Investigating the effects of preinduction on human adipose-derived precursor cells in an athymic rat model

The osteogenic potential of human adipose-derived precursor cells seeded on medical-grade polycaprolactone-tricalcium phosphate scaffolds was investigated in this in vivo study. Three study groups were investigated: (1) induced—stimulated with osteogenic factors only after seeding into scaffold; (2) preinduced—induced for 2 weeks before seeding into scaffolds; and (3) uninduced—cells without any introduced induction. For all groups, scaffolds were implanted subcutaneously into the dorsum of athymic rats. The scaffold/cell constructs were harvested at the end of 6 or 12 weeks and analyzed for osteogenesis. Gross morphological examination using scanning electron microscopy indicated good integration of host tissue with scaffold/cell constructs and extensive tissue infiltration into the scaffold interior. Alizarin Red histology and immunostaining showed a heightened level of mineralization and an increase in osteonectin, osteopontin, and collagen type I protein expression in both the induced and preinduced groups compared with the uninduced groups. However, no significant differences were observed in these indicators when compared between the induced and preinduced groups.

The aftermath of the Lehman Brothers collapse in Hong Kong : the saga, regulatory deficiencies and government responses

The paper examines the fallout of the Lehman Brothers collapse in Hong Kong. As an international financial hub in Asia, Hong Kong was profoundly affected by the collapse of this company. As a result, it impacted negatively on the public’s confidence in the Hong Kong’s banking sector. Furthermore, this event has exposed a number of regulatory deficiencies in Hong Kong. In response to this financial crisis, the Hong Kong government had made an unprecedented move to negotiate with local banks to refund the investors. In addition, the government has also sought public consultation on proposal to enhance the regulation of the sale of financial products. This paper argues that there needs to be amendments to the prevailing laws and the inclusions of legal rules to back up those proposed measures so that the disclosed information from the financial institution will not mislead the investors or misrepresent the products offered.

Migration of breast cancer cells : understanding the roles of volume exclusion and cell-to-cell adhesion

We study MCF-7 breast cancer cell movement in a transwell apparatus. Various experimental conditions lead to a variety of monotone and nonmonotone responses which are difficult to interpret. We anticipate that the experimental results could be caused by cell-to-cell adhesion or volume exclusion. Without any modeling, it is impossible to understand the relative roles played by these two mechanisms. A lattice-based exclusion process random-walk model incorporating agent-to-agent adhesion is applied to the experimental system. Our combined experimental and modeling approach shows that a low value of cell-to-cell adhesion strength provides the best explanation of the experimental data suggesting that volume exclusion plays a more important role than cell-to-cell adhesion. This combined experimental and modeling study gives insight into the cell-level details and design of transwell assays.

A regulatory on-board mass monitoring application for heavy vehicles in Australia

This paper reports on the development of specifications for an on-board mass monitoring (OBM) application for regulatory requirements in Australia. An earlier paper reported on feasibility study and pilot testing program prior to the specification development [1]. Learnings from the pilot were used to refine this testing process and a full scale testing program was conducted from July to October 2008. The results from the full scale test and evidentiary implications are presented in this report. The draft specification for an evidentiary on-board mass monitoring application is currently under development.

Franchisor failure : an assessment of the adequacy of regulatory response

Franchisor failure is one of the most problematic areas of the franchise relationship. It impacts negatively on landlords and other suppliers, but the contracting parties that are currently without legal rights to respond when a franchisor fails, and thus without consumer protection, are its franchisees. In this thesis I explore the current contractual, regulatory and commercial environment that franchisees inhabit, within the context of franchisor failure. I conclude that ex ante there are opportunities to level the playing field through consumer protection legislation. I also conclude that the task is not one solely for the consumer protection legislation; the problem should also be addressed ex post through the Corporations Act.

Selective accumulation of virus-specific CD8+ T cells within the peripheral blood stem cell compartment

