Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells

Patients with metastatic melanoma or multiple myeloma have a dismal prognosis because these aggressive malignancies resist conventional treatment. A promising new oncologic approach uses molecularly targeted therapeutics that overcomes apoptotic resistance and, at the same time, achieves tumor selectivity. The unexpected selectivity of proteasome inhibition for inducing apoptosis in cancer cells, but not in normal cells, prompted us to define the mechanism of action for this class of drugs, including Food and Drug Administration-approved bortezomib. In this report, five melanoma cell lines and a myeloma cell line are treated with three different proteasome inhibitors (MG-132, lactacystin, and bortezomib), and the mechanism underlying the apoptotic pathway is defined. Following exposure to proteasome inhibitors, effective killing of human melanoma and myeloma cells, but not of normal proliferating melanocytes, was shown to involve p53-independent induction of the BH3-only protein NOXA. Induction of NOXA at the protein level was preceded by enhanced transcription of NOXA mRNA. Engagement of mitochondrial-based apoptotic pathway involved release of cytochrome c, second mitochondria-derived activator of caspases, and apoptosis-inducing factor, accompanied by a proteolytic cascade with processing of caspases 9, 3, and 8 and poly(ADP)-ribose polymerase. Blocking NOXA induction using an antisense (but not control) oligonucleotide reduced the apoptotic response by 30% to 50%, indicating a NOXA-dependent component in the overall killing of melanoma cells. These results provide a novel mechanism for overcoming the apoptotic resistance of tumor cells, and validate agents triggering NOXA induction as potential selective cancer therapeutics for life-threatening malignancies such as melanoma and multiple myeloma.

The role of universities in building prosperous knowledge cities : the Malaysian experience

This paper explores the role and importance of universities, particularly in the Malaysian context, for building prosperous knowledge cities of the rising knowledge economy. It aims to shed light on how universities contribute to the knowledge-based development of Malaysian cities by undertaking a case study investigation. In the case of Bandar Seri Iskandar, the paper scrutinises the creation – from scratch – of a knowledge city, including the establishment of new public and private universities and hence providing a unique opportunity to understand how the idea of the knowledge economy has permeated economic development policy within a developing country context. The research findings reveal that in Malaysia, much like many of the developed countries, universities are being positioned to play a major role in supporting knowledge city (trans)formation. While there has been a tangible success on the spatial development based on a rapid land use change towards accommodating knowledge-intensive land use and activities, the research reports that a more concerted and coordinated effort from academia, public and private sectors are needed to further foster the growth and development of economical, environmental, institutional and social aspects of Bandar Seri Iskandar to become a fully functioning prosperous knowledge city.

Contributions of knowledge-based foundations of universities in knowledge city formation : a Malaysian case study

Purpose – In the 21st Century, as knowledge, technology and education are widely accepted to play key roles in the local economic development, the importance of making space and place for knowledge production is, therefore, on the rise resulting many city administrations and urban policy-makers worldwide restructuring their cities to become highly competitive and creative. Consequently, this has led to a new type of city form, knowledge city, and a new approach in their development, knowledge-based urban development. In this context, knowledge-based foundations of universities are regarded as one of the key elements for knowledge-based urban development and knowledge city formation due to their ability to provide a strong platform for knowledge generation, marketing and transfer. This paper aims to investigate the role and importance of universities and their knowledge-based foundations in the context of developing countries, particularly in Malaysia, in building prosperous knowledge cities of the era of the knowledge economy. Design/Methodology/Approach – The main methodological techniques employed in this research includes: a thorough review of the literature on the role of universities in spatial and socio-economic development of cities; a best practice analysis and policy review of urban and regional development policies targeting to use of university clusters in leveraging knowledge-based development, and; a case study in Malaysia with a review of various policy documents and strategic plans of the local universities and local and state authorities, interviews with key actors, and a trend analysis of local socio-economic and spatial changes. Originality/Value – This paper reports the findings of a pioneering research on examining the role and impact of universities and their knowledge-based foundations, in the context of Malaysia, in building knowledge cities of the era of the knowledge economy. By undertaking a case study investigation in Bandar Seri Iskandar, which is a newly emerging Malaysian knowledge city, located in Perak, Malaysia, the paper sheds light on an important issue of the 21st Century of how universities contribute to the knowledge-based development of cities. Practical Implications – Universities with their rich knowledge-based foundations are increasingly being recognised as knowledge hubs, exercising a strong influence in the intellectual vitality of the city where they are embedded. This paper reveals that universities, in joint action with business and society at large, are necessary prerequisites for constructing and maintaining knowledge societies and, therefore, building prosperous knowledge cities. In light of the literature and case findings, the paper sheds light on the contribution of knowledge-based foundations of universities in knowledge city formation and provides generic recommendations for cities and regions seeking knowledge city transformation.

