Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models

The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.

Stability and convergence of implicit numerical methods for a class of fractional advection-dispersion models

In this paper, a class of fractional advection-dispersion models (FADM) is investigated. These models include five fractional advection-dispersion models: the immobile, mobile/immobile time FADM with a temporal fractional derivative 0 < γ < 1, the space FADM with skewness, both the time and space FADM and the time fractional advection-diffusion-wave model with damping with index 1 < γ < 2. They describe nonlocal dependence on either time or space, or both, to explain the development of anomalous dispersion. These equations can be used to simulate regional-scale anomalous dispersion with heavy tails, for example, the solute transport in watershed catchments and rivers. We propose computationally effective implicit numerical methods for these FADM. The stability and convergence of the implicit numerical methods are analyzed and compared systematically. Finally, some results are given to demonstrate the effectiveness of our theoretical analysis.

Stakeholders' perceptions of data utility in the context of ERP outcomes

A substantial body of literature exists identifying factors contributing to under-performing Enterprise Resource Planning systems (ERPs), including poor communication, lack of executive support and user dissatisfaction (Calisir et al., 2009). Of particular interest is Momoh et al.’s (2010) recent review identifying poor data quality (DQ) as one of nine critical factors associated with ERP failure. DQ is central to ERP operating processes, ERP facilitated decision-making and inter-organizational cooperation (Batini et al., 2009). Crucial in ERP contexts is that the integrated, automated, process driven nature of ERP data flows can amplify DQ issues, compounding minor errors as they flow through the system (Haug et al., 2009; Xu et al., 2002). However, the growing appreciation of the importance of DQ in determining ERP success lacks research addressing the relationship between stakeholders’ requirements and perceptions of ERP DQ, perceived data utility and the impact of users’ treatment of data on ERP outcomes.

A general method to determine sampling windows for nonlinear mixed effects models with an application to population pharmacokinetic studies

Optimal design methods have been proposed to determine the best sampling times when sparse blood sampling is required in clinical pharmacokinetic studies. However, the optimal blood sampling time points may not be feasible in clinical practice. Sampling windows, a time interval for blood sample collection, have been proposed to provide flexibility in blood sampling times while preserving efficient parameter estimation. Because of the complexity of the population pharmacokinetic models, which are generally nonlinear mixed effects models, there is no analytical solution available to determine sampling windows. We propose a method for determination of sampling windows based on MCMC sampling techniques. The proposed method attains a stationary distribution rapidly and provides time-sensitive windows around the optimal design points. The proposed method is applicable to determine sampling windows for any nonlinear mixed effects model although our work focuses on an application to population pharmacokinetic models.

Using process models to support design of airport terminals

The complex design process of airport terminal needs to support a wide range of changes in operational facilities for both usual and unusual/emergency events. Process model describes how activities within a process are connected and also states logical information flow of the various activities. The traditional design process overlooks the necessity of information flow from the process model to the actual building design, which needs to be considered as a integral part of building design. The current research introduced a generic method to obtain design related information from process model to incorporate with the design process. Appropriate integration of the process model prior to the design process uncovers the relationship exist between spaces and their relevant functions, which could be missed in the traditional design approach. The current paper examines the available Business Process Model (BPM) and generates modified Business Process Model(mBPM) of check-in facilities of Brisbane International airport. The information adopted from mBPM then transform into possible physical layout utilizing graph theory.

An authorization framework using building information models

A building information model (BIM) is an electronic repository of structured, three-dimensional data that captures both the physical and dynamic functional characteristics of a facility. In addition to its more traditional function as a tool to aid design and construction, a BIM can be used throughout the life cycle of a facility, functioning as a living database that places resources contained within the building in their spatial and temporal context. Through its comprehension of spatial relationships, a BIM can meaningfully represent and integrate previously isolated control and management systems and processes, and thereby provide a more intuitive interface to users. By placing processes in a spatial context, decision-making can be improved, with positive flow-on effects for security and efficiency. In this article, we systematically analyse the authorization requirements involved in the use of BIMs. We introduce the concept of using a BIM as a graphical tool to support spatial access control configuration and management (including physical access control). We also consider authorization requirements for regulating access to the structured data that exists within a BIM as well as to external systems and data repositories that can be accessed via the BIM interface. With a view to addressing these requirements we present a survey of relevant spatiotemporal access control models, focusing on features applicable to BIMs and highlighting capability gaps. Finally, we present a conceptual authorization framework that utilizes BIMs.

