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61.
Nicholas Caffes David B. Kurland Volodymyr Gerzanich J. Marc Simard 《International journal of molecular sciences》2015,16(3):4973-4984
Ischemic and hemorrhagic strokes are associated with severe functional disability and high mortality. Except for recombinant tissue plasminogen activator, therapies targeting the underlying pathophysiology of central nervous system (CNS) ischemia and hemorrhage are strikingly lacking. Sur1-regulated channels play essential roles in necrotic cell death and cerebral edema following ischemic insults, and in neuroinflammation after hemorrhagic injuries. Inhibiting endothelial, neuronal, astrocytic and oligodendroglial sulfonylurea receptor 1–transient receptor potential melastatin 4 (Sur1–Trpm4) channels and, in some cases, microglial KATP (Sur1–Kir6.2) channels, with glibenclamide is protective in a variety of contexts. Robust preclinical studies have shown that glibenclamide and other sulfonylurea agents reduce infarct volumes, edema and hemorrhagic conversion, and improve outcomes in rodent models of ischemic stroke. Retrospective studies suggest that diabetic patients on sulfonylurea drugs at stroke presentation fare better if they continue on drug. Additional laboratory investigations have implicated Sur1 in the pathophysiology of hemorrhagic CNS insults. In clinically relevant models of subarachnoid hemorrhage, glibenclamide reduces adverse neuroinflammatory and behavioral outcomes. Here, we provide an overview of the preclinical studies of glibenclamide therapy for CNS ischemia and hemorrhage, discuss the available data from clinical investigations, and conclude with promising preclinical results that suggest glibenclamide may be an effective therapeutic option for ischemic and hemorrhagic stroke. 相似文献
62.
使用竖直管代替波动管模型开展稳压器波动管竖直管段内空气-水两相逆流限制(CCFL)特性可视化实验研究。实验现象表明:竖直管与上容器接口处的局部CCFL决定了进入竖直管内的液相流量;竖直管内的局部CCFL决定了从竖直管流出的液相流量;两处局部CCFL均随空气流量的增大而增强。在较低气量情况,进入竖直管内的液相能够完全或大部分流出,竖直管内的局部CCFL较弱,上容器和竖直管接口处的局部CCFL在整体CCFL中占主导地位,整体CCFL程度随着上容器液位升高而略有增强。在高气量情况,从上容器进入竖直管的液相大部分或者完全被限制而不能向下流出,竖直管内的局部CCFL强烈,在整体CCFL中占主导地位,整体CCFL特性不受上容器液位变化的影响。通过实验数据拟合得到了新的稳压器竖直管CCFL模型。稳压器波动管CCFL数据和稳压器竖直管CCFL数据基本重合,表明波动管CCFL主要由CCFL-U决定。 相似文献
63.
Private information retrieval(PIR) is an important privacy protection issue of secure multi-party computation, but the PIR protocols based on classical cryptography are vulnerable because of new technologies,such as quantum computing and cloud computing. The quantum private queries(QPQ) protocols available, however, has a high complexity and is inefficient in the face of large database. This paper, based on the QKD technology which is mature now, proposes a novel QPQ protocol utilizing the key dilution and auxiliary parameter. Only N quits are required to be sent in the quantum channel to generate the raw key, then the straight k bits in the raw key are added bitwise to dilute the raw key, and a final key is consequently obtained to encrypt the database. By flexible adjusting of auxiliary parameters θ and k, privacy is secured and the query success ratio is improved. Feasibility and performance analyses indicate that the protocol has a high success ratio in first-trial query and is easy to implement, and that the communication complexity of O(N) is achieved. 相似文献
64.
This paper deals with the application of wavelet transforms for the detection, classification and location of faults on transmission lines. A Global Positioning System clock is used to synchronize sampling of voltage and current signals at both the ends of the transmission line. The detail coefficients of current signals of both the ends are utilized to calculate fault indices. These fault indices are compared with threshold values to detect and classify the faults. Artificial Neural Networks are employed to locate the fault, which make use of approximate decompositions of the voltages and currents of local end. The proposed algorithm is tested successfully for different locations and types of faults. 相似文献
65.
