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排序方式: 共有8237条查询结果,搜索用时 17 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.
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
4.
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
5.
6.
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
7.
研究了不同工艺参数对980 MPa级连续退火双相钢组织及力学性能的影响,利用光学显微镜、透射电镜(TEM)以及拉伸试验对双相钢的微观组织和力学性能进行测试及分析。结果表明:DP980钢的退火组织主要由铁素体、马氏体岛和少量的贝氏体组成,马氏体岛附近的位错密度较高。随着均热温度的升高,DP980钢的抗拉强度呈现先降低后升高的趋势,屈服强度与抗拉强度的趋势一致,伸长率先升高后降低。随着过时效温度的升高,DP980钢的抗拉强度和屈服强度降低,降低幅度较小,伸长率上升,但变化不明显,说明通过调整过时效温度来调控其力学性能的作用较小。 相似文献
8.
ABSTRACTA dual-phase (12?vol.% delta-ferrite?+?78?vol.% austenite) high manganese twinning-induced plasticity (TWIP) steel was produced by hot rolled and annealing treatment. In comparison with the fully austenitic TWIP steel, both the yield and ultimate tensile strength of the dual-phase TWIP steel reinforced by hard delta-ferrite are significantly increased. It was found that the delta-ferrite in dual-phase steel exhibits a high hardness owing to the formed DO3 structured intermetallic phase within ferrite. The presence of delta-ferrite dramatically improves the strain-hardening ability of TWIP steel. This is principally attributed to the effects of strain partitioning between hard delta-ferrite and softer austenite on the kinetics of deformation twinning and/or additional geometrical necessary dislocation (GND) during the deformation process. 相似文献
9.
Qianwen Liu Guofeng Zhang Nan Chen Xixi Feng Chengzhi Wang Jiaqi Wang Xuting Jin Liangti Qu 《Advanced functional materials》2020,30(38)
Humans live today in a high‐tech and informationalized society. With the development of the emerging electronic information age, various electronic systems are inclined to be multifunctional and miniaturized. It is urgent to develop “small and powerful” micro‐batteries with flexibility and high electrochemical performance to meet the diverse needs of microelectronic components. However, low electrochemical performance exists in traditional microenergy storage devices, which fail to satisfy the energy needs for microdevices. Here, for the first time, a planar integrated flexible rechargeable dual‐ion microbattery (DIMB) is reported, which is fabricated from an interdigital pattern of graphite as an electrode and lithium hexafluorophosphate as an electrolyte. As a microbattery, the DIMB exhibits a high reversible capacity of 56.50 mAh cm?3, and excellent cycle stability with 90% capacity retention after 300 cycles under a high working voltage. The application of DIMB in microdevices, such as light‐emitting diodes (LEDs), digital electronic game consoles, and electrochromic glasses is also investigated, fully demonstrating its “small and powerful” performance. The integrated DIMB is a high‐voltage microdevice that reaches a nonpareil discharge voltage of about 100 V and a charging capacity of 102 mAh g?1. This dual ion‐based flexible microbattery could become a promising candidate for energy storage and conversion components in next‐generation microelectronic devices and integrated electronic devices. 相似文献
10.
《International Journal of Hydrogen Energy》2020,45(17):10602-10612
Owing to high specific energy and low emissions production, hydrogen is a desirable alternative fuel. The combustion and emission performance can be improved by hydrogen addition injected in-cylinder, intake manifold and aspirated with air. However, engine loads and hydrogen-air ration have a significant effect on the performance, combustion and emission of the diesel-hydrogen (high speed direct injection) HSDI engine. In this paper, the CFD method is used to calculate the combustion process of a diesel-hydrogen dual HSDI engine working at constant speed of 4000 rpm, at different hydrogen added from intake port (hydrogen volume fraction of 0%–10%) and five engine loads (equivalent to 20%, 40%, 60%, 80% and 100% of its maximum output power), respectively. The modelling results showed that the in-cylinder pressure and temperature under low engine load were more affected by hydrogen addition. With increasing hydrogen volume fraction, the indicated expansion work and in-cylinder peak pressure increased, and combustion duration decreased due to faster fuel-air mixing and spray flame speed. 相似文献