New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Characterization of commercial double-walled carbon nanotube material : composition, structure, and heat capacity

A purified commercial double-walled carbon nanotube (DWCNT) sample was investigated by transmission electron microscopy (TEM), thermogravimetry (TG), and Raman spectroscopy. Moreover, the heat capacity of the DWCNT sample was determined by temperature-modulated differential scanning calorimetry in the range of temperature between -50 and 290 °C. The main thermo-oxidation characterized by TG occurred at 474 °C with the loss of 90 wt% of the sample. Thermo-oxidation of the sample was also investigated by high-resolution TG, which indicated that a fraction rich in carbon nanotube represents more than 80 wt% of the material. Other carbonaceous fractions rich in amorphous coating and graphitic particles were identified by the deconvolution procedure applied to the derivative of TG curve. Complementary structural data were provided by TEM and Raman studies. The information obtained allows the optimization of composites based on this nanomaterial with reliable characteristics.

A natural model for architecture : the nature of the evolutionary model 1995

John Frazer's architectural work is inspired by living and generative processes. Both evolutionary and revolutionary, it explores informatin ecologies and the dynamics of the spaces between objects. Fuelled by an interest in the cybernetic work of Gordon Pask and Norbert Wiener, and the possibilities of the computer and the "new science" it has facilitated, Frazer and his team of collaborators have conducted a series of experiments that utilize genetic algorithms, cellular automata, emergent behaviour, complexity and feedback loops to create a truly dynamic architecture. Frazer studied at the Architectural Association (AA) in London from 1963 to 1969, and later became unit master of Diploma Unit 11 there. He was subsequently Director of Computer-Aided Design at the University of Ulter - a post he held while writing An Evolutionary Architecture in 1995 - and a lecturer at the University of Cambridge. In 1983 he co-founded Autographics Software Ltd, which pioneered microprocessor graphics. Frazer was awarded a person chair at the University of Ulster in 1984. In Frazer's hands, architecture becomes machine-readable, formally open-ended and responsive. His work as computer consultant to Cedric Price's Generator Project of 1976 (see P84)led to the development of a series of tools and processes; these have resulted in projects such as the Calbuild Kit (1985) and the Universal Constructor (1990). These subsequent computer-orientated architectural machines are makers of architectural form beyond the full control of the architect-programmer. Frazer makes much reference to the multi-celled relationships found in nature, and their ongoing morphosis in response to continually changing contextual criteria. He defines the elements that describe his evolutionary architectural model thus: "A genetic code script, rules for the development of the code, mapping of the code to a virtual model, the nature of the environment for the development of the model and, most importantly, the criteria for selection. In setting out these parameters for designing evolutionary architectures, Frazer goes beyond the usual notions of architectural beauty and aesthetics. Nevertheless his work is not without an aesthetic: some pieces are a frenzy of mad wire, while others have a modularity that is reminiscent of biological form. Algorithms form the basis of Frazer's designs. These algorithms determine a variety of formal results dependent on the nature of the information they are given. His work, therefore, is always dynamic, always evolving and always different. Designing with algorithms is also critical to other architects featured in this book, such as Marcos Novak (see p150). Frazer has made an unparalleled contribution to defining architectural possibilities for the twenty-first century, and remains an inspiration to architects seeking to create responsive environments. Architects were initially slow to pick up on the opportunities that the computer provides. These opportunities are both representational and spatial: computers can help architects draw buildings and, more importantly, they can help architects create varied spaces, both virtual and actual. Frazer's work was groundbreaking in this respect, and well before its time.

Lesser-known worlds : bridging the telematic flows with located human experience through game design

This paper represents a new theorization of the role of location-based games (LBGs) as potentially playing specific roles in peoples’ access to the culture of cities [22]. A LBG is a game that employs mobile technologies as tools for game play in real world environments. We argue that as a new genre in the field of mobile entertainment, research in this area tends to be preoccupied with the newness of the technology and its commercial possibilities. However, this overlooks its potential to contribute to cultural production. We argue that the potential to contribute to cultural production lies in the capacity of these experiences to enhance relationships between specific groups and new urban spaces. Given that developers can design LBGs to be played with everyday devices in everyday environments, what new creative opportunities are available to everyday people?

Respecting local, cultural contexts for assessment practice in an era of globalization

Dissatisfaction, internationally, with existing educational practices and outcomes since the early 1990s has led to increased educational reform. At the same time, there has also been a worldwide shift in control of education away from teachers toward the state for the purposes of restructuring economies. More bureaucratic forms of curriculum and assessment have resulted, with a return to the use of more techno-rational discourse in assessment and evaluation for purposes of efficiency, accountability, impact, and performance management. There has also been an increase in the use of economic and productivity models to study educational outcomes. These models fail to account for the range of outcomes achieved and fail to identify the factors responsible for such diversity in performance.

A visualisation framework for collaborative virtual environment usage information

Due to the popularity of modern Collaborative Virtual Environments, there has been a related increase in their size and complexity. Developers therefore need visualisations that expose usage patterns from logged data, to understand the structures and dynamics of these complex environments. This chapter presents a new framework for the process of visualising virtual environment usage data. Major components, such as an event model, designer task model and data acquisition infrastructure are described. Interface and implementation factors are also developed, along with example visualisation techniques that make use of the new task and event model. A case study is performed to illustrate a typical scenario for the framework, and its benefits to the environment development team.

