PCR bias Toward the wild-type k-ras and p53 sequences: Implications for PCR detection of mutations and cancer diagnosis

PCR-based cancer diagnosis requires detection of rare mutations in k- ras, p53 or other genes. The assumption has been that mutant and wild-type sequences amplify with near equal efficiency, so that they are eventually present in proportions representative of the starting material. Work on factor IX suggests that this assumption is invalid for one case of near- sequence identity. To test the generality of this phenomenon and its relevance to cancer diagnosis, primers distant from point mutations in p53 and k-ras were used to amplify wild-type and mutant sequences from these genes. A substantial bias against PCR amplification of mutants was observed for two regions of the p53 gene and one region of k-ras. For k-ras and p53, bias was observed when the wild-type and mutant sequences were amplified separately or when mixed in equal proportions before PCR. Bias was present with proofreading and non-proofreading polymerase. Mutant and wild-type segments of the factor V, cystic fibrosis transmembrane conductance regulator and prothrombin genes were amplified and did not exhibit PCR bias. Therefore, the assumption of equal PCR efficiency for point mutant and wild-type sequences is invalid in several systems. Quantitative or diagnostic PCR will require validation for each locus, and enrichment strategies may be needed to optimize detection of mutants.

Parliament, political ethics and national integrity systems

Papers on Parliament No. 55 February 2011 Charles Sampford "Parliament, Political Ethics and National Integrity Systems*" Prev | Contents |

From national integrity systems to global integrity systems

The primary focus of corruption studies and anti-corruption activism has been corruption within sovereign states. However, over the last twenty years ‘globalization’, the flow of money, goods, people and ideas across borders, has threatened to overwhelm the system of sovereign states. Much activity has moved outside the control of nation states at the same time as nation states have ‘deregulated’ and in so doing have transferred power from those exercising governmental power at the nominal behest of the majority of its citizens to those with greater wealth and/or greater knowledge in markets in which knowledge is typically asymmetric. It is now recognized that many governance problems have arisen because of globalisation and can only be addressed by global solutions. It must also be recognized that governance problems at the national level contribute to governance problems and the global level and vice versa. Nevertheless, many of the lessons learned in combating corruption at the national level are relevant to a globalized world – in particular, the need for ethics and leadership in addition to legal and institutional reform; the need to integrate these measures into integrity systems; and the awareness of corruption systems. These are applied to areas of concern within sustainable globalisation raised by the conference – including peace and security, extractive industries, climate change and sustainable banking.

Variables governing the dynamics of attacker-defender systems in team sport

This project was a step forward in the examination and identification of key variables on the perception, decision making and action of team sport athletes through theoretical insights provided by the ecological dynamics perspective. The methodology drew on experiential knowledge of elite coaches to drive further empirical investigation into the specific task, environmental and personal constraints that shape the behaviour of athletes in specific performance contexts. The thesis has provided an effective rationale for further investigation into the emergent perception, decision making and action demanded of athletes in these unpredictable, fluent, fast-paced environments.

From Greek temple to bird's nest : mapping, assessing and understanding national integrity systems

In this paper, I would like to outline the approach we have taken to mapping and assessing integrity systems and how this has led us to see integrity systems in a new light. Indeed, it has led us to a new visual metaphor for integrity systems – a bird’s nest rather than a Greek temple. This was the result of a pair of major research projects completed in partnership with Transparency International (TI). One worked on refining and extending the measurement of corruption. This, the second, looked at what was then the emerging institutional means for reducing corruption – ‘national integrity systems’

The benefits of not managing change and not communicating : towards a complex systems view of communication in evolving organisations

The relationship between change in organisations and communication about change in organisations can be analysed as a particular case of a general debate in social theory about the extent to which reality is socially constructed. Social constructivists emphasise the role of language in the construction of social realities, enacted through controlling the message agenda; material determinists assert that economic and social structural factors are more constitutive of reality as seen in strategies emphasising structural and resource interventions. Here we define a third view of language and materiality - one that leads to the potential for a reflexive, experimental approach to change based on the view that organisations are complex evolving systems.

