Chlamydial infection and spatial ascension of the female genital tract : a novel hybrid cellular automata and continuum mathematical model

Sexually transmitted chlamydial infection initially establishes in the endocervix in females, but if the infection ascends the genital tract, significant disease, including infertility, can result. Many of the mechanisms associated with chlamydial infection kinetics and disease ascension are unknown. We attempt to elucidate some of these processes by developing a novel mathematical model, using a cellular automata–partial differential equation model. We matched our model outputs to experimental data of chlamydial infection of the guinea-pig cervix and carried out sensitivity analyses to determine the relative influence of model parameters. We found that the rate of recruitment and action of innate immune cells to clear extracellular chlamydial particles and the rate of passive movement of chlamydial particles are the dominant factors in determining the early course of infection, magnitude of the peak chlamydial time course and the time of the peak. The rate of passive movement was found to be the most important factor in determining whether infection would ascend to the upper genital tract. This study highlights the importance of early innate immunity in the control of chlamydial infection and the significance of motility-diffusive properties and the adaptive immune response in the magnitude of infection and in its ascension.

The relationship between construction firm strategies and innovation outcomes

Survey results provide a preliminary assessment of the relative contribution of a range of tactical business strategies to innovation performance by firms in the Australian construction industry. Over 1,300 firms were surveyed in 2004, resulting in a response rate of 29%. Respondents were classified as high, medium or low innovators according to an innovation index based on the novelty and impact of their innovations and their adoption of listed technological and organizational advances. The relative significance of 23 business strategies concerning (1) employees, (2) marketing, (3) technology, (4) knowledge and (5) relationships was examined by determining the extent to which they distinguished high innovators from low innovators. The individual business strategies that most strongly distinguished high innovators were (1) ‘investing in R&D’, (2) ‘participating in partnering and alliances on projects’, (3) ‘ensuring project learnings are transferred into continuous business processes’, (4) ‘monitoring international best practice’, and (5) ‘recruiting new graduates’. Of the five types of strategies assessed, marketing strategies were the least significant in supporting innovation. The results provide practical guidance to managers in project-based industries wishing to improve their innovation performance.

Using the imagination : consumer evoking and thematizing of the fantastic imaginary

This article explores the process by which consumers evoke and thematize the fantastic imaginary when playing a fantasy-based trading card game. Interviews with 15 informants, all players of Magic: The Gathering, serve as data. The result is a new framework that reveals how the fantastic imaginary is evoked and thematized. A typology of thematizing strategies employed by consumers is also presented. Implications are discussed in relation to consumer research, imagination theory, literary theory of the evoked fantastic imaginary, and the imaginary in play.

Computational approach to localization using global energy minimization

Damage localization induced by strain softening can be predicted by the direct minimization of a global energy function. This article concerns the computational strategy for implementing this principle for softening materials such as concrete. Instead of using heuristic global optimization techniques, our strategies are a hybrid of local optimization methods with a path-finding approach to ensure a global optimum. With admissible nodal displacements being independent variables, it is easy to deal with the geometric (mesh) constraint conditions. The direct search optimization methods recover the localized solutions for a range of softening lattice models which are representative of quasi-brittle structures

Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, however they are limited in access and availability and associated with donor site morbidity, haemorrhage, risk of infection, insufficient transplant integration, graft devitalisation, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. The field of tissue engineering has emerged as an important approach to bone regeneration. However, bench to bedside translations are still infrequent as the process towards approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. The subsequent gap between research and clinical translation, hence commercialization, is referred to as the ‘Valley of Death’ and describes a large number of projects and/or ventures that are ceased due to a lack of funding during the transition from product/technology development to regulatory approval and subsequently commercialization. One of the greatest difficulties in bridging the Valley of Death is to develop good manufacturing processes (GMP) and scalable designs and to apply these in pre-clinical studies. In this article, we describe part of the rationale and road map of how our multidisciplinary research team has approached the first steps to translate orthopaedic bone engineering from bench to bedside byestablishing a pre-clinical ovine critical-sized tibial segmental bone defect model and discuss our preliminary data relating to this decisive step.

