © 1988 IRL Press Limited.

Rice ragged stunt oryzavirus genome segment S4 could encode an RNA dependent RNA polymerase and a second protein of unknown function

The complete nucleotide sequence of genome segment S4 of rice ragged stunt oryzavirus (RRSV, Thai-isolate) was determined. The 3823 bp sequence contains two large open reading frames (ORFs). ORF1, spanning nucleotides 12 to 3776, is capable of encoding a protein of M(r) 141,380 (P4a). The P4a amino acid sequence predicted from the nucleotide sequence contains sequence motifs conserved in RNA-dependent RNA polymerases (RDRPs). When compared for evolutionary relationships with RDRPs of other reoviruses using the amino acid sequences around the conserved GDD motif, P4a was shown to be more related to Nilaparvata lugens reovirus and reovirus serotype 3 than to rice dwarf phytoreovirus, bovine rotavirus or bluetongue virus. The ORF2, spanning nucleotides 491 to 1468, is out of frame with ORF1 and is capable of encoding a protein of 36, 920 (P4b). Coupled in vitro transcription-translation from cloned ORF2 in wheat germ extract confirmed the existence of ORF2 but in vivo production and possible function of P4b is yet to be determined.

The genome organization and affinities of an Australian isolate of carrot mottle umbravirus

The genomic sequence of an Australian isolate of carrot mottle umbravirus (CMoV-A) was determined from cDNA generated from dsRNA. This provides the first data on the genome organization and phylogeny of an umbravirus. The 4201-nucleotide genome contains four major open reading frames (ORFs). Analysis suggests that ORF2 encodes an RNA-dependent RNA polymerase, that ORF4 encodes a movement protein, and that the virus has no coat protein gene. The functions of ORFs 1 and 3 remain unknown. ORF2 is probably translated following ribosomal frameshifting. ORFs 3 and 4 are probably translated from a subgenomic mRNA. Sequence comparisons showed CMoV-A to be closely related to pea enation mosaic RNA2 NA2), but also to have affinities with the Bromoviridae. These findings shed light on the relationships between the luteoviruses, PEMV, and the umbraviruses and on the relationships between the carmo-like viruses and the Bromoviridae.

Humanities and social scientific research methods in porn studies

Porn studies researchers in the humanities have tended to use different research methods from those in social sciences. There has been surprisingly little conversation between the groups about methodology. This article presents a basic introduction to textual analysis and statistical analysis, aiming to provide for all porn studies researchers a familiarity with these two quite distinct traditions of data analysis. Comparing these two approaches, the article suggests that social science approaches are often strongly reliable – but can sacrifice validity to this end. Textual analysis is much less reliable, but has the capacity to be strongly valid. Statistical methods tend to produce a picture of human beings as groups, in terms of what they have in common, whereas humanities approaches often seek out uniqueness. Social science approaches have asked a more limited range of questions than have the humanities. The article ends with a call to mix up the kinds of research methods that are applied to various objects of study.

Performance-based structural fire design of steel frames using conventional computer software

Fire incident in buildings is common, so the fire safety design of the framed structure is imperative, especially for the unprotected or partly protected bare steel frames. However, software for structural fire analysis is not widely available. As a result, the performance-based structural fire design is urged on the basis of using user-friendly and conventional nonlinear computer analysis programs so that engineers do not need to acquire new structural analysis software for structural fire analysis and design. The tool is desired to have the capacity of simulating the different fire scenarios and associated detrimental effects efficiently, which includes second-order P-D and P-d effects and material yielding. Also the nonlinear behaviour of large-scale structure becomes complicated when under fire, and thus its simulation relies on an efficient and effective numerical analysis to cope with intricate nonlinear effects due to fire. To this end, the present fire study utilizes a second order elastic/plastic analysis software NIDA to predict structural behaviour of bare steel framed structures at elevated temperatures. This fire study considers thermal expansion and material degradation due to heating. Degradation of material strength with increasing temperature is included by a set of temperature-stress-strain curves according to BS5950 Part 8 mainly, which implicitly allows for creep deformation. This finite element stiffness formulation of beam-column elements is derived from the fifth-order PEP element which facilitates the computer modeling by one member per element. The Newton-Raphson method is used in the nonlinear solution procedure in order to trace the nonlinear equilibrium path at specified elevated temperatures. Several numerical and experimental verifications of framed structures are presented and compared against solutions in literature. The proposed method permits engineers to adopt the performance-based structural fire analysis and design using typical second-order nonlinear structural analysis software.

