Unsettling portrait of family strife

Review of 'The Wishing Well', Queensland Theatre Company, published in The Australian, 30 March 2009.

Kallikrein-related peptidase 4 activation of protease-activated receptor family members and association with prostate cancer

Two areas of particular importance in prostate cancer progression are primary tumour development and metastasis. These processes involve a number of physiological events, the mediators of which are still being discovered and characterised. Serine proteases have been shown to play a major role in cancer invasion and metastasis. The recently discovered phenomenon of their activation of a receptor family known as the protease activated receptors (PARs) has extended their physiological role to that of signaling molecule. Several serine proteases are expressed by malignant prostate cancer cells, including members of the kallikreinrelated peptidase (KLK) serine protease family, and increasingly these are being shown to be associated with prostate cancer progression. KLK4 is highly expressed in the prostate and expression levels increase during prostate cancer progression. Critically, recent studies have implicated KLK4 in processes associated with cancer. For example, the ectopic over-expression of KLK4 in prostate cancer cell lines results in an increased ability of these cells to form colonies, proliferate and migrate. In addition, it has been demonstrated that KLK4 is a potential mediator of cellular interactions between prostate cancer cells and osteoblasts (bone forming cells). The ability of KLK4 to influence cellular behaviour is believed to be through the selective cleavage of specific substrates. Identification of relevant in vivo substrates of KLK4 is critical to understanding the pathophysiological roles of this enzyme. Significantly, recent reports have demonstrated that several members of the KLK family are able to activate PARs. The PARs are relatively new members of the seven transmembrane domain containing G protein coupled receptor (GPCR) family. PARs are activated through proteolytic cleavage of their N-terminus by serine proteases, the resulting nascent N-terminal binds intramolecularly to initiate receptor activation. PARs are involved in a number of patho-physiological processes, including vascular repair and inflammation, and a growing body of evidence suggests roles in cancer. While expression of PAR family members has been documented in several types of cancers, including prostate, the role of these GPCRs in prostate cancer development and progression is yet to be examined. Interestingly, several studies have suggested potential roles in cellular invasion through the induction of cytoskeletal reorganisation and expression of basement membrane-degrading enzymes. Accordingly, this program of research focussed on the activation of the PARs by the prostate cancer associated enzyme KLK4, cellular processing of activated PARs and the expression pattern of receptor and agonist in prostate cancer. For these studies KLK4 was purified from the conditioned media of stably transfected Sf9 insect cells expressing a construct containing the complete human KLK4 coding sequence in frame with a V5 epitope and poly-histidine encoding sequences. The first aspect of this study was the further characterisation of this recombinant zymogen form of KLK4. The recombinant KLK4 zymogen was demonstrated to be activatable by the metalloendopeptidase thermolysin and amino terminal sequencing indicated that thermolysin activated KLK4 had the predicted N-terminus of mature active KLK4 (31IINED). Critically, removal of the pro-region successfully generated a catalytically active enzyme, with comparable activity to a previously published recombinant KLK4 produced from S2 insect cells. The second aspect of this study was the activation of the PARs by KLK4 and the initiation of signal transduction. This study demonstrated that KLK4 can activate PAR-1 and PAR-2 to mobilise intracellular Ca2+, but failed to activate PAR-4. Further, KLK4 activated PAR-1 and PAR-2 over distinct concentration ranges, with KLK4 activation and mobilisation of Ca2+ demonstrating higher efficacy through PAR-2. Thus, the remainder of this study focussed on PAR-2. KLK4 was demonstrated to directly cleave a synthetic peptide that mimicked the PAR-2 Nterminal activation sequence. Further, KLK4 mediated Ca2+ mobilisation through PAR-2 was accompanied by the initiation of the extra-cellular regulated kinase (ERK) cascade. The specificity of intracellular signaling mediated through PAR-2 by KLK4 activation was demonstrated by siRNA mediated protein depletion, with a reduction in PAR-2 protein levels correlating to a reduction in KLK4 mediated Ca2+mobilisation and ERK phosphorylation. The third aspect of this study examined cellular processing of KLK4 activated PAR- 2 in a prostate cancer cell line. PAR-2 was demonstrated to be expressed by five prostate derived cell lines including the prostate cancer cell line PC-3. It was also demonstrated by flow cytometry and confocal microscopy analyses that activation of PC-3 cell surface PAR-2 by KLK4 leads to internalisation of this receptor in a time dependent manner. Critically, in vivo relevance of the interaction between KLK4 and PAR-2 was established by the observation of the co-expression of receptor and agonist in primary prostate cancer and prostate cancer bone lesion samples by immunohistochemical analysis. Based on the results of this study a number of exciting future studies have been proposed, including, delineating differences in KLK4 cellular signaling via PAR-1 and PAR-2 and the role of PAR-1 and PAR-2 activation by KLK4 in prostate cancer cells and bone cells in prostate cancer progression.

