Acquisition of estrogen independence and antiestrogen resistance in breast cancer : association with the invasive and metastatic phenotype

A significant percentage of human breast cancer (HBC) is dependent upon the ovarian hormone estrogen for its onset and progression. The presence or lack of estrogen receptors (ERs) in human breast cancer is an important determinant both of prognosis and of choice of treatment - a poorer prognosis being associated with ER–ve disease. Cell lines established from human breast cancer provide models for breast cancer in various stages of progression (Engel & Young 1978). When grown as tumors in athymic nude mice, these lines represent the major in vivo experimental model for HBC studies (Brünner et al 1987). The ease of both in vitro and in vivo maintenance, the human derivation of the tissue, and the similarities in plasma estrogen levels between ovariectomized nude mice and postmenopausal women (Seibert et al. 1983, Brünner et al. 1986), make the growth of human breast cancer cell lines in nude mice an attractive...

An application of an extended theory of planned behaviour to understand drivers' compliance with the school zones speed limit in Australia and Malaysia

This research investigated individual and situational factors that influence driver compliance with the school zones speed limit in Australia and Malaysia. Despite all the countermeasures implemented in these two countries, driver compliance with the speed limit in school zones is still poor. The findings of the research provided support for the application of the Theory of Planned Behaviour to understand and therefore influence drivers' intention to comply with the school zones speed limit in both Australia and Malaysia. The research also revealed that mindfulness, a construct rarely used in road safety before, directly influenced Australian drivers' intention to comply, while habit influenced intention to comply in Malaysia. The research raised important theoretical and cross-cultural issues for future research and highlighted the need to increase the visibility of school zones with the use of more noticeable traffic control devices.

Managed livestock grazing is compatible with the maintenance of plant diversity in semidesert grasslands

Even when no baseline data are available, the impacts of 150 years of livestock grazing on natural grasslands can be assessed using a combined approach of grazing manipulation and regional-scale assessment of the flora. Here, we demonstrate the efficacy of this method across 18 sites in the semidesert Mitchell grasslands of northeastern Australia. Fifteen-year-old exclosures (ungrazed and macropod grazed) revealed that the dominant perennial grasses in the genus Astrebla do not respond negatively to grazing disturbance typical of commercial pastoralism. Neutral, positive, intermediate, and negative responses to grazing disturbance were recorded amongst plant species with no single life-form group associated with any response type. Only one exotic species, Cenchrus ciliaris, was recorded at low frequency. The strongest negative response was from a native annual grass, Chionachne hubbardiana, an example of a species that is highly sensitive to grazing disturbance. Herbarium records revealed only scant evidence that species with a negative response to grazing have declined through the period of commercial pastoralism. A regional analysis identified 14 from a total of 433 plant species in the regional flora that may be rare and potentially threatened by grazing disturbance. However, a targeted survey precluded grazing as a cause of decline for seven of these based on low palatability and positive responses to grazing and other disturbance. Our findings suggest that livestock grazing of semidesert grasslands with a short evolutionary history of ungulate grazing has altered plant composition, but has not caused declines in the dominant perennial grasses or in species richness as predicted by the preceding literature. The biggest impact of commercial pastoralism is the spread of woody leguminous trees that can transform grassland to thorny shrubland. The conservation of plant biodiversity is largely compatible with commercial pastoralism provided these woody weeds are controlled, but reserves strategically positioned within water remote areas are necessary to protect grazing-sensitive species. This study demonstrates that a combination of experimental studies and regional surveys can be used to understand anthropogenic impacts on natural ecosystems where reference habitat is not available.

In conversation with the Honourable Ian Callinan AC

When, in 1977, the Australian electorate provided a double majority to effect a change of section 72 of the Commonwealth Constitution requiring judges of the High Court of Australia to retire at the age of 70 years old, I doubt we understood the continuing capacity of these esteemed members of the judiciary. For the opportunity to sit and talk with Ian Callinan AC who, in compliance with that amendment, retired from the High Court in September 2007, I needed to wait until he returned from The Hague where he was sitting as a Judge ad hoc on the International Court of Justice. Although a native of Casino, New South Wales, Mr Callinan is regarded as a Queenslander. Indeed, he grew up in Brisbane, finished high school at Brisbane Grammar and graduated in law at The University of Queensland. Appointed in 1978 as a Queen’s Counsel, Mr Callinan enjoyed this period of his legal career and we discussed an aspect of the Christopher Skase case, which reinforced my belief that Mr Callinan is an incredibly skilful advocate. On 14 September 1998, ABC Four Corners broadcasted the views of some prominent Australians on the appointment of Mr Callinan to the High Court. In assessing the type of person Mr Callinan is, Tony Morris QC said: “Ian Callinan isn't a coward”, while former Commonwealth Attorney-General, Michael Lavarch, said: “He was regarded as an absolutely outstanding criminal lawyer within the Queensland legal profession, I mean really a top-notch advocate”. I was not interested in raising any of the controversial issues that Mr Callinan has encountered as an advocate in high profile matters. I wanted to know how he felt about his time on the High Court, what his thoughts are on the operation of the High Court, the IP cases he decided, the real life issues that he feels impact on counsel who are appearing before the High Court and the people he regarded as role models. During our conversation, Mr Callinan laughed often and when he did his eyes lit up, revealing his passion for life. He is an incredibly genuine Australian who loved his time as a barrister, enjoyed his role on the High Court, enjoys his current job as mediator, loves writing novels, has a great desire for continual improvement in the quality of legal education and legal advocacy and sees a need for change in IP law. When I asked: “So, what might the future hold for you?”, he laughed and said: “Well, at my age I don’t have a long horizon time”. I said: “Just enjoy the journey?”, to which Mr Callinan responded: “Exactly”.

