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81.
A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.  相似文献   
82.
This work investigates the influence of niobium pentoxide (Nb2O5) as dopant, on the structural, magnetic, and dielectric properties of NiZnCo ferrites. The results showed that Nb2O5 was an effective dopant, and the Nb5+ ions entered the B site to replace Fe3+ ions, which altered the electromagnetic properties of the NiZnCo ferrite. In particular, the coercivity (Hc) was 20~24 Oe, and the magnetic quality factor (Q), was more than 200 at x = 0 and x = 0.1 wt%, which is 4~5 times higher than that of NiZn and NiCuZn ferrites. Excellent electromagnetic properties were obtained for 0.1 wt% Nb2O5-doped NiZnCo ferrite, i.e., Ms = 88.3 emu/g, Hc =20.4 Oe, ρ = 2.4 × 105 Ω m and Q = 202 @20 MHz. These excellent electromagnetic properties of Nb2O5-doped NiZnCo ferrites could be potentially applied to resonators and capacitors at high frequency.  相似文献   
83.
本文开发了一种新型的方舱夹芯板用室温固化高强度环氧结构胶黏剂,验证了其物化特性、相关力学性能和环境适应性。结果表明此胶黏剂具有优良性能,可以满足方舱用大板胶黏剂的使用需求。  相似文献   
84.
The uniform refinement mechanisms and methods of deformed mixed and coarse grains inside a solution-treatment Ni-based superalloy during two-stage annealing treatment have been investigated.The two-stage heat treatment experiments include an aging annealing treatment(AT)and a subsequent recrystallization annealing treatment(RT).The object of AT is to precipitate some δ phases and consume part of storage energy to inhibit the grain growth during RT,while the RT is to refine mixed and coarse grains by recrystallization.It can be found that the recrystallization grains will quickly grow up to a large size when the AT time is too low or the RT temperature is too high,while the deformed coarse grains cannot be eliminated when the AT time is too long or the RT temperature is too low.In addition,the mixed microstructure composed of some abnormal coarse recrystallization grains(ACRGs)and a large number of fine grains can be observed in the annealed specimen when the AT time is 3 h and RT tem-perature is 980℃.The phenomenon attributes to the uneven distribution of δ phase resulted from the heterogeneous deformation energy when the AT time is too short.In the regions with a large number of δ phases,the recrystallization nucleation rate is promoted and the growth of grains is limited,which results in fine grains.However,in the regions with few δ phases,the recrystallization grains around grain boundaries can easily grow up,and the new recrystallization nucleus is difficult to form inside grain,which leads to ACRGs.Thus,in order to obtain uniform and fine annealed microstructure,it is a prereq-uisite to precipitate even-distributed δ phase by choosing a suitable AT time,such as 12 h.Moreover,a relative high RT temperature is also needed to promote the recrystallization nucleation around δ phase.The optimal annealing parameters range for uniformly refining mixed crystal can be summarized as:900℃×12 h+990℃×(40-60 min)and 900℃×12 h+1000℃×(10-15 min).  相似文献   
85.
Radicals are closely related to human life and health and have been widely used in biology, chemistry, functional materials, etc. However, the high reactivity, disorder, and short half-lives limit their wide applications. Therefore, it remains a great challenge to prepare stable and ordered radicals. Herein, radicals are prepared with protective umbrellas (diethylmethyleneamine, DEMA) that are integrated on the surface of 2D layered materials to isolate water and oxygen and enhance the stability of radicals. Taking 2D black phosphorus (BP) as an example: triethylamine reacts with dichloromethane to form quaternary ammonium salts with further Hoffmann elimination to produce DEMA radicals that could react with one electron of a lone pair electrons in P on the surface of BP to produce P radicals, which shows a prolonged half-life of 21 days at room temperature. First-principle calculations and electron paramagnetic resonance fitting confirm that the steric hindrance constructed by dense DEMA passivation layer acts as a protective umbrella and the 2D coupling of P radicals and other P atoms in 2D BP plane to enhance the stability and strong superexchange interaction of P radicals. Furthermore, it is a general strategy to produce stable radicals integrated on the 2D plane.  相似文献   
86.
