Inhibition of activated fibroblast growth factor receptor 2 in endometrial cancer cells induces cell death despite PTEN abrogation

KRAS activation and PTEN inactivation are frequent events in endometrial tumorigenesis, occurring in 10% to 30% and 26% to 80% of endometrial cancers, respectively. Because we have recently shown activating mutations in fibroblast growth factor receptor 2 (FGFR2) in 16% of endometrioid endometrial cancers, we sought to determine the genetic context in which FGFR2 mutations occur. Analysis of 116 primary endometrioid endometrial cancers revealed that FGFR2 and KRAS mutations were mutually exclusive, whereas FGFR2 mutations were seen concomitantly with PTEN mutations. Here, we show that shRNA knockdown of FGFR2 or treatment with a pan-FGFR inhibitor, PD173074, resulted in cell cycle arrest and induction of cell death in endometrial cancer cells with activating mutations in FGFR2. This cell death in response to FGFR2 inhibition occurred within the context of loss-of-function mutations in PTEN and constitutive AKT phosphorylation, and was associated with a marked reduction in extracellular signal-regulated kinase 1/2 activation. Together, these data suggest that inhibition of FGFR2 may be a viable therapeutic option in endometrial tumors possessing activating mutations in FGFR2, despite the frequent abrogation of PTEN in this cancer type.

Effective attacking strategies in rugby union

Evasive change-of-direction manoeuvres (agility skills) are a fundamental ability in rugby union. In this study, we explored the attributes of agility skill execution as they relate to effective attacking strategies in rugby union. Seven Super 14 games were coded using variables that assessed team patterns and individual movement characteristics during attacking ball carries. The results indicated that tackle-breaks are a key determinant of try-scoring ability and team success in rugby union. The ability of the attacking ball carrier to receive the ball at high speed with at least two body lengths from the defence line against an isolated defender promoted tackle-breaks. Furthermore, the execution of a side-step evasive manoeuvre at a change of direction angle of 20–60° and a distance of one to two body lengths from the defence, and then straightening the running line following the initial direction change at an angle of 20–60°, was associated with tackle-breaks. This study provides critical insight regarding the attributes of agility skill execution that are associated with effective ball carries in rugby union.

Higher-order spectral analysis of nonlinear ocean surface gravity waves

Higher-order spectral analysis is used to detect the presence of secondary and tertiary forced waves associated with the nonlinearity of energetic swell observed in 8- and 13-m water depths. Higher-order spectral analysis techniques are first described and then applied to the field data, followed by a summary of the results.

Multifractal analysis of geomagnetic storm and solar flare indices and their class dependence

The multifractal properties of two indices of geomagnetic activity, D st (representative of low latitudes) and a p (representative of the global geomagnetic activity), with the solar X-ray brightness, X l , during the period from 1 March 1995 to 17 June 2003 are examined using multifractal detrended fluctuation analysis (MF-DFA). The h(q) curves of D st and a p in the MF-DFA are similar to each other, but they are different from that of X l , indicating that the scaling properties of X l are different from those of D st and a p . Hence, one should not predict the magnitude of magnetic storms directly from solar X-ray observations. However, a strong relationship exists between the classes of the solar X-ray irradiance (the classes being chosen to separate solar flares of class X-M, class C, and class B or less, including no flares) in hourly measurements and the geomagnetic disturbances (large to moderate, small, or quiet) seen in D st and a p during the active period. Each time series was converted into a symbolic sequence using three classes. The frequency, yielding the measure representations, of the substrings in the symbolic sequences then characterizes the pattern of space weather events. Using the MF-DFA method and traditional multifractal analysis, we calculate the h(q), D(q), and τ (q) curves of the measure representations. The τ (q) curves indicate that the measure representations of these three indices are multifractal. On the basis of this three-class clustering, we find that the h(q), D(q), and τ (q) curves of the measure representations of these three indices are similar to each other for positive values of q. Hence, a positive flare storm class dependence is reflected in the scaling exponents h(q) in the MF-DFA and the multifractal exponents D(q) and τ (q). This finding indicates that the use of the solar flare classes could improve the prediction of the D st classes.

