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排序方式: 共有6894条查询结果,搜索用时 31 毫秒
1.
Dr. Christine Brotschi Dr. Martin H. Bolli Dr. John Gatfield Dr. Bibia Heidmann Dr. Francois Jenck Dr. Catherine Roch Dr. Thierry Sifferlen Dr. Alexander Treiber Dr. Jodi T. Williams Dr. Christoph Boss 《ChemMedChem》2020,15(5):430-448
The orexin system is responsible for regulating the sleep-wake cycle. Suvorexant, a dual orexin receptor antagonist (DORA) is approved by the FDA for the treatment of insomnia disorders. Herein, we report the optimization efforts toward a DORA, where our starting point was (5-methoxy-4-methyl-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-[5-(2-trifluoromethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrrolidin-1-yl}methanone ( 6 ), a compound which emerged from our in-house research program. Compound 6 was shown to be a potent, brain-penetrating DORA with in vivo efficacy similar to suvorexant in rats. However, shortcomings from low metabolic stability, high plasma protein binding (PPB), low brain free fraction (fu brain), and low aqueous solubility, were identified and hence, compound 6 was not an ideal candidate for further development. Our optimization efforts addressing the above-mentioned shortcomings resulted in the identification of (4-chloro-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-methyl-2-[5-(2-trifluoromethoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-1-yl}l-methanone ( 42 ), a DORA with improved in vivo efficacy compared to 6 . 相似文献
2.
In view of the shortcomings of silicon micro acceleration sensor based on piezoresistive effect and capacitance principle,
such as temperature drift, low resolution and poor anti-interference ability, a fuze acceleration sensor based on dual SAW devices is
proposed. The sensor adopts a dual saw device structure, one is coated with a sensitive film for measurement, the other is an uncoat-
ed reference channel for compensation of environmental temperature, pressure, humidity and other factors. The experimental results
show that the maximum linear error is only 1.6%, the sensitivity is 54.3Hz/g, and the maximum hysteresis error is less than 1%.
Compared with piezoresistive accelerometer and capacitive accelerometer, the linear error of the accelerometer is small, the sensitivi-
ty is high, and it has strong anti-interference ability. 相似文献
3.
Enzymolysis reaction kinetics and thermodynamics of rapeseed protein with sequential dual‐frequency ultrasound pretreatment 下载免费PDF全文
Asif Wali Haile Ma Khizar Hayat Xiaofeng Ren Zeshan Ali Yuqing Duan Muhammad Tayyab Rashid 《International Journal of Food Science & Technology》2018,53(1):72-80
We evaluated the effect of sequential dual‐frequency ultrasound (SDFU) pretreatments on rapeseed protein enzymolysis, using alcalase as a model enzyme. Hydrolysed protein concentrations, enzymolysis kinetics and thermodynamic parameters were investigated. The results showed that the hydrolysed rapeseed protein concentration following SDFU pretreatments was higher compared to that of the control for up to 75 min of enzymolysis at various substrate concentrations of 5–25 g L?1; both control and SDFU pretreatment groups showed first‐order reaction kinetics. Compared to the control, the Michaelis–Menten constant (KM) value decreased remarkably by 17.61%, while an increase in the binding frequency between enzyme and substrate (KA) by 10.47% was observed. The thermodynamic parameters, enthalpy, entropy and activation energy were reduced in the SDFU pretreatment group compared to the control by 31.78%, 18.0% and 29.56%, respectively. SDFU pretreatment showed little effect on Gibbs free energy at the various temperatures studied. 相似文献
4.
利用一级轻气炮对TC4双相钛合金进行加载, 获得初期的层裂状态, 在加载中采用多普勒激光干涉测速技术对样品自由面粒子速度进行测试。在软回收经过加载的样品之后, 借助于金相显微镜、X射线断层扫描、纳米压痕等检测手段进行多维分析, 探讨了相界面对孔洞形核位置的影响。结果表明, 孔洞绝大部分都在α相内形核, 而不是如准静态损伤理论预测的形核于α/β相界面。这是由于相界面的反射与透射作用, 当冲击波从高阻抗α相传入到低阻抗β相时, 会在α相内产生拉伸脉冲, 当拉伸脉冲足够大时, 导致在α相内产生孔洞。 相似文献
5.
6.