Cabergoline Decreases Alcohol Drinking and Seeking Behaviors Via Glial Cell Line-Derived Neurotrophic Factor

Background: Cabergoline is an ergotamine derivative that increases the expression of glial cell line-derived neurotrophic factor (GDNF) in vitro. We recently showed that GDNF in the ventral tegmental area (VTA) reduces the motivation to consume alcohol. We therefore set out to determine whether cabergoline administration decreases alcohol-drinking and -seeking behaviors via GDNF. Methods: Reverse transcription polymerase chain reaction (RT-PCR) and Enzyme-Linked ImmunoSorbent Assay (ELISA) were used to measure GDNF levels. Western blot analysis was used for phosphorylation experiments. Operant self-administration in rats and a two-bottle choice procedure in mice were used to assess alcohol-drinking behaviors. Instrumental performance tested during extinction was used to measure alcohol-seeking behavior. The [35S]GTPγS binding assay was used to assess the expression and function of the dopamine D2 receptor (D2R). Results: We found that treatment of the dopaminergic-like cell line SH-SY5Y with cabergoline and systemic administration of cabergoline in rats resulted in an increase in GDNF level and in the activation of the GDNF pathway. Cabergoline treatment decreased alcohol-drinking and -seeking behaviors including relapse, and its action to reduce alcohol consumption was localized to the VTA. Finally, the increase in GDNF expression and the decrease in alcohol consumption by cabergoline were abolished in GDNF heterozygous knockout mice. Conclusions: Together, these findings suggest that cabergoline-mediated upregulation of the GDNF pathway attenuates alcohol-drinking behaviors and relapse. Alcohol abuse and addiction are devastating and costly problems worldwide. This study puts forward the possibility that cabergoline might be an effective treatment for these disorders. © 2009 Society of Biological Psychiatry.

Developing a transition pedagogy : intentional curriculum design in first and final year law programs

This chapter will first consider the rationale for a transition pedagogy for first and final year law students. It then discusses the elements of a transition pedagogy for both years, noting the synergies and differences between programs designed to assist transition into and out of a law degree. In doing so, the authors attempt to explore the extent to which the first year curriculum principles identified by Sally Kift under an Australian Learning and Teaching Council (ALTC) Senior Fellowship may also be applied to the final year university experience. During the course of the discussion, examples are drawn from universities and Law Schools in Australia and internationally which seek to address these imperatives...

Professional capabilities for twenty-first century creative careers : lessons from outstandingly successful Australian artists and designers

Artists and designers are positioned at the centre of the 21st century creative economy. In order to recognise and make the most of the opportunities afforded by this new era, artists and designers still require the creativity, disciplinary depth of knowledge, and technical skills traditionally possessed by professionals in these fields – skills which are a core strength of higher and further art and design education. However, they may also require a range of other, ‘21st century’ creative capabilities which are harder to define, teach for and assess, and are not the focus of traditional art and design pedagogies. This article draws upon the findings of nine in-depth interviews with award-winning Australian artists and designers about their careers and working practices, along with recent international research about the characteristics of the 21st century creative career, in order to highlight the importance of certain professional capabilities for art and design. It discusses the implications of these findings for art and design educators in universities, and curricular and pedagogic considerations associated with embedding these capabilities into undergraduate courses.

