Mutation analysis of the CDKN2A promoter in Australian melanoma families

Approximately 50% of all melanoma families worldwide show linkage to 9p21-22, but only about half of these have been shown to contain germ line CDKN2A mutations. It has been hypothesized that a proportion of these families carry mutations in the noncoding regions of CDKN2A. Several Canadian families have been reported to carry a mutation in the 5' UTR, at position -34 relative to the start site, which gives rise to a novel AUG translation initiation codon that markedly decreases translation from the wild-type AUG (Liu et al., 1999). Haplotype sharing in these Canadian families suggested that this mutation is of British origin. We sequenced 1,327 base pairs (bp) of CDKN2A, making up 1,116 bp of the 5' UTR and promoter, all of exon 1, and 61 bp of intron 1, in at least one melanoma case from 110 Australian families with three or more affected members known not to carry mutations within the p16 coding region. In addition, 431 bp upstream of the start codon was sequenced in an additional 253 affected probands from two-case melanoma families for which the CDKN2A mutation status was unknown. Several known polymorphisms at positions -33, -191, -493, and -735 were detected, in addition to four novel variants at positions 120, -252, -347, and -981 relative to the start codon. One of the probands from a two-case family was found to have the previously reported Q50R mutation. No family member was found to carry the mutation at position -34 or any other disease-associated mutation. For further investigation of noncoding CDKN2A mutations that may affect transcription, allele-specific expression analysis was carried out in 31 of the families with at least three affected members who showed either complete or "indeterminate" 9p haplotype sharing without CDKN2A exonic mutations. Reverse transcription polymerase chain reaction and automated sequencing showed expression of both CDKN2A alleles in all family members tested. The lack of CDKN2A promoter mutations and the absence of transcriptional silencing in the germ line of this cohort of families suggest that mutations in the promoter and 5' UTR play a very limited role in melanoma predisposition.

Spatial analysis of biomineralization associated gene expression from the mantle organ of the pearl oyster Pinctada maxima

Background: Biomineralization is a process encompassing all mineral containing tissues produced within an organism. One of the most dynamic examples of this process is the formation of the mollusk shell, comprising a variety of crystal phases and microstructures. The organic component incorporated within the shell is said to dictate this architecture. However general understanding of how this process is achieved remains ambiguous. The mantle is a conserved organ involved in shell formation throughout molluscs. Specifically the mantle is thought to be responsible for secreting the protein component of the shell. This study employs molecular approaches to determine the spatial expression of genes within the mantle tissue to further the elucidation of the shell biomineralization. Results: A microarray platform was custom generated (PmaxArray 1.0) from the pearl oyster Pinctada maxima. PmaxArray 1.0 consists of 4992 expressed sequence tags (ESTs) originating from mantle tissue. This microarray was used to analyze the spatial expression of ESTs throughout the mantle organ. The mantle was dissected into five discrete regions and analyzed for differential gene expression with PmaxArray 1.0. Over 2000 ESTs were determined to be differentially expressed among the tissue sections, identifying five major expression regions. In situ hybridization validated and further localized the expression for a subset of these ESTs. Comparative sequence similarity analysis of these ESTs revealed a number of the transcripts were novel while others showed significant sequence similarities to previously characterized shell related genes.

Numerical analysis for a variable-order nonlinear cable equation

In this paper, a variable-order nonlinear cable equation is considered. A numerical method with first-order temporal accuracy and fourth-order spatial accuracy is proposed. The convergence and stability of the numerical method are analyzed by Fourier analysis. We also propose an improved numerical method with second-order temporal accuracy and fourth-order spatial accuracy. Finally, the results of a numerical example support the theoretical analysis.

