A plasmonic 'ac Wheatstone bridge' circuit for high-sensitivity phase measurement and single-molecule detection

In this paper, a plasmonic “ac Wheatstone bridge” circuit is proposed and theoretically modeled for the first time. The bridge circuit consists of three metallic nanoparticles, shaped as rectangular prisms, with two nanoparticles acting as parallel arms of a resonant circuit and the third bridging nanoparticle acting as an optical antenna providing an output signal. Polarized light excites localized surface plasmon resonances in the two arms of the circuit, which generate an optical signal dependent on the phase-sensitive excitations of surface plasmons in the antenna. The circuit is analyzed using a plasmonic coupling theory and numerical simulations. The analyses show that the plasmonic circuit is sensitive to phase shifts between the arms of the bridge and has the potential to detect the presence of single molecules.

Business cycle dynamics with duration dependence and leading indicators

Durland and McCurdy [Durland, J.M., McCurdy, T.H., 1994. Duration-dependent transitions in a Markov model of US GNP growth. Journal of Business and Economic Statistics 12, 279–288] investigated the issue of duration dependence in US business cycle phases using a Markov regime-switching approach, introduced by Hamilton [Hamilton, J., 1989. A new approach to the analysis of time series and the business cycle. Econometrica 57, 357–384] and extended to the case of variable transition parameters by Filardo [Filardo, A.J., 1994. Business cycle phases and their transitional dynamics. Journal of Business and Economic Statistics 12, 299–308]. In Durland and McCurdy’s model duration alone was used as an explanatory variable of the transition probabilities. They found that recessions were duration dependent whilst expansions were not. In this paper, we explicitly incorporate the widely-accepted US business cycle phase change dates as determined by the NBER, and use a state-dependent multinomial Logit modelling framework. The model incorporates both duration and movements in two leading indexes – one designed to have a short lead (SLI) and the other designed to have a longer lead (LLI) – as potential explanatory variables. We find that doing so suggests that current duration is not only a significant determinant of transition out of recessions, but that there is some evidence that it is also weakly significant in the case of expansions. Furthermore, we find that SLI has more informational content for the termination of recessions whilst LLI does so for expansions.

SwarmPS: Rapid, semi-automated single particle selection software

Single particle analysis (SPA) coupled with high-resolution electron cryo-microscopy is emerging as a powerful technique for the structure determination of membrane protein complexes and soluble macromolecular assemblies. Current estimates suggest that ∼104–105 particle projections are required to attain a 3 Å resolution 3D reconstruction (symmetry dependent). Selecting this number of molecular projections differing in size, shape and symmetry is a rate-limiting step for the automation of 3D image reconstruction. Here, we present SwarmPS, a feature rich GUI based software package to manage large scale, semi-automated particle picking projects. The software provides cross-correlation and edge-detection algorithms. Algorithm-specific parameters are transparently and automatically determined through user interaction with the image, rather than by trial and error. Other features include multiple image handling (∼102), local and global particle selection options, interactive image freezing, automatic particle centering, and full manual override to correct false positives and negatives. SwarmPS is user friendly, flexible, extensible, fast, and capable of exporting boxed out projection images, or particle coordinates, compatible with downstream image processing suites.

Mean and variance of estimates of the bispectrum of a harmonic random process-an analysis including leakage effects

Analytical expressions are derived for the mean and variance, of estimates of the bispectrum of a real-time series assuming a cosinusoidal model. The effects of spectral leakage, inherent in discrete Fourier transform operation when the modes present in the signal have a nonintegral number of wavelengths in the record, are included in the analysis. A single phase-coupled triad of modes can cause the bispectrum to have a nonzero mean value over the entire region of computation owing to leakage. The variance of bispectral estimates in the presence of leakage has contributions from individual modes and from triads of phase-coupled modes. Time-domain windowing reduces the leakage. The theoretical expressions for the mean and variance of bispectral estimates are derived in terms of a function dependent on an arbitrary symmetric time-domain window applied to the record. the number of data, and the statistics of the phase coupling among triads of modes. The theoretical results are verified by numerical simulations for simple test cases and applied to laboratory data to examine phase coupling in a hypothesis testing framework

