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.

Folk opera and theatre for development

The research field was intercultural theatre, specifically adapting indigenous performance forms for applied theatre purposes. The context was the rich performative traditions of Papua New Guinean cultures, which have remained largely untapped over several decades of "theatre for development" and "entertainment education". Papua New Guinean company Raun Raun Theatre developed Folk Opera from a similar concept in African theatre in the 1970s. The form incorporates elements of song, dance, ritual, chant, metaphor, music, and body adornment from traditional cultures. The form’s spectacular scope suited international touring in large theatrical venues, and the themes of emerging nationalism with which Raun Raun was concerned. The research team made three key innovations in the use of Folk Opera: adapting the form from theatres to community contexts, using the form to address issues of individual choice for health promotion, and emphasising experiential education over entertainment. Field-testing in Karkar Island showed community members gained clearer understandings of relevant health issues through participating in the folk opera form than through other educational approaches. The significance of the research was recognised by the members of the cross-cultural workshop team and the community of Karkar Island including the local Member of Parliament. The success of the Folk Opera form as an approach to sexual health promotion was recognised through the provision of AUD$74,000 funding by the National AIDS Council Secretariat of Papua New Guinea for a train-the-trainer program incorporating this innovative form of applied theatre. The research has been presented at a number of national and international conferences including the 6th International Research in Drama Education conference in 2009.

The pomegranate cycle : reconfiguring opera through performance, technology & composition

The Pomegranate Cycle is a practice-led enquiry consisting of a creative work and an exegesis. This project investigates the potential of self-directed, technologically mediated composition as a means of reconfiguring gender stereotypes within the operatic tradition. This practice confronts two primary stereotypes: the positioning of female performing bodies within narratives of violence and the absence of women from authorial roles that construct and regulate the operatic tradition. The Pomegranate Cycle redresses these stereotypes by presenting a new narrative trajectory of healing for its central character, and by placing the singer inside the role of composer and producer. During the twentieth and early twenty-first century, operatic and classical music institutions have resisted incorporating works of living composers into their repertory. Consequently, the canon’s historic representations of gender remain unchallenged. Historically and contemporarily, men have almost exclusively occupied the roles of composer, conductor, director and critic, and therefore men have regulated the pedagogy, performance practices, repertoire and organisations that sustain classical music. In this landscape, women are singers, and few have the means to challenge the constructions of gender they are asked to reproduce. The Pomegranate Cycle uses recording technologies as the means of driving change because these technologies have already challenged the regulation of the classical tradition by changing people’s modes of accessing, creating and interacting with music. Building on the work of artists including Phillips and van Veen, Robert Ashley and Diamanda Galas, The Pomegranate Cycle seeks to broaden the definition of what opera can be. This work examines the ways in which the operatic tradition can be hybridised with contemporary musical forms such as ambient electronica, glitch, spoken word and concrete sounds as a way of bringing the form into dialogue with contemporary music cultures. The ultilisation of other sound cultures within the context of opera enables women’s voices and stories to be presented in new ways, while also providing a point of friction with opera’s traditional storytelling devices. The Pomegranate Cycle simulates aesthetics associated with Western art music genres by drawing on contemporary recording techniques, virtual instruments and sound-processing plug-ins. Through such simulations, the work disrupts the way virtuosic human craft has been used to generate authenticity and regulate access to the institutions that protect and produce Western art music. The DIY approach to production, recording, composition and performance of The Pomegranate Cycle demonstrates that an opera can be realised by a single person. Access to the broader institutions which regulate the tradition are not necessary. In short, The Pomegranate Cycle establishes that a singer can be more than a voice and a performing body. She can be her own multimedia storyteller. Her audience can be anywhere.

Folk opera : stories crossing borders in Papua New Guinea

The Life Drama project is a drama-based sexual health promotion project, developed by a cross-cultural research team in Papua New Guinea (PNG) over the past four years. Recognising the limitations of established theatre-in-education and theatre-for-development approaches when working across cultures, the research team explored ways of tapping into the everyday performativity of PNG participants and their communities in order to communicate more powerfully about the personal and social issues involved in sexual health. Through the Folk Opera form, developed by PNG theatre company Raun Raun Theatre around the time of national Independence, the research explored the importance of ‘story’ in identity formation, maintenance and change, the communication of meaning, and the transmission of tacit local knowledges. In a highly diverse and rapidly-changing country like PNG, enacted stories inherently compel the exchange and exploration of different knowledges, and promote the dialogue and ownership that drives social change. The paper will present and unpack the folk opera form as developed in the Life Drama program, drawing conclusions which may apply to other programs which to promote health and social justice across cultures.

Sun, sea, sex, sand and conservatism in the Australian television soap opera

A recent issue of Young People Now (November 1995) mentioned the new (UK) television soap opera Hollyoaks by Phil Redmond, which raises the issue of the role of ‘soap operas’ (hereafter referred to as soaps) in the daily lives of young people. The term ‘soap’ originates with the sponsorship of radio and television programmes by companies such as Proctor and Gamble who in America in 1932 used a daytime radio domestic comedy, The Puddle Family to advertise Oxydol, a washing powder. The first British television soap was The Grove Family (BBC 1954-7) was followed by Emergency Ward Ten (ATV 1957-67), Coronation Street (Granada Television 1960-present) and Eastenders (BBC 1985-present). Australian soaps are especially popular in Britain and of potential interest to those who work with young people, because they have a high proportion of youthful looking actors and actresses and frequently depict scenes involving young people and apparent ‘real’ teenage dilemmas. On one level it may be commendable that actors who are young(ish) somewhere between the ages of 14 and 25 play roles that are ostensibly about young people and their alleged problems. However, the casting of young, largely unknown, actors reflects more the political economy of soaps in their relative cheapness and dispensability, rather than any genuine attempt to create an oppositional text for, about and by young people (Paterson 1986).

