41,990 research outputs found

    On-chip temperature-compensated Love mode surface acoustic wave device for gravimetric sensing

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    Love mode surface acoustic wave (SAW) sensors have been recognized as one of the most sensitive devices for gravimetric sensors in liquid environments such as bio sensors. Device operation is based upon measuring changes in the transmitted (S21) frequency and phase of the first-order Love wave resonance associated with the device upon on attachment of mass. However, temperature variations also cause a change in the first order S21 parameters. In this work, shallow grooved reflectors and a ‘dotted’ single phase unidirectional interdigitated transducer (D-SPUDT) have been added to the basic SAW structure which promote unidirectional Love wave propagation from the device’s input interdigitated transducers. Not only does this enhance the first-order S21 signal, but it also allows propagation of a third-order Love wave. The attenuation coefficient of the third-order wave is sufficiently great that, whilst there is a clear reflected S11 signal, the third-order wave does not propagate into the gravimetric sensing area of the device. As a result, whilst the third-order S11 signal is affected by temperature changes, it is unaffected by mass attachment in the sensing area. It is shown that this signal can be used to remove temperature effects from the first-order S21 signal in real time. This allows gravimetric sensing to take place in an environment without the need for any other temperature measurement or temperature control; this is a particular requirement of gravimetric biosensors.This is the accepted manuscript. The following article appeared in Applied Physics Letters and may be found at http://scitation.aip.org/content/aip/journal/apl/105/21/10.1063/1.4902989. Copyright 2014 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics

    Fake news: a technological approach to proving the origins of content, using blockchains

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    In this paper, we introduce a prototype of an innovative technology for proving the origins of captured digital media. In an era of fake news, when someone shows us a video or picture of some event, how can we trust its authenticity? It seems the public no longer believe that traditional media is a reliable reference of fact, perhaps due, in part, to the onset of many diverse sources of conflicting information, via social media. Indeed, the issue of ‘fake’ reached a crescendo during the 2016 US Presidential Election, when the winner, Donald Trump, claimed that the New York Times was trying to discredit him by pushing disinformation. Current research into overcoming the problem of fake news does not focus on establishing the ownership of media resources used in such stories - the blockchain-based application introduced in this article is technology that is capable of indicating the authenticity of digital media. Put simply; by using the trust mechanisms of blockchain technology, the tool can show, beyond doubt, the provenance of any source of digital media, including images used out of context in attempts to mislead. Although the application is an early prototype and its capability to find fake resources is Peer Review Only/Not for Distributionsomewhat limited, we outline future improvements that would overcome such limitations. Furthermore, we believe our application (and its use of blockchain technology and standardised metadata), introduces a novel approach to overcoming falsities in news reporting and the provenance of media resources used therein. However, while our application has the potential to be able to verify the originality of media resources, we believe technology is only capable of providing a partial solution to fake news. That is because it is incapable of proving the authenticity of a news story as a whole. We believe that takes human skills

    Neural crest stem cells and their potential therapeutic applications

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    The neural crest (NC) is a remarkable transient structure generated during early vertebrate development. The neural crest progenitors have extensive migratory capacity and multipotency, harboring stem cell-like characteristics such as self-renewal. They can differentiate into a variety of cell types from craniofacial skeletal tissues to the trunk peripheral nervous system (PNS). Multiple regulators such as signaling factors, transcription factors, and migration machinery components are expressed at different stages of NC development. Gain- and loss-of-function studies in various vertebrate species revealed epistatic relationships of these molecules that could be assembled into a gene regulatory network defining the processes of NC induction, specification, migration, and differentiation. These basic developmental studies led to the subsequent establishment and molecular validation of neural crest stem cells (NCSCs) derived by various strategies. We provide here an overview of the isolation and characterization of NCSCs from embryonic, fetal, and adult tissues; the experimental strategies for the derivation of NCSCs from embryonic stem cells, induced pluripotent stem cells, and skin fibroblasts; and recent developments in the use of patient-derived NCSCs for modeling and treating neurocristopathies. We discuss future research on further refinement of the culture conditions required for the differentiation of pluripotent stem cells into axial-specific NC progenitors and their derivatives, developing non-viral approaches for the generation of induced NC cells (NCCs), and using a genomic editing approach to correct genetic mutations in patient-derived NCSCs for transplantation therapy. These future endeavors should facilitate the therapeutic applications of NCSCs in the clinical setting.postprin

