439 research outputs found

    A thermalization energy analysis of the threshold voltage shift in amorphous indium gallium zinc oxide thin film transistors under positive gate bias stress

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    Thin film transistors (TFTs) employing an amorphous indium gallium zinc oxide (a-IGZO) channel layer exhibit a positive shift in the threshold voltage under the application of positive gate bias stress (PBS). The time and temperature dependence of the threshold voltage shift was measured and analysed using the thermalization energy concept. The peak energy barrier to defect conversion is extracted to be 0.75 eV and the attempt-to-escape frequency is extracted to be 107 s−1. These values are in remarkable agreement with measurements in a-IGZO TFTs under negative gate bias illumination stress (NBIS) reported recently (Flewitt and Powell, J. Appl. Phys. 115, 134501 (2014)). This suggests that the same physical process is responsible for both PBS and NBIS, and supports the oxygen vacancy defect migration model that the authors have previously proposed.The research leading to these results has received funding from the European Community’s 7th Framework Programme under grant agreement NMP3-LA-2010-246334. Financial support of the European Commission is therefore gratefully acknowledged. The work has also received funding from FEDER through the COMPETE 2020 Programme and National Funds through FCT–Portuguese Foundation for Science and Technology under the Project No. UID/CTM/50025/2013.This is the author accepted manuscript. The final version is available from AIP Publishing via http://dx.doi.org/10.1063/1.494324

    MicroRNAs regulate Ca2+ homeostasis in murine embryonic stem cells

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    MicroRNAs (miRNAs) are important regulators of embryonic stem cell (ESC) biology, and their study has identified key regulatory mechanisms. To find novel pathways regulated by miRNAs in ESCs, we undertook a bioinformatics analysis of gene pathways differently expressed in the absence of miRNAs due to the deletion of Dicer, which encodes an RNase that is essential for the synthesis of miRNAs. One pathway that stood out was Ca2+ signaling. Interestingly, we found that Dicer-/- ESCs had no difference in basal cytoplasmic Ca2+ levels but were hyperresponsive when Ca2+ import into the endoplasmic reticulum (ER) was blocked by thapsigargin. Remarkably, the increased Ca2+ response to thapsigargin in ESCs resulted in almost no increase in apoptosis and no differences in stress response pathways, despite the importance of miRNAs in the stress response of other cell types. The increased Ca2+ response in Dicer-/- ESCs was also observed during purinergic receptor activation, demonstrating a physiological role for the miRNA regulation of Ca2+ signaling pathways. In examining the mechanism of increased Ca2+ responsiveness to thapsigargin, neither store-operated Ca2+ entry nor Ca2+ clearance mechanisms from the cytoplasm appeared to be involved. Rather, it appeared to involve an increase in the expression of one isoform of the IP3 receptors (Itpr2). miRNA regulation of Itpr2 expression primarily appeared to be indirect, with transcriptional regulation playing a major role. Therefore, the miRNA regulation of Itpr2 expression offers a unique mechanism to regulate Ca2+ signaling pathways in the physiology of pluripotent stem cells

    Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

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    BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

    Using Search Query Surveillance to Monitor Tax Avoidance and Smoking Cessation following the United States' 2009 “SCHIP” Cigarette Tax Increase