RAD51-associated Protein 1 (RAD51AP1) Interacts with the Meiotic Recombinase DMC1 through a Conserved Motif

Homologous recombination (HR) reactions mediated by the RAD51 recombinase are essential for DNA and replication fork repair, genome stability, and tumor suppression. RAD51-associated protein 1 (RAD51AP1) is an important HR factor that associates with and stimulates the recombinase activity of RAD51. We have recently shown that RAD51AP1 also partners with the meiotic recombinase DMC1, displaying isoform-specific interactions with DMC1. Here, we have characterized the DMC1 interaction site in RAD51AP1 by a series of truncations and point mutations to uncover a highly conserved WVPP motif critical for DMC1 interaction but dispensable for RAD51 association. This RAD51AP1 motif is reminiscent of the FVPP motif in the tumor suppressor protein BRCA2 that mediates DMC1 interaction. These results further implicate RAD51AP1 in meiotic HR via RAD51 and DMC1.

Treatment with the vascular disruptive agent OXi4503 induces an immediate and widespread epithelial to mesenchymal transition in the surviving tumor

Epithelial to mesenchymal transition (EMT) is considered an important mechanism in tumor resistance to drug treatments; however, in vivo observation of this process has been limited. In this study we demonstrated an immediate and widespread EMT involving all surviving tumor cells following treatment of a mouse model of colorectal liver metastases with the vascular disruptive agent OXi4503. EMT was characterized by significant downregulation of E-cadherin, relocation and nuclear accumulation of b-catenin as well as significant upregulation of ZEB1 and vimentin. Concomitantly, significant temporal upregulation in hypoxia and the pro-angiogenic growth factors hypoxia-inducible factor 1-alpha, hepatocyte growth factor, vascular endothelial growth factor and transforming growth factor-beta were seen within the surviving tumor. The process of EMT was transient and by 5 days after treatment tumor cell reversion to epithelial morphology was evident. This reversal, termed mesenchymal to epithelial transition (MET) is a process implicated in the development of new metastases but has not been observed in vivo histologically. Similar EMT changes were observed in response to other antitumor treatments including chemotherapy, thermal ablation, and antiangiogenic treatments in our mouse colorectal metastasis model and in a murine orthotopic breast cancer model after OXi4503 treatment. These results suggest that EMT may be an early mechanism adopted by tumors in response to injury and hypoxic stress, such that inhibition of EMT in combination with other therapies could play a significant role in future cancer therapy.

Surface magnetoplasma waves at the interface between a plasma-like medium and a metal in the Voigt geometry

Theoretical and experimental results associated with the studies of different properties of surface-type waves (SW) in plasma-like medium-metal structures are reviewed. The propagation of surface waves in the Voigt geometry (the SW propagate across the external magnetic field, which is parallel to the interface) is considered. Various problems dealing with the linear properties of the SW (dispersion characteristics, electromagnetic fields topography, influence of the inhomogeneity of the medium, etc.); excitation mechanisms of the plasma-metal waveguide structures (parametric, drift, diffraction, etc. mechanisms); nonlinear effects associated with SW propagation (higher harmonics generation, self-interaction, nonlinear damping, nonlinear interactions, etc.) are presented. In many cases the results are valid for both gaseous and solid-state plasmas. © 1999 Elsevier Science B.V. All rights reserved.

Troubling dissemination : experimentations with the salon as conference event

Salons became popular in Europe in 17th Century as sites of philosophic and literary conversation. A group of female academics interested in Deleuzian theories experimented with the salon to challenge presentation and dissemination norms that hierarchize and centralize the human. For Deleuze and Guattari (1987), assemblages are shifting and decentering, so how might assemblages of chairs, tables, bodies, lights, space, help to trouble thinking about the methodological conventions around academic disseminations? The authors discuss the salon as a critical-cultural site: Cumming presents Deleuze and play-dough, an exploration of how the playful dissemination format of the salon prompted a re-reading of a methodological vignette from earlier research. Knight, an arts-based researcher, uses video art as a creative methodology to examine conceptualizations of rhizomes and assemblages at the salon as a dissemination site. The authors conclude that the salon, as a critical, cultural site disrupts hierarchized ways of approaching and presenting research.