    Remodelling of human atrial K+ currents but not ion channel expression by chronic β-blockade

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    Chronic β-adrenoceptor antagonist (β-blocker) treatment in patients is associated with a potentially anti-arrhythmic prolongation of the atrial action potential duration (APD), which may involve remodelling of repolarising K+ currents. The aim of this study was to investigate the effects of chronic β-blockade on transient outward, sustained and inward rectifier K+ currents (ITO, IKSUS and IK1) in human atrial myocytes and on the expression of underlying ion channel subunits. Ion currents were recorded from human right atrial isolated myocytes using the whole-cell-patch clamp technique. Tissue mRNA and protein levels were measured using real time RT-PCR and Western blotting. Chronic β-blockade was associated with a 41% reduction in ITO density: 9.3 ± 0.8 (30 myocytes, 15 patients) vs 15.7 ± 1.1 pA/pF (32, 14), p < 0.05; without affecting its voltage-, time- or rate dependence. IK1 was reduced by 34% at −120 mV (p < 0.05). Neither IKSUS, nor its increase by acute β-stimulation with isoprenaline, was affected by chronic β-blockade. Mathematical modelling suggested that the combination of ITO- and IK1-decrease could result in a 28% increase in APD90. Chronic β-blockade did not alter mRNA or protein expression of the ITO pore-forming subunit, Kv4.3, or mRNA expression of the accessory subunits KChIP2, KChAP, Kvβ1, Kvβ2 or frequenin. There was no reduction in mRNA expression of Kir2.1 or TWIK to account for the reduction in IK1. A reduction in atrial ITO and IK1 associated with chronic β-blocker treatment in patients may contribute to the associated action potential prolongation, and this cannot be explained by a reduction in expression of associated ion channel subunits

    An avalanche-photodiode-based photon-number-resolving detector

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    Avalanche photodiodes are widely used as practical detectors of single photons.1 Although conventional devices respond to one or more photons, they cannot resolve the number in the incident pulse or short time interval. However, such photon number resolving detectors are urgently needed for applications in quantum computing,2-4 communications5 and interferometry,6 as well as for extending the applicability of quantum detection generally. Here we show that, contrary to current belief,3,4 avalanche photodiodes are capable of detecting photon number, using a technique to measure very weak avalanches at the early stage of their development. Under such conditions the output signal from the avalanche photodiode is proportional to the number of photons in the incident pulse. As a compact, mass-manufactured device, operating without cryogens and at telecom wavelengths, it offers a practical solution for photon number detection.Comment: 12 pages, 4 figure

    An Investigation of the Role of Radiative and Nonradiative Recombination Processes in InAs/GaAs 1−x Sb x Quantum Dot Solar Cells

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    An InAs/GaAs0.86 Sb 0.14 quantum dot solar cell and a GaAsSb control cell were investigated using temperature-dependent current density–voltage (J–V), external quantum efficiency, photoluminescence (PL), and electroluminescence (EL) measurements. Thermally activated defect states associated with the GaAsSb matrix material are found to account for the reduction of the performance of the solar cell. The rapid quenching of the PL and EL intensity, along with the shift (above 150 K) of the dominant recombination process during spontaneous emission (EL), further indicates the prevalence of nonradiative processes at elevated temperatures in these systems. These findings are also supported by a reduction in the open-circuit voltage at elevated temperatures in these devices

    Levosimendan for the prevention of acute organ dysfunction in sepsis

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    BACKGROUND Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. METHODS We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events. RESULTS The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04). CONCLUSIONS The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials number, ISRCTN12776039.

    Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation.

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    Advances in genomic profiling present new challenges of explaining how changes in DNA and RNA are translated into proteins linking genotype to phenotype. Here we compare the genome-scale proteomic and transcriptomic changes in human primary haematopoietic stem/progenitor cells and erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are selectively regulated through protein translation during erythroid specification. Depletion of TFAM in erythroid cells alters intracellular metabolism, leading to elevated histone acetylation, deregulated gene expression, and defective mitochondria and erythropoiesis. Mechanistically, mTORC1 signalling is enhanced to promote translation of mitochondria-associated transcripts through TOP-like motifs. Genetic and pharmacological perturbation of mitochondria or mTORC1 specifically impairs erythropoiesis in vitro and in vivo. Our studies support a mechanism for post-transcriptional control of erythroid mitochondria and may have direct relevance to haematologic defects associated with mitochondrial diseases and ageing
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