Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed intercellular variability of rabbit ventricular action potential repolarisation.

Development of non-intrusive monitoring for reactive switching of high voltage circuit breaker

High-voltage circuit breakers are among the most important equipments for ensuring the efficient and safe operation of an electric power system. On occasion, circuit breaker operators may wish to check whether equipment is performing satisfactorily and whether controlled switching systems are producing reliable and repeatable stress control. Monitoring of voltage and current waveforms during switching using established methods will provide information about the magnitude and frequency of voltage transients as a result of re-ignitions and restrikes. However, high frequency waveform measurement requires shutdown of circuit breaker and use of specialized equipment. Two utilities, Hydro-Québec in Canada and Powerlink Queensland in Australia, have been working on the development and application of a non-intrusive, cost-effective and flexible diagnostic system for monitoring high-voltage circuit breakers for reactive switching. The proposed diagnostic approach relies on the non-intrusive assessment of key parameters such as operating times, prestrike characteristics, re-ignition and restrike detection. Transient electromagnetic emissions have been identified as a promising means to evaluate the abovementioned parameters non-intrusively. This paper describes two complimentary methods developed concurrently by Powerlink and Hydro-Québec. Also, return of experiences on the application to capacitor bank and shunt reactor switching is presented.

Wolbachia reduces the transmission potential of Dengue-infected Aedes aegypti

BACKGROUND: Dengue viruses (DENV) are the causative agents of dengue, the world's most prevalent arthropod-borne disease with around 40% of the world's population at risk of infection annually. Wolbachia pipientis, an obligate intracellular bacterium, is being developed as a biocontrol strategy against dengue because it limits replication of the virus in the mosquito. The Wolbachia strain wMel, which has been introduced into the mosquito vector, Aedes aegypti, has been shown to invade and spread to near fixation in field releases. Standard measures of Wolbachia's efficacy for blocking virus replication focus on the detection and quantification of virus in mosquito tissues. Examining the saliva provides a more accurate measure of transmission potential and can reveal the extrinsic incubation period (EIP), that is, the time it takes virus to arrive in the saliva following the consumption of DENV viremic blood. EIP is a key determinant of a mosquito's ability to transmit DENVs, as the earlier the virus appears in the saliva the more opportunities the mosquito will have to infect humans on subsequent bites. METHODOLOGY/PRINCIPAL FINDINGS: We used a non-destructive assay to repeatedly quantify DENV in saliva from wMel-infected and Wolbachia-free wild-type control mosquitoes following the consumption of a DENV-infected blood meal. We show that wMel lengthens the EIP, reduces the frequency at which the virus is expectorated and decreases the dengue copy number in mosquito saliva as compared to wild-type mosquitoes. These observations can at least be partially explained by an overall reduction in saliva produced by wMel mosquitoes. More generally, we found that the concentration of DENV in a blood meal is a determinant of the length of EIP, saliva virus titer and mosquito survival. CONCLUSIONS/SIGNIFICANCE: The saliva-based traits reported here offer more disease-relevant measures of Wolbachia's effects on the vector and the virus. The lengthening of EIP highlights another means, in addition to the reduction of infection frequencies and DENV titers in mosquitoes, by which Wolbachia should operate to reduce DENV transmission in the field.

MicroRNA regulation of epithelial-to-mesenchymal transition during re-epithelialisation: Assessing an open wound

It is becoming increasing clear that microRNAs contribute to the regulation of many biological processes, including wound healing. After injury, keratinocytes need to undergo what is known as an epithelial-to-mesenchymal transition (EMT) to initiate re-epithelialisation. During this process, keratinocytes reduce their attachment to the underlying matrix, extend membrane protrusions, become motile and migrate over the wound bed, affecting wound closure. MicroRNAs that regulate EMT are aberrantly upregulated in keratinocytes at the edge of non-healing wounds and potentially play a role in the chronicity of these wounds. In vitro and in vivo, downregulation of these microRNAs promotes EMT and migration, facilitating re-epithelialisation in wound models. This review will focus on the role of microRNAs that regulate or have potential to regulate EMT and re-epithelialisation during wound healing

A simple circuit to aid direct measurement of capture cross sections of deep level impurities

An inexpensive and simple circuit to aid the direct measurement of majority carrier capture cross sections of impurity levels in the band gap of a semiconductor by the variable width filling pulse technique is presented. With proper synchronisation, during the period of application of the pulse, the device is disconnected from the capacitance meter to avoid distortion of the pulse and is reconnected again to the meter to record the emission transient. Modes of operation include manual triggering for long emission transients, repetitive triggering for isothermal and DLTS measurements and the DLTS mode which is to be used with signal analysers that already provide a synchronising pulse for disconnection.