Understanding hydrochemical processes using 3D models and hydrochemical facies in Wairau Plain groundwater, Marlborough

Three dimensional models and groundwater quality are combined to better understand and conceptualise groundwater systems in complex geological settings in the Wairau Plain, Marlborough. Hydrochemical facies, which are characteristic of distinct evolutionary pathways and a common hydrologic history of groundwaters, are identified within geological formations to assess natural water-rock interactions, redox potential and human agricultural impact on groundwater quality in the Wairau Plain.

Development of zonal cartilage constructs : effects of chondrocyte subpopulation, compressive stimulation, and culture models

Articular cartilage is a highly resilient tissue located at the ends of long bones. It has a zonal structure, which has functional significance in load-bearing. Cartilage does not spontaneously heal itself when damaged, and untreated cartilage lesions or age-related wear often lead to osteoarthritis (OA). OA is a degenerative condition that is highly prevalent, age-associated, and significantly affects patient mobility and quality of life. There is no cure for OA, and patients usually resort to replacing the biological joint with an artificial prosthesis. An alternative approach is to dynamically regenerate damaged or diseased cartilage through cartilage tissue engineering, where cells, materials, and stimuli are combined to form new cartilage. However, despite extensive research, major limitations remain that have prevented the wide-spread application of tissue-engineered cartilage. Critically, there is a dearth of information on whether autologous chondrocytes obtained from OA patients can be used to successfully generate cartilage tissues with structural hierarchy typically found in normal articular cartilage. I aim to address these limitations in this thesis by showing that chondrocyte subpopulations isolated from macroscopically normal areas of the cartilage can be used to engineer stratified cartilage tissues and that compressive loading plays an important role in zone-dependent biosynthesis of these chondrocytes. I first demonstrate that chondrocyte subpopulations from the superficial (S) and middle/deep (MD) zones of OA cartilage are responsive to compressive stimulation in vitro, and that the effect of compression on construct quality is zone-dependent. I also show that compressive stimulation can influence pericelluar matrix production, matrix metalloproteinase secretion, and cytokine expression in zonal chondrocytes in an alginate hydrogel model. Subsequently, I focus on recreating the zonal structure by forming layered constructs using the alginate-released chondrocyte (ARC) method either with or without polymeric scaffolds. Resulting zonal ARC constructs had hyaline morphology, and expressed cartilage matrix molecules such as proteoglycans and collagen type II in both scaffold-free and scaffold-based approaches. Overall, my findings demonstrate that chondrocyte subpopulations obtained from OA joints respond sensitively to compressive stimulation, and are able to form cartilaginous constructs with stratified organization similar to native cartilage using the scaffold-free and scaffold-based ARC technique. The ultimate goal in tissue engineering is to help provide improved treatment options for patients suffering from debilitating conditions such as OA. Further investigations in developing functional cartilage replacement tissues using autologous chondrocytes will bring us a step closer to improving the quality of life for millions of OA patients worldwide.

Forecasting volatility and correlation : the role of option implied measures

Forecasts of volatility and correlation are important inputs into many practical financial problems. Broadly speaking, there are two ways of generating forecasts of these variables. Firstly, time-series models apply a statistical weighting scheme to historical measurements of the variable of interest. The alternative methodology extracts forecasts from the market traded value of option contracts. An efficient options market should be able to produce superior forecasts as it utilises a larger information set of not only historical information but also the market equilibrium expectation of options market participants. While much research has been conducted into the relative merits of these approaches, this thesis extends the literature along several lines through three empirical studies. Firstly, it is demonstrated that there exist statistically significant benefits to taking the volatility risk premium into account for the implied volatility for the purposes of univariate volatility forecasting. Secondly, high-frequency option implied measures are shown to lead to superior forecasts of the intraday stochastic component of intraday volatility and that these then lead on to superior forecasts of intraday total volatility. Finally, the use of realised and option implied measures of equicorrelation are shown to dominate measures based on daily returns.