Semantic modeling method for configurable enterprise information systems

Business practices vary from one company to another and business practices often need to be changed due to changes of business environments. To satisfy different business practices, enterprise systems need to be customized. To keep up with ongoing business practice changes, enterprise systems need to be adapted. Because of rigidity and complexity, the customization and adaption of enterprise systems often takes excessive time with potential failures and budget shortfall. Moreover, enterprise systems often drag business behind because they cannot be rapidly adapted to support business practice changes. Extensive literature has addressed this issue by identifying success or failure factors, implementation approaches, and project management strategies. Those efforts were aimed at learning lessons from post implementation experiences to help future projects. This research looks into this issue from a different angle. It attempts to address this issue by delivering a systematic method for developing flexible enterprise systems which can be easily tailored for different business practices or rapidly adapted when business practices change. First, this research examines the role of system models in the context of enterprise system development; and the relationship of system models with software programs in the contexts of computer aided software engineering (CASE), model driven architecture (MDA) and workflow management system (WfMS). Then, by applying the analogical reasoning method, this research initiates a concept of model driven enterprise systems. The novelty of model driven enterprise systems is that it extracts system models from software programs and makes system models able to stay independent of software programs. In the paradigm of model driven enterprise systems, system models act as instructors to guide and control the behavior of software programs. Software programs function by interpreting instructions in system models. This mechanism exposes the opportunity to tailor such a system by changing system models. To make this true, system models should be represented in a language which can be easily understood by human beings and can also be effectively interpreted by computers. In this research, various semantic representations are investigated to support model driven enterprise systems. The significance of this research is 1) the transplantation of the successful structure for flexibility in modern machines and WfMS to enterprise systems; and 2) the advancement of MDA by extending the role of system models from guiding system development to controlling system behaviors. This research contributes to the area relevant to enterprise systems from three perspectives: 1) a new paradigm of enterprise systems, in which enterprise systems consist of two essential elements: system models and software programs. These two elements are loosely coupled and can exist independently; 2) semantic representations, which can effectively represent business entities, entity relationships, business logic and information processing logic in a semantic manner. Semantic representations are the key enabling techniques of model driven enterprise systems; and 3) a brand new role of system models; traditionally the role of system models is to guide developers to write system source code. This research promotes the role of system models to control the behaviors of enterprise.

Reaction to the mandatory write-down provisions of AASB 1010 : accounting for the revaluation of non-current assets

Commentators in the financial press claimed that the amendments to AASB 1010, Accounting for the Revaluation of Non-Current Assets, issued in September 1991, would have “disastrous” implications for the accounts of companies. This paper is concerned with whether the amendments did indeed affect asset write-down activities. An analysis of write-down practices of 75 Australian companies before and after the amendments were operative suggests that the commentators' judgment could have been hasty.

Use of virtual index for measuring efficiency of innovation systems : a cross-country study

In this study we propose a virtual index for measuring the relative innovativeness of countries. Using a multistage virtual benchmarking process, the best and rational benchmark is extracted for inefficient ISs. Furthermore, Tobit and Ordinary Least Squares (OLS) regression models are used to investigate the likelihood of changes in inefficiencies by investigating country-specific factors. The empirical results relating to the virtual benchmarking process suggest that the OLS regression model would better explain changes in the performance of innovation- inefficient countries.

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.

Exploiting the 1,2,3-triazolium motif in anion-templated formation of a bromide-selective rotaxane host assembly

Stimulated by the efficacy of copper (I) catalysed Huisgen-type 1,3-dipolar cycloaddition of terminal alkynes and organic azides to generate 1,4-disubstituted 1,2,3-triazole derivatives, the importance of ‘click’ chemistry in the synthesis of organic and biological molecular systems is ever increasing.[1] The mild reaction conditions have also led to this reaction gaining favour in the construction of interlocked molecular architectures.[2-4] In the majority of cases however, the triazole group simply serves as a covalent linkage with no function in the resulting organic molecular framework. More recently a renewed interest has been shown in the transition metal coordination chemistry of triazole ligands.[3, 5, 6] In addition novel aryl macrocyclic and acyclic triazole based oligomers have been shown to recognise halide anions via cooperative triazole C5-H….anion hydrogen bonds.[7] In light of this it is surprising the potential anion binding affinity of the positively charged triazolium motif has not, with one notable exception,[8] been investigated. With the objective of manipulating the unique topological cavities of mechanically bonded molecules for anion recognition purposes, we have developed general methods of using anions to template the formation of interpenetrated and interlocked structures.[9-13] Herein we report the first examples of exploiting the 1,2,3-triazolium group in the anion templated formation of pseudorotaxane and rotaxane assemblies. In an unprecedented discovery the bromide anion is shown to be a superior templating reagent to chloride in the synthesis of a novel triazolium axle containing [2]rotaxane. Furthermore the resulting rotaxane interlocked host system exhibits the rare selectivity preference for bromide over chloride...