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.

Data distribution and task scheduling for distributed computing of all-to-all comparison problems

This research studied distributed computing of all-to-all comparison problems with big data sets. The thesis formalised the problem, and developed a high-performance and scalable computing framework with a programming model, data distribution strategies and task scheduling policies to solve the problem. The study considered storage usage, data locality and load balancing for performance improvement in solving the problem. The research outcomes can be applied in bioinformatics, biometrics and data mining and other domains in which all-to-all comparisons are a typical computing pattern.

The biology and natural history of Tripogon loliiformis (Poaceae, Chloridoideae), an Australian resurrection grass

Tripogon loliiformis is a desiccation-tolerant grass that occurs throughout mainland Australia. There has been recent interest in this species as a model system for understanding desiccation tolerance in a native grass at the structural, molecular and physiological levels. However, not much is known about the biology and natural history of this species, despite its widespread geographic distribution and remarkable capability of withstanding prolonged drying. We provide an overview of the genus by consolidating information from a wide variety of sources. We report a variety of new and interesting observations on the general biology, ecology and desiccation response of T. loliiformis and conclude by highlighting areas for future research.

On reconsideration of IT governance structures to govern cloud computing services

There is an increase in the uptake of cloud computing services (CCS). CCS is adopted in the form of a utility, and it incorporates business risks of the service providers and intermediaries. Thus, the adoption of CCS will change the risk profile of an organization. In this situation, organisations need to develop competencies by reconsidering their IT governance structures to achieve a desired level of IT-business alignment and maintain their risk appetite to source business value from CCS. We use the resource-based theories to suggest that collaborative board oversight of CCS, competencies relating to CCS information and financial management, and a CCS-related continuous audit program can contribute to business process performance improvements and overall firm performance. Using survey data, we find evidence of a positive association between these IT governance considerations and business process performance. We also find evidence of positive association between business process performance improvements and overall firm performance. The results suggest that the suggested considerations on IT governance structures can contribute to CCS-related IT-business alignment and lead to anticipated business value from CCS. This study provides guidance to organizations on competencies required to secure business value from CCS.

Cloud computing services for the small and medium enterprises: Key considerations for sourcing sustainable business value

The concept of cloud computing services (CCS) is appealing to small and medium enterprises (SMEs). However, while there is a significant push by various authorities on SMEs to adopt the CCS, knowledge of the key considerations to adopt the CCS is very limited. We use the technology-organization-environment (TOE) framework to suggest that a strategic and incremental intent, understanding the organizational structure and culture, understanding the external factors, and consideration of the human resource capacity can contribute to sustainable business value from CCS. Using survey data, we find evidence of a positive association between these considerations and the CCS-related business objectives. We also find evidence of positive association between the CCS-related business objectives and CCS-related financial objectives. The results suggest that the proposed considerations can ensure sustainable business value from the CCS. This study provides guidance to SMEs on a path to adopting the CCS with the intention of a long-term commitment and achieving sustainable business value from these services.

Governing cloud computing services: Reconsideration of IT governance structures

There is an increase in the uptake of cloud computing services (CCS). CCS is adopted in the form of a utility, and it incorporates business risks of the service providers and intermediaries. Thus, the adoption of CCS will change the risk profile of an organization. In this situation, organizations need to develop competencies by reconsidering their IT governance structures to achieve a desired level of IT-business alignment and maintain their risk appetite to source business value from CCS. We use the resource-based theories to suggest that collaborative board oversight of CCS, competencies relating to CCS information and financial management, and a CCS-related continuous audit program can contribute to business process performance improvements and overall firm performance. Using survey data, we find evidence of a positive association between these IT governance considerations and business process performance. We also find evidence of positive association between business process performance improvements and overall firm performance. The results suggest that the suggested considerations on IT governance structures can contribute to CCS-related IT-business alignment and lead to anticipated business value from CCS. This study provides guidance to organizations on competencies required to secure business value from CCS.