Declining youth membership : the views of union officials

Across the industrialized west there has been a sharp decline in union membership (Frege and Kelly2003, Peetz 2002). Even more alarming are the lower unionization rates of young people and the steeper decline in these rates compared to older workers (Serrano and Waddington 2000). At the same time increasing numbers of young people still at school are participating in the labour market. There have been a number of explorations internationally of young people's union membership, but most either track membership decline over time, comparing adult and youth union density (Blanden and Machin 2003, Bryson et al. 2005, Haynes, Vowles and Boxall 2005, Canny 2002, OECD 2006), explore the general experience of young people in the labour market (for example, Lizen, Bolton and Pole 1999) or examine young people's view of unions (for example, Bulbeck 2008). This chapter however takes a different approach, exploring union officials' constructions of 'the problem' of low union density amongst youth. While the data in this study was obtained from Australia, the Australian context has strong similarities with those in other industrialized economies, not least because globalization has meant the spread of neo-liberal industrial relations (IR) policies and structures. Assuming that unions have choices open to them as to how they recruit and retain young people, it is important to analyse officials' construction of 'the problem', as this affects union strategizing and action.

Comparing retail union strategy in a neoliberal context : the case of Australia and New Zealand

Retail employees are amongst the most vulnerable workers in the context of neoliberal market economies. In many countries, low paid retail employees comprise around 10 per cent of the workforce (ABS 2011). The retail labour market is typically highly feminised and youthful, with many employees in part time and various forms of precarious employment (Tailby & Pollert 2011). However, the industry and its trade unions have rarely been the focus of academic study (Tilly & Carré 2011). This paper thus aims to analyse and compare trade union strategies in the retail industry in Australia and New Zealand, by utilising findings from a larger comparative study. The respective unions studied are the Shop Distributive and Allied Workers Union (SDA) in Australia and the National Distribution Union (NDU) in New Zealand. Data from interviews with union officials at different levels and from different regional locations in Australia and NZ are analysed. Union policy documents are also utilised to support the empirical data. Key findings from the comparison of retail unions’ strategy in Australia and NZ include: 1) the importance of institutional factors and internal political differences in shaping and constraining union strategies; 2) different emphases on external relationships and variations in partnership approaches; 3) the need to recruit to ‘stand still’ by retail unions in both countries; and, 4) similarities and differences in the unions’ organising approaches. The paper concludes by examining the implications of these findings for retail unions’ strategic choices and their ability to deliver workplace justice for employees.