The absence of cellular immunity is central to the pathogenesis of herpesvirus-mediated diseases after allogeneic hemopoietic stem cell transplantation (HSCT). For both bone marrow (BM)– and granulocyte-colony stimulating factor–mobilized peripheral blood stem cells (PBSCs) HSCT, donor-derived Epstein-Barr virus (EBV) and cytomegalovirus (CMV) peptide–specific CD8+ T cells clones undergo early expansion and persist long-term, with additional diversification arising from novel antigen-specific clones from donor-derived progenitors. Whether BM or PBSC is the superior source of antiviral CD8+ T cells is unclear. Given that PBSC has largely replaced BM as a source of stem cells for HSCT, it is unlikely that herpesvirus effector T-cell reconstitution will ever be compared prospectively. PBSC grafts contain 10 to 30 times more T cells than BM and a randomized study found proven viral infections were more frequent in BM than PBSC recipients, suggesting viral-specific T-cell immunity is enhanced in PBSC. Recently Moss showed in lung cancer patients that herpesvirus-specific BM-derived CD8+ T cells have unique homing properties relative to herpesvirus-specific CD8+ T cells present in unmobilized peripheral blood (PB). Immunodominant EBV-lytic peptide–specific CD8+ T cells were enriched in BM but were reduced for CMV peptide–specific CD8+ T cells relative to PB. EBV-latent peptide–specific CD8+ T cells were equivalent, which has relevance in the context of posttransplantation lymphoproliferative disorder for which impaired EBV-latent CD8+ T-cell immunity is a risk-factor. A comparison of herpesvirus-specific cellular immunity in PBSC versus PB has yet to be performed.

Ovine bone and marrow derived progenitor cells : isolation, characterization, and osteogenic potential

Recently, research has focused on bone marrow derived multipotent mesenchymal precursor cells (MPC) for their potential clinical use in bone engineering. Prior to clinical application, MPC-based treatment concepts need to be evaluated in preclinical, immunocompetent, large animal models. Sheep in particular are considered a valid model for orthopaedic and trauma related research. However, ovine MPC and their osteogenic potential remain poorly characterized. In the present study, ex vivo expanded MPC isolated from ovine bone marrow proliferated at a higher rate than osteoblasts (OB) derived from tibial compact bone as assessed using standard 2D culture. MPC expressed the respective phenotypic profile typical for different mesenchymal cell populations (CD14-/CD31-/CD45- /CD29+/CD44+/CD166+) and showed a multilineage differentiation potential. When compared to OB, MPC had a higher mineralization potential under standard osteogenic culture conditions and expressed typical markers such as osteocalcin, osteonectin and type I collagen at the mRNA and protein level. After 4 weeks in 3D culture, MPC constructs demonstrated higher cell density and mineralization, whilst cell viability on the scaffolds was assessed >90%. Cells displayed a spindle-like morphology and formed an interconnected network. Implanted subcutaneously into NOD/SCID mice on type I collagen coated polycaprolactone-tricalciumphosphate (mPCL-TCP) scaffolds, MPC presented a higher developmental potential than osteoblasts. In summary, this study provides a detailed in vitro characterisation of ovine MPC from a bone engineering perspective and suggests that MPC provide promising means for future bone disease related treatment applications.

Contracting bubbles in Hele-Shaw cells with a power-law fluid

The problem of bubble contraction in a Hele-Shaw cell is studied for the case in which the surrounding fluid is of power-law type. A small perturbation of the radially symmetric problem is first considered, focussing on the behaviour just before the bubble vanishes, it being found that for shear-thinning fluids the radially symmetric solution is stable, while for shear-thickening fluids the aspect ratio of the bubble boundary increases. The borderline (Newtonian) case considered previously is neutrally stable, the bubble boundary becoming elliptic in shape with the eccentricity of the ellipse depending on the initial data. Further light is shed on the bubble contraction problem by considering a long thin Hele-Shaw cell: for early times the leading-order behaviour is one-dimensional in this limit; however, as the bubble contracts its evolution is ultimately determined by the solution of a Wiener-Hopf problem, the transition between the long-thin limit and the extinction limit in which the bubble vanishes being described by what is in effect a similarity solution of the second kind. This same solution describes the generic (slit-like) extinction behaviour for shear-thickening fluids, the interface profiles that generalise the ellipses that characterise the Newtonian case being constructed by the Wiener-Hopf calculation.

A chimeric vitronectin : IGF-I protein supports feeder-cell-free and serum-free culture of human embryonic stem cells

This paper was retracted by the Journal of Stem Cells and Development on February 15, 2013.

Differences between in vitro viability and differentiation and in vivo bone-forming efficacy of human mesenchymal stem cells cultured on PCL-TCP scaffolds