A heterogeneous computing approach to simulation of the Heston Stochastic Volatility Model

Stochastic volatility models are of fundamental importance to the pricing of derivatives. One of the most commonly used models of stochastic volatility is the Heston Model in which the price and volatility of an asset evolve as a pair of coupled stochastic differential equations. The computation of asset prices and volatilities involves the simulation of many sample trajectories with conditioning. The problem is treated using the method of particle filtering. While the simulation of a shower of particles is computationally expensive, each particle behaves independently making such simulations ideal for massively parallel heterogeneous computing platforms. In this paper, we present our portable Opencl implementation of the Heston model and discuss its performance and efficiency characteristics on a range of architectures including Intel cpus, Nvidia gpus, and Intel Many-Integrated-Core (mic) accelerators.

LRP5 regulates human body fat distribution by modulating adipose progenitor biology in a dose- and depot-specific fashion

Summary Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired β-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/β-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders. © 2015 The Authors.

A cloud-based intelligent computing system for contextual exploration on personal sleep-tracking data using association rule mining

With the development of wearable and mobile computing technology, more and more people start using sleep-tracking tools to collect personal sleep data on a daily basis aiming at understanding and improving their sleep. While sleep quality is influenced by many factors in a person’s lifestyle context, such as exercise, diet and steps walked, existing tools simply visualize sleep data per se on a dashboard rather than analyse those data in combination with contextual factors. Hence many people find it difficult to make sense of their sleep data. In this paper, we present a cloud-based intelligent computing system named SleepExplorer that incorporates sleep domain knowledge and association rule mining for automated analysis on personal sleep data in light of contextual factors. Experiments show that the same contextual factors can play a distinct role in sleep of different people, and SleepExplorer could help users discover factors that are most relevant to their personal sleep.

Stimulating immune responses to fight cancer: Basic biology and mechanisms

Chronic inflammation is now recognized as a major cause of malignant disease. In concert with various mechanisms (including DNA instability), hypoxia and activation of inflammatory bioactive lipid pathways and pro-inflammatory cytokines open the doorway to malignant transformation and proliferation, angiogenesis, and metastasis in many cancers. A balance between stimulatory and inhibitory signals regulates the immune response to cancer. These include inhibitory checkpoints that modulate the extent and duration of the immune response and may be activated by tumor cells. This contributes to immune resistance, especially against tumor antigen-specific T-cells. Targeting these checkpoints is an evolving approach to cancer immunotherapy, designed to foster an immune response. The current focus of these trials is on the programmed cell death protein 1 (PD-1) receptor and its ligands (PD-L1, PD-L2) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Researchers have developed anti-PD-1 and anti-PDL-1 antibodies that interfere with the ligands and receptor and allow the tumor cell to be recognized and attacked by tumor-infiltrating T-cells. These are currently being studied in lung cancer. Likewise, CTLA-4 inhibitors, which have had success treating advanced melanoma, are being studied in lung cancer with encouraging results.

Germination biology and occurrence of pol-yembryony in two forms of cats claw creeper vine, Dolichandra unguis-cati (Bignonia-ceae): implications for its invasiveness and management

Cat’s claw creeper, Dolichandra unguis-cati (L.) Lohmann (syn. Macfadyena unguis-cati (L.) Gentry) is a major environmental weed in Australia. Two forms (‘long’ and ‘short’ pod) of the weed occur in Australia. This investigation aimed to evaluate and compare germination behavior and occurrence of polyembryony in the two forms of the weed. Seeds were germinated in growth chambers set to 10/20 °C, 15/25 °C, 20/30 °C, 30/45 °C and 25 °C. Germination and polyembryony were monitored over a period of 12 weeks. For all the treatments in this study, seeds from the short pod form exhibited significantly higher germination rates and higher occurrence of polyembryony than those from the long pod form. Seeds from the long pod form did not germinate at the lowest temperature of 10/20 °C; in contrast, those of the short pod form germinated under this condition, albeit at a lower rate. Results from this study could explain why the short pod form of D. unguis-cati is the more widely distributed form in Australia, while the long pod form is confined to a few localities. The results have implication in predicting future ranges of both forms of the invasive D. unguis-cati, as well as inform management decisions for control of the weed.