Altered cell interactions of subchondral bone osteoblasts and articular chondrocytes in osteoarthritis is through the mediation of ERK1/2 phosphorylation

Introduction: Osteoarthritis (OA) is the most common musculoskeletal disorder and represents a major health burden to society. In the course of the pathological development of OA, articular cartilage chondrocytes (ACCs) undergo a typical phenotype changes characterized by the expression of hypertrophic differentiation markers. Also, the adjacent subchondral bone shows signs of abnormal mineral density and enhanced production of bone turnover markers, indicative of osteoblast dysfunction. However, the mechanism(s) by which these changes occur during the OA development are not completely understood. Materials and Methods: ACCs and subchondral bone osteoblasts (SBOs) were harvested from OA and healthy patients for the cross-talk studies between normal and OA ACCs and SBOs. The involvement of mitogen activated protein kinase (MAPK) signalling pathway during the cell-cell interactions was analysed by zymography, ELISA and western blotting methods. Results: The direct and in-direct co-culture studies showed that OA (ACCs and SBOs) cells induced osteoarthritic changes of normal (ACC and SBOs) cells. This altered cell interaction induced by OA cells significantly aggravated the proteolytic activity, which resulted cartilage degeneration. The altered cell interaction appeared to significantly activate ERK 1/2 phosphorylation and inhibition of MAPK-ERK 1/2 pathway reversed the osteoarthrtitic phenotypic changes. Discussion and Conclusion: Our study has demonstrated that the altered bi-directional communication of SBOs and ACCs are critical for initiation and progression of OA related changes and that this process is mediated by MAPK signalling pathways. Targeting these altered interactions by the use of MAPK inhibitors may provide the scientific rationale for the development of novel therapeutic strategies in the treatment and management of OA related disorders.

Preparing students for international study : the use of technology

About 1.6 million students currently study outside their home country. Despite this, and the fact that Australia, the United States, the United Kingdom and many of the other host countries of international students are themselves extremely culturally diverse communities, business education remains essentially mono-cultural in form and Anglo American in content. Whilst it is true that these international students may want to understand the "Western" way of doing things, they may not be familiar or comfortable with the processes used to facilitate learning. This paper explores a project undertaken to create a tool that provides essential pre-orientation information and advice to students before they leave home. Where cultural adjustment is required, catching students before departure is a very effective time to introduce key information about lifestyle, culture and approaches to teaching and learning that would assist students with the complex and difficult adjustment to studying abroad, so that they could make a smoother transition to their new place of learning. Welcome to Studying Business at QUT is a Data DVD with 19 short videos capturing a student perspective on life and study. Forty percent of the content is related to living and studying and includes sections on accommodation, lifestyle, food and transport etc., and 60% takes an in-depth look at studying business, featuring students and academics talking about issues such as assessment, academic writing and working in groups. This paper outlines the process of developing the DVD and the range of issues addressed.

Discovery & effective use of quality association rules in multi-level datasets

In today’s electronic world vast amounts of knowledge is stored within many datasets and databases. Often the default format of this data means that the knowledge within is not immediately accessible, but rather has to be mined and extracted. This requires automated tools and they need to be effective and efficient. Association rule mining is one approach to obtaining knowledge stored with datasets / databases which includes frequent patterns and association rules between the items / attributes of a dataset with varying levels of strength. However, this is also association rule mining’s downside; the number of rules that can be found is usually very big. In order to effectively use the association rules (and the knowledge within) the number of rules needs to be kept manageable, thus it is necessary to have a method to reduce the number of association rules. However, we do not want to lose knowledge through this process. Thus the idea of non-redundant association rule mining was born. A second issue with association rule mining is determining which ones are interesting. The standard approach has been to use support and confidence. But they have their limitations. Approaches which use information about the dataset’s structure to measure association rules are limited, but could yield useful association rules if tapped. Finally, while it is important to be able to get interesting association rules from a dataset in a manageable size, it is equally as important to be able to apply them in a practical way, where the knowledge they contain can be taken advantage of. Association rules show items / attributes that appear together frequently. Recommendation systems also look at patterns and items / attributes that occur together frequently in order to make a recommendation to a person. It should therefore be possible to bring the two together. In this thesis we look at these three issues and propose approaches to help. For discovering non-redundant rules we propose enhanced approaches to rule mining in multi-level datasets that will allow hierarchically redundant association rules to be identified and removed, without information loss. When it comes to discovering interesting association rules based on the dataset’s structure we propose three measures for use in multi-level datasets. Lastly, we propose and demonstrate an approach that allows for association rules to be practically and effectively used in a recommender system, while at the same time improving the recommender system’s performance. This especially becomes evident when looking at the user cold-start problem for a recommender system. In fact our proposal helps to solve this serious problem facing recommender systems.

