Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein

A major challenge for Streptococcus pyogenes vaccine development is the identification of epitopes that confer protection from infection by multiple S. pyogenes M-types. Here we have identified and characterised the distribution of common variant sequences from individual repeat units of the C-repeat region (CRR) of M-proteins representing 77 different M-types. Three polyvalent fusion vaccine candidates (SV1, SV2 and SV3) incorporating the most common variants were subsequently expressed and purified, and demonstrated to be alpha-helical by Circular Dichroism (CD), a secondary conformational characteristic of the CRR in the M-protein. Antibodies raised against each of these constructs recognise M-proteins that vary in their CRR, and bind to the surface of multiple S. pyogenes isolates. Antibodies raised against SV1, containing five variant sequences, also kill heterologous S. pyogenes isolates in in vitro bactericidal assays. Further structural characterisation of this construct demonstrated the conformation of SV1 was stable at different pHs, and thermal unfolding of SV1 a reversible process. Our findings demonstrate that linkage of multiple variant sequences into a single recombinant construct overcomes the need to embed the variant sequences in foreign helix promoting flanking sequences for conformational stability, and demonstrates the viability of the polyvalent candidates as global S. pyogenes vaccine candidates.

Pre-clinical evaluation of amphiphilic silicone oligomers for scar remediation

The formation of hypertrophic scars is a frequent outcome of wound repair and often requires further therapy with treatments such as silicone gel sheets (SGS; Perkins et al., 1983). Although widely used, knowledge regarding SGS and their mechanism of action on hypertrophic scars is limited. Furthermore, SGS require consistent application for at least twelve hours a day for up to twelve consecutive months, beginning as soon as wound reepithelialisation has occurred. Preliminary research at QUT has shown that some species of silicone present in SGS have the ability to permeate into collagen gel skin mimetics upon exposure. An analogue of these species, GP226, was found to decrease both collagen synthesis and the total amount of collagen present following exposure to cultures of cells derived from hypertrophic scars. This silicone of interest was a crude mixture of silicone species, which resolved into five fractions of different molecular weight. These five fractions were found to have differing effects on collagen synthesis and cell viability following exposure to fibroblasts derived from hypertrophic scars (HSF), keloid scars (KF) and normal skin (nHSF and nKF). The research performed herein continues to further assess the potential of GP226 and its fractions for scar remediation by determining in more detail its effects on HSF, KF, nHSF, nKF and human keratinocytes (HK) in terms of cell viability and proliferation at various time points. Through these studies it was revealed that Fraction IV was the most active fraction as it induced a reduction in cell viability and proliferation most similar to that observed with GP226. Cells undergoing apoptosis were also detected in HSF cultures exposed to GP226 and Fraction IV using the Tunel assay (Roche). These investigations were difficult to pursue further as the fractionation process used for GP226 was labour-intensive and time inefficient. Therefore a number of silicones with similar structure to Fraction IV were synthesised and screened for their effect following application to HSF and nHSF. PDMS7-g-PEG7, a silicone-PEG copolymer of low molecular weight and low hydrophilic-lipophilic balance factor, was found to be the most effective at reducing cell proliferation and inducing apoptosis in cultures of HSF, nHSF and HK. Further studies investigated gene expression through microarray and superarray techniques and demonstrated that many genes are differentially expressed in HSF following treatment with GP226, Fraction IV and PDMS7-g-PEG7. In brief, it was demonstrated that genes for TGFβ1 and TNF are not differentially regulated while genes for AIFM2, IL8, NSMAF, SMAD7, TRAF3 and IGF2R show increased expression (>1.8 fold change) following treatment with PDMS7-g-PEG7. In addition, genes for αSMA, TRAF2, COL1A1 and COL3A1 have decreased expression (>-1.8 fold change) following treatment with GP226, Fraction IV and PDMS7-g-PEG7. The data obtained suggest that many different pathways related to apoptosis and collagen synthesis are affected in HSF following exposure to PDMS7-g-PEG7. The significance is that silicone-PEG copolymers, such as GP226, Fraction IV and PDMS7-g-PEG7, could potentially be a non-invasive substitute to apoptosis-inducing chemical agents that are currently used as scar treatments. It is anticipated that these findings will ultimately contribute to the development of a novel scar therapy with faster action and improved outcomes for patients suffering from hypertrophic scars.

