DNA methylation at the novel CpG sites in the promoter of MED15/PCQAP gene as a biomarker for head and neck cancers

Head and neck cancers (HNCs) represent a significant and ever-growing burden to the modern society, mainly due to the lack of early diagnostic methods. A significant number of HNCs is often associated with drinking, smoking, chewing beetle nut, and human papilloma virus (HPV) infections. We have analyzed DNA methylation patterns in tumor and normal tissue samples collected from head and neck squamous cell carcinoma (HNSCC) patients who were smokers. We have identified novel methylation sites in the promoter of the mediator complex subunit 15 (MED15/PCQAP) gene (encoing a co-factor important for regulation of transcription initiation for promoters of many genes), hypermethylated specifically in tumor cells. Two clusters of CpG dinucleotides methylated in tumors, but not in normal tissue from the same patients, were identified. These CpG methylation events in saliva samples were further validated in a separate cohort of HNSCC patients (who developed cancer due to smoking or HPV infections) and healthy controls using methylation-specific PCR (MSP). We used saliva as a biological medium because of its non-invasive nature, close proximity to the tumors, easiness and it is an economically viable option for large-scale screening studies. The methylation levels for the two identified CpG clusters were significantly different between the saliva samples collected from healthy controls and HNSCC individuals (Welch's t-test returning P, 0.05 and Mann-Whitney test P, 0.01 for both). The developed MSP assays also provided a good discriminative ability with AUC values of 0.70 (P, 0.01) and 0.63 (P, 0.05). The identified novel CpG methylation sites may serve as potential non-invasive biomarkers for detecting HNSCC. © the authors.

Stepping accuracy and visuomotor control among older adults : effect of target contrast and refractive blur

Purpose: Older adults have increased visual impairment, including refractive blur from presbyopic multifocal spectacle corrections, and are less able to extract visual information from the environment to plan and execute appropriate stepping actions; these factors may collectively contribute to their higher risk of falls. The aim of this study was to examine the effect of refractive blur and target visibility on the stepping accuracy and visuomotor stepping strategies of older adults during a precision stepping task. Methods: Ten healthy, visually normal older adults (mean age 69.4 ± 5.2 years) walked up and down a 20 m indoor corridor stepping onto selected high and low-contrast targets while viewing under three visual conditions: best-corrected vision, +2.00 DS and +3.00 DS blur; the order of blur conditions was randomised between participants. Stepping accuracy and gaze behaviours were recorded using an eyetracker and a secondary hand-held camera. Results: Older adults made significantly more stepping errors with increasing levels of blur, particularly exhibiting under-stepping (stepping more posteriorly) onto the targets (p<0.05), while visuomotor stepping strategies did not significantly alter. Stepping errors were also significantly greater for the low compared to the high contrast targets and differences in visuomotor stepping strategies were found, including increased duration of gaze and increased interval between gaze onset and initiation of the leg swing when stepping onto the low contrast targets. Conclusions: These findings highlight that stepping accuracy is reduced for low visibility targets, and for high levels of refractive blur at levels typically present in multifocal spectacle corrections, despite significant changes in some of the visuomotor stepping strategies. These findings highlight the importance of maximising the contrast of objects in the environment, and may help explain why older adults wearing multifocal spectacle corrections exhibit an increased risk of falling.

Audio signalling as a backup communication channel for multi-robot systems

This paper presents a low-bandwidth multi-robot communication system designed to serve as a backup communication channel in the event a robot suffers a network device fault. While much research has been performed in the area of distributing network communication across multiple robots within a system, individual robots are still susceptible to hardware failure. In the past, such robots would simply be removed from service, and their tasks re-allocated to other members. However, there are times when a faulty robot might be crucial to a mission, or be able to contribute in a less communication intensive area. By allowing robots to encode and decode messages into unique sequences of DTMF symbols, called words, our system is able to facilitate continued low-bandwidth communication between robots without access to network communication. Our results have shown that the system is capable of permitting robots to negotiate task initiation and termination, and is flexible enough to permit a pair of robots to perform a simple turn taking task.

Improving treatment for obese women with early stage cancer of the uterus : rationale and design of the levonorgestrel intrauterine device ±Metformin ±weight loss in endometrial cancer (feMME) trial

Purpose Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. Methods An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. Conclusions There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment.