Human mesenchymal stem cells (hMSCs) possess great therapeutic potential for the treatment of bone disease and fracture non-union. Too often however, in vitro evidence alone of the interaction between hMSCs and the biomaterial of choice is used as justification for continued development of the material into the clinic. Clearly for hMSC-based regenerative medicine to be successful for the treatment of orthopaedic trauma, it is crucial to transplant hMSCs with a suitable carrier that facilitates their survival, optimal proliferation and osteogenic differentiation in vitro and in vivo. This motivated us to evaluate the use of polycaprolactone-20% tricalcium phosphate (PCL-TCP) scaffolds produced by fused deposition modeling for the delivery of hMSCs. When hMSCs were cultured on the PCL-TCP scaffolds and imaged by a combination of phase contrast, scanning electron and confocal laser microscopy, we observed five distinct stages of colonization over a 21-day period that were characterized by cell attachment, spreading, cellular bridging, the formation of a dense cellular mass and the accumulation of a mineralized extracellular matrix when induced with osteogenic stimulants. Having established that PCL-TCP scaffolds are able to support hMSC proliferation and osteogenic differentiation, we next tested the in vivo efficacy of hMSC-loaded PCL-TCP scaffolds in nude rat critical-sized femoral defects. We found that fluorescently labeled hMSCs survived in the defect site for up to 3 weeks post-transplantation. However, only 50% of the femoral defects treated with hMSCs responded favorably as determined by new bone volume. As such, we show that verification of hMSC viability and differentiation in vitro is not sufficient to predict the efficacy of transplanted stem cells to consistently promote bone formation in orthotopic defects in vivo.

Monitoring and regulatory role of the balanced scorecard in controlling organisational identities

