An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity

Recent evidence indicates that the estrogen receptor-a-negative, androgen receptor (AR)- positive molecular apocrine subtype of breast cancer is driven by AR signaling. The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype; its proliferation is stimulated by androgens such as 5a-dihydrotestosterone (DHT) but inhibited by the progestin medroxyprogesterone acetate (MPA) via AR-mediated mechanisms. We report here that the AR gene in MDAMB- 453 cells contains a G-T transversion in exon 7, resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 (Q865H) in the ligand binding domain. Compared with wild-type AR, the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists. Ligand binding, molecular modeling, mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation, AR intramolecular interactions, and receptor stability. Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells. Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway. These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant. This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype. Endocrine-Related Cancer (2012) 19 599–613

Sovereignty, song and 'The Sapphires' (Wayne Blair 2012)

With its foregrounding of the political issue of the denial of Aboriginal Australian sovereignty by British invaders in its big budget, mainstream narrative, 'The Sapphires' (Wayne Blair 2012) is shown to be another example of a "fourth formation" (Starrs 2012) in Moore and Muecke's 1985 model. Blair's feel-good movie features an all-Aboriginal Australian troupe of singers, The Sapphires, who undertake a journey of self-discovery whereby they learn the importance of choosing the protest songs of black Soul over the white coloniser's "whining" Country and Western songs and this is historically contextualised with a discussion of Aboriginal Australians and popular radio. Furthermore, this paper argues the iconic 'Welcome to Country' is twice subverted to reinforce this theme, firstly in the Cummeragunja pub and secondly in war-torn Vietnam. Finally, the prediction is made that a "fifth formation", in which seeking recognition of Aboriginal Australian sovereignty is no longer the goal because it has become the ongoing reality, will soon be the project of Australian film-makers as they celebrate this long overdue societal shift.

Misunderstanding or Misdirection?: Whistleblower Protection in Queensland

In his report into corruption in Queensland, Fitzgerald listed whistleblower protection as a necessary part of a strong governance regime. "What is required is an accessible, independent body to which disclosures can be made, confidentially (at least in the first instance) and in any event free from fear of reprisals." It was one of the reforms studied by the Electoral and Administrative Review Committee, the report of which resulted in the Whistleblowers Protection Act 1994 (WPA). The need for whistleblower protection was supported by all sides of Parliament. The Premier, Wayne Goss, in his Second Reading Speech on the Public Sector Ethics Bill , said that that Act and the WPA would form a package with the former outlining required behaviour and the WPA encouraging staff to report wrongdoing. The WPA was subsequently passed and has remained virtually unamended for over a decade. Such consistency is either an indication of skilled drafting and effectiveness or the fact that the Act has been neglected. It is the hypothesis of this paper that the latter is the case. This hypothesis will be tested by examining the sincerity and diligence with which the Act has been treated during, and following, its passage.

A review of LCADesign

Objective The review addresses two distinct sets of issues: 1. specific functionality, interface, and calculation problems that presumably can be fixed or improved; and 2. the more fundamental question of whether the system is close to being ready for ‘commercial prime time’ in the North American market. Findings Many of our comments relate to the first set of issues, especially sections B and C. Sections D and E deal with the second set. Overall, we feel that LCADesign represents a very impressive step forward in the ongoing quest to link CAD with LCA tools and, more importantly, to link the world of architectural practice and that of environmental research. From that perspective, it deserves continued financial support as a research project. However, if the decision is whether or not to continue the development program from a purely commercial perspective, we are less bullish. In terms of the North American market, there are no regulatory or other drivers to press design teams to use a tool of this nature. There is certainly interest in this area, but the tools must be very easy to use with little or no training. Understanding the results is as important in this regard as knowing how to apply the tool. Our comments are fairly negative when it comes to that aspect. Our opinion might change to some degree when the ‘fixes’ are made and the functionality improved. However, as discussed in more detail in the following sections, we feel that the multi-step process — CAD to IFC to LCADesign — could pose a serious problem in terms of market acceptance. The CAD to IFC part is impossible for us to judge with the information provided, and we can’t even begin to answer the question about the ease of using the software to import designs, but it appears cumbersome from what we do know. There does appear to be a developing North American market for 3D CAD, with a recent survey indicating that about 50% of the firms use some form of 3D modeling for about 75% of their projects. However, this does not mean that full 3D CAD is always being used. Our information suggests that AutoDesk accounts for about 75 to 80% of the 3D CAD market, and they are very cautious about any links that do not serve a latent demand. Finally, other system that link CAD to energy simulation are using XML data transfer protocols rather than IFC files, and it is our understanding that the market served by AutoDesk tends in that direction right now. This is a subject that is outside our area of expertise, so please take these comments as suggestions for more intensive market research rather than as definitive findings.

Trip to Sunshine Coast Queensland, September 2004 visit to bridge and foreshore

A trip was undertaken to look at concerns of Public Works and Main Roads Departments of Queensland. David Paterson and Wayne Ganther from CSIRO travelled to the Sunshine Coast with Alan Carse of Queensland Department of Main Roads and Michael Ball of Queensland Department of Public Works. We were also joined for part of the visits by Ed Bowers of QBuild which is a commercial unit of Public Works responsible for maintenance of Public Works. During the trip we visited a bridge on the David Low Way at Sunrise Beach near Noosa. This bridge was in a serve marine environment with high salt content in the concrete and corrosion of the galvanised guardrails and barriers. Also the foreshore at Coolum was visited and the use of stainless steel was examined. This is discussed in this report. Most problems stemmed from incorrect specification due to lack of awareness of the severity of the environment. The companion report Visit to Schools Report 2002-059-B No 7. covers the visit to four schools north of Caloundra.

The relationship between closeness to significant others and self-esteem

One hundred and forty-three children (61 boys and 82 girls) between 8 and 12 years of age participated in a study which focused on closeness to significant others and its relationship with self-esteem. A closeness rating scale was developed to determine quantitatively how close children feel to their mother, father, two closest peers, and current teacher. Marsh's (1990) eight general self-concept items from the Self-Description Questionnaire 1 (SDQI), together with eight items from Burnett's (1994) Self-scale, were administered to the children, who ranged in age from 8 to 12 years, to measure their self-esteem. Closeness to mother was found to correlate most significantly with a child's self-esteem, while closeness to teacher was related more strongly to self-esteem for girls than for boys.

Using picture books in the Secondary English classroom

This Chapter explores how teachers can use children's picture books in the Secondary English classroom.

Using Media Technologies in English

English has long been the subject where print text has reigned supreme. Increasingly in our networked and electronically connected world, however, we can be using digital technologies to create and respond to texts studied in English classrooms. The current approach to English includes the concept of ‘multiliteracies,’ which suggests that print texts alone are necessary but not sufficient’ (E.Q, 2000) and that literacy includes the flexible and sustainable mastery of a repertoire of practices. This also includes the decoding and deployment of media technologies (E.Q, 2000). This has become more possible in Australia as secondary students have increasing access to computers and online platforms at home and at school. With the advent of web 2.0., with its interactive platforms and free media making software, teachers and students can use this software to access information and emerging online literature in English covering a range of text types and new forms for authentic audiences and contexts. This chapter is concerned with responding to literary and mediated texts through the use of technologies. If we remain open to trying out new textual forms and see our digital ‘native students’ (Prensky, 2007) as our best resource, we can move beyond technophobia, become digital travellers’ ourselves and embrace new digital forms in our classrooms.