Truck overloading study in developing countries and strategies to minimize its impact

Overloading truck traffic is an untenable problem around the world. The occurrence of overloaded truck traffic can be evidence of rapid development of an economy. Most of the developing countries emphasize the development of economy, thus supporting reform of infrastructure is limited. This research investigates the relationship between truck overloading and the condition of road damage. The objective of this research is to determine the amount of economic loss due to overloaded truck traffic is. Axle load will be used to calculate the total ESAL to pavement. This study intends to provide perspective on the relationship between change in axle load due to overloading and the resultant service life of pavement. It can then be used in the estimation of pavement damage in other developing countries facing the problem of truck overloading. In conclusion, economical loss was found, which include reduction of pavement life and increase in maintenance and rehabilitation (M&R) cost. As a result, net present value (NPV) of pavement investment with overloading truck traffic is higher than normal truck traffic.

One size doesn't fit all. Exploring marketing strategies for influencing three dimensions of brand loyalty

Brand loyalty is a concept that has garnered considerable interest over recent years from both marketing practitioners and academics alike. While marketers are primarily interested in ways they can generate and increase brand loyalty from their customers, academics strive to conducts research which investigates the antecedents and consequences of customer loyalty (See DeWitt, Nguyen and Marshall 2008; Russell-Bennett, McColl-Kennedy and Coote 2007).

