Computational analyses of the catalytic and heparin-binding sites and their interactions with glycosaminoglycans in glycoside hydrolase family 79 endo-d-glucuronidase (heparanase)

Mammalian heparanase is an endo-β-glucuronidase associated with cell invasion in cancer metastasis, angiogenesis and inflammation. Heparanase cleaves heparan sulfate proteoglycans in the extracellular matrix and basement membrane, releasing heparin/heparan sulfate oligosaccharides of appreciable size. This in turn causes the release of growth factors, which accelerate tumor growth and metastasis. Heparanase has two glycosaminoglycan-binding domains; however, no three-dimensional structure information is available for human heparanase that can provide insights into how the two domains interact to degrade heparin fragments. We have constructed a new homology model of heparanase that takes into account the most recent structural and bioinformatics data available. Heparin analogs and glycosaminoglycan mimetics were computationally docked into the active site with energetically stable ring conformations and their interaction energies were compared. The resulting docked structures were used to propose a model for substrates and conformer selectivity based on the dimensions of the active site. The docking of substrates and inhibitors indicates the existence of a large binding site extending at least two saccharide units beyond the cleavage site (toward the nonreducing end) and at least three saccharides toward the reducing end (toward heparin-binding site 2). The docking of substrates suggests that heparanase recognizes the N-sulfated and O-sulfated glucosamines at subsite +1 and glucuronic acid at the cleavage site, whereas in the absence of 6-O-sulfation in glucosamine, glucuronic acid is docked at subsite +2. These findings will help us to focus on the rational design of heparanase-inhibiting molecules for anticancer drug development by targeting the two heparin/heparan sulfate recognition domains.

The Expanded Human Kallikrein (KLK) gene family : genomic organisation, tissue specific expression and potential functions

The tissue kallikreins are serine proteases encoded by highly conserved multigene families. The rodent kallikrein (KLK) families are particularly large, consisting of 13 26 genes clustered in one chromosomal locus. It has been recently recognised that the human KLK gene family is of a similar size (15 genes) with the identification of another 12 related genes (KLK4-KLK15) within and adjacent to the original human KLK locus (KLK1-3) on chromosome 19q13.4. The structural organisation and size of these new genes is similar to that of other KLK genes except for additional exons encoding 5 or 3 untranslated regions. Moreover, many of these genes have multiple mRNA transcripts, a trait not observed with rodent genes. Unlike all other kallikreins, the KLK4-KLK15 encoded proteases are less related (25–44%) and do not contain a conventional kallikrein loop. Clusters of genes exhibit high prostatic (KLK2-4, KLK15) or pancreatic (KLK6-13) expression, suggesting evolutionary conservation of elements conferring tissue specificity. These genes are also expressed, to varying degrees, in a wider range of tissues suggesting a functional involvement of these newer human kallikrein proteases in a diverse range of physiological processes.

The legality of tissue transplants for the benefit of family members in the UK and Australia : implications for saviour siblings

The ethics of creating ‘saviour siblings’ for the benefit of another has received much attention, but little consideration has been given to the legal position of those saviours born who may be asked to provide tissue for transplantation to another during childhood. This article examines the ethical issues surrounding minor donation as well as the existing legal framework in the UK and Australia that regulates minors providing tissue for the benefit of another. Against this background the position of minor saviours, who are called upon to donate bone marrow or peripheral blood stem cells, is examined. This analysis suggests that the law does not provide sufficient protection for minor saviours who are called upon to donate to another. It is argued that specific ethical obligations are owed to saviours—that ought to be reflected in the law—in order to protect them from exploitation while they remain minors.

Continuation rates and reasons for removal among Implanon® users accessing two family planning clinics in Queensland, Australia

Background - This study examined demographic profile, continuation rates and reasons for removal among Implanon^® users accessing two family planning clinics in Queensland, Australia. Study Design - A retrospective chart audit of 976 women who attended for implant insertion over a 3-year period between May 2001 and May 2004. Results - Continuation rates showed that at 6 months after insertion, 94% of women continued, 74% continued at 1 year and 50% continued at 2 years. Metropolitan women were more likely than rural women to discontinue use because of dissatisfaction with bleeding patterns. Cox regression analysis showed that those attending the regional clinic experienced significantly shorter time to removal. Conclusions - Implanon® continuation rates and reasons for removal differ between clinics in metropolitan and rural locations. A cooling-off period did not affect the likelihood of continuation with Implanon®. Preinsertion counselling should emphasize potential changes in bleeding patterns.