Cerebellar grey matter deficits in first-episode schizophrenia mapped using cortical pattern matching

Cerebellar dysfunction has been proposed to lead to “cognitive dysmetria” in schizophrenia via the cortico-cerebellar-thalamic-cortical circuit, contributing to a range of cognitive and clinical symptoms of the disorder. Here we investigated total cerebellar grey and white matter volumes and cerebellar regional grey matter abnormalities in 13 remitted first-episode schizophrenia patients with less than 2 years’ duration of illness. Patient data were compared to 13 pair-wise age, gender, and handedness-matched healthy volunteers using cortical pattern averaging on high-resolution magnetic resonance images. Total cerebellar volume and total grey matter volumes in first-episode schizophrenia patients did not differ from healthy control subjects, but total cerebellar white matter was increased and total grey to white matter ratios were reduced in patients. Four clusters of cerebellar grey matter reduction were identified: (i) in superior vermis; (ii) in the left lobuli VI; (iii) in right-inferior lobule IX, extending into left lobule IX; and (iv) bilaterally in the areas of lobuli III, peduncle and left flocculus. Grey matter deficits were particularly prominent in right lobuli III and IX, left flocculus and bilateral pedunculi. These cerebellar areas have been implicated in attention control, emotional regulation, social functioning, initiation of smooth pursuit eye movements, eye-blink conditioning, language processing, verbal memory, executive function and the processing of spatial and emotional information. Consistent with common clinical, cognitive, and pathophysiological signs of established illness, our findings demonstrate cerebellar pathology as early as in first-episode schizophrenia.

Implementation and evaluation of open source unified communications for SMBs

Unified Communication (UC) is the integration of two or more real time communication systems into one platform. Integrating core communication systems into one overall enterprise level system delivers more than just cost saving. These real-time interactive communication services and applications over Internet Protocol (IP) have become critical in boosting employee accessibility and efficiency, improving customer support and fostering business agility. However, some small and medium-sized businesses (SMBs) are far from implementing this solution due to the high cost of initial deployment and ongoing support. In this paper, we will discuss and demonstrate an open source UC solution, viz. “Asterisk” for use by SMBs, and report on some performance tests using SIPp. The contribution from this research is the provision of technical advice to SMBs in deploying UC, which is manageable in terms of cost, ease of deployment and support.

Making scenes : Reggae, punk, and death metal in 1990s Bali

In 1996, Emma Baulch went to live in Bali to do research on youth culture. Her chats with young people led her to an enormously popular regular outdoor show dominated by local reggae, punk, and death metal bands. In this rich ethnography, she takes readers inside each scene: hanging out in the death metal scene among unemployed university graduates clad in black T-shirts and ragged jeans; in the punk scene among young men sporting mohawks, leather jackets, and hefty jackboots; and among the remnants of the local reggae scene in Kuta Beach, the island’s most renowned tourist area. Baulch tracks how each music scene arrived and grew in Bali, looking at such influences as the global extreme metal underground, MTV Asia, and the internationalization of Indonesia’s music industry. Making Scenes is an exploration of the subtle politics of identity that took place within and among these scenes throughout the course of the 1990s. Participants in the different scenes often explained their interest in death metal, punk, or reggae in relation to broader ideas about what it meant to be Balinese, which reflected views about Bali’s tourism industry and the cultural dominance of Jakarta, Indonesia’s capital and largest city. Through dance, dress, claims to public spaces, and onstage performances, participants and enthusiasts reworked “Balinese-ness” by synthesizing global media, ideas of national belonging, and local identity politics. Making Scenes chronicles the creation of subcultures at a historical moment when media globalization and the gradual demise of the authoritarian Suharto regime coincided with revitalized, essentialist formulations of the Balinese self.

Increasing leucine concentration stimulates mechanistic target of rapamycin signaling and cell growth in C2C12 skeletal muscle cells

Leucine is a key amino acid for initiating translation in muscle cells, but the dose-dependent effects of leucine on intracellular signaling are poorly characterized. This study examined the effect that increasing doses of leucine would have on changes in mechanistic target of rapamycin (mTOR)–mediated signaling, rates of protein synthesis, and cell size in C2C12 cells. We hypothesized that a leucine “threshold” exists, which represents the minimum stimulus required to initiate mTOR signaling in muscle cells. Acute exposure to 1.5, 3.2, 5.0, and 16.1 mM leucine increased phosphorylation of mTORSer2448 (~1.4-fold; P < .04), 4E-BP1 Thr37/46 (~1.9-fold; P < .001), and rpS6Ser235/6 (~2.3-fold; P < .001). However, only p70S6kThr389 exhibited a dose-dependent response to leucine with all treatments higher than control (~4-fold; P < .001) and at least 5 mM higher than the 1.5-mM concentration (1.2-fold; P < .02). Rates of protein synthesis were not altered by any treatment. Seven days of exposure to 0.5, 1.5, 5.0, and 16.5 mM leucine resulted in an increase in cell size in at least 5 mM treatments (~1.6-fold, P < .001 vs control). Our findings indicate that even at low leucine concentrations, phosphorylation of proteins regulating translation initiation signaling is enhanced. The phosphorylation of p70S6kThr389 follows a leucine dose-response relationship, although this was not reflected by the acute protein synthetic response. Nevertheless, under the conditions of the present study, it appears that leucine concentrations of at least 5 mM are necessary to enhance cell growth.

