Long-term effects of hydrogel properties on human chondrocyte behavior

Hydrogels provide a 3-dimensional network for embedded cells and offer promise for cartilage tissue engineering applications. Nature-derived hydrogels, including alginate, have been shown to enhance the chondrocyte phenotype but are variable and not entirely controllable. Synthetic hydrogels, including polyethylene glycol (PEG)-based matrices, have the advantage of repeatability and modularity; mechanical stiffness, cell adhesion, and degradability can be altered independently. In this study, we compared the long-term in vitro effects of different hydrogels (alginate and Factor XIIIa-cross-linked MMP-sensitive PEG at two stiffness levels) on the behavior of expanded human chondrocytes and the development of construct properties. Monolayer-expanded human chondrocytes remained viable throughout culture, but morphology varied greatly in different hydrogels. Chondrocytes were characteristically round in alginate but mostly spread in PEG gels at both concentrations. Chondrogenic gene (COL2A1, aggrecan) expression increased in all hydrogels, but alginate constructs had much higher expression levels of these genes (up to 90-fold for COL2A1), as well as proteoglycan 4, a functional marker of the superficial zone. Also, chondrocytes expressed COL1A1 and COL10A1, indicative of de-differentiation and hypertrophy. After 12 weeks, constructs with lower polymer content were stiffer than similar constructs with higher polymer content, with the highest compressive modulus measured in 2.5% PEG gels. Different materials and polymer concentrations have markedly different potency to affect chondrocyte behavior. While synthetic hydrogels offer many advantages over natural materials such as alginate, they must be further optimized to elicit desired chondrocyte responses for use as cartilage models and for development of functional tissue-engineered articular cartilage.

Using GIS to visualise and evaluate student travel behaviour

Using GIS to evaluate travel behaviour is an important technique to increase our understanding of the relationship between accessibility and transport demand. In this paper, the activity space concept was used to identify the nature of participation in activities (or lack of it) amongst a group of students using a 2 day travel-activity diary. Three different indicators such as the number of unique locations visited, average daily distance travelled, and average daily activity duration were used to measure the size of activity spaces. These indicators reflect levels of accessibility, personal mobility, and the extent of participation respectively. Multiple regression analyses were used to assess the impacts of students socio-economic status and the spatial characteristics of home location. Although no differences were found in the levels of accessibility and the extent of participation measures, home location with respect to a demand responsive transport (DRT) service was found to be the most important determinant of their mobility patterns. Despite being able to travel longer distances, students who live outside of the DRT service area were found to be temporally excluded from some opportunities. Student activity spaces were also visualised within a GIS environment and a spatial analysis was conducted to underpin the evaluation of the performance of the DRT. This approach was also used to identify the activity spaces of individuals that are geographically excluded from the service. Evaluation of these results indicated that although the service currently covers areas of high demand, 90% of the activity spaces remained un-served by the DRT service. Using this data six new routes were designed to meet the coverage goal of public transport based on a measure of network impedance based on inverse activity density. Following assessment of public transport service coverage, the study was extended using a Spatial Multi Criteria Evaluation (SMCE) technique to assess the effect of service provision on patronage.

Tailoring secretion of proteoglycan 4 (PRG4) in tissue-engineered cartilage

Articular cartilage provides a low-friction surface for joint articulation, with boundary lubrication facilitated by proteoglycan 4 (PRG4), which is secreted by chondrocytes of the superficial zone. Chondrocytes from different zones are phenotypically distinct, and their phenotypes in vitro are influenced by the system in which they are cultured. We hypothesized that culturing cells from the superficial (S) zone in two-dimensional monolayer or three-dimensional alginate would affect their synthesis of PRG4, and that subsequently seeding them atop alginate-recovered cells from the middle/ deep (M) zone in various proportions would result in tissue-engineered constructs with varying levels of PRG4 secretion and matrix accumulation. During monolayer culture, S cells retained their PRG4-secreting phenotype, whereas in alginate culture the percentage of cells secreting PRG4 decreased with time. Constructs formed with increasing percentages of S cells decreased in thickness and matrix accumulation, depending on both the culture conditions before construct formation and the S-cell density. PRG4-secreting cells were localized to the S-cell seeded construct surface, with secretion rates of 0.1–4 pg/cell/day or 0.1–1 pg/cell/day for constructs formed with monolayer-recovered or alginate-recovered S cells, respectively. Tailoring secretion of PRG4 in cartilage constructs may be useful for enhancing low-friction properties at the articular surface, while maintaining other surfaces free of PRG4 for enhancing integration with surrounding tissues.