Teaching to disrupt preconceptions : education for social justice in the imperial aftermath

In this paper I discuss some of the approaches that I take in challenging student teachers to understand education in global context, rather than in a decontextualized or instrumental way. These approaches draw on my experience of being an educator from the ‘global South’ (the Caribbean) now working in the ‘global North’ (Australia). As the first black teacher that most Australian student teachers have encountered in their entire education, I find that I can offer them provocative educational narratives and questions stemming from a lifetime career in education, studying and working in various roles in schools, colleges, universities and ministries of education in Jamaica, Grenada, Hong Kong, the UK, the USA and Australia. I set out to disrupt the preconceptions of my students as a starting point in a collective journey of thinking differently about education.

Collaborative academic/practitioner research in project management : examples and applications

Purpose – The purpose of this paper is to present a cost-benefit interpretation of academic-practitioner research by describing and analysing several recent relevant examples of academic-practitioner research with a focus on doctoral theses carried out at universities and business schools in clusters of research centred in North America, Australia and Europe. Design/methodology/approach – Using case study examples, a value proposition framework for undertaking collaborative research for higher degree level study is developed and presented. Findings – Value proposition benefits from this level of collaborative research can be summarised as enhancing competencies at the individual and organisational level as well as providing participating universities with high-quality candidates/students and opportunities for industry engagement. The project management (PM) professional bodies can also extend PM knowledge but they need to be prepared to provide active support. Practical implications – A model for better defining the value proposition of collaborative research from a range of stakeholder perspectives is offered that can be adapted for researchers and industry research sponsors. Originality/value – Few papers offer a value proposition framework for explaining collaborative research benefits. This paper addresses that need.

Indigenous knowledge and effective parent–school partnerships : issues and insights

Towards the last decade of the last millennium, Indigenous knowledge was central to international scholarly debates relating to decolonising knowledge. Indigenous scholars, particularly those from Australia, New Zealand, Canada, and the United States, advanced many of these debates. They argued for Indigenous knowledge to be used as the epistemological standpoint for intellectual engagements and the methodology for resisting colonial constructions of the colonised other (Rigney 1997; Smith 1999, 2005). However, the challenge of engaging Indigenous knowledge to inform research and educational processes, in many respects, is still a contested debate in Western-oriented universities and institutions of higher education. This chapter discusses findings of the Parent–School Partnership Initiative (hereafter referred to as PSPI) project conducted by the Oodgeroo Unit staff and the Aboriginal and Torres Strait Islander Education Focus Group for the Caboolture Shire, in South East Queensland. The state government sponsored initiative examined factors that promote and enhance parent–school engagement with students’ schooling, and contributed to Aboriginal and Torres Strait Islander students’ learning and completion of secondary schooling within the participating schools. We argue in this chapter for the importance of recognising Indigenous knowledge and its place in enhancing parent–school partnerships.

Academics’ work and the concept of “profession” : an Australian case study

Universities in Australia and elsewhere have changed considerably in recent years. Inevitably, this has meant that the work of academics has also changed. Academics’ work is of importance because they are key players in universities and universities matter to the nation economically and intellectually in advancing knowledge and its practical application. Through the changes and challenges that have characterised academia in recent years, there is an assumption that academics’ work is representative of a profession. This research study investigates how academics construct their own perspectives regarding the academic "profession". The study is theoretically informed by Freidson’s theory that conceptualises professions as occupations if they are in control of their work rather than it being under the control of either the market or of their employing institutions. Two research questions guide this study. The first question investigates how academics might construct their work in ideal terms and the second one investigates the extent to which such constructions might constitute a "profession". A qualitative case study was conducted within two Australian universities. In all, twenty academics from ten disciplines took part in the study that consisted of a focus group and fifteen individual interviews. The study was conducted in three phases during which a conceptual framework of academics’ work was developed across three versions. This framework acted both a prompt to discussion and as a potential expression of academics’ work. The first version of the framework was developed from the literature during the first phase of the study. This early framework was used during the second phase of the study when five academics took part in a focus group. After the focus group, the second version of the framework was developed and used with fifteen academics in individual interviews during phase three of the study. The third version of the framework was the outcome of a synthesis of the themes that were identified in the data. The discussion data from the focus group and the individual interviews were analysed through a content analysis approach that identified four major themes. The first theme was that academics reported that their work would ideally be located within universities committed to using their expert knowledge to serve the world. The second theme was that academics reported that they wanted sufficient thinking time and reasonable workloads to undertake the intellectual work that they regard as their core responsibility, particularly in relation to undertaking research. They argued against heavy routine administrative workloads and sought a continuation of current flexible working arrangements. The third theme was that teaching qualifications should not be mandated but that there should be a continuation of the present practice of universities offering academics the opportunity to undertake formal teaching qualifications if they wish to. Finally, academics reported that they wanted values that have traditionally mattered to academia to continue to be respected and practised: autonomy, collegiality and collaborative relationships, altruism and service, and intellectual integrity. These themes are sympathetic to Freidson’s theory of professions in all but one matter: the non-mandatory nature of formal qualifications which he regards as absolutely essential for the performance of the complex intellectual work that characterises occupations that are professions. The study places the issue of academic professionalism on the policy agenda for universities wishing to identify academics’ work as a profession. The study contributes a theory-based and data-informed conceptual framework for academics’ work that can be considered in negotiating the nature and extent of their work. The framework provides a means of analysing what "academic professionalism" might mean; it adds specificity to such discussions by exploring a particular definition of profession, namely Freidson’s theory of professions as occupations that are in control of their own work. The study contributes to the development of theories around higher education concepts of academic professionalism and, in so doing, links that theoretical contribution to the wider professions field.

