Glibenclamide for the Treatment of Ischemic and Hemorrhagic Stroke

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 K_ATP (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.     

Dietary advanced glycation end‐products: Perspectives linking food processing with health implications

Dietary advanced glycation end products (dAGEs) are complex and heterogeneous compounds derived from nonenzymatic glycation reactions during industrial processing and home cooking. There is mounting evidence showing that dAGEs are closely associated with various chronic diseases, where the absorbed dAGEs fuel the biological AGEs pool to exhibit noxious effects on human health. Currently, due to the uncertain bioavailability and rapid renal clearance of dAGEs, the relationship between dAGEs and biological AGEs remains debatable. In this review, we provide the most updated information on dAGEs including their generation in processed foods, analytical and characterization techniques, metabolic fates, interaction with AGE receptors, implications on human health and reducing strategies. Available evidence demonstrating a relevance between dAGEs and food allergy is also included. AGEs are ubiquitous in foods and their contents largely depend on the reactivity of carbonyl and amino groups, along with surrounding condition mainly pH and heating procedures. Once being digested and absorbed into the circulation, two separate pathways can be involved in the deleterious effects of dAGEs: an AGE receptor‐dependent way to stimulate cell signals, and an AGE receptor‐independent way to dysregulate proteins via forming complexes. Inhibition of AGEs formation during food processing and reduction in the diet are two potent approaches to restrict health‐hazardous dAGEs. To elucidate the biological role of dAGEs toward human health, the following significant perspectives are raised: molecular size and complexity of dAGEs; interactions between unabsorbed dAGEs and gut microbiota; and roles played by concomitant compounds in the heat‐processed foods.     

一种北斗联合低轨星座的导航增强方法研究

单纯依靠北斗导航系统提供定位导航授时服务,存在卫星信号落地功率低、易受遮蔽和阻断的不足。针对此问题,研究了一种北斗联合低轨星座实现导航增强的系统架构;提出了一种新的适应严重遮蔽或干扰条件下,基于到达时间(TOA)和到达频率(FOA)联合观测的定位解算算法;对高中低轨混合星座条件下的覆盖特性和精度衰减因子进行了仿真分析。分析结果表明,用户可见星数平均增加了64.2%,位置精度衰减因子(PDOP)平均改善了28.7%。研究结果可为下一代北斗的论证设计与研制建设提供参考借鉴。     

Comparative evaluation of different statistical tools for the prediction of uniaxial compressive strength of rocks

In this study, uniaxial compressive strength (UCS), unit weight (UW), Brazilian tensile strength (BTS), Schmidt hardness (SHH), Shore hardness (SSH), point load index (Is₅₀) and P-wave velocity (V_p) properties were determined. To predict the UCS, simple regression (SRA), multiple regression (MRA), artificial neural network (ANN), adaptive neuro-fuzzy inference system (ANFIS) and genetic expression programming (GEP) have been utilized. The obtained UCS values were compared with the actual UCS values with the help of various graphs. Datasets were modeled using different methods and compared with each other. In the study where the performance indice PI_at was used to determine the best performing method, MRA method is the most successful method with a small difference. It is concluded that the mean PI_at equal to 2.46 for testing dataset suggests the superiority of the MRA, while these values are 2.44, 2.33, and 2.22 for GEP, ANFIS, and ANN techniques, respectively. The results pointed out that the MRA can be used for predicting UCS of rocks with higher capacity in comparison with others. According to the performance index assessment, the weakest model among the nine model is P7, while the most successful models are P2, P9, and P8, respectively.     

Hetero-assembly of colloidal particles in concentrated non-aqueous suspensions by polymer dispersant design

Although many colloidal assembling systems have been reported, most systems suffer from severe aggregation under high solid concentrations, which can often be observed in typical hetero-aggregation system. In this study, we created a hetero-assembly system using concentrated (~50 vol%) suspensions by mixing large SiO₂ particles modified with polyacrylic acid partially complexed with oleylamine (PAA-OAm) and small SiO₂ particles modified with polyethyleneimine partially complexed with oleic acid (PEI-OA) in a non-aqueous solvent. We demonstrated that hetero-assembly is driven by the interactions between the uncomplexed carboxyl/amine groups of the PAA/PEI present on the particles, while severe aggregation is simultaneously prevented by the steric repulsions of the aliphatic oleyl chains. Comparison of the cross sections of the in-situ solidified hetero-assembled suspensions with those of ideally assembled structures which were reproduced by a simulation considering the statistical distribution of particles strongly supported successful particle assembling via the proposed approach. The results revealed that the OA content in the PEI-OA complex was the dominant factor that controlled the dispersion and assembling state of the binary particles. The significance of this study is that our findings will provide a class of colloidal dispersion state which binary particles were assembled in a high solid content suspension without forming strong aggregates.     

川西彭州地区雷口坡组潮坪相薄储层辨识机理研究

川西彭州地区三叠系雷口坡组雷四上亚段潮坪相薄储层识别难度极大。围绕如何从复合地震强反射中区分并识别上、下两套储层面临的地球物理难题,采用先“分”后“合”的研究思路,基于实际地层结构及不同储层叠加样式建立正演模型,利用全波场波动方程正演模拟技术,剖析了不同主频条件下薄储层的地震响应特征,通过波形差异化分析,从复合地震响应中“剥离”出了两套储层所引起的地震响应特征及变化规律,明确了两套储层在不同频带下的地震识别标志和识别方法,为该区强反射界面干扰下两套薄互层储层辨识机理分析及精准预测奠定了基础。基于不同频带下薄储层辨识机理的分析结果,定性预测了薄储层平面展布,提出了深层潮坪相薄储层识别和预测难题的解决方案,为该区地震资料品质评价、面向薄储层的地震采集技术设计、地震资料处理及薄储层预测提供了依据和指导。     

燃煤锅炉除尘专用滤料的开发

介绍机械制造厂燃煤锅炉的烟尘特点,分析滤料失效的原因,提出一套针对该工况的滤料解决方案。介绍针对复杂工况条件所选用的纤维种类以及复合面层原料成分配比的确定,最终选用针刺工艺加工并对该新产品的基本性能进行了测试分析。     

The Interplay of Modulus,Strength, and Ductility in Adhesive Design Using Biomimetic Polymer Chemistry

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.     

Gradient-based recursive parameter estimation for a periodically nonuniformly sampled-data Hammerstein–Wiener system based on the key-term separation

The identification of the Hammerstein–Wiener (H-W) systems based on the nonuniform input–output dataset remains a challenging problem. This article studies the identification problem of a periodically nonuniformly sampled-data H-W system. In addition, the product terms of the parameters in the H-W system are inevitable. In order to solve the problem, the key-term separation is applied and two algorithms are proposed. One is the key-term-based forgetting factor stochastic gradient (KT-FFSG) algorithm based on the gradient search. The other is the key-term-based hierarchical forgetting factor stochastic gradient (KT-HFFSG) algorithm. Compared with the KT-FFSG algorithm, the KT-HFFSG algorithm gives more accurate estimates. The simulation results indicate that the proposed algorithms are effective.     

The control of sea lice in Atlantic salmon by selective breeding

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.