Computational epigenetic profiling of CpG islets in MTHFR

Computational epigenetics is a new area of research focused on exploring how DNA methylation patterns affect transcription factor binding that affect gene expression patterns. The aim of this study was to produce a new protocol for the detection of DNA methylation patterns using computational analysis which can be further confirmed by bisulfite PCR with serial pyrosequencing. The upstream regulatory element and pre-initiation complex relative to CpG islets within the methylenetetrahydrofolate reductase gene were determined via computational analysis and online databases. The 1,104 bp long CpG island located near to or at the alternative promoter site of methylenetetrahydrofolate reductase gene was identified. The CpG plot indicated that CpG islets A and B, within the island, contained 62 and 75 % GC content CpG ratios of 0.70 and 0.80–0.95, respectively. Further exploration of the CpG islets A and B indicates that the transcription start sites were GGC which were absent from the TATA boxes. In addition, although six PROSITE motifs were identified in CpG B, no motifs were detected in CpG A. A number of cis-regulatory elements were found in different regions within the CpGs A and B. Transcription factors were predicted to bind to CpGs A and B with varying affinities depending on the DNA methylation status. In addition, transcription factor binding may influence the expression patterns of the methylenetetrahydrofolate reductase gene by recruiting chromatin condensation inducing factors. These results have significant implications for the understanding of the architecture of transcription factor binding at CpG islets as well as DNA methylation patterns that affect chromatin structure.

Association of the SNP rs2623047 in the HSPG modification enzyme SULF1 with an Australian Caucasian Breast Cancer Cohort

Breast cancer is the second most common cancer worldwide and the most common cancer reported in women. This malignant tumour is characterised by a number of specific features including uncontrolled cell proliferation. It ranks fifth in the world as a cause of cancer death in women. Early diagnosis increases 5 year survival rates up to 95%. Heparan sulfate proteoglycans (HSPGs) are complex proteins composed of a core protein to which a number of highly sulfated side chains are synthesised by a highly co-ordinated process resulting in distinct sulfation patterns, which determine specific interations with cell-signaling partners including growth factors, their receptors, ligands and morphogens. The enzymes responsible for chain initiation, elongation and sulfation are critical for creating HS chain variability conferring biological functionality. This study investigated single nucleotide polymorphism in SULF1, the enzyme responsible for the 6-0 desulfation of heparan sulfate side chains. We investigated this SNP in an Australian Caucasian case-control breast cancer population and found a significant association between SULF1 and breast cancer at both the allelic and genotypic level (allele, p=0.016; genotype, p=0.032). Our results suggest the res2623047 SNP in SULF1 may impact breast cancer susceptibility. Specifically, the T allele of rs2623047 in SULF1 is associated with a increased risk of developing breast cancer in our cohort. The identification of markers including SULF1 may improve detection of this disease at its earliest stages improving patient treatment and prognosis.

Effects of strain artefacts arising from a pre-defined callus domain in models of bone healing mechanobiology

Iterative computational models have been used to investigate the regulation of bone fracture healing by local mechanical conditions. Although their predictions replicate some mechanical responses and histological features, they do not typically reproduce the predominantly radial hard callus growth pattern observed in larger mammals. We hypothesised that this discrepancy results from an artefact of the models’ initial geometry. Using axisymmetric finite element models, we demonstrated that pre-defining a field of soft tissue in which callus may develop introduces high deviatoric strains in the periosteal region adjacent to the fracture. These bone-inhibiting strains are not present when the initial soft tissue is confined to a thin periosteal layer. As observed in previous healing models, tissue differentiation algorithms regulated by deviatoric strain predicted hard callus forming remotely and growing towards the fracture. While dilatational strain regulation allowed early bone formation closer to the fracture, hard callus still formed initially over a broad area, rather than expanding over time. Modelling callus growth from a thin periosteal layer successfully predicted the initiation of hard callus growth close to the fracture site. However, these models were still susceptible to elevated deviatoric strains in the soft tissues at the edge of the hard callus. Our study highlights the importance of the initial soft tissue geometry used for finite element models of fracture healing. If this cannot be defined accurately, alternative mechanisms for the prediction of early callus development should be investigated.

