A novel saliva-based microRNA biomarker panel to detect head and neck cancers

Background MicroRNAs (miRNAs) are known to play an important role in cancer development by post-transcriptionally affecting the expression of critical genes. The aims of this study were two-fold: (i) to develop a robust method to isolate miRNAs from small volumes of saliva and (ii) to develop a panel of saliva-based diagnostic biomarkers for the detection of head and neck squamous cell carcinoma (HNSCC). Methods Five differentially expressed miRNAs were selected from miScript™ miRNA microarray data generated using saliva from five HNSCC patients and five healthy controls. Their differential expression was subsequently confirmed by RT-qPCR using saliva samples from healthy controls (n = 56) and HNSCC patients (n = 56). These samples were divided into two different cohorts, i.e., a first confirmatory cohort (n = 21) and a second independent validation cohort (n = 35), to narrow down the miRNA diagnostic panel to three miRNAs: miR-9, miR-134 and miR-191. This diagnostic panel was independently validated using HNSCC miRNA expression data from The Cancer Genome Atlas (TCGA), encompassing 334 tumours and 39 adjacent normal tissues. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic capacity of the panel. Results On average 60 ng/μL miRNA was isolated from 200 μL of saliva. Overall a good correlation was observed between the microarray data and the RT-qPCR data. We found that miR-9 (P <0.0001), miR-134 (P <0.0001) and miR-191 (P <0.001) were differentially expressed between saliva from HNSCC patients and healthy controls, and that these miRNAs provided a good discriminative capacity with area under the curve (AUC) values of 0.85 (P <0.0001), 0.74 (P < 0.001) and 0.98 (P < 0.0001), respectively. In addition, we found that the salivary miRNA data showed a good correlation with the TCGA miRNA data, thereby providing an independent validation. Conclusions We show that we have developed a reliable method to isolate miRNAs from small volumes of saliva, and that the saliva-derived miRNAs miR-9, miR-134 and miR-191 may serve as novel biomarkers to reliably detect HNSCC. © 2014 International Society for Cellular Oncology.

Troubling silences and taboo texts : constructing safer and more positive school climates for same-sex attracted high school students in Australia

This chapter offers three insights into the relationship between curriculum decision making, positive school climate, and academic achievement for same-sex attracted (SSA) students, highlighting the need for students to be offered more than heteronormative narratives and silence on issues of sexuality in the official school curriculum. The authors firstly provide a review of research and report on findings of a doctoral study (Mikulsky, 2007) explaining the impact of SSA students’ perceptions of school climate on their motivation and academic self-concept. Situating the work in the context of the Australian Curriculum for English and associated classroom texts, the dominant discourse of ‘straight, white female’ heroines as exemplified in the globally popular young adult novel The hunger games and other texts popular with Australian students are critiqued, with an argument made for expanding notions of what it means to ‘attend to’ gender and sexuality through textual choice and critical pedagogy. The authors show how texts that feature LGBTQ characters and storylines continue to be marginalized and constructed as taboo and demonstrate how curricular choices can and do impact academic outcomes for marginalized students. Issues of gender and sexuality are framed as a cross-curriculum imperative, with recommendations made for the explicit inclusion of materials exploring gender and sexuality in the official curriculum of all key learning areas.

A novel manoeuvering model based on low-aspect-ratio lift theory and Lagrangian mechanics

This paper proposes a physically motivated reappraisal of manoeuvring models for ships and presents a new model developed from first principles by application of low aspect-ratio aerodynamic theory and Lagrangian mechanics. The coefficients of the model are shown to be related to physical processes, and validation is presented using the results from a planar motion mechanism dataset.

Novel approaches for SER spectroscopic analysis of protein cofactors

Biomimetic systems employed for biotechnological applications i.e. as biosensors or bio fuel cells, require initial formation of conducting support/protein complexes with controlled properties. The specific interaction of the protein with the support determines important qualities of the device such as electrical communication, long-term stability and catalytic efficiency. In this respect the system parameters have to be chosen in a way that high protein loading on the support is achieved while protein denaturation upon adsorption is prevented. The conditions on the surface have to be adjusted in such a way that the desired surface reaction of the protein i.e. electron transfer to either the electrode or a second redox partner, is still guaranteed. Hence the choice of support, its functionlisation as well as the right adjustment of solution parameters play a crucial role in the rational design of these support/protein constructs.