Modulation of the SHBG signalling axis

Sex hormone-binding globulin (SHBG) is a homodimeric plasma glycoprotein that is the major sex steroid carrier-protein in the bloodstream and functions also as a key regulator of steroid bioavailability within target tissues, such as the prostate. Additionally, SHBG binds to prostatic cell membranes via the putative and unidentified SHBG receptor (RSHBG), activating a signal transduction pathway implicated in stimulating both proliferation and expression of prostate specific antigen (PSA) in prostate cell lines in vitro. A yeast-two hybrid assay suggested an interaction between SHBG and kallikrein-related protease (KLK) 4, which is a serine protease implicated in the progression of prostate cancer. The potential interaction between these two proteins was investigated in this PhD thesis to determine whether SHBG is a proteolytic substrate of KLK4 and other members of the KLK family including KLK3/PSA, KLK7 and KLK14. Furthermore, the effects from SHBG proteolytic degradation on SHBG-regulated steroid bioavailability and the activation of the putative RSHBG signal transduction pathway were examined in the LNCaP prostate cancer cell line. SHBG was found to be a proteolytic substrate of the trypsin-like KLK4 and KLK14 in vitro, yielding several proteolysis fragments. Both chymotrypsin-like PSA and KLK7 displayed insignificant proteolytic activity against SHBG. The kinetic parameters of SHBG proteolysis by KLK4 and KLK14 demonstrate a strong enzyme-substrate binding capacity, possessing a Km of 1.2 ± 0.7 µM and 2.1 ± 0.6 µM respectively. The catalytic efficiencies (kcat/Km) of KLK4 and KLK14 proteolysis of SHBG were 1.6 x 104 M-1s-1 and 3.8 x 104 M-1s-1 respectively, which were comparable to parameters previously reported for peptide substrates. N-terminal sequencing of the fragments revealed cleavage near the junction of the N- and C-terminal laminin globulin-like (G-like) domains of SHBG, resulting in the division of the two globulins and ultimately the full degradation of these fragments by KLK4 and KLK14 over time. Proteolytic fragments that may retain steroid binding were rapidly degraded by both proteases, while fragments containing residues beyond the steroid binding pocket were less degraded over the same period of time. Degradation of SHBG was inhibited by the divalent metal cations calcium and zinc for KLK4, and calcium, zinc and magnesium for KLK14. The human secreted serine protease inhibitors (serpins), α1-antitrypsin and α2-antiplasmin, inhibited KLK4 and KLK14 proteolysis of SHBG; α1-antichymotrypsin inhibited KLK4 but not KLK14 activity. The inhibition by these serpins was comparable and in some cases more effective than general trypsin protease inhibitors such as aprotinin and phenylmethanesulfonyl fluoride (PMSF). The binding of 5α-dihydrotestosterone (DHT) to SHBG modulated interactions with KLK4 and KLK14. Steroid-free SHBG was more readily digested by both enzymes than DHT-bound SHBG. Moreover, a binding interaction exists between SHBG and pro-KLK4 and pro-KLK14, with DHT strengthening the binding to pro-KLK4 only. The inhibition of androgen uptake by cultured prostate cancer cells, mediated by SHBG steroid-binding, was examined to assess whether SHBG proteolysis by KLK4 and KLK14 modulated this process. Proteolytic digestion eliminated the ability of SHBG to inhibit the uptake of DHT from conditioned media into LNCaP cells. Therefore, the proteolysis of SHBG by KLK4 and KLK14 increased steroid bioavailability in vitro, leading to an increased uptake of androgens by prostate cancer cells. Interestingly, different transcriptional responses of PSA and KLK2, which are androgen-regulated genes, to DHT-bounsd SHBG treatment were observed between low and high passage number LNCaP cells (lpLNCaP and hpLNCaP respectively). HpLNCaP cells treated with DHT-bound SHBG demonstrated a significant synergistic upregulation of PSA and KLK2 above DHT or SHBG treatment alone, which is similar to previously reported downstream responses from RSHBG-mediated signaling activation. As this result was not seen in lpLNCaP cells, only hpLNCaP cells were further investigated to examine the modulation of potential RSHBG activity by KLK4 and KLK14 proteolysis of SHBG. Contrary to reported results, no increase in intracellular cAMP was observed in hpLNCaP cells when treated with SHBG in the presence and absence of either DHT or estradiol. As a result, the modulation of RSHBG-mediated signaling activation could not be determined. Finally, the identification of the RSHBG from both breast (MCF-7) and prostate cancer (LNCaP) cell lines was attempted. Fluorescently labeled peptides corresponding to the putative receptor binding domain (RBD) of SHBG were shown to be internalized by MCF-7 cells. Crosslinking of the RBD peptide to the cell surfaces of both MCF-7 and LNCaP cells, demonstrated the interaction of the peptide with several targets. These targets were then captured using RBD peptides synthesized onto a hydrophilic scaffold and analysed by mass spectrometry. The samples captured by the RBD peptide returned statistically significantly matches for cytokeratin 8, 18 and 19 as well as microtubule-actin crosslinking factor 1, which may indicate a novel interaction between SHBG and these proteins, but ultimately failed to detect a membrane receptor potentially responsible for the putative RSHBG-mediated signaling. This PhD project has reported the proteolytic processing of SHBG by two members of the kallikrein family, KLK4 and KLK14. The effect of SHBG proteolysis by KLK4 and KLK14 on RSHBG-mediated signaling activation was unable to be determined as the reported signal transduction pathway was not activated after treatment with SHBG, in combination with either DHT or estradiol. However, the digestion of SHBG by these two proteases positively regulated androgen bioavailability to prostate cancer cells in vitro. The increased uptake of androgens is deleterious in prostate cancer due to the promotion of proliferation, metastasis, invasion and the inhibition of apoptosis. The increased bioavailability of androgens, from SHBG proteolysis by KLK4 and KLK14, may therefore promote both carcinogenesis and progression of prostate cancer. Finally, this information may contribute to the development of therapeutic treatment strategies for prostate cancer by inhibiting the proteolysis of SHBG, by KLK4 and KLK14, to prevent the increased uptake of androgens by hormone-dependent cancerous tissues.