The first 25 years of the Queensland Rugby Football League: Claims to legitimacy in annual reports

Despite the cultural importance of sporting organisations, little academic attention has been paid to the legitimising role of their annual reports. In this paper we examine the role of annual reports in establishing the legitimacy of a new organisation, the Queensland Rugby Football League (QRFL), founded in 1908. Contextualised with media reports from newspapers of the day, twelve annual reports from QRFL’s first 25 years are analysed and interpreted using insights from legitimacy theory. Through the presentation of audited financial statements and persuasive narrative accounts of its operations and success, QRFL made claims to pragmatic, moral and cognitive legitimacy as it sought to establish a niche as a new football code and organisation. This contextualised study situates the annual reports in their historical landscape, providing insights about how they contributed to QRFL’s efforts in overcoming the liability of newness in a competitive sports environment.

Computational micromodel for epigenetic mechanisms

Characterization of the epigenetic profile of humans since the initial breakthrough on the human genome project has strongly established the key role of histone modifications and DNA methylation. These dynamic elements interact to determine the normal level of expression or methylation status of the constituent genes in the genome. Recently, considerable evidence has been put forward to demonstrate that environmental stress implicitly alters epigenetic patterns causing imbalance that can lead to cancer initiation. This chain of consequences has motivated attempts to computationally model the influence of histone modification and DNA methylation in gene expression and investigate their intrinsic interdependency. In this paper, we explore the relation between DNA methylation and transcription and characterize in detail the histone modifications for specific DNA methylation levels using a stochastic approach.

A ‘Big Data’ Approach to Mapping the Australian Twittersphere

This chapter discusses the methodological aspects and empirical findings of a large-scale, funded project investigating public communication through social media in Australia. The project concentrates on Twitter, but we approach it as representative of broader current trends toward the integration of large datasets and computational methods into media and communication studies in general, and social media scholarship in particular. The research discussed in this chapter aims to empirically describe networks of affiliation and interest in the Australian Twittersphere, while reflecting on the methodological implications and imperatives of ‘big data’ in the humanities. Using custom network crawling technology, we have conducted a snowball crawl of Twitter accounts operated by Australian users to identify more than one million users and their follower/followee relationships, and have mapped their interconnections. In itself, the map provides an overview of the major clusters of densely interlinked users, largely centred on shared topics of interest (from politics through arts to sport) and/or sociodemographic factors (geographic origins, age groups). Our map of the Twittersphere is the first of its kind for the Australian part of the global Twitter network, and also provides a first independent and scholarly estimation of the size of the total Australian Twitter population. In combination with our investigation of participation patterns in specific thematic hashtags, the map also enables us to examine which areas of the underlying follower/followee network are activated in the discussion of specific current topics – allowing new insights into the extent to which particular topics and issues are of interest to specialised niches or to the Australian public more broadly. Specifically, we examine the Twittersphere footprint of dedicated political discussion, under the #auspol hashtag, and compare it with the heightened, broader interest in Australian politics during election campaigns, using #ausvotes; we explore the different patterns of Twitter activity across the map for major television events (the popular competitive cooking show #masterchef, the British #royalwedding, and the annual #stateoforigin Rugby League sporting contest); and we investigate the circulation of links to the articles published by a number of major Australian news organisations across the network. Such analysis, which combines the ‘big data’-informed map and a close reading of individual communicative phenomena, makes it possible to trace the dynamic formation and dissolution of issue publics against the backdrop of longer-term network connections, and the circulation of information across these follower/followee links. Such research sheds light on the communicative dynamics of Twitter as a space for mediated social interaction. Our work demonstrates the possibilities inherent in the current ‘computational turn’ (Berry, 2010) in the digital humanities, as well as adding to the development and critical examination of methodologies for dealing with ‘big data’ (boyd and Crawford, 2011). Out tools and methods for doing Twitter research, released under Creative Commons licences through our project Website, provide the basis for replicable and verifiable digital humanities research on the processes of public communication which take place through this important new social network.

Testing times for the implementation of curriculum change: Analysis and extension of a curriculum change model

School curriculum change processes have traditionally been managed internally. However, in Queensland, Australia, as a response to the current high-stakes accountability regime, more and more principals are outsourcing this work to external change agents (ECAs). In 2009, one of the authors (a university lecturer and ECA) developed a curriculum change model (the Controlled Rapid Approach to Curriculum Change (CRACC)), specifically outlining the involvement of an ECA in the initiation phase of a school’s curriculum change process. The purpose of this paper is to extend the CRACC model by unpacking the implementation phase, drawing on data from a pilot study of a single school. Interview responses revealed that during the implementation phase, teachers wanted to be kept informed of the wider educational context; use data to constantly track students; relate pedagogical practices to testing practices; share information between departments and professional levels; and, own whole school performance. It is suggested that the findings would be transferable to other school settings and internal leadership of curriculum change. The paper also strikes a chord of concern – Do the responses from teachers operating in such an accountability regime live their professional lives within this corporate and globalised ideology whether they want to or not?