Investigation of electrophoretic loading and enhanced mechanical properties of hydrogels for delivery of therapeutic proteins

Hydrogels, which are three-dimensional crosslinked hydrophilic polymers, have been used and studied widely as vehicles for drug delivery due to their good biocompatibility. Traditional methods to load therapeutic proteins into hydrogels have some disadvantages. Biological activity of drugs or proteins can be compromised during polymerization process or the process of loading protein can be really timeconsuming. Therefore, different loading methods have been investigated. Based on the theory of electrophoresis, an electrochemical gradient can be used to transport proteins into hydrogels. Therefore, an electrophoretic method was used to load protein in this study. Chemically and radiation crosslinked polyacrylamide was used to set up the model to load protein electrophoretically into hydrogels. Different methods to prepare the polymers have been studied and have shown the effect of the crosslinker (bisacrylamide) concentration on the protein loading and release behaviour. The mechanism of protein release from the hydrogels was anomalous diffusion (i.e. the process was non-Fickian). The UV-Vis spectra of proteins before and after reduction show that the bioactivities of proteins after release from hydrogel were maintained. Due to the concern of cytotoxicity of residual monomer in polyacrylamide, poly(2-hydroxyethyl- methacrylate) (pHEMA) was used as the second tested material. In order to control the pore size, a polyethylene glycol (PEG) porogen was introduced to the pHEMA. The hydrogel disintegrated after immersion in water indicating that the swelling forces exceeded the strength of the material. In order to understand the cause of the disintegration, several different conditions of crosslinker concentration and preparation method were studied. However, the disintegration of the hydrogel still occurred after immersion in water principally due to osmotic forces. A hydrogel suitable for drug delivery needs to be biocompatible and also robust. Therefore, an approach to improving the mechanical properties of the porogen-containing pHEMA hydrogel by introduction of an inter-penetrating network (IPN) into the hydrogel system has been researched. A double network was formed by the introduction of further HEMA solution into the system by both electrophoresis and slow diffusion. Raman spectroscopy was used to observe the diffusion of HEMA into the hydrogel prior to further crosslinking by ã-irradiation. The protein loading and release behaviour from the hydrogel showing enhanced mechanical property was also studied. Biocompatibility is a very important factor for the biomedical application of hydrogels. Different hydrogels have been studied on both a three-dimensional HSE model and a HSE wound model for their biocompatibilities. They did not show any detrimental effect to the keratinocyte cells. From the results reported above, these hydrogels show good biocompatibility in both models. Due to the advantage of the hydrogels such as the ability to absorb and deliver protein or drugs, they have potential to be used as topical materials for wound healing or other biomedical applications.

Conceptualising use for information systems (IS) success

This thesis conceptualises Use for IS (Information Systems) success. While Use in this study describes the extent to which an IS is incorporated into the user’s processes or tasks, success of an IS is the measure of the degree to which the person using the system is better off. For IS success, the conceptualisation of Use offers new perspectives on describing and measuring Use. We test the philosophies of the conceptualisation using empirical evidence in an Enterprise Systems (ES) context. Results from the empirical analysis contribute insights to the existing body of knowledge on the role of Use and demonstrate Use as an important factor and measure of IS success. System Use is a central theme in IS research. For instance, Use is regarded as an important dimension of IS success. Despite its recognition, the Use dimension of IS success reportedly suffers from an all too simplistic definition, misconception, poor specification of its complex nature, and an inadequacy of measurement approaches (Bokhari 2005; DeLone and McLean 2003; Zigurs 1993). Given the above, Burton-Jones and Straub (2006) urge scholars to revisit the concept of system Use, consider a stronger theoretical treatment, and submit the construct to further validation in its intended nomological net. On those considerations, this study re-conceptualises Use for IS success. The new conceptualisation adopts a work-process system-centric lens and draws upon the characteristics of modern system types, key user groups and their information needs, and the incorporation of IS in work processes. With these characteristics, the definition of Use and how it may be measured is systematically established. Use is conceptualised as a second-order measurement construct determined by three sub-dimensions: attitude of its users, depth, and amount of Use. The construct is positioned in a modified IS success research model, in an attempt to demonstrate its central role in determining IS success in an ES setting. A two-stage mixed-methods research design—incorporating a sequential explanatory strategy—was adopted to collect empirical data and to test the research model. The first empirical investigation involved an experiment and a survey of ES end users at a leading tertiary education institute in Australia. The second, a qualitative investigation, involved a series of interviews with real-world operational managers in large Indian private-sector companies to canvass their day-to-day experiences with ES. The research strategy adopted has a stronger quantitative leaning. The survey analysis results demonstrate the aptness of Use as an antecedent and a consequence of IS success, and furthermore, as a mediator between the quality of IS and the impacts of IS on individuals. Qualitative data analysis on the other hand, is used to derive a framework for classifying the diversity of ES Use behaviour. The qualitative results establish that workers Use IS in their context to orientate, negotiate, or innovate. The implications are twofold. For research, this study contributes to cumulative IS success knowledge an approach for defining, contextualising, measuring, and validating Use. For practice, research findings not only provide insights for educators when incorporating ES for higher education, but also demonstrate how operational managers incorporate ES into their work practices. Research findings leave the way open for future, larger-scale research into how industry practitioners interact with an ES to complete their work in varied organisational environments.