Electrochemical current rectification – a novel signal amplification strategy for highly sensitive and selective aptamer-based biosensor

Electrochemical aptamer-based (E-AB) sensors represent an emerging class of recently developed sensors. However, numerous of these sensors are limited by a low surface density of electrode-bound redox-oligonucleotides which are used as probe. Here we propose to use the concept of electrochemical current rectification (ECR) for the enhancement of the redox signal of E-AB sensors. Commonly, the probe-DNA performs a change in conformation during target binding and enables a nonrecurring charge transfer between redox-tag and electrode. In our system, the redox-tag of the probe-DNA is continuously replenished by solution-phase redox molecules. A unidirectional electron transfer from electrode via surface-linked redox-tag to the solution-phase redox molecules arises that efficiently amplifies the current response. Using this robust and straight-forward strategy, the developed sensor showed a substantial signal amplification and consequently improved sensitivity with a calculated detection limit of 114 nM for ATP, which was improved by one order of magnitude compared with the amplification-free detection and superior to other previous detection results using enzymes or nanomaterials-based signal amplification. To the best of our knowledge, this is the first demonstration of an aptamer-based electrochemical biosensor involving electrochemical rectification, which can be presumably transferred to other biomedical sensor systems.

Detection of DNA mutations using novel SERS (Surface-Enhanced Raman Spectroscopy) diagnostic platform

This article describes the detection of DNA mutations using novel Au-Ag coated GaN substrate as SERS (surface-enhanced Raman spectroscopy) diagnostic platform. Oligonucleotide sequences corresponding to the BCR-ABL (breakpoint cluster region-Abelson) gene responsible for development of chronic myelogenous leukemia were used as a model system to demonstrate the discrimination between the wild type and Met244Val mutations. The thiolated ssDNA (single-strand DNA) was immobilized on the SERS-active surface and then hybridized to a labeled target sequence from solution. An intense SERS signal of the reporter molecule MGITC was detected from the complementary target due to formation of double helix. The SERS signal was either not observed, or decreased dramatically for a negative control sample consisting of labeled DNA that was not complementary to the DNA probe. The results indicate that our SERS substrate offers an opportunity for the development of novel diagnostic assays.

Novel solutions for a model of wound healing angiogenesis

We prove the existence of novel, shock-fronted travelling wave solutions to a model of wound healing angiogenesis studied in Pettet et al (2000 IMA J. Math. App. Med. 17 395–413) assuming two conjectures hold. In the previous work, the authors showed that for certain parameter values, a heteroclinic orbit in the phase plane representing a smooth travelling wave solution exists. However, upon varying one of the parameters, the heteroclinic orbit was destroyed, or rather cut-off, by a wall of singularities in the phase plane. As a result, they concluded that under this parameter regime no travelling wave solutions existed. Using techniques from geometric singular perturbation theory and canard theory, we show that a travelling wave solution actually still exists for this parameter regime. We construct a heteroclinic orbit passing through the wall of singularities via a folded saddle canard point onto a repelling slow manifold. The orbit leaves this manifold via the fast dynamics and lands on the attracting slow manifold, finally connecting to its end state. This new travelling wave is no longer smooth but exhibits a sharp front or shock. Finally, we identify regions in parameter space where we expect that similar solutions exist. Moreover, we discuss the possibility of more exotic solutions.

Hyperlinking history and illegitimate imagination : the historiographic metafictional E-novel

‘Historiographic Metafiction’ (HM) is a literary term first coined by creative writing academic Linda Hutcheon in 1988, and which refers to the postmodern practice of a fiction author inserting imagined--or illegitimate--characters into narratives that are intended to be received as authentic and historically accurate, that is, ostensibly legitimate. Such adventurous and bold authorial strategies frequently result in “novels which are both intensely self-reflexive and yet paradoxically also lay claim to historical events and personages” (Hutcheon, A Poetics 5). They can be so entertaining and engaging that the overtly intertextual, explicitly inventive work of biographical HM can even change the “hegemonic discourse of history” (Nunning 353) for, as Philippa Gregory, the author of HM novel The Other Boleyn Girl (2001), has said regarding this genre of creative writing: “Fiction is about imagined feelings and thoughts. History depends on the outer life. The novel is always about the inner life. Fiction can sometimes do more than history. It can fill the gaps” (University of Sussex). In a way, this article will be filling one of the gaps regarding HM...

H2AX phosphorylation screen of cells from radiosensitive cancer patients reveals a novel DNA double-strand break repair cellular phenotype

BACKGROUND: About 1-5% of cancer patients suffer from significant normal tissue reactions as a result of radiotherapy (RT). It is not possible at this time to predict how most patients' normal tissues will respond to RT. DNA repair dysfunction is implicated in sensitivity to RT particularly in genes that mediate the repair of DNA double-strand breaks (DSBs). Phosphorylation of histone H2AX (phosphorylated molecules are known as gammaH2AX) occurs rapidly in response to DNA DSBs, and, among its other roles, contributes to repair protein recruitment to these damaged sites. Mammalian cell lines have also been crucial in facilitating the successful cloning of many DNA DSB repair genes; yet, very few mutant cell lines exist for non-syndromic clinical radiosensitivity (RS). METHODS: Here, we survey DNA DSB induction and repair in whole cells from RS patients, as revealed by gammaH2AX foci assays, as potential predictive markers of clinical radiation response. RESULTS: With one exception, both DNA focus induction and repair in cell lines from RS patients were comparable with controls. Using gammaH2AX foci assays, we identified a RS cancer patient cell line with a novel ionising radiation-induced DNA DSB repair defect; these data were confirmed by an independent DNA DSB repair assay. CONCLUSION: gammaH2AX focus measurement has limited scope as a pre-RT predictive assay in lymphoblast cell lines from RT patients; however, the assay can successfully identify novel DNA DSB repair-defective patient cell lines, thus potentially facilitating the discovery of novel constitutional contributions to clinical RS.