Optimal monitoring in family-owned companies? Evidence from Asia

Manuscript Type: Empirical Research Issue: We propose that high levels of monitoring are not always in the best interests of minority shareholders. In family-owned companies the optimal level of board monitoring required by minority shareholders is expected to be lower than that of other companies. This is because the relative benefits and costs of monitoring are different in family-owned companies. Research Findings: At moderate levels of board monitoring, we find concave relationships between board monitoring variables and firm performance for family-owned companies but not for other companies. The optimal level of board monitoring for our sample of Asian family-owned companies equates to board independence of 38%, separation of the Chairman and CEO positions and establishment of audit and remuneration committees. Additional testing shows that the optimal level of board monitoring is sensitive to the magnitude of the agency conflict between the family group and minority shareholders and the presence of substitute monitoring. Practitioner/Policy Implications: For policymakers, the results show that more monitoring is not always in the best interests of minority shareholders. Therefore, it may be inappropriate for regulators to advise all companies to follow the same set of corporate governance guidelines. However, our results also indicate that the board governance practices of family-owned companies are still well below the identified optimal levels. Keywords: Corporate Governance, Board Independence, Board of Directors, Family Firms, Monitoring.

A new family of multi-output DC-DC converter topologies to supply an asymmetrical four-level diode-clamped inverter

Purpose Multi-level diode-clamped inverters have the challenge of capacitor voltage balancing when the number of DC-link capacitors is three or more. On the other hand, asymmetrical DC-link voltage sources have been applied to increase the number of voltage levels without increasing the number of switches. The purpose of this paper is to show that an appropriate multi-output DC-DC converter can resolve the problem of capacitor voltage balancing and utilize the asymmetrical DC-link voltages advantages. Design/methodology/approach A family of multi-output DC-DC converters is presented in this paper. The application of these converters is to convert the output voltage of a photovoltaic (PV) panel to regulate DC-link voltages of an asymmetrical four-level diode-clamped inverter utilized for domestic applications. To verify the versatility of the presented topology, simulations have been directed for different situations and results are presented. Some related experiments have been developed to examine the capabilities of the proposed converters. Findings The three-output voltage-sharing converters presented in this paper have been mathematically analysed and proven to be appropriate to improve the quality of the residential application of PV by means of four-level asymmetrical diode-clamped inverter supplying highly resistive loads. Originality/value This paper shows that an appropriate multi-output DC-DC converter can resolve the problem of capacitor voltage balancing and utilize the asymmetrical DC-link voltages advantages and that there is a possibility of operation at high-modulation index despite reference voltage magnitude and power factor variations.

Farm it right : the sustainable farming simulation

Farm It Right is an innovative creative work that simulates sustainable farming techniques using ecological models prepared by academics at Bradford University (School of Life Sciences). This interactive work simulates the farming conditions and options of our ancestors and demonstrates the direct impact their actions had on their environment and on the ’future of their cultures’ (Schmidt 2008). Specifically, the simulation allows users to explore and experiment with the complex relationships between environmental factors and human decision making within the harsh conditions of an early (9th century) Nordic farm. The simulation interface displays both statistical and graphical feedback in response to the users selections regarding animal reproduction rates, shelter provisions, food supplies etc. as well as demonstrating resulting impacts to soil erosion, water supply, animal population sizes etc.---------- 'Farm It Right' is now used at Bradford University (School of Life Sciences) as a dynamic e-Learning resource for incorporating environmental archaeology with sustainable development education, improving the engagement with complex data and the appreciation of human impacts on the environment and the future of their cultures. 'Farm It Right' is also demonstrated as an exemplar case study for interaction design students at Queensland University of Technology.