This thesis employs the theoretical fusion of disciplinary knowledge, interlacing an analysis from both functional and interpretive frameworks and applies these paradigms to three concepts—organisational identity, the balanced scorecard performance measurement system, and control. As an applied thesis, this study highlights how particular public sector organisations are using a range of multi-disciplinary forms of knowledge constructed for their needs to achieve practical outcomes. Practical evidence of this study is not bound by a single disciplinary field or the concerns raised by academics about the rigorous application of academic knowledge. The study’s value lies in its ability to explore how current communication and accounting knowledge is being used for practical purposes in organisational life. The main focus of this thesis is on identities in an organisational communication context. In exploring the theoretical and practical challenges, the research questions for this thesis were formulated as: 1. Is it possible to effectively control identities in organisations by the use of an integrated performance measurement system—the balanced scorecard—and if so, how? 2. What is the relationship between identities and an integrated performance measurement system—the balanced scorecard—in the identity construction process? Identities in the organisational context have been extensively discussed in graphic design, corporate communication and marketing, strategic management, organisational behaviour, and social psychology literatures. Corporate identity is the self-presentation of the personality of an organisation (Van Riel, 1995; Van Riel & Balmer, 1997), and organisational identity is the statement of central characteristics described by members (Albert & Whetten, 2003). In this study, identity management is positioned as a strategically complex task, embracing not only logo and name, but also multiple dimensions, levels and facets of organisational life. Responding to the collaborative efforts of researchers and practitioners in identity conceptualisation and methodological approaches, this dissertation argues that analysis can be achieved through the use of an integrated framework of identity products, patternings and processes (Cornelissen, Haslam, & Balmer, 2007), transforming conceptualisations of corporate identity, organisational identity and identification studies. Likewise, the performance measurement literature from the accounting field now emphasises the importance of ‘soft’ non-financial measures in gauging performance—potentially allowing the monitoring and regulation of ‘collective’ identities (Cornelissen et al., 2007). The balanced scorecard (BSC) (Kaplan & Norton, 1996a), as the selected integrated performance measurement system, quantifies organisational performance under the four perspectives of finance, customer, internal process, and learning and growth. Broadening the traditional performance measurement boundary, the BSC transforms how organisations perceived themselves (Vaivio, 2007). The rhetorical and communicative value of the BSC has also been emphasised in organisational self-understanding (Malina, Nørreklit, & Selto, 2007; Malmi, 2001; Norreklit, 2000, 2003). Thus, this study establishes a theoretical connection between the controlling effects of the BSC and organisational identity construction. Common to both literatures, the aspects of control became the focus of this dissertation, as ‘the exercise or act of achieving a goal’ (Tompkins & Cheney, 1985, p. 180). This study explores not only traditional technical and bureaucratic control (Edwards, 1981), but also concertive control (Tompkins & Cheney, 1985), shifting the locus of control to employees who make their own decisions towards desired organisational premises (Simon, 1976). The controlling effects on collective identities are explored through the lens of the rhetorical frames mobilised through the power of organisational enthymemes (Tompkins & Cheney, 1985) and identification processes (Ashforth, Harrison, & Corley, 2008). In operationalising the concept of control, two guiding questions were developed to support the research questions: 1.1 How does the use of the balanced scorecard monitor identities in public sector organisations? 1.2 How does the use of the balanced scorecard regulate identities in public sector organisations? This study adopts qualitative multiple case studies using ethnographic techniques. Data were gathered from interviews of 41 managers, organisational documents, and participant observation from 2003 to 2008, to inform an understanding of organisational practices and members’ perceptions in the five cases of two public sector organisations in Australia. Drawing on the functional and interpretive paradigms, the effective design and use of the systems, as well as the understanding of shared meanings of identities and identifications are simultaneously recognised. The analytical structure guided by the ‘bracketing’ (Lewis & Grimes, 1999) and ‘interplay’ strategies (Schultz & Hatch, 1996) preserved, connected and contrasted the unique findings from the multi-paradigms. The ‘temporal bracketing’ strategy (Langley, 1999) from the process view supports the comparative exploration of the analysis over the periods under study. The findings suggest that the effective use of the BSC can monitor and regulate identity products, patternings and processes. In monitoring identities, the flexible BSC framework allowed the case study organisations to monitor various aspects of finance, customer, improvement and organisational capability that included identity dimensions. Such inclusion legitimises identity management as organisational performance. In regulating identities, the use of the BSC created a mechanism to form collective identities by articulating various perspectives and causal linkages, and through the cascading and alignment of multiple scorecards. The BSC—directly reflecting organisationally valued premises and legitimised symbols—acted as an identity product of communication, visual symbols and behavioural guidance. The selective promotion of the BSC measures filtered organisational focus to shape unique identity multiplicity and characteristics within the cases. Further, the use of the BSC facilitated the assimilation of multiple identities by controlling the direction and strength of identifications, engaging different groups of members. More specifically, the tight authority of the BSC framework and systems are explained both by technical and bureaucratic controls, while subtle communication of organisational premises and information filtering is achieved through concertive control. This study confirms that these macro top-down controls mediated the sensebreaking and sensegiving process of organisational identification, supporting research by Ashforth, Harrison and Corley (2008). This study pays attention to members’ power of self-regulation, filling minor premises of the derived logic of their organisation through the playing out of organisational enthymemes (Tompkins & Cheney, 1985). Members are then encouraged to make their own decisions towards the organisational premises embedded in the BSC, through the micro bottom-up identification processes including: enacting organisationally valued identities; sensemaking; and the construction of identity narratives aligned with those organisationally valued premises. Within the process, the self-referential effect of communication encouraged members to believe the organisational messages embedded in the BSC in transforming collective and individual identities. Therefore, communication through the use of the BSC continued the self-producing of normative performance mechanisms, established meanings of identities, and enabled members’ self-regulation in identity construction. Further, this research establishes the relationship between identity and the use of the BSC in terms of identity multiplicity and attributes. The BSC framework constrained and enabled case study organisations and members to monitor and regulate identity multiplicity across a number of dimensions, levels and facets. The use of the BSC constantly heightened the identity attributes of distinctiveness, relativity, visibility, fluidity and manageability in identity construction over time. Overall, this research explains the reciprocal controlling relationships of multiple structures in organisations to achieve a goal. It bridges the gap among corporate and organisational identity theories by adopting Cornelissen, Haslam and Balmer’s (2007) integrated identity framework, and reduces the gap in understanding between identity and performance measurement studies. Parallel review of the process of monitoring and regulating identities from both literatures synthesised the theoretical strengths of both to conceptualise and operationalise identities. This study extends the discussion on positioning identity, culture, commitment, and image and reputation measures in integrated performance measurement systems as organisational capital. Further, this study applies understanding of the multiple forms of control (Edwards, 1979; Tompkins & Cheney, 1985), emphasising the power of organisational members in identification processes, using the notion of rhetorical organisational enthymemes. This highlights the value of the collaborative theoretical power of identity, communication and performance measurement frameworks. These case studies provide practical insights about the public sector where existing bureaucracy and desired organisational identity directions are competing within a large organisational setting. Further research on personal identity and simple control in organisations that fully cascade the BSC down to individual members would provide enriched data. The extended application of the conceptual framework to other public and private sector organisations with a longitudinal view will also contribute to further theory building.

