Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

Receivers' future liability for costs

In Juniper Property Holdings No.15 Pty Ltd v Caltabiano [2015] QSC 95, Jackson J considered what he described as a 'novel point' as to whether the court had jurisdiction to make a determination of the liability of receivers and managers appointed to the plaintiff to pay any costs orders that may be made in favour of the defendant.

Costs assessor selection: A question of timing, or cost?

In Lessbrook Pty Ltd (in liq) v Whap; Stephen; Bowie; Kepa & Kepa [2014] QCA 63 the Queensland Court of Appeal dealt with significant questions of general application relating to the appointment of assessors to conduct an assessment of costs under the Uniform Civil Procedure Rules 1999 (Qld) (UCPR).

Emerging issues for road construction and maintenance – A futuristic view

In the coming decades the design, construction and maintenance of roads will face a range of new issues and as such will require a number of new approaches. In particular, road authorities will be required to consider and respond to a range of issues related to climate change, and associated extreme weather events, such as the extensive flooding in January 2011 in Queensland, Australia Figure 1). Coupled with diminishing access to road construction supplies (such as aggregate), water scarcity, and the potential for increases in oil and electricity prices, this range of challenges bear little resemblance to those previously faced. In Australia, state and federal authorities face further pressures given the variety of needs resulting from the country's geographical and population diversity, expansive road networks, road freight requirements and relatively small population base.

Research outcomes for improved management of insulated rail joints

Insulated Rail Joints (IRJs) are safety critical component of the automatic block signalling and broken rail detection systems. IRJs exhibit several failure modes due to complex interaction between the railhead ends and the wheel tread near the gap. These localised zones could not be monitored using automatic sensing devices and hence are resorted to visual inspection only, which is error prone and expensive. In Australia alone currently there are 50,000 IRJs across 80,000 km of rail track. The significance of the problem around the world could thus be realised as there exists one IRJ for each 1.6 km track length. IRJs exhibit extremely low and variable service life; further the track substructure underneath IRJs degrade faster. Thus presence of the IRJs incur significant costs to track maintenance. IRJ failures have also contributed to some train derailments and various traffic disruptions in rail lines. This paper reports a systematic research carried out over seven years on the mechanical behaviour of IRJs for practically relevant outcomes. The research has scientifically established that stiffening the track bed for reduction in impact force is an ill-conceived concept and the most effective method is to reduce the gap size. Further it is established that hardening the railhead ends through laser coating (or other) cannot adequately address the metal flow problem in the long run; modification of the railhead profile is the only appropriate technique to completely eliminate the problem. Part of these outcomes has been adopted by the rail infrastructure owners in Australia.

How will the future of roads be navigated?

In the coming decades the design, construction and maintenance of roads will face a range of new challenges - that in many ways will bear little resemblance to the challenges previously faced - and as such will require a number of new approaches. Such challenges will result from a growing number of interconnected environmental, social and economic factors, which are set to apply significant pressure on the future of roads. For instance, environmental pressures will include the impacts of climate change on rainfall patterns and temperature profiles; economic pressure will be affected by shifting global economic balances and flows, and will include materials and resources shortages, along with predicted increases in energy and resource prices globally,i and social pressures will include potential shifts to lighter vehicles, reduced use of cars due to higher fuel costs, and political pressure to respond to climate change.

Projecting excess emergency department visits and associated costs in Brisbane, Australia, under population growth and climate change scenarios

The direct and indirect health effects of increasingly warmer temperatures are likely to further burden the already overcrowded hospital emergency departments (EDs). Using current trends and estimates in conjunction with future population growth and climate change scenarios, we show that the increased number of hot days in the future can have a considerable impact on EDs, adding to their workload and costs. The excess number of visits in 2030 is projected to range between 98–336 and 42–127 for younger and older groups, respectively. The excess costs in 2012–13 prices are estimated to range between AU$51,000–184,000 (0–64) and AU$27,000–84,000 (65+). By 2060, these estimates will increase to 229–2300 and 145–1188 at a cost of between AU$120,000–1,200,000 and AU$96,000–786,000 for the respective age groups. Improvements in climate change mitigation and adaptation measures are likely to generate synergistic health co-benefits and reduce the impact on frontline health services.

Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human

Genome maintenance (GM) is an essential defense system against aging and cancer, as both are characterized by increased genome instability. Here, we compared the copy number variation and mutation rate of 518 GM-associated genes in the naked mole rat (NMR), mouse, and human genomes. GM genes appeared to be strongly conserved, with copy number variation in only four genes. Interestingly, we found NMR to have a higher copy number of CEBPG, a regulator of DNA repair, and TINF2, a protector of telomere integrity. NMR, as well as human, was also found to have a lower rate of germline nucleotide substitution than the mouse. Together, the data suggest that the long-lived NMR, as well as human, has more robust GM than mouse and identifies new targets for the analysis of the exceptional longevity of the NMR.

Integration of Geospatial and Built Environment - National Data Policy

Digital technology offers enormous benefits (economic, quality of design and efficiency in use) if adopted to implement integrated ways of representing the physical world in a digital form. When applied across the full extent of the built and natural world, it is referred to as the Digital Built Environment (DBE) and encompasses a wide range of approaches and technology initiatives, all aimed at the same end goal: the development of a virtual world that sufficiently mirrors the real world to form the basis for the smart cities of the present and future, enable efficient infrastructure design and programmed maintenance, and create a new foundation for economic growth and social well-being through evidence-based analysis. The creation of a National Data Policy for the DBE will facilitate the creation of additional high technology industries in Australia; provide Governments, industries and citizens with greater knowledge of the environments they occupy and plan; and offer citizen-driven innovations for the future. Australia has slipped behind other nations in the adoption and execution of Building Information Modelling (BIM) and the principal concern is that the gap is widening. Data driven innovation added $67 billion to the Australian economy in 20131. Strong open data policy equates to $16 billion in new value2. Australian Government initiatives such as the Digital Earth inspired “National Map” offer a platform and pathway to embrace the concept of a “BIM Globe”, while also leveraging unprecedented growth in open source / open data collaboration. Australia must address the challenges by learning from international experiences—most notably the UK and NZ—and mandate the use of BIM across Government, extending the Framework for Spatial Data Foundation to include the Built Environment as a theme and engaging collaboration through a “BIM globe” metaphor. This proposed DBE strategy will modernise the Australian urban planning and the construction industry. It will change the way we develop our cities by fundamentally altering the dynamics and behaviours of the supply chains and unlocking new and more efficient ways of collaborating at all stages of the project life-cycle. There are currently two major modelling approaches that contribute to the challenge of delivering the DBE. Though these collectively encompass many (often competing) approaches or proprietary software systems, all can be categorised as either: a spatial modelling approach, where the focus is generally on representing the elements that make up the world within their geographic context; and a construction modelling approach, where the focus is on models that support the life cycle management of the built environment. These two approaches have tended to evolve independently, addressing two broad industry sectors: the one concerned with understanding and managing global and regional aspects of the world that we inhabit, including disciplines concerned with climate, earth sciences, land ownership, urban and regional planning and infrastructure management; the other is concerned with planning, design, construction and operation of built facilities and includes architectural and engineering design, product manufacturing, construction, facility management and related disciplines (a process/technology commonly known as Building Information Modelling, BIM). The spatial industries have a strong voice in the development of public policy in Australia, while the construction sector, which in 2014 accounted for around 8.5% of Australia’s GDP3, has no single voice and because of its diversity, is struggling to adapt to and take advantage of the opportunity presented by these digital technologies. The experience in the UK over the past few years has demonstrated that government leadership is very effective in stimulating industry adoption of digital technologies by, on the one hand, mandating the use of BIM on public procurement projects while at the same time, providing comparatively modest funding to address the common issues that confront the industry in adopting that way of working across the supply chain. The reported result has been savings of £840m in construction costs in 2013/14 according to UK Cabinet Office figures4. There is worldwide recognition of the value of bringing these two modelling technologies together. Australia has the expertise to exercise leadership in this work, but it requires a commitment by government to recognise the importance of BIM as a companion methodology to the spatial technologies so that these two disciplinary domains can cooperate in the development of data policies and information exchange standards to smooth out common workflows. buildingSMART Australasia, SIBA and their academic partners have initiated this dialogue in Australia and wish to work collaboratively, with government support and leadership, to explore the opportunities open to us as we develop an Australasian Digital Built Environment. As part of that programme, we must develop and implement a strategy to accelerate the adoption of BIM processes across the Australian construction sector while at the same time, developing an integrated approach in concert with the spatial sector that will position Australia at the forefront of international best practice in this area. Australia and New Zealand cannot afford to be on the back foot as we face the challenges of rapid urbanisation and change in the global environment. Although we can identify some exemplary initiatives in this area, particularly in New Zealand in response to the need for more resilient urban development in the face of earthquake threats, there is still much that needs to be done. We are well situated in the Asian region to take a lead in this challenge, but we are at imminent risk of losing the initiative if we do not take action now. Strategic collaboration between Governments, Industry and Academia will create new jobs and wealth, with the potential, for example, to save around 20% on the delivery costs of new built assets, based on recent UK estimates.