Contribution of take-out food consumption to socioeconomic differences in fruit and vegetable intake : a mediation analysis

Lower fruit and vegetable intake among socioeconomically disadvantaged groups has been well documented, and may be a consequence of a higher consumption of take-out foods. This study examined whether, and to what extent, take-out food consumption mediated (explained) the association between socioeconomic position and fruit and vegetable intake. A cross-sectional postal survey was conducted among 1500 randomly selected adults aged 25–64 years in Brisbane, Australia in 2009 (response rate = 63.7%, N = 903). A food frequency questionnaire assessed usual daily servings of fruits and vegetables (0 to 6), overall take-out consumption (times/week) and the consumption of 22 specific take-out items (never to ≥once/day). These specific take-out items were grouped into “less healthy” and “healthy” choices and indices were created for each type of choice (0 to 100). Socioeconomic position was ascertained by education. The analyses were performed using linear regression, and a bootstrap re-sampling approach estimated the statistical significance of the mediated effects. Mean daily serves of fruits and vegetables was 1.89 (SD 1.05) and 2.47 (SD 1.12) respectively. The least educated group were more likely to consume fewer serves of fruit (B= –0.39, p<0.001) and vegetables (B= –0.43, p<0.001) compared with the highest educated. The consumption of “less healthy” take-out food partly explained (mediated) education differences in fruit and vegetable intake; however, no mediating effects were observed for overall and “healthy” take-out consumption. Regular consumption of “less healthy” take-out items may contribute to socioeconomic differences in fruit and vegetable intake, possibly by displacing these foods.

Why evolutionary realism underpins evolutionary economic analysis and theory

This paper offers a reply to Jochen Runde's critical appraisal of the ontological framework underpinning Dopfer and Potts's (2008) General Theory of Economic Evolution. We argue that Runde's comprehensive critique contains several of what we perceive to be misunderstandings in relation to the key concepts of ‘generic’ and ‘meso’ that we seek here to unpack and redress.

Vibrational spectroscopic analysis of the mineral crandallite CaAl3(PO4)2(OH)5•(H2O) from the Jenolan Caves, Australia

The mineral crandallite CaAl3(PO4)2(OH)5•(H2O) has been identified in deposits found in the Jenolan Caves, New South Wales, Australia by using a combination of X-ray diffraction and Raman spectroscopic techniques. A comparison is made between the vibrational spectra of crandallite found in the Jenolan Caves and a standard crandallite. Raman and infrared bands are assigned to PO43- and HPO42- stretching and bending modes. The predominant features are the internal vibrations of the PO43 and HPO42- groups. A mechanism for the formation of crandallite is presented and the conditions for the formation are elucidated.

Large scale participatory acoustic sensor data analysis : tools and reputation models to enhance effectiveness

Acoustic sensors play an important role in augmenting the traditional biodiversity monitoring activities carried out by ecologists and conservation biologists. With this ability however comes the burden of analysing large volumes of complex acoustic data. Given the complexity of acoustic sensor data, fully automated analysis for a wide range of species is still a significant challenge. This research investigates the use of citizen scientists to analyse large volumes of environmental acoustic data in order to identify bird species. Specifically, it investigates ways in which the efficiency of a user can be improved through the use of species identification tools and the use of reputation models to predict the accuracy of users with unidentified skill levels. Initial experimental results are reported.

Stochastic analysis of the VEGF receptor response curve

Recently, an analysis of the response curve of the vascular endothelial growth factor (VEGF) receptor and its application to cancer therapy was described in [T. Alarcón, and K. Page, J. R. Soc. Lond. Interface 4, 283–304 (2007)]. The analysis is significantly extended here by demonstrating that an alternative computational strategy, namely the Krylov FSP algorithm for the direct solution of the chemical master equation, is feasible for the study of the receptor model. The new method allows us to further investigate the hypothesis of symmetry in the stochastic fluctuations of the response. Also, by augmenting the original model with a single reversible reaction we formulate a plausible mechanism capable of realizing a bimodal response, which is reported experimentally but which is not exhibited by the original model. The significance of these findings for mechanisms of tumour resistance to antiangiogenic therapy is discussed.

Assessing students in senior science: an analysis of questions in contextualised chemistry exams

This study explores the development of a coding system for analysing test questions in two context-based chemistry exams. We describe our unique analytical procedures before contrasting the data from both tests. Our findings indicate that when a new curriculum is developed such as a context-based curriculum, teachers are required to combine the previously separate domains of context and concept to develop contextualised assessment. We argue that constructing contextualised assessment items requires teachers to view concepts and context as interconnected rather than as separate entities that may polarise scientific endeavour. Implications for practice, curriculum and assessment-development in context-based courses are proposed.