Evaluating the success of large-scale, integrated information systems through the lens of IS-impact and IS-support

This study proceeds from a central interest in the importance of systematically evaluating operational large-scale integrated information systems (IS) in organisations. The study is conducted within the IS-Impact Research Track at Queensland University of Technology (QUT). The goal of the IS-Impact Track is, "to develop the most widely employed model for benchmarking information systems in organizations for the joint benefit of both research and practice" (Gable et al, 2009). The track espouses programmatic research having the principles of incrementalism, tenacity, holism and generalisability through replication and extension research strategies. Track efforts have yielded the bicameral IS-Impact measurement model; the ‘impact’ half includes Organisational-Impact and Individual-Impact dimensions; the ‘quality’ half includes System-Quality and Information-Quality dimensions. Akin to Gregor’s (2006) analytic theory, the ISImpact model is conceptualised as a formative, multidimensional index and is defined as "a measure at a point in time, of the stream of net benefits from the IS, to date and anticipated, as perceived by all key-user-groups" (Gable et al., 2008, p: 381). The study adopts the IS-Impact model (Gable, et al., 2008) as its core theory base. Prior work within the IS-Impact track has been consciously constrained to Financial IS for their homogeneity. This study adopts a context-extension strategy (Berthon et al., 2002) with the aim "to further validate and extend the IS-Impact measurement model in a new context - i.e. a different IS - Human Resources (HR)". The overarching research question is: "How can the impacts of large-scale integrated HR applications be effectively and efficiently benchmarked?" This managerial question (Cooper & Emory, 1995) decomposes into two more specific research questions – In the new HR context: (RQ1): "Is the IS-Impact model complete?" (RQ2): "Is the ISImpact model valid as a 1st-order formative, 2nd-order formative multidimensional construct?" The study adhered to the two-phase approach of Gable et al. (2008) to hypothesise and validate a measurement model. The initial ‘exploratory phase’ employed a zero base qualitative approach to re-instantiating the IS-Impact model in the HR context. The subsequent ‘confirmatory phase’ sought to validate the resultant hypothesised measurement model against newly gathered quantitative data. The unit of analysis for the study is the application, ‘ALESCO’, an integrated large-scale HR application implemented at Queensland University of Technology (QUT), a large Australian university (with approximately 40,000 students and 5000 staff). Target respondents of both study phases were ALESCO key-user-groups: strategic users, management users, operational users and technical users, who directly use ALESCO or its outputs. An open-ended, qualitative survey was employed in the exploratory phase, with the objective of exploring the completeness and applicability of the IS-Impact model’s dimensions and measures in the new context, and to conceptualise any resultant model changes to be operationalised in the confirmatory phase. Responses from 134 ALESCO users to the main survey question, "What do you consider have been the impacts of the ALESCO (HR) system in your division/department since its implementation?" were decomposed into 425 ‘impact citations.’ Citation mapping using a deductive (top-down) content analysis approach instantiated all dimensions and measures of the IS-Impact model, evidencing its content validity in the new context. Seeking to probe additional (perhaps negative) impacts; the survey included the additional open question "In your opinion, what can be done better to improve the ALESCO (HR) system?" Responses to this question decomposed into a further 107 citations which in the main did not map to IS-Impact, but rather coalesced around the concept of IS-Support. Deductively drawing from relevant literature, and working inductively from the unmapped citations, the new ‘IS-Support’ construct, including the four formative dimensions (i) training, (ii) documentation, (iii) assistance, and (iv) authorisation (each having reflective measures), was defined as: "a measure at a point in time, of the support, the [HR] information system key-user groups receive to increase their capabilities in utilising the system." Thus, a further goal of the study became validation of the IS-Support construct, suggesting the research question (RQ3): "Is IS-Support valid as a 1st-order reflective, 2nd-order formative multidimensional construct?" With the aim of validating IS-Impact within its nomological net (identification through structural relations), as in prior work, Satisfaction was hypothesised as its immediate consequence. The IS-Support construct having derived from a question intended to probe IS-Impacts, too was hypothesised as antecedent to Satisfaction, thereby suggesting the research question (RQ4): "What is the relative contribution of IS-Impact and IS-Support to Satisfaction?" With the goal of testing the above research questions, IS-Impact, IS-Support and Satisfaction were operationalised in a quantitative survey instrument. Partial least squares (PLS) structural equation modelling employing 221 valid responses largely evidenced the validity of the commencing IS-Impact model in the HR context. ISSupport too was validated as operationalised (including 11 reflective measures of its 4 formative dimensions). IS-Support alone explained 36% of Satisfaction; IS-Impact alone 70%; in combination both explaining 71% with virtually all influence of ISSupport subsumed by IS-Impact. Key study contributions to research include: (1) validation of IS-Impact in the HR context, (2) validation of a newly conceptualised IS-Support construct as important antecedent of Satisfaction, and (3) validation of the redundancy of IS-Support when gauging IS-Impact. The study also makes valuable contributions to practice, the research track and the sponsoring organisation.