Solving navigational uncertainty using grid cells on robots

To successfully navigate their habitats, many mammals use a combination of two mechanisms, path integration and calibration using landmarks, which together enable them to estimate their location and orientation, or pose. In large natural environments, both these mechanisms are characterized by uncertainty: the path integration process is subject to the accumulation of error, while landmark calibration is limited by perceptual ambiguity. It remains unclear how animals form coherent spatial representations in the presence of such uncertainty. Navigation research using robots has determined that uncertainty can be effectively addressed by maintaining multiple probabilistic estimates of a robot's pose. Here we show how conjunctive grid cells in dorsocaudal medial entorhinal cortex (dMEC) may maintain multiple estimates of pose using a brain-based robot navigation system known as RatSLAM. Based both on rodent spatially-responsive cells and functional engineering principles, the cells at the core of the RatSLAM computational model have similar characteristics to rodent grid cells, which we demonstrate by replicating the seminal Moser experiments. We apply the RatSLAM model to a new experimental paradigm designed to examine the responses of a robot or animal in the presence of perceptual ambiguity. Our computational approach enables us to observe short-term population coding of multiple location hypotheses, a phenomenon which would not be easily observable in rodent recordings. We present behavioral and neural evidence demonstrating that the conjunctive grid cells maintain and propagate multiple estimates of pose, enabling the correct pose estimate to be resolved over time even without uniquely identifying cues. While recent research has focused on the grid-like firing characteristics, accuracy and representational capacity of grid cells, our results identify a possible critical and unique role for conjunctive grid cells in filtering sensory uncertainty. We anticipate our study to be a starting point for animal experiments that test navigation in perceptually ambiguous environments.

Public regulatory reform and management earnings forecasts in a low private litigation environment

We examine the impact of continuous disclosure regulatory reform on the likelihood, frequency and qualitative characteristics of management earnings forecasts issued in New Zealand’s low private litigation environment. Using a sample of 720 earnings forecasts issued by 94 firms listed on the New Zealand Exchange before and after the reform (1999–2005), we provide strong evidence of significant changes in forecasting behaviour in the post-reform period. Specifically, firms were more likely to issue earnings forecasts to pre-empt earnings announcements and, in contrast to findings in other legal settings, those earnings forecasts exhibited higher frequency and improved qualitative characteristics (better precision and accuracy). An important implication of our findings is that public regulatory reforms may have a greater benefit in a low private litigation environment and thus add to the global debate about the effectiveness of alternative public regulatory reforms of corporate requirements.

Ovine cortical osteoblasts outperform bone marrow cells in an ectopic bone assay

Reviewing the available literature, one could conclude that marrow-derived mesenchymal stem cells (BMSCs) are the ‘gold standard’ source for bone tissue engineering applications, due to their multilineage differentiation potential and easy accessibility. However, comprehensive studies comparing their osteogenic potential with bone-derived osteoblasts (OBs) to justify the preferred application of BMSCs based on performance are few. To address these shortfalls, in the present study, ovine BMSCs and OBs seeded onto scaffolds were characterized in vitro and transplanted subcutaneously into NOD/SCID mice in combination with and without recombinant human bone morphogenetic protein 7 (rhBMP-7). It was hypothesized that cell origin, ossification type and degree of vascularization and ossification depends on the nature and commitment of transplanted cells and stimulating growth factors, such as rhBMP-7. After retrieval, specimens were analysed by biomechanical testing, µCT analysis, scanning electron microscopy/energy-dispersive X-ray spectroscopy and histo- and immunohistochemistry for osteocalcin, type II collagen and BrdU. The results showed a high degree of cell survival and proliferation ectopically, resulting in active contribution to endochondral osteogenesis. When compared to BMSCs, OBs showed a higher degree of bone deposition while OB-derived bone was of higher maturation. Stimulation with rhBMP-7 increased the rate of bone synthesis for both BMSCs and OBs, additionally promoting neovascularization and osteoclast activity. These results suggest that the origin and commitment of transplanted cells highly influence the type and degree of ossification, that rhBMP-7 represents a powerful adjuvant for bone tissue-engineering applications, and that mature bone is an adequate alternative cell source for bone tissue-engineering applications.

Chlamydial infection of immune cells : altered function and implications for disease

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects the genital and ocular mucosa of humans, causing infections that can lead to pelvic inflammatory disease, infertility, and blinding trachoma. C. pneumoniae is a respiratory pathogen that is the cause of 12–15% of community-acquired pneumonia. Both chlamydial species were believed to be restricted to the epithelia of the genital, ocular, and respiratory mucosa; however, increasing evidence suggests that both these pathogens can be isolated from peripheral blood of both healthy individuals and patients with inflammatory conditions such as coronary artery disease and asthma. Chlamydia can also be isolated from brain tissues of patients with degenerative neurological disorders such as Alzheimer’s disease and multiple sclerosis, and also from certain lymphomas. An increasing number of in vitro studies suggest that some chlamydial species can infect immune cells, at least at low levels. These infections may alter immune cell function in a way that promotes chlamydial persistence in the host and contributes to the progression of several chronic inflammatory diseases. In this paper, we review the evidence for the growth of Chlamydia in immune cells, particularly monocytes/macrophages and dendritic cells, and describe how infection may affect the function of these cells.