A Dual Seven-Level Inverter Supply for an Open-End Winding Induction Motor Drive

This paper develops a seven-level inverter structure for open-end winding induction motor drives. The inverter supply is realized by cascading four two-level and two three-level neutral-point-clamped inverters. The inverter control is designed in such a way that the common-mode voltage (CMV) is eliminated. DC-link capacitor voltage balancing is also achieved by using only the switching-state redundancies. The proposed power circuit structure is modular and therefore suitable for fault-tolerant applications. By appropriately isolating some of the inverters, the drive can be operated during fault conditions in a five-level or a three-level inverter mode, with preserved CMV elimination and DC-link capacitor voltage balancing, within a reduced modulation range.

A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to ischemic stroke risk

Background and Purpose Stroke is a multifactorial disease that may be associated with aberrant DNA methylation profiles.We investigated epigenetic dysregulation for the MTHFR gene among ischaemic stroke patients. Methods Cases (n=297) and controls (n=110) were recruited after obtaining signed written informed consent, following a screening process against the inclusion/exclusion criteria. Serum vitamin metabolites (folate, vitamin B12 and homocysteine) were determined using immunoassays and methylation profiles for CpGs A and B in the MTHFR gene were determined using bisulfitepyrosequencing method. Results Methylation of MTHFR significantly increased the susceptibility risk for ischemic stroke. In particular, CpG A outperformed CpG B in mediating folate and vitamin B12 levels to increase ischemic stroke susceptibility risks by 4.73 fold. CpGs A and B were not associated with either serum homocysteine levels or ischemic stroke severity. Conclusion CpG A is a potential epigenetic marker in mediating serum folate and vitamin B12 to contribute to ischemic stroke.

Open educational resources: Enhancing education provision and practice

Open educational resources (OERs), a disruptive technology, made their appearance in early 2002 as a promising tool for enhancing the quality of and access to education generally and higher education in particular. OERs were also perceived to have the potential to reduce costs by reusing learning materials. This brief draws on a study that reviewed the uptake of OERs and related activities in six institutions in Hong Kong, China; India; Malaysia; Pakistan; and Thailand.

Commentary: Chronic SSRI stimulation of astrocytic 5-HT2B receptors change multiple gene expressions/editings and metabolism of glutamate, glucose and glycogen: A potential paradigm shift

Working on the serotonin (5-hydroxytryptamine, 5-HT) 5-HT2B receptor since several years, we have read with high interest the review by Hertz et al. (2015). Previous studies from our group demonstrated that a direct injection in mouse raphe nucleus of the 5-HT2B agonist BW723C86 has the ability to increase extracellular levels of serotonin, which can be blocked by the selective 5-HT2B receptor antagonist RS127445 (Doly et al., 2008, 2009). We also reported that an acute injection of paroxetine 2 mg/kg in mice knocked out for the 5-HT2B receptor gene or in wild type mice injected with RS127445 (0.5 mg/kg) triggers a strong reduction in extracellular accumulation of 5-HT in hippocampus (Diaz et al., 2012). Following these observations, we showed that acute and chronic BW723C86 injection (3 mg/kg) can mimic the fluoxetine (3 mg/kg) and paroxetine (1 mg/kg) behavioral and biochemical antidepressant effects in mice (Diaz and Maroteaux, 2011; Diaz et al., 2012)...

Assessing the potential of the rust fungus Puccinia spegazzinii as a classical biological control agent for the invasive weed Mikania micrantha in Papua New Guinea

The rust fungus Puccinia spegazzinii was introduced into Papua New Guinea (PNG) in 2008 as a classical biological control agent of the invasive weed Mikania micrantha (Asteraceae), following its earlier release in India, mainland China and Taiwan. Prior to implementing field releases in PNG, assessments were conducted to determine the most suitable rust pathotype for the country, potential for damage to non-target species, most efficient culturing method and potential impact to M. micrantha. The pathotype from eastern Ecuador was selected from the seven pathotypes tested, since all the plant populations evaluated from PNG were highly susceptible to it. None of the 11 plant species (representing eight families) tested to confirm host specificity showed symptoms of infection, supporting previous host range determination. A method of mass-producing inoculum of the rust fungus, using a simple technology which can be readily replicated in other countries, was developed. Comparative growth trials over one rust generation showed that M. micrantha plants infected with the rust generally had both lower growth rates and lower final dry weights, and produced fewer nodes than uninfected plants. There were significant correlations between the number of pustules and (a) the growth rate, (b) number of new nodes and (c) final total dry weight of single-stemmed plants placed in open sunlight and between the number of pustules and number of new nodes of multi-stemmed plants placed under cocoa trees. The trials suggest that field densities of M. micrantha could be reduced if the rust populations are sufficiently high. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.