The Interplay of Modulus,Strength, and Ductility in Adhesive Design Using Biomimetic Polymer Chemistry 下载免费PDF全文
High‐performance adhesives require mechanical properties tuned to demands of the surroundings. A mismatch in stiffness between substrate and adhesive leads to stress concentrations and fracture when the bonding is subjected to mechanical load. Balancing material strength versus ductility, as well as considering the relationship between adhesive modulus and substrate modulus, creates stronger joints. However, a detailed understanding of how these properties interplay is lacking. Here, a biomimetic terpolymer is altered systematically to identify regions of optimal bonding. Mechanical properties of these terpolymers are tailored by controlling the amount of a methyl methacrylate stiff monomer versus a similar monomer containing flexible poly(ethylene glycol) chains. Dopamine methacrylamide, the cross‐linking monomer, is a catechol moiety analogous to 3,4‐dihydroxyphenylalanine, a key component in the adhesive proteins of marine mussels. Bulk adhesion of this family of terpolymers is tested on metal and plastic substrates. Incorporating higher amounts of poly(ethylene glycol) into the terpolymer introduces flexibility and ductility. By taking a systematic approach to polymer design, the region in which material strength and ductility are balanced in relation to the substrate modulus is found, thereby yielding the most robust joints. 相似文献
66.
Marta Gabasa Marselina Arshakyan Alejandro Llorente Lourdes Chuli-Peris Irina Pavelescu Antoni Xaubet Javier Pereda Jordi Alcaraz 《International journal of molecular sciences》2020,21(22)
Pro-inflammatory cytokines like interleukin-1β (IL-1β) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1β on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1β and used Atomic Force Microscopy to unveil that IL-1β significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1β stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1β may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1β-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1β provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair. 相似文献
67.
Karim Gharbi Louise Matthews James Bron Ron Roberts Alan Tinch Michael Stear 《Journal of the Royal Society Interface》2015,12(110)
Sea lice threaten the welfare of farmed Atlantic salmon and the sustainability of fish farming across the world. Chemical treatments are the major method of control but drug resistance means that alternatives are urgently needed. Selective breeding can be a cheap and effective alternative. Here, we combine experimental trials and diagnostics to provide a practical protocol for quantifying resistance to sea lice. We then combined quantitative genetics with epidemiological modelling to make the first prediction of the response to selection, quantified in terms of reduced need for chemical treatments. We infected over 1400 young fish with Lepeophtheirus salmonis, the most important species in the Northern Hemisphere. Mechanisms of resistance were expressed early in infection. Consequently, the number of lice per fish and the ranking of families were very similar at 7 and 17 days post infection, providing a stable window for assessing susceptibility to infection. The heritability of lice numbers within this time window was moderately high at 0.3, confirming that selective breeding is viable. We combined an epidemiological model of sea lice infection and control on a salmon farm with genetic variation in susceptibility among individuals. We simulated 10 generations of selective breeding and examined the frequency of treatments needed to control infection. Our model predicted that substantially fewer chemical treatments are needed to control lice outbreaks in selected populations and chemical treatment could be unnecessary after 10 generations of selection. Selective breeding for sea lice resistance should reduce the impact of sea lice on fish health and thus substantially improve the sustainability of Atlantic salmon production. 相似文献
68.
69.
《Intermetallics》2015
An equiatomic CoCrFeNiMn high-entropy alloy was synthesized by mechanical alloying (MA) and spark plasma sintering (SPS). During MA, a solid solution with refined microstructure of 10 nm which consists of a FCC phase and a BCC phase was formed. After SPS consolidation, only one FCC phase can be detected in the HEA bulks. The as-sintered bulks exhibit high compressive strength of 1987 MPa. An interesting magnetic transition associated with the structure coarsening and phase transformation was observed during SPS process. 相似文献
70.
针对高可靠度机载多余度EWIS各组成部分寿命服从指数分布但参数未知的情况,提出采用无失效数据可靠度分析方法评估EWIS的可靠度水平。通过Monte-Carlo仿真方法对连接形式为“先并联、后串联”EWIS各组成部分寿命进行抽样,利用“最小最大值”方法获得系统寿命的抽样值,用概率纸检验法初步判断EWIS寿命是否服从威布尔分布,再用Pearson拟合优度检验法判断EWIS寿命是否服从威布尔分布。结合无故障飞行时间的样本值与EWIS寿命服从威布尔分布的假设,采用无失效数据分析方法评估EWIS的可靠度水平。研究方法对机载多余度EWIS无失效数据可靠度分析有一定的贡献。 相似文献