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    Smokers can use the web to continue or quit their habit. Online vendors sell reduced or tax-free cigarettes lowering smoking costs, while health advocates use the web to promote cessation. We examined how smokers' tax avoidance and smoking cessation Internet search queries were motivated by the United States' (US) 2009 State Children's Health Insurance Program (SCHIP) federal cigarette excise tax increase and two other state specific tax increases. Google keyword searches among residents in a taxed geography (US or US state) were compared to an untaxed geography (Canada) for two years around each tax increase. Search data were normalized to a relative search volume (RSV) scale, where the highest search proportion was labeled 100 with lesser proportions scaled by how they relatively compared to the highest proportion. Changes in RSV were estimated by comparing means during and after the tax increase to means before the tax increase, across taxed and untaxed geographies. The SCHIP tax was associated with an 11.8% (95% confidence interval [95%CI], 5.7 to 17.9; p<.001) immediate increase in cessation searches; however, searches quickly abated and approximated differences from pre-tax levels in Canada during the months after the tax. Tax avoidance searches increased 27.9% (95%CI, 15.9 to 39.9; p<.001) and 5.3% (95%CI, 3.6 to 7.1; p<.001) during and in the months after the tax compared to Canada, respectively, suggesting avoidance is the more pronounced and durable response. Trends were similar for state-specific tax increases but suggest strong interactive processes across taxes. When the SCHIP tax followed Florida's tax, versus not, it promoted more cessation and avoidance searches. Efforts to combat tax avoidance and increase cessation may be enhanced by using interventions targeted and tailored to smokers' searches. Search query surveillance is a valuable real-time, free and public method, that may be generalized to other behavioral, biological, informational or psychological outcomes manifested online

    Konstruktivistische Ansätze in der Erwachsenenbildung und Weiterbildung

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    Theoretical approaches in the field of further education and advanced vocational training have to face multifaceted demands: the analysis of knowledge aquisition and knowledge transfer and its instructional support as well as the revealment of the mechanisms which influence further education on an organisational level in companies. This article describes, that herefore especially moderate constructivistic approaches are useful. After an introduction to the philosophical tradition of these approaches and important characteristics of adult learning, two examples of constructivistic models are being described particularly: The theory of situated learning environments and career counseling. Concluding it is shown, that a moderate constructive perspective fulfils important criteria for the theoretic modelling of further education processes.Theoretische Ansätze in der Erwachsenen- und insbesondere in der beruflichen Weiterbildung müssen sich vielfältigen Ansprüchen stellen: der Analyse des Wissenserwerbs und Wissenstransfers und seiner instruktionalen Unterstützung ebenso wie der Aufdeckung der Mechanismen, die in den Betrieben auf organisatorischer Ebene die Weiterbildung beeinflussen. In diesem Beitrag wird die Auffassung vertreten, daß dafür insbesondere liberalisierte konstruktivistische Ansätze gut geeignet sind. Nach einer Einführung in die philosophische Tradition dieser Ansätze und wichtiger Merkmale des Lernens im Erwachsenenalter werden zwei Beispiele konstruktivistischer Modelle genauer beschrieben: die Theorie situierter Lernumgebungen und das career counseling. Abschließend wird gezeigt, daß eine liberalisierte konstruktivistische Perspektive wichtige Kriterien für die theoretische Modellierung von Weiterbildungsprozessen erfüllt

    Western Indian Ocean marine and terrestrial records of climate variability: a review and new concepts on land-ocean interactions since AD 1660

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    We examine the relationship between three tropical and two subtropical western Indian Ocean coral oxygen isotope time series to surface air temperatures (SAT) and rainfall over India, tropical East Africa and southeast Africa. We review established relationships, provide new concepts with regard to distinct rainfall seasons, and mean annual temperatures. Tropical corals are coherent with SAT over western India and East Africa at interannual and multidecadal periodicities. The subtropical corals correlate with Southeast African SAT at periodicities of 16–30 years. The relationship between the coral records and land rainfall is more complex. Running correlations suggest varying strength of interannual teleconnections between the tropical coral oxygen isotope records and rainfall over equatorial East Africa. The relationship with rainfall over India changed in the 1970s. The subtropical oxygen isotope records are coherent with South African rainfall at interdecadal periodicities. Paleoclimatological reconstructions of land rainfall and SAT reveal that the inferred relationships generally hold during the last 350 years. Thus, the Indian Ocean corals prove invaluable for investigating land–ocean interactions during past centuries

    South China Sea hydrological changes and Pacific Walker Circulation variations over the last millennium

