940 resultados para Voltage-sensitive Sodium Channels


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The first fiber Bragg grating (FBG) accelerometer using direct transverse forces is demonstrated by fixing the FBG by its two ends and placing a transversely moving inertial object at its middle. It is very sensitive because a lightly stretched FBG is more sensitive to transverse forces than axial forces. Its resonant frequency and static sensitivity are analyzed by the classic spring-mass theory, assuming the axial force changes little. The experiments show that the theory can be modified for cases where the assumption does not hold. The resonant frequency can be modified by a linear relationship experimentally achieved, and the static sensitivity by an alternative method proposed. The principles of the over-range protection and low cross axial sensitivity are achieved by limiting the movement of the FBG and were validated experimentally. The sensitivities 1.333 and 0.634 nm/g were experimentally achieved by 5.29 and 2.83 gram inertial objects at 10 Hz from 0.1 to 0.4 g (g = 9.8 m/s 2), respectively, and their resonant frequencies were around 25 Hz. Their theoretical static sensitivities and resonant frequencies found by the modifications are 1.188 nm/g and 26.81 Hz for the 5.29 gram one and 0.784 nm/g and 29.04 Hz for the 2.83 gram one, respectively.

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The paper examines the influence of unemployment insurance on the duration of employment spells in Canada using the 1988–90 Labour Market Activity Survey. The primary focus of the paper is to evaluate whether estimated UI effects are sensitive to the degree to which institutional rules and regulations governing UI eligibility and entitlement are explicitly modelled. The key result of the paper is that it is indeed important to allow for institutional detail when estimating unemployment insurance effects. Estimates using simple proxies for eligibility indicate small, often insignificant UI effects. The size and significance of the effects rise as more realistic versions of the variables are adopted. The estimates using the eligibility variables incorporating the greatest level of institutional detail suggest that a jump in the hazard rate by a factor of 2.3 may not be an unreasonable estimate of the effect.

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A loss of function mutation in the TRESK K2P potassium channel (KCNK18), has recently been linked with typical familial migraine with aura. We now report the functional characterisation of additional TRESK channel missense variants identified in unrelated patients. Several variants either had no apparent functional effect, or they caused a reduction in channel activity. However, the C110R variant was found to cause a complete loss of TRESK function, yet is present in both sporadic migraine and control cohorts, and no variation in KCNK18 copy number was found. Thus despite the previously identified association between loss of TRESK channel activity and migraine in a large multigenerational pedigree, this finding indicates that a single non-functional TRESK variant is not alone sufficient to cause typical migraine and highlights the genetic complexity of this disorder. Migraine is a common, disabling neurological disorder with a genetic, environmental and in some cases hormonal component. It is characterized by attacks of severe, usually unilateral and throbbing headache, can be accompanied by nausea, vomiting and photophobia and is clinically divided into two main subtypes, migraine with aura (MA) when a migraine is accompanied by transient and reversible focal neurological symptoms and migraine without aura (MO)1. The multifactorial and clinical heterogeneity of the disorder have considerably hindered the identification of common migraine susceptibility genes and most of our current understanding comes from the studies of familial hemiplegic migraine (FHM), a rare monogenic autosomal dominant form of MA2. So far, the three susceptibility genes that have been convincingly identified in FHM families all encode ion channels or transporters: CACNA1A encoding the α1 subunit of the Cav2.1 calcium channel3, SCN1A encoding the Nav1.1 sodium channel4 and ATP1A2 encoding the α2 subunit of the Na+/K+ pump5. It is believed that mutations in these genes may lead to increased efflux of glutamate and potassium in the synapse and thereby cause migraine by rendering the brain more susceptible to cortical spreading depression (CSD)6 which is thought to play a role in initiating a migraine attack7,8. However, these genes have not to date been implicated in common forms of migraine9. Nevertheless, current opinion suggests that typical migraine, like FHM, is also disorder of neuronal excitability, ion homeostasis and neurotransmitter release10,11,12. Mutations in the SLC4A4 gene encoding the sodium-bicarbonate cotransporter NBCe1, have recently been implicated in several different forms of migraine13, and a variety of genes involved in glutamate homeostasis (PGCP, MTDH14 and LRP115) and a cation channel (TRPM8)15 have also recently been implicated in migraine via genome-wide association studies. Ion channels are therefore highly likely to play an important role in the pathogenesis of typical migraine. TRESK (KCNK18), is a member of the two-pore domain (K2P) family of potassium channels involved in the control of cellular electrical excitability16. Regulation of TRESK activity by the calcium-dependent phosphatase calcineurin17, as well as its expression in dorsal root ganglia (DRG)18 and trigeminal ganglia (TG)19,20 has led to a proposed role for this channel in a variety of pain pathways. In a recent study, a frameshift mutation (F139Wfsx24) in TRESK was identified in a large multigenerational pedigree where it co-segregated perfectly with typical MA and a significant genome-wide linkage LOD score of 3.0. Furthermore, functional analysis revealed that this mutation caused a complete loss of TRESK function and that the truncated subunit was also capable of down regulating wild-type channel function. This therefore highlighted KCNK18 as potentially important candidate gene and suggested that TRESK dysfunction might play a possible role in the pathogenesis of familial migraine with visual aura20. Additional screening for KCNK18 mutations in unrelated sporadic migraine and control cohorts also identified a number of other missense variants; R10G, A34V, C110R, S231P and A233V20. The A233V variant was found only in the control cohort, whilst A34V was identified in a single Australian migraine proband for which family samples were not available, but it was not detected in controls. By contrast, the R10G, C110R, and S231P variants were found in both migraineurs and controls in both cohorts. In this study, we have investigated the functional effect of these variants to further probe the potential association of TRESK dysfunction with typical migraine.

