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The sodium-activated potassium channel Slack (KNa1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (IKNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated IKNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated IKNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.  相似文献   
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Semiconductor heterostructures are intrinsic to a wide range of modern‐day electronic devices, such as computers, light‐emitting devices, and photodetectors. Knowledge of chemical interfacial profiles in these structures is critical to the task of optimizing the device performance. This work presents an analysis of the composition profile and strain across the noncommon‐atom heterovalent CdTe/InSb interface, carried out using a combination of electron microscopy imaging techniques. Because of the close atomic numbers of the constituent elements, techniques such as high‐angle annular‐dark‐field and large‐angle bright‐field scanning transmission electron microscopy, as well as electron energy‐loss spectroscopy, give results from the interface region that are inherently difficult to interpret. By contrast, use of the 002 dark‐field imaging technique emphasizes the interface location by comparing differences in structure factors between the two materials. Comparisons of experimental and simulated CdTe‐on‐InSb profiles reveal that the interface is structurally abrupt to within about 1.5 nm (10–90% criterion), while geometric phase analysis based on aberration‐corrected electron microscopy images reveals a minimal level of interfacial strain. The present investigation opens new routes to the systematic investigation of heterovalent interfaces, formed by the combination of other valence‐mismatched material systems.  相似文献   
74.
In this paper we introduce the concept of controllability into a closed subspace for time-varying linear systems. Various characterizations are given and the dual relation is discussed. This concept is used to present a necessary and sufficient condition for the stabilizability of systems with exponential dichotomy.  相似文献   
75.
Within the scope of the characterization of a commercial pectate lyase (PAL) the pattern of substrate degradation by that enzyme was investigated with oligogalacturonic acids as well as pectins with various degrees of esterification as substrates. For this purpose an analytical size exclusion chromatographie method (HPSEC) was elaborated in order to evaluate the reaction products of the degraded substrates over the whole range of molecular weight with the main interest lying in the emerging oligogalacturonic acids. The degradation of polygalacturonic acid by PAL was additionally investigated by means of thin-layer chromatography (TLC) and viscosimetry. Furthermore spontaneous depolymerization and deesterification of the substrates occurring under the chosen conditions were examined. The PAL showed to be anendo-enzyme both by means of TLC and HPSEC. Polygalacturonic acid was broken down, mainly generating unsaturated tri- and digalacturonic acid; the corresponding monomer was not found. The mode of cleavage is discussed.  相似文献   
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When the microemulsion formulation of the critical dose drug cyclosporine A (CsA) (Sandimmun Optoral) was introduced in the mid-1990s, it became clear that this new formulation improves the oral bioavailability of CsA and has a positive influence on its pharmacokinetic variability. Previous studies with the original CsA formulation (Sandimmun) showed that the size of the emulsion droplets and concomitant food intake has an effect on the absorption of CsA from the small intestine when orally administered. It was suggested that these effects might have an influence on the drugs' pharmacokinetic parameters.In this study, we focused on the two above-mentioned aspects and compared the first and second generations of CsA products (Sandimmun, Sandimmun Optoral) to generic CsA formulations by analyzing the contents of cyclosporine A gel capsules with respect to their emulsion droplet and micelle sizes using photon correlation spectroscopy (PCS). We tried to discern any differences in droplet size between different generations of CsA formulations, primarily the second and third generation, through simple physical tests. Because a high fat content food may influence the absorption of CsA, we also determined the distribution of CsA between hydrophilic and lipophilic phases using high-performance liquid chromatography analysis.It became clear that when compared under simple physical conditions, established cyclosporine formulations and new generic products show significant differences in droplet size and distribution between an aqueous phase and a high fat content food. Whether these differences are of clinical relevance remains to be investigated.  相似文献   
79.
In the framework of the European research project PV2GO, a new AC-module inverter was developed, taking into account all relevant aspects from a European market's point of view (standards, market, application, and research and development goals). The project goal was to achieve the overall system costs of 3 Euro per Wp for a modular plug-and-play photovoltaic system. For the photovoltaic-module, a standard 130-Wp Eurosolare module was chosen. The research and development (R&D) goal was to develop an advanced DC-control system consisting of a state-of-the-art programmable digital device and an Application Specific Integrated Circuit (ASIC) for the AC-control of the inverter. According to the topology concept, thermal and magnetic designs were optimized with regard to production technology and packaging for large-scale production. The new AC-modules were tested in a number of field-test sites in various parts of Europe and their reliability was assessed through Highly Accelerated Stress Tests. Efficiency and power quality have been tested in the laboratory. Further in the PV2GO project an optimization study of the manufacturing process of the new generation of AC-modules for high volume output was done. Another task was the pre-certification procedure to assure compliance with the European guidelines and standards.  相似文献   
80.
The development of a steady-state process model for a numerical study of transport phenomena in the fusion zone of deep penetration laser beam welded joints is described. Based on the conservation equations of energy, momentum, and mass in dimensionless form, the three-dimensional modeling considers viscous, buoyancy, and friction forces as well as surface tension gradients. The developed simulation program enables the prediction of the local temperature and velocity distribution in the molten material. Consequently, the resultant weld pool dimensions dependent on the characteristic dimensionless groups can be derived.  相似文献   
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