目的 对某福利院一起肠炎沙门菌食源性疾病进行调查和溯源,为研究相关食源性疾病提供参考。方法采用流行病学、食品卫生学和脉冲场凝胶电泳(PFGE)同源性分析等方法,分析本次食源性疾病事件。结果 确认本次事件中病例23名,患病率5.65%(23/407);现场采集病例肛拭子15份和厨房工作人员肛拭子3份、留样菜品3份、水果2份以及冰棒1份,其中从11份病例肛拭子中检出肠炎沙门菌,PFGE结果显示11株肠炎沙门菌的DNA条带图谱相似性为96.4%,聚类分析为同一型,结合流行病学调查,初步判断菌株来自同一克隆系。结论 综合流行病学、食品卫生学和实验室检测结果,确定为一起肠炎沙门菌引起的食源性疾病,福利院应加强对特殊人群的饮食安全管理,制定相应的食源性疾病突发事件应急处理预案,防止此类事故再发生。  相似文献   
87.
Pushing popular contents to the edge of the network can meet the growing demand for data traffic, reduce latency and relieve the pressure of the backhaul. However, considering the limited storage space of the base stations, it is impossible to cache all the contents, especially in ultra-dense network ( UDN). Furthermore, the uneven distribution of mobile users results in load imbalance among small base stations (SBSs) in both time and space, which also affects the caching strategy. To overcome these shortcoming, the impact of the changing load imbalance in UDN was investigated, and then a dynamic hierarchical collaborative caching (DHCC) scheme was proposed to optimize latency and caching hit rate. The storage of the SBS is logically divided into the independent caching layer and the collaborative caching layer. The independent caching layer caches the most popular contents for local users爷interest, and the collaborative caching layer caches contents as much as possible for the benefit of content diversity in the region. Different SBSs have respective storage space layer division ratios, according to their real-time traffic load. For SBSs with heavy load, the independent caching layers are allocated with more space. Otherwise, the collaborative caching layers could store more contents with larger space. The simulation results show that, DHCC improved both transmission latency and hit rate compared with existing caching schemes.  相似文献   
88.
89.
Phase change memory (PCM) is an emerging non-volatile data storage technology concerned by the semiconductor industry. To improve the performances, previous efforts have mainly focused on partially replacing or doping elements in the flagship Ge-Sb-Te (GST) alloy based on experimental “trial-and-error” methods. Here, the current largest scale PCM materials searching is reported, starting with 124 515 candidate materials, using a rational high-throughput screening strategy consisting of criteria related to PCM characteristics. In the results, there are 158 candidates screened for PCM materials, of which ≈68% are not employed. By further analyses, including cohesive energy, bond angle analyses, and Born effective charge, there are 52 materials with properties similar to the GST system, including Ge2Bi2Te5, GeAs4Te7, GeAs2Te4, so on and other candidates that have not been reported, such as TlBiTe2, TlSbTe2, CdPb3Se4, etc. Compared with GST, materials with close cohesive energy include AgBiTe2, TlSbTe2, As2Te3, TlBiTe2, etc., indicating possible low power consumption. Through further melt-quenching molecular dynamic calculation and structural/electronic analyses, Ge2Bi2Te5, CdPb3Se4, MnBi2Te4, and TlBiTe2 are found suitable for optical/electrical PCM applications, which further verifies the effectiveness of this strategy. The present study will accelerate the exploration and development of advanced PCM materials for current and future big-data applications.  相似文献   
90.
Recent advancements in isolation and stacking of layered van der Waals materials have created an unprecedented paradigm for demonstrating varieties of 2D quantum materials. Rationally designed van der Waals heterostructures composed of monolayer transition-metal dichalcogenides (TMDs) and few-layer hBN show several unique optoelectronic features driven by correlations. However, entangled superradiant excitonic species in such systems have not been observed before. In this report, it is demonstrated that strong suppression of phonon population at low temperature results in a formation of a coherent excitonic-dipoles ensemble in the heterostructure, and the collective oscillation of those dipoles stimulates a robust phase synchronized ultra-narrow band superradiant emission even at extremely low pumping intensity. Such emitters are in high demand for a multitude of applications, including fundamental research on many-body correlations and other state-of-the-art technologies. This timely demonstration paves the way for further exploration of ultralow-threshold quantum-emitting devices with unmatched design freedom and spectral tunability.  相似文献   
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