Information enrichment for quality recommender systems

The explosive growth of the World-Wide-Web and the emergence of ecommerce are the major two factors that have led to the development of recommender systems (Resnick and Varian, 1997). The main task of recommender systems is to learn from users and recommend items (e.g. information, products or books) that match the users’ personal preferences. Recommender systems have been an active research area for more than a decade. Many different techniques and systems with distinct strengths have been developed to generate better quality recommendations. One of the main factors that affect recommenders’ recommendation quality is the amount of information resources that are available to the recommenders. The main feature of the recommender systems is their ability to make personalised recommendations for different individuals. However, for many ecommerce sites, it is difficult for them to obtain sufficient knowledge about their users. Hence, the recommendations they provided to their users are often poor and not personalised. This information insufficiency problem is commonly referred to as the cold-start problem. Most existing research on recommender systems focus on developing techniques to better utilise the available information resources to achieve better recommendation quality. However, while the amount of available data and information remains insufficient, these techniques can only provide limited improvements to the overall recommendation quality. In this thesis, a novel and intuitive approach towards improving recommendation quality and alleviating the cold-start problem is attempted. This approach is enriching the information resources. It can be easily observed that when there is sufficient information and knowledge base to support recommendation making, even the simplest recommender systems can outperform the sophisticated ones with limited information resources. Two possible strategies are suggested in this thesis to achieve the proposed information enrichment for recommenders: • The first strategy suggests that information resources can be enriched by considering other information or data facets. Specifically, a taxonomy-based recommender, Hybrid Taxonomy Recommender (HTR), is presented in this thesis. HTR exploits the relationship between users’ taxonomic preferences and item preferences from the combination of the widely available product taxonomic information and the existing user rating data, and it then utilises this taxonomic preference to item preference relation to generate high quality recommendations. • The second strategy suggests that information resources can be enriched simply by obtaining information resources from other parties. In this thesis, a distributed recommender framework, Ecommerce-oriented Distributed Recommender System (EDRS), is proposed. The proposed EDRS allows multiple recommenders from different parties (i.e. organisations or ecommerce sites) to share recommendations and information resources with each other in order to improve their recommendation quality. Based on the results obtained from the experiments conducted in this thesis, the proposed systems and techniques have achieved great improvement in both making quality recommendations and alleviating the cold-start problem.

Girl in the Shadows and resilience and coping strategies in contemporary young adult fiction

The novel manuscript Girl in the Shadows tells the story of two teenage girls whose friendship, safety and sanity are pushed to the limits when an unexplained phenomenon invades their lives. Sixteen-year-old Tash has everything a teenage girl could want: good looks, brains and freedom from her busy parents. But when she looks into her mirror, a stranger’s face stares back at her. Her best friend Mal believes it’s an evil spirit and enters the world of the supernatural to find answers. But spell books and ouija boards cannot fix a problem that comes from deep within the soul. It will take a journey to the edge of madness for Tash to face the truth inside her heart and see the evil that lurks in her home. And Mal’s love and courage to pull her back into life. The exegesis examines resilience and coping strategies in adolescence, in particular, the relationship of trauma to brain development in children and teenagers. It draws on recent discoveries in neuroscience and psychology to provide a framework to examine the role of coping strategies in building resilience. Within this broader context, it analyses two works of contemporary young adult fiction, Freaky Green Eyes by Joyce Carol Oates and Sonya Hartnett’s Surrender, their use of the split persona as a coping mechanism within young adult fiction and the potential of young adult literature as a tool to help build resilience in teen readers.

HCX : an efficient hybrid clustering approach for XML documents

This paper proposes a novel Hybrid Clustering approach for XML documents (HCX) that first determines the structural similarity in the form of frequent subtrees and then uses these frequent subtrees to represent the constrained content of the XML documents in order to determine the content similarity. The empirical analysis reveals that the proposed method is scalable and accurate.

