136 research outputs found

    Is there any Evidence of Rhoticity in Historical Australian English?

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    Australian English is traditionally regarded as having been non-rhotic throughout its history, but a recent study by Trudgill and Gordon (2006) has found rhoticity levels of 1% to 20% in audio recordings of six Australian men born near the end of the 19th century, suggesting that Australian English was once a rhotic dialect. The present study re-examines the three most rhotic speakers in the Trudgill and Gordon dataset, as well as archival recordings from an additional seven speakers, to further investigate the presence of rhoticity in Australian English around the turn of the 20th century. Approximately 30 minutes of audio interview data from each speaker was examined impressionistically for the presence of non-prevocalic /r/. Other postvocalic instances of /r/ were also identified in order to explore the relationship between non-prevocalic /r/, linking /r/ and intrusive /r/. On re-examination, the three subjects from Trudgill and Gordon (2006) were found to exhibit little or no rhoticity according to our criteria. Analysis of the additional seven speakers further weakens the argument for rhoticity in Australia at the end of the nineteenth century. Some speakers do, however, have traces of rhoticity, and only one shows consistent use of linking /r/. In this paper, we will explore the phonetic conditioning environments for the vestigial rhoticity in historical Australian English and will discuss some implications for phonological theory

    The Development of a Grazing Rating Index to Identify the Biomass Removed and the Plant Species and Parts Eaten by Grazing Sheep

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    Determining the diet selection of grazing animals is inherently difficult and a trade-off exists between obtaining accurate information and interfering with the normal grazing behaviour of an animal. The botanical composition of a grazing animal’s diet may be estimated using one or a number of techniques in combination. A six-point grazing rating index was developed to identify the plant species consumed by sheep grazing within a heterogeneous native grassland and the extent to which each species within a quadrat was grazed. The method was developed to remove error from visual estimates that prevents detection of significant reductions in biomass for minor species from grazing between two samplings and to determine animal preference

    An interdisciplinary approach to enhance children’s listening, learning, and wellbeing in the classroom : The Listen to Learn for Life (L3) Assessment Framework

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    Introduction: Listening is the gateway to children learning in the mainstream classroom. However, modern classrooms are noisy and dynamic environments making listening challenging. It is therefore critical for researchers from speech and hearing, education, and health sciences to co-design and collaborate to realistically assess how children listen to learn in the classroom and to understand how listening can be improved to enhance children’s learning and wellbeing – an understanding which is currently lacking. Such highly interdisciplinary thinking demands a holistic classroom listening framework that can integrate a range of varied assessments and outcomes. Methods: An extensive review of literature into classroom listening was conducted but failed to identify a suitable framework. In this hypothesis and theory article we present a new framework that we have developed – the Listen to Learn for Life (L3) Assessment Framework. Results: The L3 Assessment Framework holistically incorporates frameworks from health, speech and hearing sciences, and education sectors. The framework accommodates a broad range of different factors that may affect listening, allowing for researchers to choose specific factors dependent on the context of use. Discussion: Selected examples of applying the framework are provided demonstrating how to assess children’s performance during different classroom activities as well as the effectiveness of a chosen intervention. For example, the framework can be used to assess the effectiveness of a wireless remote microphone intervention during group work activities for a child with autism. Conclusion: The L3 Assessment Framework provides a theoretical basis for the future development of research and practice as applied to listening in a classroom setting

    Efficacy of antimicrobial and anti-viral coated air filters to prevent the spread of airborne pathogens

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    The COVID-19 pandemic has demonstrated the real need for mechanisms to control the spread of airborne respiratory pathogens. Thus, preventing the spread of disease from pathogens has come to the forefront of the public consciousness. This has brought an increasing demand for novel technologies to prioritise clean air. In this study we report on the efficacy of novel biocide treated filters and their antimicrobial activity against bacteria, fungi and viruses. The antimicrobial filters reported here are shown to kill pathogens, such as Candida albicans, Escherichia coli and MRSA in under 15 min and to destroy SARS-CoV-2 viral particles in under 30 s following contact with the filter. Through air flow rate testing, light microscopy and SEM, the filters are shown to maintain their structure and filtration function. Further to this, the filters are shown to be extremely durable and to maintain antimicrobial activity throughout the operational lifetime of the product. Lastly, the filters have been tested in field trials onboard the UK rail network, showing excellent efficacy in reducing the burden of microbial species colonising the air conditioning system

    Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

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    Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

    Pain-causing stinging nettle toxins target TMEM233 to modulate NaV1.7 function

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    Voltage-gated sodium (NaV) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived NaV channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at NaV channels, and that co-expression of TMEM233 modulates the gating properties of NaV1.7. These findings identify TMEM233 as a previously unknown NaV1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on NaV channel gating, and provide important insights into the function of NaV channels in sensory neurons

    ROR1 and ROR2 expression in pancreatic cancer

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    Background: The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical Wnt signalling in PDAC remains largely unknown. Only one study has investigated the prognostic significance of the noncanonical Wnt signalling receptor, ROR2 in PDAC. No studies have investigated the prognostic role of ROR1 in PDAC. Methods: Here, we performed analysis of ROR1 and ROR2 mRNA expression in three publicly available datasets ICGC-PACA-AU (n = 81), TCGA-PAAD (n = 150) and CPTAC-PDAC (n = 137). ROR1 and ROR2 protein expression from the CPTAC-PDAC discovery cohort were also analysed. Immunohistochemistry (IHC) using the validated anti ROR1 monoclonal antibody (4A5) was performed on the Australian Pancreatic Cancer Genome Initiative (APGI) cohort of PDAC samples (n = 152). Association between ROR1 cytoplasmic staining intensity and clinicopathological parameters including stage, grade and overall survival (OS) was investigated. Results: High ROR1 mRNA expression levels correlated with a favourable OS outcome in all of the ICGC-PACA-AU, TCGA-PAAD and CPTAC-PDAC cohorts. ROR1 protein expression was not associated with stage, grade or OS in the APGI cohort. Conclusion: ROR1 and ROR2 have potential as prognostic markers when measured at the mRNA level in PDAC. Our IHC cohort did not support ROR1 protein expression in predicting OS, and highlighted the discrepancy of prognostic biomarkers when measured by MS, IHC and RNAseq

    DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

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    Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs

    Candidate locus analysis of the TERT-CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk.

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    Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT and CLPTM1L, but no such association has been reported with endometrial cancer. To evaluate the role of genetic variants at the TERT-CLPTM1L region in endometrial cancer risk, we carried out comprehensive fine-mapping analyses of genotyped and imputed SNPs using a custom Illumina iSelect array which includes dense SNP coverage of this region. We examined 396 SNPs (113 genotyped, 283 imputed) in 4,401 endometrial cancer cases and 28,758 controls. Single-SNP and forward/backward logistic regression models suggested evidence for three variants independently associated with endometrial cancer risk (P = 4.9 × 10(-6) to P = 7.7 × 10(-5)). Only one falls into a haplotype previously associated with other cancer types (rs7705526, in TERT intron 1), and this SNP has been shown to alter TERT promoter activity. One of the novel associations (rs13174814) maps to a second region in the TERT promoter and the other (rs62329728) is in the promoter region of CLPTM1L; neither are correlated with previously reported cancer-associated SNPs. Using TCGA RNASeq data, we found significantly increased expression of both TERT and CLPTM1L in endometrial cancer tissue compared with normal tissue (TERT P = 1.5 × 10(-18), CLPTM1L P = 1.5 × 10(-19)). Our study thus reports a novel endometrial cancer risk locus and expands the spectrum of cancer types associated with genetic variation at 5p15, further highlighting the importance of this region for cancer susceptibility.This work was supported by the NHMRC Project Grant (ID#1031333). This work was also supported by Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692)This is the published version. It first appeared at http://link.springer.com/article/10.1007%2Fs00439-014-1515-4
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