Association between prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data

Background: Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease. Objectives: We performed a comprehensive analysis of association of variants in the KLK15 gene with prostate cancer risk and aggressiveness by genotyping tagSNPs, as well as putative functional SNPs identified by extensive bioinformatics analysis. Methods and Data Sources: Twelve out of 22 SNPs, selected on the basis of linkage disequilibrium pattern, were analyzed in an Australian sample of 1,011 histologically verified prostate cancer cases and 1,405 ethnically matched controls. Replication was sought from two existing genome wide association studies (GWAS): the Cancer Genetic Markers of Susceptibility (CGEMS) project and a UK GWAS study. Results: Two KLK15 SNPs, rs2659053 and rs3745522, showed evidence of association (p, 0.05) but were not present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated with prostate cancer aggressiveness and showed evidence of association in a replication cohort of 5,051 patients from the UK, Australia, and the CGEMS dataset of US samples. A highly significant association with Gleason score was observed when the data was combined from these three studies with an Odds Ratio (OR) of 0.85 (95% CI = 0.77-0.93; p = 2.7610 24). The rs2659056 SNP is predicted to alter binding of the RORalpha transcription factor, which has a role in the control of cell growth and differentiation and has been suggested to control the metastatic behavior of prostate cancer cells. Conclusions: Our findings suggest a role for KLK15 genetic variation in the etiology of prostate cancer among men of European ancestry, although further studies in very large sample sets are necessary to confirm effect sizes.

Novel molecular markers of Chlamydia pecorum genetic diversity in the koala (Phascolarctos cinereus)

Background Chlamydia pecorum is an obligate intracellular bacterium and the causative agent of reproductive and ocular disease in several animal hosts including koalas, sheep, cattle and goats. C. pecorum strains detected in koalas are genetically diverse, raising interesting questions about the origin and transmission of this species within koala hosts. While the ompA gene remains the most widely-used target in C. pecorum typing studies, it is generally recognised that surface protein encoding genes are not suited for phylogenetic analysis and it is becoming increasingly apparent that the ompA gene locus is not congruent with the phylogeny of the C. pecorum genome. Using the recently sequenced C. pecorum genome sequence (E58), we analysed 10 genes, including ompA, to evaluate the use of ompA as a molecular marker in the study of koala C. pecorum genetic diversity. Results Three genes (incA, ORF663, tarP) were found to contain sufficient nucleotide diversity and discriminatory power for detailed analysis and were used, with ompA, to genotype 24 C. pecorum PCR-positive koala samples from four populations. The most robust representation of the phylogeny of these samples was achieved through concatenation of all four gene sequences, enabling the recreation of a "true" phylogenetic signal. OmpA and incA were of limited value as fine-detailed genetic markers as they were unable to confer accurate phylogenetic distinctions between samples. On the other hand, the tarP and ORF663 genes were identified as useful "neutral" and "contingency" markers respectively, to represent the broad evolutionary history and intra-species genetic diversity of koala C. pecorum. Furthermore, the concatenation of ompA, incA and ORF663 sequences highlighted the monophyletic nature of koala C. pecorum infections by demonstrating a single evolutionary trajectory for koala hosts that is distinct from that seen in non-koala hosts. Conclusions While the continued use of ompA as a fine-detailed molecular marker for epidemiological analysis appears justified, the tarP and ORF663 genes also appear to be valuable markers of phylogenetic or biogeographic divisions at the C. pecorum intra-species level. This research has significant implications for future typing studies to understand the phylogeny, genetic diversity, and epidemiology of C. pecorum infections in the koala and other animal species.

An exploration of affine group laws for elliptic curves

Several forms of elliptic curves are suggested for an efficient implementation of Elliptic Curve Cryptography. However, a complete description of the group law has not appeared in the literature for most popular forms. This paper presents group law in affine coordinates for three forms of elliptic curves. With the existence of the proposed affine group laws, stating the projective group law for each form becomes trivial. This work also describes an automated framework for studying elliptic curve group law, which is applied internally when preparing this work.