Every player wins a prize? Family provision applications and bequests to charity

This research deals with the interaction of family provision law and charitable bequests in wills, including qualitative research relating to the practical issues arising with both legal practitioners and charities’ bequest officers.

Listening, sharing understanding and facilitating consumer, family and community empowerment through a priority driven partnership in Far North Queensland

Objectives: This paper provides an example of a mental health research partnership underpinned by empowerment principles that seeks to foster strength among community organizations to support better outcomes for consumers, families and communities. It aims to raise awareness among researchers and service providers that empowerment approaches to assist communities to address mental health problems are not too difficult to be practical but require long-term commitment and appropriate support. Methods: A collaborative research strategy that has become known as the Priority Driven Research (PDR) Partnership emerged through literature review,consultations, Family Wellbeing Program delivery with community groups and activities in two discrete Indigenous communities. Progress to date on three of the four components of the strategy is described. Results: The following key needs were identified in a pilot study and are now being addressed in a research-based implementation phase: (i) gaining two-way understanding of perspectives on mental health and promoting universal awareness; (ii) supporting the empowerment of carers, families, consumers and at-risk groups through existing community organizations to gain greater understanding and control of their situation; (iii) developing pathways of care at the primary health centre level to enable support of social and emotional wellbeing as well as more integrated mental health care; (iv) accessing data to enable an ongoing process of analysis/sharing/planning and monitoring to inform future activity. Conclusion: One of the key learnings to emerge in this project so far is that empowerment through partnership becomes possible when there is a concerted effort to strengthen grassroots community organizations. These include social health teams and men’s and women’s groups that can engage local people in an action orientation. Key words: Aboriginal, empowerment, Indigenous, mental health.

The family attitude scale : reliability and validity of a new scale for measuring the emotional climate of families

Research on outcomes from psychiatric disorders has highlighted the importance of expressed emotion (EE), but its cost-effective measurement remains a challenge. This article describes development of the Family Attitude Scale (FAS), a 30-item instrument that can be completed by any informant. Its psychometric characteristics are reported in parents of undergraduate students and in 70 families with a schizophrenic member. The total FAS had high internal consistency in all samples, and reports of angry behaviour in FAS items showed acceptable inter-rater agreement. The FAS was associated with the reported anger, anger expression and anxiety of respondents. Substantial associations between the parents' FAS and the anger and anger expression of students was also observed. Parents of schizophrenic patients had higher FAS scores than parents of students, and the FAS was higher if disorder duration was longer or patient functioning was poorer. Hostility, high criticism and low warmth on the Camberwell Family Interview (CFI) were associated with a more negative FAS. The highest FAS in the family was a good predictor of a highly critical environment on the CFI. The FAS is a reliable and valid indicator of relationship stress and expressed anger that has wide applicability.

Application of cognitive-behavioural family intervention for schizophrenia in multidisciplinary teams : what can the matter be?

Surveyed 45 therapists who had participated in a family intervention for schizophrenia training program to examine the difficulties they had encountered, their recall of the intervention strategies, and the extent that they thought the approach had become integrated in their everyday work. Between 6 mo and 3 yrs after the family training, Ss reported the number of families they had systematically treated, and the difficulties they had encountered. Allowance of time to undertake the intervention, afterhours scheduling, and illness or holidays presented particular difficulties. Only 4% reported that their knowledge of behavioral techniques was a problem, but in a written test most therapists did not display minimum recall of the material of cognitive therapy, social skills training, or behavioral strategies. The study demonstrated significant problems in disseminating cognitive-behavioral approaches to multidisciplinary settings.

Slice of Brisbane in family shadows

Review of 'The True Story of Butterfish', Brisbane Festival / Brisbane Powerhouse, published in The Australian, 6 October 2009.

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.

Micro-family-owned business : transitory survival mechanism or long term wealth creator?