Business model construction : the importance of regime of appropriability strategies

To date, most theories of business models have theorized value capture assuming that appropriability regimes were exogenous and that the firm would face a unique, ideal-typical appropriability regime. This has led theory contributions to focus on governance structures to minimize transaction costs, to downplay the interdepencies between value capture and value creation, and to ignore revenue generation strategies. We propose a reconceptualization of business models value capture mechanisms that rely on assumptions of endogeneity and multiplicity of appropriability regimes. This new approach to business model construction highlights the interdependencies and trade-offs between value creation and value capture offered by different types and combinations of appropriability regimes. The theory is illustrated by the analysis of three cases of open source software business models

Organizational rhetoric in the prospectuses of elite private schools : unpacking strategies of persuasion

Schools have seldom been examined by scholars in studies of organizational sites. Yet schools and the educational context in which they operate, offer potentially important insights into how organizations use rhetoric in their communications to persuade audiences and leverage advantage in the marketplace. This study, which utilises rhetorical analysis to examine the persuasive, yet ambiguous strategies used in 65 school prospectuses in Australia, revealed six strategies consistently used by schools to leverage competitive advantage and persuade internal and external audiences: identification, juxtapositioning, bolstering or self-promotion, partial reporting, selfexpansion and reframing or reversal. As well as illustrating how schools operate in the context of marketisation and privatization discourses in 21st century education, the organizational theory and methods utilised for the research demonstrates how rhetorical strategies draw on, as well as reproduce, socio-political and cultural discourses around economic and social privilege.

It's time to be more serious about activating youngsters : lessons for childhood obesity

The epidemic of obesity is impacting an increasing proportion of children, adolescents and adults with a common feature being low levels of physical activity (PA). Despite having more knowledge than ever before about the benefits of PA for health and the growth and development of youngsters, we are only paying lip-service to the development of motor skills in children. Fun, enjoyment and basic skills are the essential underpinnings of meaningful participation in PA. A concurrent problem is the reported increase in sitting time with the most common sedentary behaviors being TV viewing and other screen-based games. Limitations of time have contributed to a displacement of active behaviors with inactive pursuits, which has contributed to reductions in activity energy expenditure. To redress the energy imbalance in overweight and obese children, we urgently need out-of-the-box multisectoral solutions. There is little to be gained from a shame and blame mentality where individuals, their parents, teachers and other groups are singled out as causes of the problem. Such an approach does little more than shift attention from the main game of prevention and management of the condition, which requires a concerted, whole-of-government approach (in each country). The failure to support and encourage all young people to participate in regular PA will increase the chance that our children will live shorter and less healthy lives than their parents. In short, we need novel environmental approaches to foster a systematic increase in PA. This paper provides examples of opportunities and challenges for PA strategies to prevent obesity with a particular emphasis on the school and home settings.

Generating Flash files of Your Lectures: Good Practice Strategies Helping Students Engage with Their Learning

Our students come from diverse backgrounds. They need flexibility in their learning. First year students tend to worry when they miss lectures or part of lectures. Having the lecture as an on line resource allows students to miss a lecture without stressing about it and to be more relaxed in the lecture, knowing that anything they may miss will be available later. The resource: The Windows based program from Blueberry Software (not Blackberry!) - BB Flashback - allows the simultaneous recording of the computer screen together with the audio, as well as Webcam recording. Editing capabilities include adding pause buttons, graphics and text to the file before exporting it in a flash file. Any diagrams drawn on the board or shown via visualiser can be photographed and easily incorporated. The audio from the file can be extracted if required to be posted as podcast. Exporting modes other than Flash are also available, allowing vodcasting if you wish. What you will need: - the recording software: it can be installed on the lecture hall computer just prior to lecture if needed - a computer: either the ones in lecture halls, especially if fitted with audio recording, or a laptop (I have used audio recording via Bluetooth for mobility). Feedback from students has been positive and will be presented on the poster.