Persistence of multiple genetic lineages within intra-host populations of Ross River virus

We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances

It’s always a pleasure : exploring productivity and pleasure in a writing group for early career academics

The professional development needs of early career academics (ECAs) are increasingly subject to scrutiny. The literature notes writing groups can be successful in increasing research outputs and improving research track records – a core concern for ECAs. However, the pressure on ECAs to publish takes the pleasure out of writing for many. We argue writing groups, created by and for ECAs, can provide an environment for ECAs to (re)produce pleasure in writing and participation in the processes of academic review and debate. In addition, our experience of a writing group was that it provided a platform of social and emotional support contributing to our personal well-being and professional development.

Genetic algorithms to schedule container transfers at multimodal terminals

Optimising the container transfer schedule at the multimodal terminals is known to be NP-hard, which implies that the best solution becomes computationally infeasible as problem sizes increase. Genetic Algorithm (GA) techniques are used to reduce container handling/transfer times and ships' time at the port by speeding up handling operations. The GA is chosen due to the relatively good results that have been reported even with the simplest GA implementations to obtain near-optimal solutions in reasonable time. Also discussed, is the application of the model to assess the consequences of increased scheduled throughput time as well as different strategies such as the alternative plant layouts, storage policies and number of yard machines. A real data set used for the solution and subsequent sensitivity analysis is applied to the alternative plant layouts, storage policies and number of yard machines.

A randomised controlled trial of an enhanced interdisciplinary community based group program for people with Parkinson’s disease: study rationale and protocol

Parkinson’s disease (PD) is a progressive, chronic neurodegenerative disorder for which there is no known cure. Physical exercise programs may be used to assist with the physical management of PD. Several studies have demonstrated that community based physical therapy programs are effective in reducing physical aspects of disability among people with PD. While multidisciplinary therapy interventions may have the potential to reduce disability and improve the quality of life of people with PD, there is very limited clinical trial evidence to support or refute the use of a community based multidisciplinary or interdisciplinary programs for people with PD. A two group randomized trial is being undertaken within a community rehabilitation service in Brisbane, Australia. Community dwelling adults with a diagnosis of Idiopathic Parkinson’s disease are being recruited. Eligible participants are randomly allocated to a standard exercise rehabilitation group program or an intervention group which incorporates physical, cognitive and speech activities in a multi-tasking framework. Outcomes will be measured at 6-week intervals for a period of six months. Primary outcome measures are the Montreal Cognitive Assessment (MoCA) and the Timed Up and Go (TUG) cognitive test. Secondary outcomes include changes in health related quality of life, communication, social participation, mobility, strength and balance, and carer burden measures. This study will determine the immediate and long-term effectiveness of a unique multifocal, interdisciplinary, dual-tasking approach to the management of PD as compared to an exercise only program. We anticipate that the results of this study will have implications for the development of cost effective evidence based best practice for the treatment of people with PD living in the community.

A penalty-based grouping genetic algorithm for multiple composite SaaS components clustering in Cloud

Software as a Service (SaaS) in Cloud is getting more and more significant among software users and providers recently. A SaaS that is delivered as composite application has many benefits including reduced delivery costs, flexible offers of the SaaS functions and decreased subscription cost for users. However, this approach has introduced a new problem in managing the resources allocated to the composite SaaS. The resource allocation that has been done at the initial stage may be overloaded or wasted due to the dynamic environment of a Cloud. A typical data center resource management usually triggers a placement reconfiguration for the SaaS in order to maintain its performance as well as to minimize the resource used. Existing approaches for this problem often ignore the underlying dependencies between SaaS components. In addition, the reconfiguration also has to comply with SaaS constraints in terms of its resource requirements, placement requirement as well as its SLA. To tackle the problem, this paper proposes a penalty-based Grouping Genetic Algorithm for multiple composite SaaS components clustering in Cloud. The main objective is to minimize the resource used by the SaaS by clustering its component without violating any constraint. Experimental results demonstrate the feasibility and the scalability of the proposed algorithm.