Principal Topic: Entrepreneurship is key to employment, innovation and growth (Acs & Mueller, 2008), and as such, has been the subject of tremendous research in both the economic and management literatures since Solow (1957), Schumpeter (1934, 1943), and Penrose (1959). The presence of entrepreneurs in the economy is a key factor in the success or failure of countries to grow (Audretsch and Thurik, 2001; Dejardin, 2001). Further studies focus on the conditions of existence of entrepreneurship, influential factors invoked are historical, cultural, social, institutional, or purely economic (North, 1997; Thurik 1996 & 1999). Of particular interest, beyond the reasons behind the existence of entrepreneurship, are entrepreneurial survival and good ''performance'' factors. Using cross-country firm data analysis, La Porta & Schleifer (2008) confirm that informal micro-businesses provide on average half of all economic activity in developing countries. They find that these are utterly unproductive compared to formal firms, and conclude that the informal sector serves as a social security net ''keep[ing] millions of people alive, but disappearing over time'' (abstract). Robison (1986), Hill (1996, 1997) posit that the Indonesian government under Suharto always pointed to the lack of indigenous entrepreneurship , thereby motivating the nationalisation of all industries. Furthermore, the same literature also points to the fact that small businesses were mostly left out of development programmes because they were supposed less productive and having less productivity potential than larger ones. Vial (2008) challenges this view and shows that small firms represent about 70% of firms, 12% of total output, but contribute to 25% of total factor productivity growth on average over the period 1975-94 in the industrial sector (Table 10, p.316). ---------- Methodology/Key Propositions: A review of the empirical literature points at several under-researched questions. Firstly, we assess whether there is, evidence of small family-business entrepreneurship in Indonesia. Secondly, we examine and present the characteristics of these enterprises, along with the size of the sector, and its dynamics. Thirdly, we study whether these enterprises underperform compared to the larger scale industrial sector, as it is suggested in the literature. We reconsider performance measurements for micro-family owned businesses. We suggest that, beside productivity measures, performance could be appraised by both the survival probability of the firm, and by the amount of household assets formation. We compare micro-family-owned and larger industrial firms' survival probabilities after the 1997 crisis, their capital productivity, then compare household assets of families involved in business with those who do not. Finally, we examine human and social capital as moderators of enterprises' performance. In particular, we assess whether a higher level of education and community participation have an effect on the likelihood of running a family business, and whether it has an impact on households' assets level. We use the IFLS database compiled and published by RAND Corporation. The data is a rich community, households, and individuals panel dataset in four waves: 1993, 1997, 2000, 2007. We now focus on the waves 1997 and 2000 in order to investigate entrepreneurship behaviours in turbulent times, i.e. the 1997 Asian crisis. We use aggregate individual data, and focus on households data in order to study micro-family-owned businesses. IFLS data covers roughly 7,600 households in 1997 and over 10,000 households in 2000, with about 95% of 1997 households re-interviewed in 2000. Households were interviewed in 13 of the 27 provinces as defined before 2001. Those 13 provinces were targeted because accounting for 83% of the population. A full description of the data is provided in Frankenberg and Thomas (2000), and Strauss et alii (2004). We deflate all monetary values in Rupiah with the World Development Indicators Consumer Price Index base 100 in 2000. ---------- Results and Implications: We find that in Indonesia, entrepreneurship is widespread and two thirds of households hold one or several family businesses. In rural areas, in 2000, 75% of households run one or several businesses. The proportion of households holding both a farm and a non farm business is higher in rural areas, underlining the reliance of rural households on self-employment, especially after the crisis. Those businesses come in various sizes from very small to larger ones. The median business production value represents less than the annual national minimum wage. Figures show that at least 75% of farm businesses produce less than the annual minimum wage, with non farm businesses being more numerous to produce the minimum wage. However, this is only one part of the story, as production is not the only ''output'' or effect of the business. We show that the survival rate of those businesses ranks between 70 and 82% after the 1997 crisis, which contrasts with the 67% survival rate for the formal industrial sector (Ter Wengel & Rodriguez, 2006). Micro Family Owned Businesses might be relatively small in terms of production, they also provide stability in times of crisis. For those businesses that provide business assets figures, we show that capital productivity is fairly high, with rates that are ten times higher for non farm businesses. Results show that households running a business have larger family assets, and households are better off in urban areas. We run a panel logit model in order to test the effect of human and social capital on the existence of businesses among households. We find that non farm businesses are more likely to appear in households with higher human and social capital situated in urban areas. Farm businesses are more likely to appear in lower human capital and rural contexts, while still being supported by community participation. The estimation of our panel data model confirm that households are more likely to have higher family assets if situated in urban area, the higher the education level, the larger the assets, and running a business increase the likelihood of having larger assets. This is especially true for non farm businesses that have a clearly larger and more significant effect on assets than farm businesses. Finally, social capital in the form of community participation also has a positive effect on assets. Those results confirm the existence of a strong entrepreneurship culture among Indonesian households. Investigating survival rates also shows that those businesses are quite stable, even in the face of a violent crisis such as the 1997 one, and as a result, can provide a safety net. Finally, considering household assets - the returns of business to the household, rather than profit or productivity - the returns of business to itself, shows that households running a business are better off. While we demonstrate that uman and social capital are key to business existence, survival and performance, those results open avenues for further research regarding the factors that could hamper growth of those businesses in terms of output and employment.

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.