Influence of interleukin-1 beta on platelet-poor plasma clot formation: A potential impact on early bone healing

Objectives Hematoma quality (especially the fibrin matrix) plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β) on fibrin clot formation from platelet-poor plasma (PPP). Methods Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG), blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM), confocal microscopy (CM), turbidity, and clot lysis assays. Results The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β) compared to the control group without IL-1β (543.8 ± 205.8). Maximal turbidity was observed in the control group. IL-1β (500 pg/mL) treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05). The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers. Conclusion IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

Open source computer-vision based guidance system for UAVs on-board decision making

The use of UAVs for remote sensing tasks; e.g. agriculture, search and rescue is increasing. The ability for UAVs to autonomously find a target and perform on-board decision making, such as descending to a new altitude or landing next to a target is a desired capability. Computer-vision functionality allows the Unmanned Aerial Vehicle (UAV) to follow a designated flight plan, detect an object of interest, and change its planned path. In this paper we describe a low cost and an open source system where all image processing is achieved on-board the UAV using a Raspberry Pi 2 microprocessor interfaced with a camera. The Raspberry Pi and the autopilot are physically connected through serial and communicate via MAVProxy. The Raspberry Pi continuously monitors the flight path in real time through USB camera module. The algorithm checks whether the target is captured or not. If the target is detected, the position of the object in frame is represented in Cartesian coordinates and converted into estimate GPS coordinates. In parallel, the autopilot receives the target location approximate GPS and makes a decision to guide the UAV to a new location. This system also has potential uses in the field of Precision Agriculture, plant pest detection and disease outbreaks which cause detrimental financial damage to crop yields if not detected early on. Results show the algorithm is accurate to detect 99% of object of interest and the UAV is capable of navigation and doing on-board decision making.

Potential antioxidant response to coffee - A matter of genotype?

In a human intervention trial, a coffee, combining nature green coffee bean constituents and dark roast products was studied towards its potential to activate the Nrf2/ARE-pathway in PBLs. The study coffee was identified as a strong inducer of Nrf2 and downstream GST1A1 and UGT1A1 gene transcription. However, the response of the participants was found to depend on the respective genotype. The -651 SNP in the Nrf2 gene as well as the heterozygote 6/7 sequence in the UGT1A1 gene significantly down-regulated the susceptibility to respond to coffee, proposing the existing genotype to be critical for the response to the coffee.

Knowledge unlatched : A global library consortium model for funding Open Access scholarly books

Specialist scholarly books, including monographs, allow researchers to present their work, pose questions and to test and extend areas of theory through long-form writing. In spite of the fact that research communities all over the world value monographs and depend heavily on them as a requirement of tenure and promotion in many disciplines, sales of this kind of book are in free fall, with some estimates suggesting declines of as much as 90% over twenty years (Willinsky 2006). Cashstrapped monograph publishers have found themselves caught in a negative cycle of increasing prices and falling sales, with few resources left to support experimentation, business model innovation or engagement with digital technology and Open Access (OA). This chapter considers an important attempt to tackle failing markets for scholarly monographs, and to enable the wider adoption of OA licenses for book-length works: the 2012 – 2014 Knowledge Unlatched pilot. Knowledge Unlatched is a bold attempt to reconfigure the market for specialist scholarly books: moving it beyond the sale of ‘content’ towards a model that supports the services valued by scholarly and wider communities in the context of digital possibility. Its success has powerful implications for the way we understand copyright’s role in the creative industries, and the potential for established institutions and infrastructure to support the open and networked dynamics of a digital age.

Open access and soft power: Chinese voices in international scholarship

Networked digital technologies and Open Access (OA) are transforming the processes and institutions of research, knowledge creation and dissemination globally: enabling new forms of collaboration, allowing researchers to be seen and heard in new ways and reshaping relationships between stakeholders across the global academic publishing system. This article draws on Joseph Nye’s concept of ‘Soft Power’ to explore the role that OA is playing in helping to reshape academic publishing in China. It focusses on two important areas of OA development: OA journals and national-level repositories. OA is being supported at the highest levels, and there is potential for it to play an important role in increasing the status and impact of Chinese scholarship. Investments in OA also have the potential to help China to re-position itself within international copyright discourses: moving beyond criticism for failure to enforce the rights of foreign copyright owners and progressing an agenda that places greater emphasis on equality of access to the resources needed to foster innovation. However, the potential for OA to help China to build and project its soft power is being limited by the legacies of the print era, as well as the challenges of efficiently governing the national research and innovation systems.