Zonal chondrocyte subpopulations reacquire zone-specific characteristics during in Vitro redifferentiation

Background: If chondrocytes from the superficial, middle, and deep zones of articular cartilage could maintain or regain their characteristic properties during in vitro culture, it would be feasible to create constructs comprising these distinctive zones. ----- ----- Hypothesis: Zone-specific characteristics of zonal cell populations will disappear during 2-dimensional expansion but will reappear after 3-dimensional redifferentiation, independent of the culture technique used (alginate beads versus pellet culture).----- ----- Study Design: Controlled laboratory study.----- ----- Methods: Equine articular chondrocytes from the 3 zones were expanded in monolayer culture (8 donors) and subsequently redifferentiated in pellet and alginate bead cultures for up to 4 weeks. Glycosaminoglycans and DNA were quantified, along with immunohistochemical assessment of the expression of various zonal markers, including cartilage oligomeric protein (marking cells from the deeper zones) and clusterin (specifically expressed by superficial chondrocytes).----- ----- Results: Cell yield varied between zones, but proliferation rates did not show significant differences. Expression of all evaluated zonal markers was lost during expansion. Compared to the alginate bead cultures, pellet cultures showed a higher amount of glycosaminoglycans produced per DNA after redifferentiation. In contrast to cells in pellet cultures, cells in alginate beads regained zonal differences, as evidenced by zone-specific reappearance of cartilage oligomeric protein and clusterin, as well as significantly higher glycosaminoglycans production by cells from the deep zone compared to the superficial zone.----- ----- Conclusion: Chondrocytes isolated from the 3 zones of equine cartilage can restore their zone-specific matrix expression when cultured in alginate after in vitro expansion.

Indigenous Voice : a work-integrated learning case study in journalism education

The continuing stereotypical coverage of Inigenous affairs in the Australian media suggests that journalists are still finding it difficult to come to terms with more effective ways ofm reporting such issues. The many hundreds of students who graduate from journalism programs across Australia represent an opportunity to at least challenge the predominant methods and strategies. But how prepared are journalism graduates for working with Indigenous issues? This paper explores the processas involved in an intensive reporting practices course held at the University of Queensland mid-2009. The course aimed to raise journalism student's awareness of some of the issues involved as well as enabling them to interact and work with personnel from the Brisbane Indigenous Media Community, 98.9 fm, the National Indigenous Radio Service, SBS and the ABC. The findings suggest that such structured programs have a significant impact on changing student's perceptions of, and approaches to, their role and journalists.

Causing economic harm to property developers : damages for starting an incurably bad appeal?

A recent decision of the Queensland Court of Appeal involved an unusual statement of claim made on behalf of the developer of a proposed resort in Port Douglas. The decision is The Beach Club Port Douglas Pty Ltd v Page [2005] QCA 475. The issue The defendant had objected to a development application of the plaintiff developer and lodged an appeal in the Planning and Environment Court against the council decision granting a development permit. The main issue in the Planning and Environment Court was whether the site coverage of the proposed resort was excessive. In a separate action (the subject matter of the present appeal), the plaintiff developer claimed damages for ‘negligence’ alleging that the defendant had breached a duty of care not to appeal without properly or reasonably assessing whether the development qualified for a permit given that the resort qualified for the maximum allowable site coverage. It was alleged that the appeal lodged by the defendant in the Planning and Environment Court had no reasonable prospects of success and that any reasonable person properly advised would know, or ought reasonably to have known, that to be so. The defendant had been “put on notice” that the plaintiff would incur loss of $10,000 for every day there was a delay in starting construction of the resort. The claim made by the developer required the court to consider those circumstances where a person may lawfully and deliberately cause economic harm to another. Was a duty of care owed by the defendant for negligent conduct of litigation that caused economic loss to the plaintiff?