Evaluation cortical bone elasticity in response to pulse power excitation using ultrasonic technique

This paper presents the ultrasonic velocity measurement method which investigates the possible effects of high voltage high frequency pulsed power on cortical bone material elasticity. Before applying a pulsed power signal on a live bone, it is essential to determine the safe parameters of pulsed power applied on bone non-destructively. Therefore, the possible changes in cortical bone material elasticity due to a specified pulsed power excitation have been investigated. A controllable positive buck-boost converter with adjustable output voltage and frequency has been used to generate high voltage pulses (500V magnitude at 10 KHz frequency). To determine bone elasticity, an ultrasonic velocity measurement has been conducted on two groups of control (unexposed to pulse power but in the same environmental condition) and cortical bone samples exposed to pulsed power. Young’s modulus of cortical bone samples have been determined and compared before and after applying the pulsed power signal. After applying the high voltage pulses, no significant variation in elastic property of cortical bone specimens was found compared to the control. The result shows that pulsed power with nominated parameters can be applied on cortical bone tissue without any considerable negative effect on elasticity of bone material.

Strategic project evaluation for open pit mining ventures using real options and allied econometric techniques

Open pit mine operations are complex businesses that demand a constant assessment of risk. This is because the value of a mine project is typically influenced by many underlying economic and physical uncertainties, such as metal prices, metal grades, costs, schedules, quantities, and environmental issues, among others, which are not known with much certainty at the beginning of the project. Hence, mining projects present a considerable challenge to those involved in associated investment decisions, such as the owners of the mine and other stakeholders. In general terms, when an option exists to acquire a new or operating mining project, , the owners and stock holders of the mine project need to know the value of the mining project, which is the fundamental criterion for making final decisions about going ahead with the venture capital. However, obtaining the mine project’s value is not an easy task. The reason for this is that sophisticated valuation and mine optimisation techniques, which combine advanced theories in geostatistics, statistics, engineering, economics and finance, among others, need to be used by the mine analyst or mine planner in order to assess and quantify the existing uncertainty and, consequently, the risk involved in the project investment. Furthermore, current valuation and mine optimisation techniques do not complement each other. That is valuation techniques based on real options (RO) analysis assume an expected (constant) metal grade and ore tonnage during a specified period, while mine optimisation (MO) techniques assume expected (constant) metal prices and mining costs. These assumptions are not totally correct since both sources of uncertainty—that of the orebody (metal grade and reserves of mineral), and that about the future behaviour of metal prices and mining costs—are the ones that have great impact on the value of any mining project. Consequently, the key objective of this thesis is twofold. The first objective consists of analysing and understanding the main sources of uncertainty in an open pit mining project, such as the orebody (in situ metal grade), mining costs and metal price uncertainties, and their effect on the final project value. The second objective consists of breaking down the wall of isolation between economic valuation and mine optimisation techniques in order to generate a novel open pit mine evaluation framework called the ―Integrated Valuation / Optimisation Framework (IVOF)‖. One important characteristic of this new framework is that it incorporates the RO and MO valuation techniques into a single integrated process that quantifies and describes uncertainty and risk in a mine project evaluation process, giving a more realistic estimate of the project’s value. To achieve this, novel and advanced engineering and econometric methods are used to integrate financial and geological uncertainty into dynamic risk forecasting measures. The proposed mine valuation/optimisation technique is then applied to a real gold disseminated open pit mine deposit to estimate its value in the face of orebody, mining costs and metal price uncertainties.

Personalised search – a hybrid approach for web information retrieval and its evaluation

Nowadays, everyone can effortlessly access a range of information on the World Wide Web (WWW). As information resources on the web continue to grow tremendously, it becomes progressively more difficult to meet high expectations of users and find relevant information. Although existing search engine technologies can find valuable information, however, they suffer from the problems of information overload and information mismatch. This paper presents a hybrid Web Information Retrieval approach allowing personalised search using ontology, user profile and collaborative filtering. This approach finds the context of user query with least user’s involvement, using ontology. Simultaneously, this approach uses time-based automatic user profile updating with user’s changing behaviour. Subsequently, this approach uses recommendations from similar users using collaborative filtering technique. The proposed method is evaluated with the FIRE 2010 dataset and manually generated dataset. Empirical analysis reveals that Precision, Recall and F-Score of most of the queries for many users are improved with proposed method.