Territorial strategies and regions

The notion of territorial strategy emerged in the 1990s and has become more and more popular since. It refers to that combination of factors purposely assembled by governments, private and public companies, universities, and industrial associations to exploit a specific geographic competitive advantage in order to boost economic growth through the development of entrepreneurial activity and innovation. Three factors are generally considered to be the building blocks of a territorial strategy: natural resources, human capital, and industrial capabilities. Natural resources derive from environ­ mental conditions and represent raw materials or land available in a region. The presence of natural resources characterizes the typology of an industry (related to tourism, oil, wood, fish, and so forth) that exists or could exist in a certain area. Human capital refers to the stock of competences available in a certain region resulting from education and work experience. Industrial capabilities relate to complex constructs of specialized expertise, the confidence to apply knowledge and skills in various contexts and under changing conditions, and an ability repeatedly to improve methods and processes in a specific industry.

Analysing and improving a recruitment process : a teaching case for developing business process improvement capabilities

The demand for Business Process Management (BPM) is rapidly rising and with that, the need for capable BPM professionals is also rising. Yet, only a very few structured BPM training/ education programs are available, across universities and professional trainers globally. The ‘lack of appropriate teaching resources’ has been identified as a critical issue for BPM educators in prior studies. Case-based teaching can be an effective means of educating future BPM professionals. A main reason is that cases create an authentic learning environment where the complexities and challenges of the ‘real world’ can be presented in a narrative enabling the students to develop crucial skills such as problem solving, analysis and creativity-within-constraints, and to apply the tools and techniques within a richer and real (or proxy to real) context. However, so far well documented BPM teaching cases are scarce. This article aims to contribute to address this gap by providing a comprehensive teaching case and teaching notes that facilitates the education of selected process improvement phases, namely identification, modelling, analysis, and improvement. The article is divided into three main parts: (i) Introductory teaching notes, (ii) The case narrative, and (iii) Student activities from the case and teaching notes.

Paramedic empathy levels : results from seven Australian universities

Purpose Evidence suggests that improved empathy behaviours among healthcare professionals directly impacts on healthcare outcomes. However, the ‘nebulous’ properties of empathic behaviour often means that healthcare profession educators fail to incorporate the explicit teaching and assessment of empathy within the curriculum. This represents a potential mismatch between what is taught by universities and what is actually needed in the healthcare industry. The objective of this study was to assess the extent of empathy in paramedic students across seven Australian universities. Methods A cross-sectional study using a paper-based questionnaire employing a convenience sample of first, second, and third year undergraduate paramedic students. Student empathy levels were measured using a standardised self-reporting instrument: Jefferson Scale of Physician Empathy – Health Profession Students (JSPE-HPS). Findings A total of 783 students participated in the study of which 57% were females. The overall JSPE-HPS mean score was 106.74 (SD=14.8). Females had greater mean empathy scores than males 108.69 v 103.58 (p=0.042). First year undergraduate paramedic mean empathy levels were the lowest, 106.29 (SD=15.40) with second years the highest at 107.17 (SD=14.90). Value The overall findings provide a framework for educators to begin constructing guidelines focusing on the need to incorporate, promote and instil empathy into paramedic students in order to better prepare them for future out-of-hospital healthcare practice.