Developing an IS-Impact decision tool : a literature based design science roadmap

This paper derives from research-in-progress intending both Design Research (DR) and Design Science (DS) outputs; the former a management decision tool based in IS-Impact (Gable et al. 2008) kernel theory; the latter being methodological learnings deriving from synthesis of the literature and reflection on the DR ‘case study’ experience. The paper introduces a generic, detailed and pragmatic DS ‘Research Roadmap’ or methodology, deriving at this stage primarily from synthesis and harmonization of relevant concepts identified through systematic archival analysis of related literature. The scope of the Roadmap too has been influenced by the parallel study aim to undertake DR applying and further evolving the Roadmap. The Roadmap is presented in attention to the dearth of detailed guidance available to novice Researchers in Design Science Research (DSR), and though preliminary, is expected to evolve and gradually be substantiated through experience of its application. A key distinction of the Roadmap from other DSR methods is its breadth of coverage of published DSR concepts and activities; its detail and scope. It represents a useful synthesis and integration of otherwise highly disparate DSR-related concepts.

A design science research roadmap

This paper proposes and synthesizes from previous design science(DS) methodological literature a structured and detailed DS Roadmap for the conduct of DS research. The Roadmap is a general guide for researchers to carry out DS research by suggesting reasonably detailed activities.Though highly tentative, it is believed the Roadmap usefully inter-relates many otherwise seemingly disparate, overlapping or conflicting concepts. It is hoped the DS Roadmap will aid in the planning, execution and communication of DS research,while also attracting constructive criticism, improvements and extensions. A key distinction of the Roadmap from other DS research methods is its breadth of coverage of DS research aspects and activities; its detail and scope. We demonstrate and evaluate the Roadmap by presenting two case studies in terms of the DS Roadmap.

Extending the task of diarization to speaker attribution

In this paper we extend the concept of speaker annotation within a single-recording, or speaker diarization, to a collection wide approach we call speaker attribution. Accordingly, speaker attribution is the task of clustering expectantly homogenous intersession clusters obtained using diarization according to common cross-recording identities. The result of attribution is a collection of spoken audio across multiple recordings attributed to speaker identities. In this paper, an attribution system is proposed using mean-only MAP adaptation of a combined-gender UBM to model clusters from a perfect diarization system, as well as a JFA-based system with session variability compensation. The normalized cross-likelihood ratio is calculated for each pair of clusters to construct an attribution matrix and the complete linkage algorithm is employed to conduct clustering of the inter-session clusters. A matched cluster purity and coverage of 87.1% was obtained on the NIST 2008 SRE corpus.

Multi-modal summarization of key events and top players in sports tournament videos

To detect and annotate the key events of live sports videos, we need to tackle the semantic gaps of audio-visual information. Previous work has successfully extracted semantic from the time-stamped web match reports, which are synchronized with the video contents. However, web and social media articles with no time-stamps have not been fully leveraged, despite they are increasingly used to complement the coverage of major sporting tournaments. This paper aims to address this limitation using a novel multimodal summarization framework that is based on sentiment analysis and players' popularity. It uses audiovisual contents, web articles, blogs, and commentators' speech to automatically annotate and visualize the key events and key players in a sports tournament coverage. The experimental results demonstrate that the automatically generated video summaries are aligned with the events identified from the official website match reports.

The Scottish media and politics

This chapter will explore the performance of the Scottish media in post-devolution political life, before turning its attention to the specific coverage of the 2007 election.

Glycosaminoglycan and growth factor mediated murine calvarial cell proliferation

Understanding the complex mechanisms underlying bone remodeling is crucial to the development of novel therapeutics. Glycosaminoglycans (GAGs) localised to the extracellular matrix (ECM) of bone are thought to play a key role in mediating aspects of bone development. The influence of isolated GAGs was studied by utilising in vitro murine calvarial monolayer and organ culture model systems. Addition of GAG preparations extracted from the cell surface of human osteoblasts at high concentrations (5 microg/ml) resulted in decreased proliferation of cells and decreased suture width and number of bone lining cells in calvarial sections. When we investigated potential interactions between the growth factors fibroblast growth factor-2 (FGF2), bone morphogenic protein-2 (BMP2) and transforming growth factor-beta1 (TGFbeta1) and the isolated cell surface GAGs, differences between the two model systems emerged. The cell culture system demonstrated a potentiating role for the isolated GAGs in the inhibition of FGF2 and TGFbeta1 actions. In contrast, the organ culture system demonstrated an enhanced stimulation of TFGbeta1 effects. These results emphasise the role of the ECM in mediating the interactions between GAGs and growth factors during bone development and suggest the GAG preparations contain potent inhibitory or stimulatory components able to mediate growth factor activity.