Understanding evaluation of learning support in mathematics and statistics

With rapid and continuing growth of learning support initiatives in mathematics and statistics found in many parts of the world, and with the likelihood that this trend will continue, there is a need to ensure that robust and coherent measures are in place to evaluate the effectiveness of these initiatives. The nature of learning support brings challenges for measurement and analysis of its effects. After briefly reviewing the purpose, rationale for, and extent of current provision, this article provides a framework for those working in learning support to think about how their efforts can be evaluated. It provides references and specific examples of how workers in this field are collecting, analysing and reporting their findings. The framework is used to structure evaluation in terms of usage of facilities, resources and services provided, and also in terms of improvements in performance of the students and staff who engage with them. Very recent developments have started to address the effects of learning support on the development of deeper approaches to learning, the affective domain and the development of communities of practice of both learners and teachers. This article intends to be a stimulus to those who work in mathematics and statistics support to gather even richer, more valuable, forms of data. It provides a 'toolkit' for those interested in evaluation of learning support and closes by referring to an on-line resource being developed to archive the growing body of evidence. © 2011 Taylor & Francis.

Practical decision support system evaluation for consultant selection

The widespread development of Decision Support System (DSS) in construction indicate that the evaluation of software become more important than before. However, it is identified that most research in construction discipline did not attempt to assess its usability. Therefore, little is known about the approach on how to properly evaluate a DSS for specific problem. In this paper, we present a practical framework that can be guidance for DSS evaluation. It focuses on how to evaluate software that is dedicatedly designed for consultant selection problem. The framework features two main components i.e. Sub-system Validation and Face Validation. Two case studies of consultant selection at Malaysian Department of Irrigation and Drainage were integrated in this framework. Some inter-disciplinary area such as Software Engineering, Human Computer Interaction (HCI) and Construction Project Management underpinned the discussion of the paper. It is anticipated that this work can foster better DSS development and quality decision making that accurately meet the client’s expectation and needs

Technology transfer evaluation in the high technology industry : an interdisciplinary perspective

The underlying objective of this study was to develop a novel approach to evaluate the potential for commercialisation of a new technology. More specifically, this study examined the 'ex-ante'. evaluation of the technology transfer process. For this purpose, a technology originating from the high technology sector was used. The technology relates to the application of software for the detection of weak signals from space, which is an established method of signal processing in the field of radio astronomy. This technology has the potential to be used in commercial and industrial areas other than astronomy, such as detecting water leakages in pipes. Its applicability to detecting water leakage was chosen owing to several problems with detection in the industry as well as the impact it can have on saving water in the environment. This study, therefore, will demonstrate the importance of interdisciplinary technology transfer. The study employed both technical and business evaluation methods including laboratory experiments and the Delphi technique to address the research questions. There are several findings from this study. Firstly, scientific experiments were conducted and these resulted in a proof of concept stage of the chosen technology. Secondly, validation as well as refinement of criteria from literature that can be used for „ex-ante. evaluation of technology transfer has been undertaken. Additionally, after testing the chosen technology.s overall transfer potential using the modified set of criteria, it was found that the technology is still in its early stages and will require further development for it to be commercialised. Furthermore, a final evaluation framework was developed encompassing all the criteria found to be important. This framework can help in assessing the overall readiness of the technology for transfer as well as in recommending a viable mechanism for commercialisation. On the whole, the commercial potential of the chosen technology was tested through expert opinion, thereby focusing on the impact of a new technology and the feasibility of alternate applications and potential future applications.

Patterns-based evaluation of open source BPM systems: The cases of jBPM, OpenWFE, and Enhydra Shark

In keeping with the proliferation of free software development initiatives and the increased interest in the business process management domain, many open source workflow and business process management systems have appeared during the last few years and are now under active development. This upsurge gives rise to two important questions: What are the capabilities of these systems? and How do they compare to each other and to their closed source counterparts? In other words: What is the state-of-the-art in the area?. To gain an insight into these questions, we have conducted an in-depth analysis of three of the major open source workflow management systems – jBPM, OpenWFE, and Enhydra Shark, the results of which are reported here. This analysis is based on the workflow patterns framework and provides a continuation of the series of evaluations performed using the same framework on closed source systems, business process modelling languages, and web-service composition standards. The results from evaluations of the three open source systems are compared with each other and also with the results from evaluations of three representative closed source systems: Staffware, WebSphere MQ, and Oracle BPEL PM. The overall conclusion is that open source systems are targeted more toward developers rather than business analysts. They generally provide less support for the patterns than closed source systems, particularly with respect to the resource perspective, i.e. the various ways in which work is distributed amongst business users and managed through to completion.