Visualisation of Information Uncertainty : Progress and Challenges

Information uncertainty which is inherent in many real world applications brings more complexity to the visualisation problem. Despite the increasing number of research papers found in the literature, much more work is needed. The aims of this chapter are threefold: (1) to provide a comprehensive analysis of the requirements of visualisation of information uncertainty and their dimensions of complexity; (2) to review and assess current progress; and (3) to discuss remaining research challenges. We focus on four areas: information uncertainty modelling, visualisation techniques, management of information uncertainty modelling, propagation and visualisation, and the uptake of uncertainty visualisation in application domains.

Engaging students in programming

Poor student engagement and high failure rates in first year units were addressed at the Queensland University of Technology (QUT) with a course restructure involving a fresh approach to introducing programming. Students’ first taste of programming in the new course focused less on the language and syntax, and more on problem solving and design, and the role of programming in relation to other technologies they are likely to encounter in their studies. In effect, several technologies that have historically been compartmentalised and taught in isolation have been brought together as a breadth-first introduction to IT. Incorporating databases and Web development technologies into what used to be a purely programming unit gave students a very short introduction to each technology, with programming acting as the glue between each of them. As a result, students not only had a clearer understanding of the application of programming in the real world, but were able to determine their preference or otherwise for each of the technologies introduced, which will help them when the time comes for choosing a course major. Students engaged well in an intensely collaborative learning environment for this unit which was designed to both support the needs of students and meet industry expectations. Attrition from the unit was low, with computer laboratory practical attendance rates for the first time remaining high throughout semester, and the failure rate falling to a single figure percentage.

Evaluation of aerial remote sensing techniques for vegetation management in power line corridors

The following paper presents an evaluation of airborne sensors for use in vegetation management in powerline corridors. Three integral stages in the management process are addressed including, the detection of trees, relative positioning with respect to the nearest powerline and vegetation height estimation. Image data, including multi-spectral and high resolution, are analyzed along with LiDAR data captured from fixed wing aircraft. Ground truth data is then used to establish the accuracy and reliability of each sensor thus providing a quantitative comparison of sensor options. Tree detection was achieved through crown delineation using a Pulse-Coupled Neural Network (PCNN) and morphologic reconstruction applied to multi-spectral imagery. Through testing it was shown to achieve a detection rate of 96%, while the accuracy in segmenting groups of trees and single trees correctly was shown to be 75%. Relative positioning using LiDAR achieved a RMSE of 1.4m and 2.1m for cross track distance and along track position respectively, while Direct Georeferencing achieved RMSE of 3.1m in both instances. The estimation of pole and tree heights measured with LiDAR had a RMSE of 0.4m and 0.9m respectively, while Stereo Matching achieved 1.5m and 2.9m. Overall a small number of poles were missed with detection rates of 98% and 95% for LiDAR and Stereo Matching.

Functional role of cell surface CUB domain-containing protein 1 in tumour cell dissemination

The function of CUB domain-containing protein 1 (CDCP1), a recently described transmembrane protein expressed on the surface of hematopoietic stem cells and normal and malignant cells of different tissue origin, is not well defined. The contribution of CDCP1 to tumor metastasis was analyzed by using HeLa carcinoma cells overexpressing CDCP1 (HeLa-CDCP1) and a high-disseminating variant of prostate carcinoma PC-3 naturally expressing high levels of CDCP1 (PC3-hi/diss). CDCP1 expression rendered HeLa cells more aggressive in experimental metastasis in immunodeficient mice. Metastatic colonization by HeLa-CDCP1 was effectively inhibited with subtractive immunization-generated, CDCP1-specific monoclonal antibody (mAb) 41-2, suggesting that CDCP1 facilitates relatively late stages of the metastatic cascade. In the chick embryo model, time- and dose-dependent inhibition of HeLa-CDCP1 colonization by mAb 41-2 was analyzed quantitatively to determine when and where CDCP1 functions during metastasis. Quantitative PCR and immunohistochemical analyses indicated that CDCP1 facilitated tumor cell survival soon after vascular arrest. Live cell imaging showed that the function-blocking mechanism of mAb 41-2 involved enhancement of tumor cell apoptosis, confirmed by attenuation of mAb 41-2–mediated effects with the caspase inhibitor z-VAD-fmk. Under proapoptotic conditions in vitro, CDCP1 expression conferred HeLa-CDCP1 cells with resistance to doxorubicin-induced apoptosis, whereas ligation of CDCP1 with mAb 41-2 caused additional enhancement of the apoptotic response. The functional role of naturally expressed CDCP1 was shown by mAb 41-2–mediated inhibition of both experimental and spontaneous metastasis of PC3-hi/diss. These findings confirm that CDCP1 functions as an antiapoptotic molecule and indicate that during metastasis CDCP1 facilitates tumor cell survival likely during or soon after extravasation.