Modeling prostate cancer: a perspective on transgenic mouse models

Despite considerable success in treatment of early stage localized prostate cancer (PC), acute inadequacy of late stage PC treatment and its inherent heterogeneity poses a formidable challenge. Clearly, an improved understanding of PC genesis and progression along with the development of new targeted therapies are warranted. Animal models, especially, transgenic immunocompetent mouse models, have proven to be the best ally in this respect. A series of models have been developed by modulation of expression of genes implicated in cancer-genesis and progression; mainly, modulation of expression of oncogenes, steroid hormone receptors, growth factors and their receptors, cell cycle and apoptosis regulators, and tumor suppressor genes have been used. Such models have contributed significantly to our understanding of the molecular and pathological aspects of PC initiation and progression. In particular, the transgenic mouse models based on multiple genetic alterations can more accurately address the inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis and progression but also for clinically relevant evaluation of new therapies. Further, with advances in conditional knockout technologies, otherwise embryonically lethal gene changes can be incorporated leading to the development of new generation transgenics, thus adding significantly to our existing knowledge base. Different models and their relevance to PC research are discussed.

Soil carbon sequestration rates and associated economic costs for farming systems of south-eastern Australia

Soil organic carbon (C) sequestration rates based on the Intergovernmental Panel for Climate Change (IPCC) methodology were combined with local economic data to simulate the economic potential for C sequestration in response to conservation tillage in the six agro-ecological zones within the Southern Region of the Australian grains industry. The net C sequestration rate over 20 years for the Southern Region (which includes discounting for associated greenhouse gases) is estimated to be 3.6 or 6.3 Mg C/ha after converting to either minimum or no-tillage practices, respectively, with no-till practices estimated to return 75% more carbon on average than minimum tillage. The highest net gains in C per ha are realised when converting from conventional to no-tillage practices in the high-activity clay soils of the High Rainfall and Wimmera agro-ecological zones. On the basis of total area available for change, the Slopes agro-ecological zone offers the highest net returns, potentially sequestering an additional 7.1 Mt C under no-tillage scenario over 20 years. The economic analysis was summarised as C supply curves for each of the 6 zones expressing the total additional C accumulated over 20 years for a price per t C sequestered ranging from zero to AU$200. For a price of $50/Mg C, a total of 427 000 Mg C would be sequestered over 20 years across the Southern Region, <5% of the simulated C sequestration potential of 9.1 Mt for the region. The Wimmera and Mid-North offer the largest gains in C under minimum tillage over 20 years of all zones for all C prices. For the no-tillage scenario, for a price of $50/Mg C, 1.74 Mt C would be sequestered over 20 years across the Southern Region, <10% of the simulated C sequestration potential of 18.6 Mt for the region over 20 years. The Slopes agro-ecological zone offers the best return in C over 20 years under no-tillage for all C prices. The Mallee offers the least return for both minimum and no-tillage scenarios. At a price of $200/Mg C, the transition from conventional tillage to minimum or no-tillage practices will only realise 19% and 33%, respectively, of the total biogeochemical sequestration potential of crop and pasture systems of the Southern Region over a 20-year period.

Performance analysis of business process models with advanced constructs

The importance of actively managing and analysing business processes is acknowledged more than ever in organisations nowadays. Business processes form an essential part of an organisation and their application areas are manifold. Most organisations keep records of various activities that have been carried out for auditing purposes, but they are rarely used for analysis purposes. This paper describes the design and implementation of a process analysis tool that replays, analyses and visualises a variety of performance metrics using a process definition and its corresponding execution logs. The replayer uses a YAWL process model example to demonstrate its capacity to support advanced language constructs.

Fourier active appearance models

Gaining invariance to camera and illumination variations has been a well investigated topic in Active Appearance Model (AAM) fitting literature. The major problem lies in the inability of the appearance parameters of the AAM to generalize to unseen conditions. An attractive approach for gaining invariance is to fit an AAM to a multiple filter response (e.g. Gabor) representation of the input image. Naively applying this concept with a traditional AAM is computationally prohibitive, especially as the number of filter responses increase. In this paper, we present a computationally efficient AAM fitting algorithm based on the Lucas-Kanade (LK) algorithm posed in the Fourier domain that affords invariance to both expression and illumination. We refer to this as a Fourier AAM (FAAM), and show that this method gives substantial improvement in person specific AAM fitting performance over traditional AAM fitting methods.

The impact of software-as-a-service on business models of leading software vendors : experiences from three exploratory case studies

The number of software vendors offering ‘Software-as-a-Service’ has been increasing in recent years. In the Software-as-a-Service model software is operated by the software vendor and delivered to the customer as a service. Existing business models and industry structures are challenged by the changes to the deployment and pricing model compared to traditional software. However, the full implications on the way companies create, deliver and capture value are not yet sufficiently analyzed. Current research is scattered on specific aspects, only a few studies provide a more holistic view of the impact from a business model perspective. For vendors it is, however, crucial to be aware of the potentially far reaching consequences of Software-as-a-Service. Therefore, a literature review and three exploratory case studies of leading software vendors are used to evaluate possible implications of Software-as-a-Service on business models. The results show an impact on all business model building blocks and highlight in particular the often less articulated impact on key activities, customer relationship and key partnerships for leading software vendors and show related challenges, for example, with regard to the integration of development and operations processes. The observed implications demonstrate the disruptive character of the concept and identify future research requirements.

Economic development, enlightenment and creative transformation : creative industries in the New China

This paper examines some of the implications for China of the creative industries agenda as drawn by some recent commentators. The creative industries have been seen by many commentators as essential if China is to move from an imitative low-value economy to an innovative high value one. Some suggest that this trajectory is impossible without a full transition to liberal capitalism and democracy - not just removing censorship but instituting 'enlightenment values'. Others suggest that the development of the creative industries themselves will promote social and political change. The paper suggests that the creative industries takes certain elements of a prior cultural industries concept and links it to a new kind of economic development agenda. Though this agenda presents problems for the Chinese government it does not in itself imply the kind of radical democratic political change with which these commentators associate it. In the form in which the creative industries are presented – as part of an informational economy rather than as a cultural politics – it can be accommodated by a Chinese regime doing ‘business as usual’.

Relative entropy rate based design for linear hybrid system models

Hybrid system representations have been applied to many challenging modeling situations. In these hybrid system representations, a mixture of continuous and discrete states is used to capture the dominating behavioural features of a nonlinear, possible uncertain, model under approximation. Unfortunately, the problem of how to best design a suitable hybrid system model has not yet been fully addressed. This paper proposes a new joint state measurement relative entropy rate based approach for this design purpose. Design examples and simulation studies are presented which highlight the benefits of our proposed design approaches.

Robust designs for Poisson regression models

We consider the problem of how to construct robust designs for Poisson regression models. An analytical expression is derived for robust designs for first-order Poisson regression models where uncertainty exists in the prior parameter estimates. Given certain constraints in the methodology, it may be necessary to extend the robust designs for implementation in practical experiments. With these extensions, our methodology constructs designs which perform similarly, in terms of estimation, to current techniques, and offers the solution in a more timely manner. We further apply this analytic result to cases where uncertainty exists in the linear predictor. The application of this methodology to practical design problems such as screening experiments is explored. Given the minimal prior knowledge that is usually available when conducting such experiments, it is recommended to derive designs robust across a variety of systems. However, incorporating such uncertainty into the design process can be a computationally intense exercise. Hence, our analytic approach is explored as an alternative.

Stochastic models for regulatory networks of the genetic toggle switch

Bistability arises within a wide range of biological systems from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.