An analysis of tax expenditure versus direct expenditure

Each financial year concessions, benefits and incentives are delivered to taxpayers via the tax system. These concessions, benefits and incentives, referred to as tax expenditure, differ from direct expenditure because of the recurring fiscal impact without regular scrutiny through the federal budget process. There are approximately 270 different tax expenditures existing within the current tax regime with total measured tax expenditures in the 2005-06 financial year estimated to be around $42.1 billion, increasing to $52.7 billion by 2009-10. Each year, new tax expenditures are introduced, while existing tax expenditures are modified and deleted. In recognition of some of the problems associated with tax expenditure, a Tax Expenditure Statement, as required by the Charter of Budget Honesty Act 1988, is produced annually by the Australian Federal Treasury. The Statement details the various expenditures and measures in the form of concessions, benefits and incentives provided to taxpayers by the Australian Government and calculates the tax expenditure in terms of revenue forgone. A similar approach to reporting tax expenditure, with such a report being a legal requirement, is followed by most OECD countries. The current Tax Expenditure Statement lists 270 tax expenditures and where it is able to, reports on the estimated pecuniary value of those expenditures. Apart from the annual Tax Expenditure Statement, there is very little other scrutiny of Australia’s Federal tax expenditure program. While there has been various academic analysis of tax expenditure in Australia, when compared to the North American literature, it is suggested that the Australian literature is still in its infancy. In fact, one academic author who has contributed to tax expenditure analysis recently noted that there is ‘remarkably little secondary literature which deals at any length with tax expenditures in the Australian context.’ Given this perceived gap in the secondary literature, this paper examines fundamental concept of tax expenditure and considers the role it plays in to the current tax regime as a whole, along with the effects of the introduction of new tax expenditures. In doing so, tax expenditure is contrasted with direct expenditure. An analysis of tax expenditure versus direct expenditure is already a sophisticated and comprehensive body of work stemming from the US over the last three decades. As such, the title of this paper is rather misleading. However, given the lack of analysis in Australia, it is appropriate that this paper undertakes a consideration of tax expenditure versus direct expenditure in an Australian context. Given this proposition, rather than purport to undertake a comprehensive analysis of tax expenditure which has already been done, this paper discusses the substantive considerations of any such analysis to enable further investigation into the tax expenditure regime both as a whole and into individual tax expenditure initiatives. While none of the propositions in this paper are new in a ‘tax expenditure analysis’ sense, this debate is a relatively new contribution to the Australian literature on the tax policy. Before the issues relating to tax expenditure can be determined, it is necessary to consider what is meant by ‘tax expenditure’. As such, part two if this paper defines ‘tax expenditure’. Part three determines the framework in which tax expenditure can be analysed. It is suggested that an analysis of tax expenditure must be evaluated within the framework of the design criteria of an income tax system with the key features of equity, efficiency, and simplicity. Tax expenditure analysis can then be applied to deviations from the ideal tax base. Once it is established what is meant by tax expenditure and the framework for evaluation is determined, it is possible to establish the substantive issues to be evaluated. This paper suggests that there are four broad areas worthy of investigation; economic efficiency, administrative efficiency, whether tax expenditure initiatives achieve their policy intent, and the impact on stakeholders. Given these areas of investigation, part four of this paper considers the issues relating to the economic efficiency of the tax expenditure regime, in particular, the effect on resource allocation, incentives for taxpayer behaviour and distortions created by tax expenditures. Part five examines the notion of administrative efficiency in light of the fact that most tax expenditures could simply be delivered as direct expenditures. Part six explores the notion of policy intent and considers the two questions that need to be asked; whether any tax expenditure initiative reaches its target group and whether the financial incentives are appropriate. Part seven examines the impact on stakeholders. Finally, part eight considers the future of tax expenditure analysis in Australia.

Evolution of the extinct Sabretooths and the American cheetah-like cat

The sabretooths (Smilodon and Homotherium) and the American cheetah-like cat (Miracinonyx) were the top predators in Late Pleistocene America, but became extinct about 13 thousand years ago. As the evolutionary history of these taxa remains poorly understood , we analysed their phylogenetic relationship to extant felids. In contrast to previous molecular studies , our results show that the sabretooths diverge early and are not closely related to any living cats. This supports their morphological placement in a separate subfamily (Machairodontinae). Despite its remarkable morphological similarity to the African cheetah (Acinonyx jubatus), Miracinonyx appears to have evolved from a puma-like ancestor, presumably in response to similar ecological pressures.

Tracking the magmatic evolution of island arc volcanism : insights from a high-precision Pb isotope record of Montserrat, Lesser Antilles

The volcanic succession on Montserrat provides an opportunity to examine the magmatic evolution of island arc volcanism over a ∼2.5 Ma period, extending from the andesites of the Silver Hills center, to the currently active Soufrière Hills volcano (February 2010). Here we present high-precision double-spike Pb isotope data, combined with trace element and Sr-Nd isotope data throughout this period of Montserrat's volcanic evolution. We demonstrate that each volcanic center; South Soufrière Hills, Soufrière Hills, Centre Hills and Silver Hills, can be clearly discriminated using trace element and isotopic parameters. Variations in these parameters suggest there have been systematic and episodic changes in the subduction input. The SSH center, in particular, has a greater slab fluid signature, as indicated by low Ce/Pb, but less sediment addition than the other volcanic centers, which have higher Th/Ce. Pb isotope data from Montserrat fall along two trends, the Silver Hills, Centre Hills and Soufrière Hills lie on a general trend of the Lesser Antilles volcanics, whereas SSH volcanics define a separate trend. The Soufrière Hills and SSH volcanic centers were erupted at approximately the same time, but retain distinctive isotopic signatures, suggesting that the SSH magmas have a different source to the other volcanic centers. We hypothesize that this rapid magmatic source change is controlled by the regional transtensional regime, which allowed the SSH magma to be extracted from a shallower source. The Pb isotopes indicate an interplay between subduction derived components and a MORB-like mantle wedge influenced by a Galapagos plume-like source.