Spot the differences in traditional and social entrepreneurial intention : highlighting the role of human and social capital

There is general agreement in the scientific community that entrepreneurship plays a central role in the growth and development of an economy in rapidly changing environments (Acs & Virgill 2010). In particular, when business activities are regarded as a vehicle for sustainable growth at large, that goes beyond mere economic returns of singular entities, encompassing also social problems and heavily relying on collaborative actions, then we more precisely fall into the domain of ‘social entrepreneurship’(Robinson et al. 2009). In the entrepreneurship literature, prior studies demonstrated the role of intentionality as the best predictor of planned behavior (Ajzen 1991), and assumed that the intention to start a business derives from the perception of desirability and feasibility and from a propensity to act upon an opportunity (Fishbein & Ajzen 1975). Recognizing that starting a business is an intentional act (Krueger et al. 2000) and entrepreneurship is a planned behaviour (Katz & Gartner 1988), models of entrepreneurial intentions have substantial implications for intentionality research in entrepreneurship. The purpose of this paper is to explore the emerging practice of social entrepreneurship by comparing the determinants of entrepreneurial intention in general versus those leading to startups with a social mission. Social entrepreneurial intentions clearly merit to be investigated given that the opportunity identification process is an intentional process not only typical of for profit start-ups, and yet there is a lack of research examining opportunity recognition in social entrepreneurship (Haugh 2005). The key argument is that intentionality in both traditional and social entrepreneurs during the decision-making process of new venture creation is influenced by an individual's perceptions toward opportunities (Fishbein & Ajzen 1975). Besides opportunity recognition, at least two other aspects can substantially influence intentionality: human and social capital (Davidsson, 2003). This paper is set to establish if and to what extent the social intentions of potential entrepreneurs, at the cognitive level, are influenced by opportunities recognition, human capital, and social capital. By applying established theoretical constructs, the paper draws comparisons between ‘for-profit’ and ‘social’ intentionality using two samples of students enrolled in Economy and Business Administration at the University G. d’Annunzio in Pescara, Italy. A questionnaire was submitted to 310 potential entrepreneurs to test the robustness of the model. The collected data were used to measure the theoretical constructs of the paper. Reliability of the multi-item scale for each dimension was measured using Cronbach alpha, and for all the dimensions measures of reliability are above 0.70. We empirically tested the model using structural equation modeling with AMOS. The results allow us to empirically contribute to the argument regarding the influence of human and social cognitive capital on social and non-social entrepreneurial intentions. Moreover, we highlight the importance for further researchers to look deeper into the determinants of traditional and social entrepreneurial intention so that governments can one day define better polices and regulations that promote sustainable businesses with a social imprint, rather than inhibit their formation and growth.

Productivity and time use during occupational therapy and nutrition/dietetics clinical education : a cohort study

Background: Currently in the Australian higher education sector higher productivity from allied health clinical education placements are a contested issue. This paper will report results of a study that investigated output changes associated with occupational therapy and nutrition/dietetics clinical education placements in Queensland, Australia. Supervisors’ and students’ time use during placements and how this changes for supervisors compared to when students are not present in the workplace is also presented. Methodology/Principal Findings: A cohort design was used with students from four Queensland universities, and their supervisors employed by Queensland Health. There was an increasing trend in the number of occasions of service delivered when the students were present, and a statistically significant increase in the daily mean length of occasions of service delivered during the placement compared to pre-placement levels. For project-based placements that were not directly involved in patient care, supervisors’ project activity time decreased during placements, with students undertaking considerably more time in project activities. Conclusions/Significance: A novel method for estimating productivity and time use changes during clinical education programs for allied health disciplines has been applied. During clinical education placements there was a net increase in outputs, suggesting supervisors engage in longer consultations with patients for the purpose of training students, while maintaining patient numbers. Other activities are reduced. This paper is the first time these data have been shown and form a good basis for future assessments of the economic impact of student placements for allied health disciplines.