A direct integration scheme for battery-supercapacitor hybrid energy storage systems with the use of grid side inverter

Battery-supercapacitor hybrid energy storage systems are becoming popular in the renewable energy sector due to their improved power and energy performances. These hybrid systems require separate dc-dc converters, or at least one dc-dc converter for the supercapacitor bank, to connect them to the dc-link of the grid interfacing inverter. These additional dc-dc converters increase power losses, complexity and cost. Therefore, possibility of their direct connection is investigated in this paper. The inverter system used in this study is formed by cascading two 3-level inverters, named as the “main inverter” and the “auxiliary inverter”, through a coupling transformer. In the test system the main inverter is connected with the rectified output of a wind generator while the auxiliary inverter is directly attached to a battery and a supercapacitor bank. The major issues with this approach are the dynamic changes in dc-link voltages and inevitable imbalances in the auxiliary inverter voltages, which results in unevenly distributed space vectors. A modified SVM technique is proposed to solve this issue. A PWM based time sharing method is proposed for power sharing between the battery and the supercapacitor. Simulation results are presented to verify the efficacy of the proposed modulation and control techniques.

A Battery Energy Storage interface for wind power systems with the use of grid side inverter

This paper presents a novel concept of Energy Storage System (ESS) interfacing with the grid side inverter in wind energy conversion systems. The inverter system used here is formed by cascading a 2-level inverter and a three level inverter through a coupling transformer. The constituent inverters are named as the “main inverter” and the “auxiliary inverter” respectively. The main inverter is connected with the rectified output of the wind generator while the auxiliary inverter is attached to a Battery Energy Storage System (BESS). The BESS ensures constant power dispatch to the grid irrespective of change in wind condition. Furthermore, this unique combination of BESS and inverter eliminates the need of additional dc-dc converters. Novel modulation and control techniques are proposed to address the problem of non-integer, dynamically-changing dc-link voltage ratio, which is due to random wind changes. Strategies used to handle auxiliary inverter dc-link voltage imbalances and controllers used to charge batteries at different rates are explained in detail. Simulation results are presented to verify the efficacy of the proposed modulation and control techniques in suppressing random wind power fluctuations.

Small firms and the challenge of equality, diversity and difference

Purpose The purpose of this paper is to introduce the papers contributing to this special issue and to locate them within the broader questions about the role of small firms in enabling or alleviating issues of equality, diversity, and difference for various groups in society. Design/methodology/approach The literature dealing with the issues of equality, diversity, and difference pertaining to the operation of and/or working in smaller firms was reviewed prior to drawing out the key points from the submitted papers and considering the contribution they make to this literature. Findings Overall, one's these five papers contribute to one's understanding of the issues facing those in business or self‐employment, working in small business or wanting to pursue enterprise. Originality/value Rarely are questions asked about the assumed role small firms play in mitigating social exclusion for a range of groups in society. By addressing questions which explore the challenge of equality, diversity, and difference for small business in their establishment, management, and effective operation using interdisciplinary frameworks and different methodologies, a better understanding of the role of small business in society can be developed.

Crowdsourcing in developing countries : a possible model to co-create with the poor

The interest in poverty and the moral sense of'helping the poor' are a constant topic in Western culture (Mayo 2009).ln recent years, multinational corporations (MNCs) have evolved in their understanding of how social issues, such as poverty alleviation, relate to their fundamental purposes. From a business strategy point of view, 'socially responsible' initiatives are generally born with lhe dual purpose of attaining social visibility (i.e. marketing) and increasing economic returns. Besides addressing social challenges as part of their corporate social responsibility strategies, MNCs have also begun 'selling to the poor' in emerging markets (Prahalad 2004). A few forward -looking companies consider tltis base of the pyramid (BOP) market also as a source of innovation and have started to co-create with consumers (Simanis and Hart 2008).

Lazy days of simply going with the flow

A travel article about a river cruise from Amsterdam to Basel. When Captain Plamen Veselinov invites me to join him on the bridge, I can at last put a question that’s been running through my mind for days. It’s about the locks. How does he manage to line up the vessel as it approaches? Is the ship guided in electronically? He returns my questions with a boyish smile that does a good deal to veil his many years on the river. Crunching his way through a heavy Bulgarian accent, he says, “No, it’s all in the eyes and the hands. It’s magic. Don’t tell David Copperfield. He would get very jealous...