Flammability and thermal properties of novel semi aromatic polyamide/organoclay nanocomposite

The development of semi aromatic polyamide/organoclays nanocomposites (PANC) is reported in this communication. New polyamide (PA) was successfully synthesized through direct polycondensation reaction between bio-based diacid and aromatic diamine. PA exhibited strong UV vis absorption band at 412 nm. Its photoluminescence spectrum showed maximum band at 511 nm in the green region. The surface modification of montmorillonite was carried out through ion-exchange reaction using 1,4-bis[4-aminophenoxy]butane (APB) as a modifier. Then PANCs containing 3 and 6 wt.% of the modified montmorillonite (MMT-APB) were prepared. Flammability and thermal properties of PA and the nanocomposites were studied by microscale combustion calorimeter (MCC), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). TGA results in both air and nitrogen atmospheres indicated improving in thermal properties of PANCs compared to the neat PA. According to MCC analysis, a 31.6% reduction in pHRR value has been achieved by introducing 6 wt.% of the organoclay in PA matrix.

Solar Assisted Fast Pyrolysis: A Novel Approach of Renewable Energy Production

Biofuel produced by fast pyrolysis from biomass is a promising candidate. The heart of the system is a reactor which is directly or indirectly heated to approximately 500°C by exhaust gases from a combustor that burns pyrolysis gas and some of the by-product char. In most of the cases, external biomass heater is used as heating source of the system while internal electrical heating is recently implemented as source of reactor heating. However, this heating system causes biomass or other conventional forms of fuel consumption to produce renewable energy and contributes to environmental pollution. In order to overcome these, the feasibility of incorporating solar energy with fast pyrolysis has been investigated. The main advantages of solar reactor heating include renewable source of energy, comparatively simpler devices, and no environmental pollution. A lab scale pyrolysis setup has been examined along with 1.2 m diameter parabolic reflector concentrator that provides hot exhaust gas up to 162°C. The study shows that about 32.4% carbon dioxide (CO2) emissions and almost one-third portion of fuel cost are reduced by incorporating solar heating system. Successful implementation of this proposed solar assisted pyrolysis would open a prospective window of renewable energy.

Development of a log-quadratic model to describe microbial inactivation, illustrated by thermal inactivation of Clostridium botulinum

In the commercial food industry, demonstration of microbiological safety and thermal process equivalence often involves a mathematical framework that assumes log-linear inactivation kinetics and invokes concepts of decimal reduction time (DT), z values, and accumulated lethality. However, many microbes, particularly spores, exhibit inactivation kinetics that are not log linear. This has led to alternative modeling approaches, such as the biphasic and Weibull models, that relax strong log-linear assumptions. Using a statistical framework, we developed a novel log-quadratic model, which approximates the biphasic and Weibull models and provides additional physiological interpretability. As a statistical linear model, the log-quadratic model is relatively simple to fit and straightforwardly provides confidence intervals for its fitted values. It allows a DT-like value to be derived, even from data that exhibit obvious "tailing." We also showed how existing models of non-log-linear microbial inactivation, such as the Weibull model, can fit into a statistical linear model framework that dramatically simplifies their solution. We applied the log-quadratic model to thermal inactivation data for the spore-forming bacterium Clostridium botulinum and evaluated its merits compared with those of popular previously described approaches. The log-quadratic model was used as the basis of a secondary model that can capture the dependence of microbial inactivation kinetics on temperature. This model, in turn, was linked to models of spore inactivation of Sapru et al. and Rodriguez et al. that posit different physiological states for spores within a population. We believe that the log-quadratic model provides a useful framework in which to test vitalistic and mechanistic hypotheses of inactivation by thermal and other processes. Copyright © 2009, American Society for Microbiology. All Rights Reserved.