An experimental research investigation into disused flat rail wagons as bridges with applications for low volume rural roads in Australia

An experimental laboratory investigation was carried out to assess the structural adequacy of a disused PHO Class Flat Bottom Rail Wagon (FRW) for a single lane low volume road bridge application as per the design provisions of the Australian Bridge Design Standard AS 5100(2004). The investigation also encompassed a review into the risk associated with the pre-existing damage in wagons incurred during their service life on rail. The main objective of the laboratory testing of the FRW was to physically measure its performance under the same applied traffic loading it would be required to resist as a road bridge deck. In order to achieve this a full width (5.2m) single lane, single span (approximately 10m), simply supported bridge would be required to be constructed and tested in a structural laboratory. However, the available clear spacing between the columns of the loading portal frame encountered within the laboratory was insufficient to accommodate the 5.2m wide bridge deck excluding clearance normally considered necessary in structural testing. Therefore, only half of the full scale bridge deck (single FRW of width 2.6m) was able to be accommodated and tested; with the continuity of the bridge deck in the lateral direction applied as boundary constraints along the full length of the FRW at six selected locations. This represents a novel approach not yet reported in the literature for bridge deck testing to the best of the knowledge of the author. The test was carried out under two loadings provided in AS 5100 (2004) – one stationary W80 wheel load and the second a moving axle load M1600. As the bridge investigated in the study is a single lane single span low volume road bridge, the risk of pre-existing damage and the expected high cycle fatigue failure potential was assessed as being minimal and hence the bridge deck was not tested structurally for fatigue/ fracture. The high axle load requirements have instead been focussed upon the investigation into the serviceability and ultimate limit state requirements. The testing regime adopted however involved extensive recording of strains and deflections at several critical locations of the FRW. Three locations of W80 point load and two locations of the M1600 Axle load were considered for the serviceability testing; the FRW was also tested under the ultimate load dictated by the M1600. The outcomes of the experimental investigation have demonstrated that the FRW is structurally adequate to resist the prescribed traffic loadings outlaid in AS 5100 (2004). As the loading was directly applied on to the FRW, the laboratory testing is assessed as being significantly conservative. The FRW bridge deck in the field would only resist the load transferred by the running platform, where, depending on the design, composite action might exist – thereby the share of the loading which needs to be resisted by the FRW would be smaller than the system tested in the lab. On this basis, a demonstration bridge is under construction at the time of writing this thesis and future research will involve field testing in order to assess its performance.

Analysis of the CDKN2A, CDKN2B and CDK4 genes in 48 Australian melanoma kindreds

Germline mutations within the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and one of its targets, the cyclin dependent kinase 4 (CDK4) gene, have been identified in a proportion of melanoma kindreds. In the case of CDK4, only one specific mutation, resulting in the substitution of a cysteine for an arginine at codon 24 (R24C), has been found to be associated with melanoma. We have previously reported the identification of germline CDKN2A mutations in 7/18 Australian melanoma kindreds and the absence of the R24C CDK4 mutation in 21 families lacking evidence of a CDKN2A mutation. The current study represents an expansion of these efforts and includes a total of 48 melanoma families from Australia. All of these families have now been screened for mutations within CDKN2A and CDK4, as well as for mutations within the CDKN2A homolog and 9p21 neighbor, the CDKN2B gene, and the alternative exon 1 (E1beta) of CDKN2A. Families lacking CDKN2A mutations, but positive for a polymorphism(s) within this gene, were further evaluated to determine if their disease was associated with transcriptional silencing of one CDKN2A allele. Overall, CDKN2A mutations were detected in 3/30 (10%) of the new kindreds. Two of these mutations have been observed previously: a 24 bp duplication at the 5' end of the gene and a G to C transversion in exon 2 resulting in an M531 substitution. A novel G to A transition in exon 2, resulting in a D108N substitution was also detected. Combined with our previous findings, we have now detected germline CDKN2A mutations in 10/48 (21%) of our melanoma kindreds. In none of the 'CDKN2A-negative' families was melanoma found to segregate with either an untranscribed CDKN2A allele, an R24C CDK4 mutation, a CDKN2B mutation, or an E1beta mutation. The last three observations suggest that these other cell cycle control genes (or alternative gene products) are either not involved at all, or to any great extent, in melanoma predisposition.