In search of good governance for Asian family listed companies : a case study on Hong Kong

Discusses the importation of Western concepts of corporate governance into Hong Kong where many companies are family companies to which Asian culture is more familiar. Considers different models of corporate governance and questions the application of Western structures to family owned companies. Examines the weaknesses inherent in the typical structure of Asian companies, particularly from the point of view of minority shareholders. Suggests that a system of governance based on Confucian philosophy may be more effective in Hong Kong.

Combining the parts to make the whole : integrated child and family services in Queensland

Over the past decade, the promotion of 'integrated child and family services' has emerged as a strong and consistent theme within Australian early childhood policy. Fuelling this trend is the belief that integrated service provision is more responsive to holistic family needs, offering better support to parents and thereby promoting better outcomes for young children. Adding further strength is the prevention and early intervention literature, and suggested social and economic benefits of 'effective' early years services and supports. States and territories are introducing new integrated child and family service models and Reflections is continuing to profile these. In this edition, we look at directions and new service models in Queensland, in particular, the new Early Years Centre service model.

Role of farm real estate in a globally diversified asset portfolio

Purpose - The paper examines the benefits of further diversifying a global portfolio of financial assets with New Zealand farm real estate (FRE). ---------- Design/methodology/approach - We compare efficient sets generated with and without farm real estate using portfolio theory. ---------- Findings - The results show that given the predominantly negative correlation between FRE and financial assets, the risk-return tradeoffs of portfolios of financial assets can be improved significantly. The diversification benefits measured in terms of risk reduction, return enhancement, and improvement in the Sharpe performance ratios are robust under a number of FRE risk-return scenarios as well as under high and low inflationary periods. Using 5- and 10-year rolling periods we also find that FRE is a consistent part of risk efficient portfolios. Consistent with the results reported in Lee and Stevenson (2006) for UK real estate the risk reduction benefits of diversifying with FRE are larger than the risk enhancement benefits. ---------- Practical implication - The results suggest that FRE takes on a consistent role of risk-reducer rather than a return-enhancer in a globally diversified portfolio. FRE appears to deserve more serious consideration by investment practitioners that it has been accorded in the past. Originality/value – The study examines the role of direct real estate in a globally diversified portfolio of financial assets.

Results from the farm

This paper reports on a large, long-term mobile wireless sensor network deployment. The trial was part of an animal study involving 45 animals. During the trial, 15 animals were equipped with wireless sensor nodes for a week. The paper discusses various issues with such a deployment including electronic design, software design, animal ethics clearance, logistics, and wearable computing equipment for animals. The paper also presents some preliminary analysis of the data obtained from the deployment, both from the perspective of network parameters and animal movement behavior.

Wireless adhoc sensor and actuator networks on the farm

Agriculture accounts for a significant portion of the GDP in most developed countries. However, managing farms, particularly largescale extensive farming systems, is hindered by lack of data and increasing shortage of labour. We have deployed a large heterogeneous sensor network on a working farm to explore sensor network applications that can address some of the issues identified above. Our network is solar powered and has been running for over 6 months. The current deployment consists of over 40 moisture sensors that provide soil moisture profiles at varying depths, weight sensors to compute the amount of food and water consumed by animals, electronic tag readers, up to 40 sensors that can be used to track animal movement (consisting of GPS, compass and accelerometers), and 20 sensor/actuators that can be used to apply different stimuli (audio, vibration and mild electric shock) to the animal. The static part of the network is designed for 24/7 operation and is linked to the Internet via a dedicated high-gain radio link, also solar powered. The initial goals of the deployment are to provide a testbed for sensor network research in programmability and data handling while also being a vital tool for scientists to study animal behavior. Our longer term aim is to create a management system that completely transforms the way farms are managed.