‘Pop Melayu vs. Pop Indonesia: Marketeers, producers and new interpretations of a genre into the 2000s’ in Sonic Modernities in Southeast Asia Leiden: Brill pp. 187- 215

Kangen Band, as an example of reclaiming of the derisive term kampungan. In it, I argue that this reclaiming represents an interesting case of genre manipulation, and consider what this can reveal about how Indonesian pop genres are constituted, what they ‘are’ and what they ‘do’. In so doing, I seek to rework existing scholarship relating to Indonesian pop genres and modernity, as well as interrogate some broader theories of genre. In this essay, I extend the argument that Indonesian pop genres are not purely technical categories, they touch on myths of class and nation (Wallach 2008; Weintraub 2010; Yampolsky 1989. As we shall see, in the New Order period, pop music genres reached out to these myths by positioning themselves variously vis-à-vis the capital city, Jakarta. Such positioning, achieved through use of the terms gedongan (a term that strives to infer refinement by stressing the non-masses’ central position in the urban environment) and kampungan (a term that strives to enforce subalterns’ marginal position in relation to the metropolis, see also the previous contribution by Weintraub), continues to haunt the constitution of genre in the post-New Order period, but in novel ways. These novel ways, I argue, may be seen to result from industrial transformation and new systems of knowledge production.

A novel ambiguity acceptance test threshold determination method with controllable failure rate

Ambiguity validation as an important procedure of integer ambiguity resolution is to test the correctness of the fixed integer ambiguity of phase measurements before being used for positioning computation. Most existing investigations on ambiguity validation focus on test statistic. How to determine the threshold more reasonably is less understood, although it is one of the most important topics in ambiguity validation. Currently, there are two threshold determination methods in the ambiguity validation procedure: the empirical approach and the fixed failure rate (FF-) approach. The empirical approach is simple but lacks of theoretical basis. The fixed failure rate approach has a rigorous probability theory basis, but it employs a more complicated procedure. This paper focuses on how to determine the threshold easily and reasonably. Both FF-ratio test and FF-difference test are investigated in this research and the extensive simulation results show that the FF-difference test can achieve comparable or even better performance than the well-known FF-ratio test. Another benefit of adopting the FF-difference test is that its threshold can be expressed as a function of integer least-squares (ILS) success rate with specified failure rate tolerance. Thus, a new threshold determination method named threshold function for the FF-difference test is proposed. The threshold function method preserves the fixed failure rate characteristic and is also easy-to-apply. The performance of the threshold function is validated with simulated data. The validation results show that with the threshold function method, the impact of the modelling error on the failure rate is less than 0.08%. Overall, the threshold function for the FF-difference test is a very promising threshold validation method and it makes the FF-approach applicable for the real-time GNSS positioning applications.

Landform characterization using geophysics—Recent advances, applications, and emerging tools

This paper presents an overview of the strengths and limitations of existing and emerging geophysical tools for landform studies. The objectives are to discuss recent technical developments and to provide a review of relevant recent literature, with a focus on propagating field methods with terrestrial applications. For various methods in this category, including ground-penetrating radar (GPR), electrical resistivity (ER), seismics, and electromagnetic (EM) induction, the technical backgrounds are introduced, followed by section on novel developments relevant to landform characterization. For several decades, GPR has been popular for characterization of the shallow subsurface and in particular sedimentary systems. Novel developments in GPR include the use of multi-offset systems to improve signal-to-noise ratios and data collection efficiency, amongst others, and the increased use of 3D data. Multi-electrode ER systems have become popular in recent years as they allow for relatively fast and detailed mapping. Novel developments include time-lapse monitoring of dynamic processes as well as the use of capacitively-coupled systems for fast, non-invasive surveys. EM induction methods are especially popular for fast mapping of spatial variation, but can also be used to obtain information on the vertical variation in subsurface electrical conductivity. In recent years several examples of the use of plane wave EM for characterization of landforms have been published. Seismic methods for landform characterization include seismic reflection and refraction techniques and the use of surface waves. A recent development is the use of passive sensing approaches. The use of multiple geophysical methods, which can benefit from the sensitivity to different subsurface parameters, is becoming more common. Strategies for coupled and joint inversion of complementary datasets will, once more widely available, benefit the geophysical study of landforms.Three cases studies are presented on the use of electrical and GPR methods for characterization of landforms in the range of meters to 100. s of meters in dimension. In a study of polygonal patterned ground in the Saginaw Lowlands, Michigan, USA, electrical resistivity tomography was used to characterize differences in subsurface texture and water content associated with polygon-swale topography. Also, a sand-filled thermokarst feature was identified using electrical resistivity data. The second example is on the use of constant spread traversing (CST) for characterization of large-scale glaciotectonic deformation in the Ludington Ridge, Michigan. Multiple CST surveys parallel to an ~. 60. m high cliff, where broad (~. 100. m) synclines and narrow clay-rich anticlines are visible, illustrated that at least one of the narrow structures extended inland. A third case study discusses internal structures of an eolian dune on a coastal spit in New Zealand. Both 35 and 200. MHz GPR data, which clearly identified a paleosol and internal sedimentary structures of the dune, were used to improve understanding of the development of the dune, which may shed light on paleo-wind directions.