p53 prevents progression of nevi to melanoma predominantly through cell cycle regulation

p53 is the central member of a critical tumor suppressor pathway in virtually all tumor types, where it is silenced mainly by missense mutations. In melanoma, p53 predominantly remains wild type, thus its role has been neglected. To study the effect of p53 on melanocyte function and melanomagenesis, we crossed the 'high-p53'Mdm4+/- mouse to the well-established TP-ras0/+ murine melanoma progression model. After treatment with the carcinogen dimethylbenzanthracene (DMBA), TP-ras0/+ mice on the Mdm4+/- background developed fewer tumors with a delay in the age of onset of melanomas compared to TP-ras0/+ mice. Furthermore, we observed a dramatic decrease in tumor growth, lack of metastasis with increased survival of TP-ras0/+: Mdm4+/- mice. Thus, p53 effectively prevented the conversion of small benign tumors to malignant and metastatic melanoma. p53 activation in cultured primary melanocyte and melanoma cell lines using Nutlin-3, a specific Mdm2 antagonist, supported these findings. Moreover, global gene expression and network analysis of Nutlin-3-treated primary human melanocytes indicated that cell cycle regulation through the p21WAF1/CIP1 signaling network may be the key anti-melanomagenic activity of p53.

Narratives of complexity : an ethnographic exploration of resilience and wellbeing among single refugee women in Brisbane

This study aimed to explore resilience and wellbeing among a group of eight refugee women originating from several countries (mainly African) and living in Brisbane, most of whom were single mothers. To challenge mostly quantitative and gender-blind explorations of mental health concepts among refugee groups, the project sought an emic and contextual understanding of resilience and wellbeing. Established perspectives, while useful, tend to overlook the complexities of refugee mental health experiences and can neglect the dense nature of individual stories. The purpose of my study was to contest relatively simplistic narratives of mental health constructs that tend to dominate migrant and refugee studies and influence practice paradigms in the human services field. In this ethnographic exploration of mental health constructs conducted in 2008 and 2009, the use of in-depth interviews, participant observations, and visual ethnographic elements provided an opportunity for refugee women to tell their own stories. The participants’ unique narratives of pre- and post-migration experiences, shaped by specific gender, age, social, cultural and political aspects prevailing in their lives, yielded ‘thick’ ethnographic description (Geertz, 1973) of their social worlds. The findings explored in this study, namely language issues, the impact of community dynamics, and the single status of refugee women, clearly demonstrate that mental health constructs are fluid, multifaceted and complex in reality. In fact, language, community dynamics, and being a single mother, represented both opportunities and barriers in the lives of participants. In some contexts, these factors were conducive to resilience and wellbeing, while in other circumstances, these three elements acted as a hindrance to positive mental health outcomes. There are multiple dimensions to the findings, signifying that the social worlds of refugee women cannot be simplified using set definitions and neat notions of resilience and wellbeing. Instead, the intricacies and complexities embedded in the mundane of the everyday highlight novel conceptualisations of resilience and wellbeing. Based on the particular circumstances of single refugee mothers, whose experiences differ from that of married women, this thesis presents novel articulations of mental health constructs, as an alternative view to existing trends in the literature on refugee issues. Rich and multi-dimensional meanings associated with the socio-cultural determinants of mental health emerged in the process. This thesis’ findings highlight a significant gap in diasporic studies as well as simplistic assumptions about refugee women’s resettlement experiences. Single refugee women’s distinct issues are so complex and dense, that a contextual approach is critical to yield accurate depictions of their circumstances. It is therefore essential to understand refugee lived experiences within broader socio-political contexts to truly appreciate the depth of these narratives. In this manner, critical aspects salient to refugee journeys can inform different understandings of resilience, wellbeing and mental health, and shape contemporary policy and human service practice paradigms.