Understanding IT business value creation and evaluation in least developed economies

Information Technology (IT) is an important resource that can facilitate growth and development in both the developed and developing economies. The forces of globalisation increase the digital divide between the developed and developing economies is increasing. The least developed economies (LDEs) are the most vulnerable within this environment. Intense competition for IT resources means that LDEs need a deeper understanding of how to source and evaluate their IT-related efforts. This effort puts LDEs in a better position to source funding from various stakeholders and promote localized investment in IT. This study presents a complementary approach to securing better IT-related business value in organizations in the LDEs. It further evaluates how IT and the complementaries need to managed within the LDEs. Analysis of data collected from five LDEs show that organizations that invest in IT and related complementaries are able to better their business processes. The data also suggest that improved business processes lead to overall business processes improvements. The above is only possible if organizations adopt IT and make related changes in the complementary resources within the established culture and localizing the required changes.

Evaluation of design-builder qualifications through the analysis of Requests for Qualifications (RFQs)

The two-phrase best-value process has been widely used by public agencies for Design and Build (DB) procurement, with a key issue in the first phase of pre-qualification being the determination of evaluation criteria. This study identified a set of general qualification criteria for design-builders and compares their relative importance by a thorough content analysis of 97 Requests for Qualification (RFQ) for public DB projects advertised between 2000 and 2011 in various regions of the USA. The thirty-nine qualification criteria found are summarized and classified into eight categories comprising: experience; project understanding and approach; organizational structure and capacity; past performance record; professional qualifications; responsiveness to RFQs, office location and familiarity with local environment; and legal status in descending order of their relative importance. A comparative analysis of different types of projects shows that the relative weightings of the qualification criteria vary according to different characteristics of the DB projects involved.

A process evaluation of a comprehensive school based injury prevention program

A process evaluation enables understanding of critical issues that can inform the improved, ongoing implementation of an intervention program. This study describes the process evaluation of a comprehensive, multi-level injury prevention program for adolescents. The program targets change in injury associated with violence, transport and alcohol risks and incorporates two primary elements: an 8-week, teacher delivered attitude and behaviour change curriculum for Grade 8 students; and a professional development program for teachers on school level methods of protection, focusing on strategies to increase students’ connectedness to school.

How effective is the new child restraint legislation in Queensland? A mixed methods evaluation

Research Interests: Are parents complying with the legislation? Is this the same for urban, regional and rural parents? Indigenous parents? What difficulties do parents experience in complying? Do parents understand why the legislation was put in place? Have there been negative consequences for other organisations or sectors of the community?

An evaluation framework for assessing the impact of public bicycle share schemes

INTRODUCTION • Public bicycle share schemes have emerged as a method of increasing rates of bicycle riding. • The overwhelming majority of schemes have begun since 2005, taking advantage of various tracking and payment technologies making short term rental practical and affordable. • Very little research has been undertaken to determine their potentially broad impact on transport behaviour and consequently, it is difficult to understand the performance of these schemes in terms of reduced emissions and congestion, as well as possible increases in physical activity.

When non-significance maybe significant: lessons learned from a study into the development, implementation and evaluation of a risk assessment tool for fleet settings

Introduction This study reports on the development of a self report assessment tool to increase the efficacy of crash prediction within Australian Fleet settings Over last 20 years an array of measures have been produced (Driver anger scale, Driving Skill Inventory, Manchester Driver Behaviour Questionnaire, Driver Attitude Questionnaire, Driver Stress Inventory, Safety Climate Questionnaire) While these tools are useful, research has demonstrated limited ability to accurately identify individuals most likely to be involved in a crash. Reasons cited include; - Crashes are relatively rare - Other competing factors may influence crash event - Ongoing questions regarding the validity of self report measures (common method variance etc) - Lack of contemporary issues relating to fleet driving performance