Material yielding by both axial and bending spring stiffness at elevated temperature

Material yielding is typically modeled either by plastic zone or plastic hinge methods under the context of geometric and material nonlinear finite element methods. In fire analysis of steel structures, the plastic zone method is widely used, but it requires extensively more computational efforts. The objective of this paper is to develop the nonlinear material model allowing for interaction of both axial force and bending moment, which relies on the plastic hinge method to achieve numerical efficiency and reduce computational effort. The biggest advantage of the plastic-hinge approach is its computational efficiency and easy verification by the design code formulae of the axial force–moment interaction yield criterion for beam–column members. Further, the method is reliable and robust when used in analysis of practical and large structures. In order to allow for the effect of catenary action, axial thermal expansion is considered in the axial restraint equations. The yield function for material yielding incorporated in the stiffness formulation, which allows for both axial force and bending moment effects, is more accurate and rational to predict the behaviour of the frames under fire. In the present fire analysis, the mechanical properties at elevated temperatures follow mainly the Eurocode 3 [Design of steel structures, Part 1.2: Structural fire design. European Committee for Standisation; 2003]. Example of a tension member at a steady state heating condition is modeled to verify the proposed spring formulation and to compare with results by others. The behaviour of a heated member in a highly redundant structure is also studied by the present approach.

Constructing a frame of cube : connecting 3D shapes with direction, location and movement

With the advancement of new technologies, this author has in 2010 started to engineer an online learning environment for investigating the nature and development of spatial abilities, and the teaching and learning of geometry. This paper documents how this new digital learning environment can afford the opportunity to integrate the learning about 3D shapes with direction, location and movement, and how young children can mentally and visually construct virtual 3D shapes using movements in both egocentric and fixed frames of reference (FOR). Findings suggest that year 4 (aged 9) children can develop the capacity to construct a cube using egocentric FOR only, fixed FOR only or a combination of both FOR. However, these young participants were unable to articulate the effect of individual or combined FOR movements. Directions for future research are proposed.

Laser-camera data discrepancies and reliable perception in outdoor robotics

This work aims to promote integrity in autonomous perceptual systems, with a focus on outdoor unmanned ground vehicles equipped with a camera and a 2D laser range finder. A method to check for inconsistencies between the data provided by these two heterogeneous sensors is proposed and discussed. First, uncertainties in the estimated transformation between the laser and camera frames are evaluated and propagated up to the projection of the laser points onto the image. Then, for each pair of laser scan-camera image acquired, the information at corners of the laser scan is compared with the content of the image, resulting in a likelihood of correspondence. The result of this process is then used to validate segments of the laser scan that are found to be consistent with the image, while inconsistent segments are rejected. Experimental results illustrate how this technique can improve the reliability of perception in challenging environmental conditions, such as in the presence of airborne dust.

Oscar Pistorius and the death of Reeva Steenkamp : mapping public opinions on Twitter using frame analysis and data mining

This paper uses innovative content analysis techniques to map how the death of Oscar Pistorius' girlfriend, Reeva Steenkamp, was framed on Twitter conversations. Around 1.5 million posts from a two-week timeframe are analyzed with a combination of syntactic and semantic methods. This analysis is grounded in the frame analysis perspective and is different than sentiment analysis. Instead of looking for explicit evaluations, such as “he is guilty” or “he is innocent”, we showcase through the results how opinions can be identified by complex articulations of more implicit symbolic devices such as examples and metaphors repeatedly mentioned. Different frames are adopted by users as more information about the case is revealed: from a more episodic one, highly used in the very beginning, to more systemic approaches, highlighting the association of the event with urban violence, gun control issues, and violence against women. A detailed timeline of the discussions is provided.