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A new bioluminescent creatine kinase (CK) assay using purified luciferase was used to analyse CK activity in serum samples dried on filter paper. Enzyme activity was preserved for over 1 wk on paper stored at room temperature. At 60°C, CK activity in liquid serum samples was rapidly inactivated, but the activity of enzyme stored on paper was preserved for at least 2 days.

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This study investigates the impact of polystyrene sodium sulfonate (PolyNaSS) grafting onto the osseo-integration of a polyethylene terephthalate artificial ligament (Ligament Advanced Reinforcement System, LARS™) used for Anterior Cruciate Ligament (ACL). The performance of grafted and non-grafted ligaments was assessed in vitro by culturing human osteoblasts under osteogenic induction and this demonstrated that the surface modification was capable of up-regulating the secretion of ALP and induced higher level of mineralisation as measured 6 weeks post-seeding by Micro-Computed Tomography. Grafted and non-grafted LARS™ were subsequently implanted in an ovine model for ACL reconstruction and the ligament-to-bone interface was evaluated by histology and biomechanical testings 3 and 12 months post-implantation. The grafted ligaments exhibited more frequent direct ligament-to-bone contact and bone formation in the core of the ligament at the later time point than the non-grafted specimens, the grafting also significantly reduced the fibrous encapsulation of the ligament 12 months post-implantation. However, this improved osseo-integration was not translated into a significant increase in the biomechanical pull-out loads. These results provide evidences that PolyNaSS grafting improved the osseo-integration of the artificial ligament within the bone tunnels. This might positively influence the outcome of the surgical reconstructions, as higher ligament stability is believed to limit micro-movement and therefore permits earlier and enhanced healing.

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The current approach for protecting the receiving water environment from urban stormwater pollution is the adoption of structural measures commonly referred to as Water Sensitive Urban Design (WSUD). The treatment efficiency of WSUD measures closely depends on the design of the specific treatment units. As stormwater quality can be influenced by rainfall characteristics, the selection of appropriate rainfall events for treatment design is essential to ensure the effectiveness of WSUD systems. Based on extensive field investigation of four urban residential catchments and computer modelling, this paper details a technically robust approach for the selection of rainfall events for stormwater treatment design using a three-component model. The modelling outcomes indicate that selecting smaller average recurrence interval (ARI) events with high intensity-short duration as the threshold for the treatment system design is the most feasible since these events cumulatively generate a major portion of the annual pollutant load compared to the other types of rainfall events, despite producing a relatively smaller runoff volume. This implies that designs based on small and more frequent rainfall events rather than larger rainfall events would be appropriate in the context of efficiency in treatment performance, cost-effectiveness and possible savings in land area needed.

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A design for a cascaded multilevel DC-DC converter is proposed. The applications of a multilevel converter and the design issues involved in changing from a single converter to multiple converters are discussed. Implementation of the multilevel system using multiple Cuk converters is suggested and explanations of design decisions are given. The merits of the proposed design are discussed.

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Collagen crosslinking (CXL) has shown promising results in the prevention of the progression of keratoconus and corneal ectasia. However, techniques for in vivo and in situ assessment of the treatment are limited. In this study, ex vivo porcine eyes were treated with a chemical CXL agent (glutaraldehyde), during which polarization sensitive optical coherence tomography (PS-OCT) recordings were acquired simultaneously to assess the sensitivity of the technique to assess changes in the cornea. The results obtained in this study suggest that PS-OCT may be a suitable technique to measure CXL changes in situ and to assess the local changes in the treated region of the cornea.

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Pavlovian fear conditioning is a robust technique for examining behavioral and cellular components of fear learning and memory. In fear conditioning, the subject learns to associate a previously neutral stimulus with an inherently noxious co-stimulus. The learned association is reflected in the subjects' behavior upon subsequent re-exposure to the previously neutral stimulus or the training environment. Using fear conditioning, investigators can obtain a large amount of data that describe multiple aspects of learning and memory. In a single test, researchers can evaluate functional integrity in fear circuitry, which is both well characterized and highly conserved across species. Additionally, the availability of sensitive and reliable automated scoring software makes fear conditioning amenable to high-throughput experimentation in the rodent model; thus, this model of learning and memory is particularly useful for pharmacological and toxicological screening. Due to the conserved nature of fear circuitry across species, data from Pavlovian fear conditioning are highly translatable to human models. We describe equipment and techniques needed to perform and analyze conditioned fear data. We provide two examples of fear conditioning experiments, one in rats and one in mice, and the types of data that can be collected in a single experiment. © 2012 Springer Science+Business Media, LLC.

