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.

Developing a research method to test a new first-order decision making model for the procurement of public sector major infrastructure

Given global demand for new infrastructure, governments face substantial challenges in funding new infrastructure and simultaneously delivering Value for Money (VfM). The paper begins with an update on a key development in a new early/first-order procurement decision making model that deploys production cost/benefit theory and theories concerning transaction costs from the New Institutional Economics, in order to identify a procurement mode that is likely to deliver the best ratio of production costs and transaction costs to production benefits, and therefore deliver superior VfM relative to alternative procurement modes. In doing so, the new procurement model is also able to address the uncertainty concerning the relative merits of Public-Private Partnerships (PPP) and non-PPP procurement approaches. The main aim of the paper is to develop competition as a dependent variable/proxy for VfM and a hypothesis (overarching proposition), as well as developing a research method to test the new procurement model. Competition reflects both production costs and benefits (absolute level of competition) and transaction costs (level of realised competition) and is a key proxy for VfM. Using competition as a proxy for VfM, the overarching proposition is given as: When the actual procurement mode matches the predicted (theoretical) procurement mode (informed by the new procurement model), then actual competition is expected to match potential competition (based on actual capacity). To collect data to test this proposition, the research method that is developed in this paper combines a survey and case study approach. More specifically, data collection instruments for the surveys to collect data on actual procurement, actual competition and potential competition are outlined. Finally, plans for analysing this survey data are briefly mentioned, along with noting the planned use of analytical pattern matching in deploying the new procurement model and in order to develop the predicted (theoretical) procurement mode.

Space : Irrealis objects and their role in a new political economy

In this paper, I show how new spaces are being prefigured for colonisation in the language of contemporary technology policy. Drawing on a corpus of 1.3 million words collected from technology policy centres throughout the world, I show the role of policy language in creating the foundations of an emergent form of political economy. The analysis is informed by principles from critical discourse analysis (CDA) and classical political economy. It foregrounds a functional aspect of language called process metaphor to show how aspects of human activity are prefigured for mass commodification by the manipulation of irrealis spaces. I also show how the fundamental element of any new political economy, the property element, is being largely ignored. The potential creation of a global space as concrete as landed property – electromagnetic spectrum – has significant ramifications for the future of social relations in any global “knowledge economy”.

The evaluation of new and isotopically labeled isoindoline nitroxides and an azaphenalene nitroxide for EPR oximetry

Isoindoline nitroxides are potentially useful probes for viable biological systems, exhibiting low cytotoxicity, moderate rates of biological reduction and favorable Electron Paramagnetic Resonance (EPR) characteristics. We have evaluated the anionic (5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl; CTMIO), cationic (5-(N,N,N-trimethylammonio)-1,1,3,3-tetramethylisoindolin-2-yloxyl iodide, QATMIO) and neutral (1,1,3,3-tetramethylisoindolin-2-yloxyl; TMIO) nitroxides and their isotopically labeled analogs ((2)H(12)- and/or (2)H(12)-(15)N-labeled) as potential EPR oximetry probes. An active ester analogue of CTMIO, designed to localize intracellularly, and the azaphenalene nitroxide 1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl (TMAO) were also studied. While the EPR spectra of the unlabeled nitroxides exhibit high sensitivity to O(2) concentration, deuteration resulted in a loss of superhyperfine features and a subsequent reduction in O(2) sensitivity. Labeling the nitroxides with (15)N increased the signal intensity and this may be useful in decreasing the detection limits for in vivo measurements. The active ester nitroxide showed approximately 6% intracellular localization and low cytotoxicity. The EPR spectra of TMAO nitroxide indicated an increased rigidity in the nitroxide ring, due to dibenzo-annulation.

Going native : a review of Jing Wang’s 'Brand New China’

Jing Wang's book is confused about its audience and fails to give an adequate account of either the specific knowledge available to advertising research or the nature of Chinese consumption. In addition its critique of cultural studies is misplaced and misguided.

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’.

Boosting the margin: A new explanation for the effectiveness of voting methods

One of the surprising recurring phenomena observed in experiments with boosting is that the test error of the generated classifier usually does not increase as its size becomes very large, and often is observed to decrease even after the training error reaches zero. In this paper, we show that this phenomenon is related to the distribution of margins of the training examples with respect to the generated voting classification rule, where the margin of an example is simply the difference between the number of correct votes and the maximum number of votes received by any incorrect label. We show that techniques used in the analysis of Vapnik's support vector classifiers and of neural networks with small weights can be applied to voting methods to relate the margin distribution to the test error. We also show theoretically and experimentally that boosting is especially effective at increasing the margins of the training examples. Finally, we compare our explanation to those based on the bias-variance decomposition.

A new control-volume finite-element scheme for heterogeneous porous media : application to the drying of softwood

An improved mesoscopic model is presented for simulating the drying of porous media. The aim of this model is to account for two scales simultaneously: the scale of the whole product and the scale of the heterogeneities of the porous medium. The innovation of this method is the utilization of a new mass-conservative scheme based on the Control-Volume Finite-Element (CV-FE) method that partitions the moisture content field over the individual sub-control volumes surrounding each node within the mesh. Although the new formulation has potential for application across a wide range of transport processes in heterogeneous porous media, the focus here is on applying the model to the drying of small sections of softwood consisting of several growth rings. The results conclude that, when compared to a previously published scheme, only the new mass-conservative formulation correctly captures the true moisture content evolution in the earlywood and latewood components of the growth rings during drying.

Virion : new media and the development of the discursive museum

The historical rhetoric established with the very first public art museums declared that the purpose of such institutions was to provide a space where art could be accessible to all citizens. However contrary to this aim, studies show that art museums are one of the least accessed cultural institutions in the western world. The prevailing consensus for this can be attributed to the perception that museums are elitist, irrelevant and restricted to a small and privileged group. The focus of this research project is to address the issues that lead to these perceptions, and to identify possible curatorial strategies to encourage greater access to, and participation in the visual arts. This will be done through designing and curating an open submission exhibition that utilises new media technologies to increase access and dialogue between artists and audiences. This is part of a hybrid practice-based methodology that also includes scholarly research to critically investigate a number of historical and contemporary theories concerned with public museums and approaches to curatorial practice. This research will culminate in the development of Virion, an Internet based exhibition that aims to develop a curatorial model that facilitates open and democratic participation in arts practice from a diverse public audience.

Functional heterogeneity as a two-dimensional concept : empirical evidence for new venture teams

Previous research on entrepreneurial teams has failed to settle the controversy over whether team heterogeneity helps or hinders new venture performance. Reconciling this inconsistency, this paper suggests a new conceptual approach to disentangle differential effects of team heterogeneity by modeling two separate heterogeneity dimensions, namely knowledge scope and knowledge disparity. Analyzing unique data on functional experiences of the members of 337 start-up teams, we find support for our contention of team heterogeneity as a two-dimensional concept. Results suggest that knowledge disparity negatively relates to both start-ups’ entrepreneurial and innovative performance. In contrast, we find knowledge scope to positively affect entrepreneurial performance, while it shows an inverse U-shaped relationship to innovative start-up performance.