A CCG virtual system for big data application communication costs analysis

Network topology and routing are two important factors in determining the communication costs of big data applications at large scale. As for a given Cluster, Cloud, or Grid system, the network topology is fixed and static or dynamic routing protocols are preinstalled to direct the network traffic. Users cannot change them once the system is deployed. Hence, it is hard for application developers to identify the optimal network topology and routing algorithm for their applications with distinct communication patterns. In this study, we design a CCG virtual system (CCGVS), which first uses container-based virtualization to allow users to create a farm of lightweight virtual machines on a single host. Then, it uses software-defined networking (SDN) technique to control the network traffic among these virtual machines. Users can change the network topology and control the network traffic programmingly, thereby enabling application developers to evaluate their applications on the same system with different network topologies and routing algorithms. The preliminary experimental results through both synthetic big data programs and NPB benchmarks have shown that CCGVS can represent application performance variations caused by network topology and routing algorithm.

Communicating consequences with costs: A commentary on Corso et al's cost of injury

Estimating the economic burden of injuries is important for setting priorities, allocating scarce health resources and planning cost-effective prevention activities. As a metric of burden, costs account for multiple injury consequences—death, severity, disability, body region, nature of injury—in a single unit of measurement. In a 1989 landmark report to the US Congress, Rice et al1 estimated the lifetime costs of injuries in the USA in 1985. By 2000, the epidemiology and burden of injuries had changed enough that the US Congress mandated an update, resulting in a book on the incidence and economic burden of injury in the USA.2 To make these findings more accessible to the larger realm of scientists and practitioners and to provide a template for conducting the same economic burden analyses in other countries and settings, a summary3 was published in Injury Prevention. Corso et al reported that, between 1985 and 2000, injury rates declined roughly 15%. The estimated lifetime cost of these injuries declined 20%, totalling US$406 billion, including US$80 billion in medical costs and US$326 billion in lost productivity. While incidence reflects problem size, the relative burden of injury is better expressed using costs.

Director independence or decision bias? An investigation of alternative sources of agency costs in board decision making

Research into boards traditionally focuses on independent monitoring of management, with studies focused on the effect of board independence on firm performance. This thesis aims to broaden the research tradition by consolidating prior research and investigating how agents may circumvent independent monitoring. Meta-analysis of previous board independence-firm performance studies indicated no systematic relationship between board independence and firm performance. Next, a series of experiments demonstrated that the presentation of recommendations to directors may bias decision making irrespective of other information presented and the independence of the decision maker. Together, results suggest that independence may be less important than the agent's motivation to misdirect the monitoring process.

The impact of home loan key facts sheets on borrowers' comparisons of loan costs

This thesis evaluates the effectiveness of the prescribed design and distribution requirements of the Australian Government's home loan key facts sheets (KFS) aimed at helping borrowers compare loan costs. The findings show that despite effectively improving borrower decision-making, few borrowers were aware of their existence and function. It was also demonstrated that KFS have had limited market impact over the four year window since introduction, likely due to the requirement that KFS provision is not required unless formally requested by a borrower. Recommendations include transferring the burden of disclosure to lenders in the first instance to address this information gap.

Costs assessment not an each-way bet: Radich v Kenway [2014] QDC 60

In Radich v Kenway [2014] QDC 60 McGinness DCJ considered issues relating to the assessment of costs under the Legal Profession Act 2007 (Qld). This recent costs assessment case from the District Court clearly illustrates the interplay between the relevant elements of the Legal Profession Act 2007 and Uniform Civil Procedure Rules 1999.

Keeping clear on costs: Geatches v Anglo Coal (Moranbah North Management Pty Ltd) [2014] QSC 106

In Geatches v Anglo Coal (Moranbah North Management Pty Ltd [2014] QSC 106, a dispute arose in the context of an assessment of costs as to the meaning to be attributed to particular terms of settlement and discharge signed by the parties. The court was required to consider the implications of those documents, and of a subsequent consent order intended to reflect the agreed settlement. Recovery of costs - terms of settlement and discharge exclude recovery of costs against one party and require other party to pay costs of claim against it - whether only subsequent consent order should be construed - implications where costs were common and mixed costs - whether costs should be apportioned