Folk opera : stories crossing borders in Papua New Guinea

The Life Drama project is a drama-based sexual health promotion project, developed by a cross-cultural research team in Papua New Guinea (PNG) over the past four years. Recognising the limitations of established theatre-in-education and theatre-for-development approaches when working across cultures, the research team explored ways of tapping into the everyday performativity of PNG participants and their communities in order to communicate more powerfully about the personal and social issues involved in sexual health. Through the Folk Opera form, developed by PNG theatre company Raun Raun Theatre around the time of national Independence, the research explored the importance of "story" in identity formation, maintenance and change, the communication of meaning, and the transmission of tacit local knowledges. In a highly diverse and rapidly-changing country like PNG, enacted stories inherently compel the exchange and exploration of different knowledges, and promote the dialogue and ownership that drives social change. The paper will present and unpack the Folk Opera form as developed in the Life Drama program, drawing conclusions which may apply to other programs which to promote health and social justice across cultures.

Creating new folk opera forms of applied theatre for HIV and AIDS education in Papua New Guinea

This research investigated the potential of folk opera as a tool for HIV and AIDS education in Papua New Guinea. It began with an investigation on the indigenous performativities and theatricalities of Papua New Guineans, conducting an audit of eight selected performance traditions in Papua New Guinea. These traditions were analysed, and five cultural forms and twenty performance elements were drawn out for further exploration. These elements were fused and combined with theatre techniques from western theatre traditions, through a script development process involving Australians, Papua New Guineans and international collaborators. The resulting folk opera, entitled Kumul, demonstrates what Murphy (2010) has termed story force, picture force, and feeling force, in the service of a story designed to educate Papua New Guinean audiences about HIV and the need to adopt safer sexual practices. Kumul is the story of a young man faced with decisions on whether or not to engage in risky sexual behaviours. Kumul's narrative is carefully framed within selected Papua New Guinean beliefs drawn from the audit to deliver HIV and AIDS messages using symbolic and metaphoric communication techniques without offending people. The folk opera Kumul was trialled in two communities in Papua New Guinea: a village community and an urban settlement area. Kumul is recognisable to Papua New Guinean audiences because it reflects their lifestyle and a worldview, which connects them to their beliefs and spirituality, and the larger cosmological order. Feedback from audience members indicated that the performance facilitated HIV and AIDS communication, increased people's awareness of HIV and AIDS, and encouraged behaviour change. Tellingly, in one performance venue, forty people queued for Voluntary Testing and Counseling immediately after the performance. Twenty of these people were tested on that night and the other twenty were tested the following day. Many of the volunteers were young men – a demographic historically difficult to engage in HIV testing. This encouraging result indicates that the Kumul folk opera form of applied theatre could be useful for facilitating communication and education regarding sexual health and safer sexual behaviours in Papua New Guinea. Feedback from participants, audience members and other research stakeholders suggests that the form might also be adapted to address other social and development issues, particularly in the areas of health and social justice.

Live from the Sydney Opera House: Remote musical interactions for teacher professional development

A significant challenge for the implementation of the Australian Curriculum: The Arts is the professional development of primary school teachers in all parts of the country. During 2012, the Sydney Symphony Orchestra (SSO) conducted a remote music professional development workshop as part of the Sydney Opera House’s Digital Education Program for teachers in New South Wales using the Department of Education’s Connected Classroom system which allows live synchronous interaction between facilitators and participants in multiple sites. In this article, we analyse observational and videotape data collected during this live professional development event to consider the opportunities and challenges presented by this type of professional learning experience in the arts. In particular, consideration is given to the impact of a remote musical interaction on embodied learning and aesthetic experience. We draw on actor-network theory to consider the ways in which a remote professional development experience differs to one in which all participants are present in the same space. Finally, we conclude that although there are significant differences in the type of learning that occurs in a remote music interaction, the online space provides a legitimate and potentially transforming experience for primary school teachers.

Novel schmitt trigger based on lahbda diode

A new circuit to realise a Schmitt trigger has been conceived. This circuit, which is based on the well known lambda diode, is suitable for integration using CMOS technology. It requires only three devices and is probably simpler than any other conventional Schmitt trigger circuit.

Novel CMOS Schmitt trigger

A novel CMOS Schmitt trigger using only four MOS transistors is discussed. This circuit, which works on the principle of load-coupled regenerative feedback, can be implemented using conventional CMOS technology with only one extra fabrication step. It can be implemented even more easily in CMOS/SOS (silicon-on-sapphire) integrated circuits. The hysteresis of this Schmitt trigger can be controlled by a proper choice of the transistor geometries.

A ternary Schmitt trigger

A new ternary circuit, namely, a ternary Schmitt trigger, is presented. This novel circuit which is based on the well-known lambda diode, is suitable for integration using CMOS technology. The circuit has been simulated using the SPICE 2G Program. The results of the simulation are presented. The circuit offers a high degree of design flexibility. This circuit is expected to be a very useful functional block in the processing of ternary and pseudoternary signals.