Shuangjiang Feng Shuxue Wang Yuanfei Lv Lei He Qiurong Li Tao Zhang 《Polymer International》2019,68(3):494-502
Hydrogels have been widely used as mild biomaterials due to their bio‐affinity, high drug loading capability and controllable release profiles. However, hydrogel‐based carriers are greatly limited for the delivery of hydrophobic payloads due to the lack of hydrophobic binding sites. Herein, nano‐liposome micelles were embedded in semi‐interpenetrating poly[(N‐isopropylacrylamide)‐co‐chitosan] (PNIPAAm‐co‐CS) and poly[(N‐isopropylacrylamide)‐co‐(sodium alginate)] (PNIPAAm‐co‐SA) hydrogels which were responsive to both temperature and pH, thereby establishing tunable nanocomposite hydrogel delivery systems. Nano‐micelles formed via the self‐assembly of phospholipid could serve as the link between hydrophobic drug and hydrophilic hydrogel due to their special amphiphilic structure. The results of transmission and scanning electron microscopies and infrared spectroscopy showed that the porous hydrogels were successfully fabricated and the liposomes encapsulated with baicalein could be well contained in the network. In addition, the experimental results of response release in vitro revealed that the smart hydrogels showed different degree of sensitiveness under different pH and temperature stimuli. The results of the study demonstrate that combining PNIPAAm‐co‐SA and PNIPAAm‐co‐CS hydrogels with liposomes encapsulated with hydrophobic drugs is a feasible method for hydrophobic drug delivery and have potential application prospects in the medical field. © 2018 Society of Chemical Industry 相似文献
7.
智能交通的出现使得车辆自组织网络受到越来越多的关注。车辆自组织网络的动态拓扑结构变化非常剧烈,这对网络的吞吐率、传输速率等性能提出了很高的要求。提出1种具有握手机制协议的自适应多通道双时钟NP-CSMA随机多址接入协议。该协议首先区分2种P-CSMA协议,握手机制成功解决了隐藏的终端问题,双时钟机制减少了平均空闲时间,多通道机制增加通道数量和划分用户优先级的同时提高了系统吞吐率,自适应机制能够使系统在高负载下保持稳定吞吐率。还对该协议的传输速率进行了分析,得出该协议的传输速率相对较高的结论。通过平均周期方法推导吞吐率和传输速率的计算公式,仿真结果与理论推导一致。 相似文献
8.
Reinforcing Paper Strength by Dual Treatment of a Cationic Water-soluble Polymer and Cellulose Nanofibril 下载免费PDF全文
Cellulose nanofibril (CNF) was used as the anionic component of two dual strengthening systems wherein polyamidopolyamine epichlorohydrin resin (PAE) or cationic starch (CS) was used as the cationic component. Their strengthening effects were investigated for low-basis-weight (30 g/m2) paper composed of a mixture of fully bleached softwood and hardwood pulp in a 4:1 mass ratio. Using the PAE/CNF or CS/CNF dual system, it was generally easier to achieve higher wet and dry tensile strengths of paper compared to the paper using the single PAE or CS system. For example, the paper using the PAE (0.4%)/CNF (0.3%) dual system exhibited 89% higher wet tensile strength than the paper using the single PAE (0.4%) system, and the paper using CS (1.3%)/CNF (0.3%) dual treatment showed 21% higher dry strength than that using the single CS (1.3%) system. However, the PAE/CNF system only showed small improvement in the dry strength of paper (11% higher than that of paper using the single PAE system), so did the CS/NFC system on wet strength improvement (only 17% higher than that of paper using the single CS system). 相似文献
9.
10.
This paper presents a dual Newton scheme for tree‐sparse quadratic programs as they may arise in the field of stochastic programming. Previous work suggests to introduce auxiliary variables to decompose the tree into scenarios and use Newton's method to solve a dual problem formulation. Following a different approach, we apply the same principle directly on the tree‐sparse problem, avoiding the increase in dimensionality. In combination with a tailored algorithm for the calculation of the step direction, which is typically the most expensive operation per iteration, the proposed algorithm achieves a linear complexity in the number of nodes and supports parallel processing of the tree branches in a stage‐wise fashion. An open‐source implementation of the presented dual Newton strategy is publicly available in treeQP , a toolbox of open‐source solvers for tree‐sparse quadratic programs. 相似文献