Utility of routine data sources for feedback on the quality of cancer care: an assessment based on clinical practice guidelines

Background Not all cancer patients receive state-of-the-art care and providing regular feedback to clinicians might reduce this problem. The purpose of this study was to assess the utility of various data sources in providing feedback on the quality of cancer care. Methods Published clinical practice guidelines were used to obtain a list of processes-of-care of interest to clinicians. These were assigned to one of four data categories according to their availability and the marginal cost of using them for feedback. Results Only 8 (3%) of 243 processes-of-care could be measured using population-based registry or administrative inpatient data (lowest cost). A further 119 (49%) could be measured using a core clinical registry, which contains information on important prognostic factors (e.g., clinical stage, physiological reserve, hormone-receptor status). Another 88 (36%) required an expanded clinical registry or medical record review; mainly because they concerned long-term management of disease progression (recurrences and metastases) and 28 (11.5%) required patient interview or audio-taping of consultations because they involved information sharing between clinician and patient. Conclusion The advantages of population-based cancer registries and administrative inpatient data are wide coverage and low cost. The disadvantage is that they currently contain information on only a few processes-of-care. In most jurisdictions, clinical cancer registries, which can be used to report on many more processes-of-care, do not cover smaller hospitals. If we are to provide feedback about all patients, not just those in larger academic hospitals with the most developed data systems, then we need to develop sustainable population-based data systems that capture information on prognostic factors at the time of initial diagnosis and information on management of disease progression.

Dinuclear Ru-Cu complexes : electronic characterisation and application to dye-sensitised solar cells

Dye-sensitised solar cells have emerged as an important developing technology for low-cost solar energy conversion and a crucial element of these is the dye, responsible for light harvesting and control of interfacial electron-transfer processes.[1] A number of examples of dye exist in the literature which link a ruthenium polypyridyl complex to another platinum group metal complex such as Ru (II), Os (II), Re (I) or Rh (III) via a bridging ligand.[2-6] These systems are often referred to as heterosupramolecular triads when adsorbed on the surface of TiO2 as the semiconductor becomes an active component in the system. A number of problems can arise with these types of sensitisers, for example if a flexible linker, e.g. bis-pyridylethane, is used to couple the two complexes it can be hard to control the orientation of the whole dye. This may lead to the resultant dye cation hole being closer to the surface than desired, and hence the long-lived charge-separated state is not achieved. In addition the size of these dyes may be much larger than that of a mononuclear complex and can lead to poor pore filling on the TiO2 and lower dye coverage, leading to a lower efficiency cell.[7] Despite these issues, efficient charge-separation has been achieved with polynuclear complexes and a long-lived state on the millisecond timescale has been observed for a trinuclear ruthenium complex.[8]

Hypothetical model of hydrophilic lubrication in synovial joints

This paper presents a new insight into the mechanism of biolubrication of articulating mammalian joints that includes the function of surface-active phospholipids (SAPLs). SAPLs can be adsorbed on surface of cartilage membranes as a hydrophobic monolayer (H-phobic-M Madel or Hills' Model) or as a newly proposed hydrophilic bilayer (H-philic-B Model). With respect to the synovial joint's frictionless work, three processes are identified namely: monolayer/bilayer phospholipids binding to cartilage with lubricin interaction; influence of induced-pressure on interaction of hyaluronan with phospholipids; and biolubrication arising from two gliding articular hydrophilic surfaces acting as reverse micelle. Lubricin is considered to play critical role as a supplier of phospholipids, which overlay the articular surface of articular cartilage. Hyaluronic acid is considered to play a critical mediating role in the interaction between the hydrophilic part of phospholipids, the articular surface and water (hydration) in facilitating the lubrication process. Tivo models of frictionless lubrication processes, namely hydrophobic (H-phobic-M Model) and our conceptual hydrophilic (H-philic-B Model), are compared. © Institution of Engineers Australia, 2008.