Energy-efficient virtual machine placement in data centers by genetic algorithm

Server consolidation using virtualization technology has become an important technology to improve the energy efficiency of data centers. Virtual machine placement is the key in the server consolidation. In the past few years, many approaches to the virtual machine placement have been proposed. However, existing virtual machine placement approaches to the virtual machine placement problem consider the energy consumption by physical machines in a data center only, but do not consider the energy consumption in communication network in the data center. However, the energy consumption in the communication network in a data center is not trivial, and therefore should be considered in the virtual machine placement in order to make the data center more energy-efficient. In this paper, we propose a genetic algorithm for a new virtual machine placement problem that considers the energy consumption in both the servers and the communication network in the data center. Experimental results show that the genetic algorithm performs well when tackling test problems of different kinds, and scales up well when the problem size increases.

Innovative planning approaches for generator interconnection group study

Today, a large number of wind generator interconnection requests have been queued and are being processed. The generator interconnection group study is a way to reduce the generator interconnection cycle time and increase interconnection certainty. However, it is very challenging to identify the “best” transmission upgrades for a large group of generator interconnections. It is also very important to differentiate the constraints caused by each generator interconnection request and identify their responsibilities for transmission upgrades. This paper outlines some innovative study approaches that can be used in a group study with large numbers of generator interconnection requests in a constrained area. Improved study methods are introduced, and a summary and conclusions are derived from the study.

An expressed sequence tag (EST) library for Drosophila serrata, a model system for sexual selection and climatic adaptation studies

The native Australian fly Drosophila serrata belongs to the highly speciose montium subgroup of the melanogaster species group. It has recently emerged as an excellent model system with which to address a number of important questions, including the evolution of traits under sexual selection and traits involved in climatic adaptation along latitudinal gradients. Understanding the molecular genetic basis of such traits has been limited by a lack of genomic resources for this species. Here, we present the first expressed sequence tag (EST) collection for D. serrata that will enable the identification of genes underlying sexually-selected phenotypes and physiological responses to environmental change and may help resolve controversial phylogenetic relationships within the montium subgroup.

Australian lungfish (Neoceratodus forsteri: Dipnoi) have low genetic variation at allozyme and mitochondrial DNA loci : a conservation alert?

Genetic variation at allozyme and mitochondrial DNA loci was investigated in the Australian lungfish, Neoceratodus forsteri Krefft 1870. Tissue samples for genetic analysis were taken non-lethally from 278 individuals representing two spatially distinct endemic populations (Mary and Burnett rivers), as well as one population thought to be derived from an anthropogenic translocation in the 1890's (Brisbane river). Two of 24 allozyme loci resolved from muscle tissue were polymorphic. Mitochondrial DNA nucleotide sequence diversity estimated across 2,235 base pairs in each of 40 individuals ranged between 0.000423 and 0.001470 per river. Low genetic variation at allozyme and mitochondrial loci could be attributed to population bottlenecks, possibly induced by Pleistocene aridity. Limited genetic differentiation was detected among rivers using nuclear and mitochondrial markers suggesting that admixture may have occurred between the endemic Mary and Burnett populations during periods of low sea level when the drainages may have converged before reaching the ocean. Genetic data was consistent with the explanation that lungfish were introduced to the Brisbane river from the Mary river. Further research using more variable genetic loci is needed before the conservation status of populations can be determined, particularly as anthropogenic demands on lungfish habitat are increasing. In the interim we recommend a management strategy aimed at conserving existing genetic variation within and between rivers.

Mission drift or strategic shift? Group formation strategies within MEPs

Microenterprise development programs (MEPs) have been recognised as a valuable way to help the poor engage in micro-businesses (Green et al., 2006; Vargas, 2000), presenting a way out of poverty (Choudhury et al., 2008; Strier, 2010). Concerns have been raised however, that the benefits of MEPs often don’t reach the extremely poor (Jones et al., 2004; Midgley, 2008; Mosley and Hulme, 1998; Nawaz, 2010; Pritchett, 2006). Balancing reach of these programs with depth is a challenging task. Targeting as many poor people as possible often results in MEPs focusing on the upper or middle poor, overlooking the most challenging group. As such, MEPs have been criticised for mission drift – losing sight of the organisation’s core purpose; assisting those more likely to succeed.