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Isofraxidin is one of the main bioactive constituents in the root of Acanthopanax senticosus, which has antifatigue, antistress, and immuno-accommondating effects. In this study, an ultraperformance LC (UPLC)-ESI MS method was developed for analyzing isofraxidin and its metabolites in rat plasma. The analysis was performed on a UPLC coupled with ESI MS (quadropole MS tandem TOF MS). The lower LOD (LLOD) for isofraxidin was 0.25 ng/mL, the intraday precision was less than 10%, the interday precision was less than 10%, and the extraction recovery was more than 80%. Isofraxidin and two metabolites (M1 and M2) were detected in rat plasma after oral administration of isofraxidin, and the molecular polarities of M1 and M2 were both increased compared to isofraxidin. The metabolites were identified as 5,6-dihydroxyl-7-methoxycoumarin and 5-hydroxyl-6,7-dimethoxycoumarin when subjected to parent ion spectra, product ion spectra, and extract mass and element composition analyses.

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Electrochemical processes in mesoporous TiO2-Nafion thin films deposited on indium tin oxide (ITO) electrodes are inherently complex and affected by capacitance, Ohmic iR-drop, RC-time constant phenomena, and by potential and pH-dependent conductivity. In this study, large-amplitude sinusoidally modulated voltammetry (LASMV) is employed to provide access to almost purely Faradaic-based current data from second harmonic components, as well as capacitance and potential domain information from the fundamental harmonic for mesoporous TiO2-Nafion film electrodes. The LASMV response has been investigated with and without an immobilized one-electron redox system, ferrocenylmethyltrimethylammonium+. Results clearly demonstrate that the electron transfer associated with the immobilized ferrocene derivative follows two independent pathways i) electron hopping within the Nafion network and ii) conduction through the TiO2 backbone. The pH effect on the voltammetric response for the TiO2 reduction pathway (ii) can be clearly identified in the 2nd harmonic LASMV response with the diffusion controlled ferrocene response (i) acting as a pH independent reference. Application of second harmonic data derived from LASMV measurement, because of the minimal contribution from capacitance currents, may lead to reference-free pH sensing with systems like that found for ferrocene derivatives.

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We present a mini-review of the development and contemporary applications of diffusion-sensitive nuclear magnetic resonance (NMR) techniques in biomedical sciences. Molecular diffusion is a fundamental physical phenomenon present in all biological systems. Due to the connection between experimentally measured diffusion metrics and the microscopic environment sensed by the diffusing molecules, diffusion measurements can be used for characterisation of molecular size, molecular binding and association, and the morphology of biological tissues. The emergence of magnetic resonance was instrumental to the development of biomedical applications of diffusion. We discuss the fundamental physical principles of diffusion NMR spectroscopy and diffusion MR imaging. The emphasis is placed on conceptual understanding, historical evolution and practical applications rather than complex technical details. Mathematical description of diffusion is presented to the extent that it is required for the basic understanding of the concepts. We present a wide range of spectroscopic and imaging applications of diffusion magnetic resonance, including colloidal drug delivery vehicles; protein association; characterisation of cell morphology; neural fibre tractography; cardiac imaging; and the imaging of load-bearing connective tissues. This paper is intended as an accessible introduction into the exciting and growing field of diffusion magnetic resonance.

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Integration of small-scale electricity generators, known as Distributed Generation (DG), into the distribution networks has become increasingly popular at the present. This tendency together with the falling price of synchronous-type generator has potential to give the DG a better chance in participating in the voltage regulation process together with other devices already available in the system. The voltage control issue turns out to be a very challenging problem for the distribution engineers since existing control coordination schemes would need to be reconsidered to take into account the DG operation. In this paper, we propose a control coordination technique, which is able to utilize the ability of the DG as a voltage regulator, and at the same time minimizes interaction with other active devices, such as On-load Tap Changing Transformer (OLTC) and voltage regulator. The technique has been developed based on the concept of control zone, Line Drop Compensation (LDC), as well as the choice of controller's parameters. Simulations carried out on an Australian system show that the technique is suitable and flexible for any system with multiple regulating devices including DG.

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Plug-in electric vehicles will soon be connected to residential distribution networks in high quantities and will add to already overburdened residential feeders. However, as battery technology improves, plug-in electric vehicles will also be able to support networks as small distributed generation units by transferring the energy stored in their battery into the grid. Even though the increase in the plug-in electric vehicle connection is gradual, their connection points and charging/discharging levels are random. Therefore, such single-phase bidirectional power flows can have an adverse effect on the voltage unbalance of a three-phase distribution network. In this article, a voltage unbalance sensitivity analysis based on charging/discharging levels and the connection point of plug-in electric vehicles in a residential low-voltage distribution network is presented. Due to the many uncertainties in plug-in electric vehicle ratings and connection points and the network load, a Monte Carlo-based stochastic analysis is developed to predict voltage unbalance in the network in the presence of plug-in electric vehicles. A failure index is introduced to demonstrate the probability of non-standard voltage unbalance in the network due to plug-in electric vehicles.