Study of the interaction between 10-hydroxycamptothecine and DNA with the use of ethidium bromide dye as a fluorescence probe

The interaction of 10-hydroxycamptothecine (HCPT) with DNA under pseudo-physiological conditions (Tris-HCl buffer of pH 7.4), using ethidium bromide (EB) dye as a probe, was investigated with the use of spectrofluorimetry, UV-vis spectrometry and viscosity measurement. The binding constant and binding number for HCPT with DNA were evaluated as (7.1 ± 0.5) × 104 M-1 and 1.1, respectively, by multivariate curve resolution-alternating least squares (MCR-ALS). Moreover, parallel factor analysis (PARAFAC) was applied to resolve the three-way fluorescence data obtained from the interaction system, and the concentration information for the three components of the system at equilibrium was simultaneously obtained. It was found that there was a cooperative interaction between the HCPT-DNA complex and EB, which produced a ternary complex of HCPT-DNA-EB. © 2011 Elsevier B.V.

Discussions on conceptual knowledge and the use of blogs

In both Australia and Norway and through a number of Technology projects conducted since 2007, the authors – together and with other collaborators - have attempted to create positive learning environments supported by Web 2.0 communication tools. Through protected public sites and the oz-Teachernet [http://www.otn.edu.au], we have consistently chosen to use blogs to support the social construction of knowledge, that is, to allow students the opportunity to discuss, share and collaborate on their classroom activities and engagement with Technology artefacts and processes. Through comparisons with findings from a small-scale project in Norway and a large-scale project in Australia, this paper will argue for the potential of discussion through blogs but recommend that the purposeful use of scientific language in student communication will not occur without teacher intervention and scaffolding.

Fleet safety : risk reduction for work related vehicle use

Research has demonstrated that driving a vehicle for work is potentially one of the most dangerous workplace activities. Although organisations are required to meet legislative obligations under workplace health and safety in relation to work related vehicle use, organisations are often reluctant to acknowledge and address the risks associated with the vehicle as a workplace. Recent research undertaken investigating the challenges associated with driver and organisational aspects of fleet safety are discussed. This paper provides a risk management framework to assist organisations to meet legislative requirements and reduce the risk associated with vehicle use in the workplace. In addition the paper argues that organisations need to develop and maintain a positive fleet safety culture to proactively mitigate risk in an effort to reduce the frequency and severity of vehicle related incidents within the workplace.

Mesoporous bioactive glasses as drug delivery and bone tissue regeneration platforms

The use of mesoporous bioactive glasses (MBG) for drug delivery and bone tissue regeneration has grown significantly over the past 5 years. In this review, we highlight the recent advances made in the preparation of MBG particles, spheres, fibers and scaffolds. The advantages of MBG for drug delivery and bone scaffold applications are related to this material’s well-ordered mesopore channel structure, superior bioactivity, and the application for the delivery of both hydrophilic and hydrophobic drugs. A brief forward-looking perspective on the potential clinical applications of MBG in regenerative medicine is also discussed.

The spermostatic and microbicidal actions of quinones and malemides : towards a dual-purpose contraceptive agent

There is an urgent need to develop safe, effective, dual-purpose contraceptive agents that combine the prevention of pregnancy with protection against sexually transmitted diseases. Here we report the identification of a group of compounds that on contact with human spermatozoa induce a state of “spermostasis,” characterized by the extremely rapid inhibition of sperm movement without compromising cell viability. These spermostatic agents were more active and significantly less toxic than the reagent in current clinical use, nonoxynol 9, giving therapeutic indices (ratio of spermostatic to cytotoxic activity) that were orders of magnitude greater than this traditional spermicide. Although certain compounds could trigger reactive oxygen species generation by spermatozoa, this activity was not correlated with spermostasis. Rather, the latter was associated with alkylation of two major sperm tail proteins that were identified as A Kinase-Anchoring Proteins (AKAP3 and AKAP4) by mass spectrometry. As a consequence of disrupted AKAP function, the abilities of cAMP to drive protein kinase A-dependent activities in the sperm tail, such as the activation of SRC and the consequent stimulation of tyrosine phosphorylation, were suppressed. Furthermore, analysis of microbicidal activity using Chlamydia muridarum revealed powerful inhibitory effects at the same low micromolar doses that suppressed sperm movement. In this case, the microbicidal action was associated with alkylation of Major Outer Membrane Protein (MOMP), a major chlamydial membrane protein. Taken together, these results have identified for the first time a novel set of cellular targets and chemical principles capable of providing simultaneous defense against both fertility and the spread of sexually transmitted disease.