Arterial traffic congestion analysis using Bluetooth duration data

The aim of this study is to assess the potential use of Bluetooth data for traffic monitoring of arterial road networks. Bluetooth data provides the direct measurement of travel time between pairs of scanners, and intensive research has been reported on this topic. Bluetooth data includes “Duration” data, which represents the time spent by Bluetooth devices to pass through the detection range of Bluetooth scanners. If the scanners are located at signalised intersections, this Duration can be related to intersection performance, and hence represents valuable information for traffic monitoring. However the use of Duration has been ignored in previous analyses. In this study, the Duration data as well as travel time data is analysed to capture the traffic condition of a main arterial route in Brisbane. The data consists of one week of Bluetooth data provided by Brisbane City Council. As well, micro simulation analysis is conducted to further investigate the properties of Duration. The results reveal characteristics of Duration, and address future research needs to utilise this valuable data source.

Analysis of rural activity spaces and transport disadvantage using a multi-method approach

Current knowledge about the relationship between transport disadvantage and activity space size is limited to urban areas, and as a result, very little is known about this link in a rural context. In addition, although research has identified transport disadvantaged groups based on their size of activity space, these studies have, however, not empirically explained such differences and the result is often a poor identification of the problems facing disadvantaged groups. Research has shown that transport disadvantage varies over time. The static nature of analysis using the activity space concept in previous research studies has lacked the ability to identify transport disadvantage in time. Activity space is a dynamic concept; and therefore possesses a great potential in capturing temporal variations in behaviour and access opportunities. This research derives measures of the size and fullness of activity spaces for 157 individuals for weekdays, weekends, and for a week using weekly activity-travel diary data from three case study areas located in rural Northern Ireland. Four focus groups were also conducted in order to triangulate quantitative findings and to explain the differences between different socio-spatial groups. The findings of this research show that despite having a smaller sized activity space, individuals were not disadvantaged because they were able to access their required activities locally. Car-ownership was found to be an important life line in rural areas. Temporal disaggregation of the data reveals that this is true only on weekends due to a lack of public transport services. In addition, despite activity spaces being at a similar size, the fullness of activity spaces of low-income individuals was found to be significantly lower compared to their high-income counterparts. Focus group data shows that financial constraint, poor connections both between public transport services and between transport routes and opportunities forced individuals to participate in activities located along the main transport corridors.

Funding grant proposals for scientific research : retrospective analysis of scores by members of grant review panel

Objectives: To quantify randomness and cost when choosing health and medical research projects for funding. Design: Analysis of retrospective data from grant review panels. Setting: The National Health & Medical Research Council of Australia. Participants/Data: All panel members’ scores for grant proposals submitted in 2009. Main outcome measure: The proportion of grant proposals that were always, sometimes and never funded after accounting for random variability arising from variation in panel members’ scores; the cost-effectiveness of different size assessment panels. Results: 59% of 620 funded grants were sometimes not funded when random variability was accounted for. Only 9% of grant proposals were always funded, 61% were never funded and 29% were sometimes funded. The extra cost per grant effectively funded from the most effective system was $18,541. Conclusions: Allocating funding for scientific research in health and medicine is costly and somewhat random. There are many useful research questions to be addressed that could improve current processes.

Higher order spectral analysis of Chua's circuit

Higher order spectral analysis is used to investigate nonlinearities in time series of voltages measured from a realization of Chua's circuit. For period-doubled limit cycles, quadratic and cubic nonlinear interactions result in phase coupling and energy exchange between increasing numbers of triads and quartets of Fourier components as the nonlinearity of the system is increased. For circuit parameters that result in a chaotic Rossler-type attractor, bicoherence and tricoherence spectra indicate that both quadratic and cubic nonlinear interactions are important to the dynamics. When the circuit exhibits a double-scroll chaotic attractor the bispectrum is zero, but the tricoherences are high, consistent with the importance of higher-than-second order nonlinear interactions during chaos associated with the double scroll.

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.