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    © Macmillan Publishers Limited, 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 2 (2011): 293, doi:10.1038/ncomms1297.The relative importance of north–south migrations of the intertropical convergence zone (ITCZ) versus El Niño-Southern Oscillation and its associated Pacific Walker Circulation (PWC) variability for past hydrological change in the western tropical Pacific is unclear. Here we show that north–south ITCZ migration was not the only mechanism of tropical Pacific hydrologic variability during the last millennium, and that PWC variability profoundly influenced tropical Pacific hydrology. We present hydrological reconstructions from Cattle Pond, Dongdao Island of the South China Sea, where multi-decadal rainfall and downcore grain size variations are correlated to the Southern Oscillation Index during the instrumental era. Our downcore grain size reconstructions indicate that this site received less precipitation during relatively warm periods, AD 1000–1400 and AD 1850–2000, compared with the cool period (AD 1400–1850). Including our new reconstructions in a synthesis of tropical Pacific records results in a spatial pattern of hydrologic variability that implicates the PWC.This work was supported by the Natural Science Foundation of China (NSFC) (40730107) and the Major State Basic Research Development Program of China (973 Program) (No.2010CB428902). DWO acknowledges support from the US NSF

    Assessment of angle velocity in girls with adolescent idiopathic scoliosis

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    <p>Abstract</p> <p>Background</p> <p>Although it has been demonstrated that the peak height velocity (PHV) is a predictive factor of progression in adolescent idiopathic scoliosis (AIS), little is known about the usefulness of angle progression in clinical practice. The purpose of this study was to establish a relationship between height and angle velocities, as well as to determine if peak angle velocity (PAV) occurs at the same time than PHV.</p> <p>Methods</p> <p>A retrospective study of a cohort of girls with idiopathic scoliotic curves greater than 10°. Data of 132 girls who participated in a previous retrospective study about growth in AIS were used to calculate height and angle velocities. Relationship between height and angle velocities was estimated by the use of a Linear Mixed Model.</p> <p>Results</p> <p>PHV and PAV take place simultaneously 1 year before menarche in progressive curves managed with a brace in AIS. Changes in angle velocity are influenced by changes in height growth velocity, in such a way that as from 6 months post-menarche, height growth velocity in this group of girls estimates curve progression velocity (β-coefficient -0.88, p = 0.04).</p> <p>Conclusion</p> <p>As from 6 months post-menarche, there is an inverse relationship between height velocity and curve progression in the group of AIS girls with progressive curves managed with a brace. Because height velocity is decreasing from 1 year before menarche, this finding corroborates that at the end of puberty, there is still a risk of progression in this group of girls despite bracing. The assessment of both height and angle velocity might be useful in clinical practice at the time of assessing brace effectiveness and how long bracing has to be indicated.</p

    El Niño, tropical Atlantic warmth, and Atlantic hurricanes over the past 1500 years

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    Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 460 (2009): 880-883, doi:10.1038/nature08219.Atlantic Tropical Cyclone (TC) activity, as measured by annual storm counts, reached anomalous levels over the past decade. The short nature of the historical record and potential issues with its reliability in earlier decades, however, has prompted an ongoing debate regarding the reality and significance of the recent rise. Here, we place recent activity in a longer-term context, by comparing two independent estimates of TC activity over the past 1500 years. The first estimate is based on a composite of regional sedimentary evidence of landfalling hurricanes, while the second estimate employs a previously published statistical model of Atlantic TC activity driven by proxy-reconstructions of past climate changes. Both approaches yield consistent evidence of a peak in Atlantic TC activity during Medieval times (around AD 1000) followed by a subsequent lull in activity. The Medieval peak, which rivals or even exceeds (within uncertainties) recent levels of activity, results in the statistical model from a ‘perfect storm’ of La Niña-like climate conditions and relative tropical Atlantic warmth.M.E.M. and Z.Z. acknowledge support from the ATM programme of the National Science Foundation (grant ATM-0542356). J.P.D. acknowledges support from the EAR and OCE programmes of the National Science Foundation (grants EAR-0519118 and OCE-0402746), the Risk Prediction Initiative at the Bermuda Institute for Ocean Sciences, and the Inter-American Institute for Global Change Research
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