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31.
Under water-rich conditions, small amphiphilic and hydrophobic drug molecules self-assemble into supramolecular nanostructures. Thus, substantial modifications in their interaction with cellular structures and the ability to reach intracellular targets could happen. Additionally, drug aggregates could be more toxic than the non-aggregated counterparts, or vice versa. Moreover, since self-aggregation reduces the number of effective “monomeric” molecules that interact with the target, the drug potency could be underestimated. In other cases, the activity could be ascribed to the non-aggregated molecule while it stems from its aggregates. Thus, drug self-assembly could mislead from drug throughput screening assays to advanced preclinical and clinical trials. Finally, aggregates could serve as crystallization nuclei. The impact that this phenomenon has on the biological performance of active compounds, the inconsistent and often controversial nature of the published data and the need for recommendations/guidelines as preamble of more harmonized research protocols to characterize drug self-aggregation were main motivations for this review. First, the key molecular and environmental parameters governing drug self-aggregation, the main drug families for which this phenomenon and the methods used for its characterization are described. Then, promising nanotechnology platforms investigated to prevent/control it towards a more efficient drug development process are briefly discussed. 相似文献
32.
Gaoyong Lin Yuyong Wei Ke Zhou Hongyang Wang Weiyuan Song 《Materials and Manufacturing Processes》2018,33(2):232-238
AZ80 hollow profile was produced by porthole-die extrusion. The mechanical behavior and microstructure characteristic of extrusion welds in AZ80 hollow profile during different T5 heat treatments were investigated. Five kinds of morphologies of β-Mg17Al12 were observed in turn in weld regions under various temperatures. Extrusion weld is not weakest region in AZ80 hollow profile in terms of hardness, the peak hardness of weld regions is roughly equal to the weld-free regions at different aging temperatures, which is attributed to similar volume fraction, morphology, and size of β-Mg17Al12 precipitate in weld regions and weld-free regions. The precipitate-free zones (PFZs) usually form near the welds interface in aging process, and the hardness of PFZs is usually lower than those of weld regions and weld-free regions. Aging at 200°C for 24?h is suitable heat treatment system for AZ80 hollow profile, which can achieve excellent mechanical property and simultaneously reduce the width of PFZs. 相似文献
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The critical role of βTrCP1 in cancer development makes it a discerning target for the development of small drug like molecules. Currently, no inhibitor exists that is able to target its substrate binding site. Through molecular docking and dynamics simulation assays, we explored the comparative binding pattern of βTrCP1-WD40 domain with ACV and its phospho-derivatives (ACVMP, ACVDP and ACVTP). Consequently, through principal component analysis, βTrCP1-ACVTP was found to be more stable complex by obscuring a reduced conformational space than other systems. Thus based on the residual contribution and hydrogen bonding pattern, ACVTP was considered as a noteworthy inhibitor which demarcated binding in the cleft formed by βTrCP1-WD40 specific β-propeller. The outcomes of this study may provide a platform for rational design of specific and potent inhibitor against βTrCP1, with special emphasis on anticancer activity. 相似文献
36.
C. Celiktas 《仪器科学与技术》2013,41(4):411-418
Abstract A β+–γ discrimination set‐up was developed and applied to the 22Na radioisotope. The radioisotope emits positrons (β+) and these positrons create γ rays by annihilating with electrons. These annihilation γ rays were used here, and the discrimination between these positrons and γ rays was investigated by the coincidence measurement between time signals and the energy signals. The detection system presented here uses a 3 inch (diameter) by 3 inch (length) NaI(Tl) inorganic scintillation detector for γ detection and 3 inch (diameter) by 3 inch (length) plastic scintillation detector for β+ detection. 相似文献
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SUMMARY An inexpensive gas chromatographic integrator with digital readout is described. The device is precise to ±1 count and shows linear response to within ±2%. It is directly compatible with flame ionization detectors and is easily adapted to thermal conductivity detectors. 相似文献
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沿湖泊沉积物垂直高度取表层(SL,0~2cm)、中层(ML,14~16cm)、底层(BL,28~30cm)3层底泥微生物为对象,研究了湖泊沉积物对17β-雌二醇(17β-estradiol,E2)的生物降解效能。结果表明:无论在好氧还是厌氧条件下,E2及其副产物雌激素酮(estrone,E1)的降解行为与沉积物沉积深度和环境温度有密切关系:底泥沉积深度愈深,E2降解速率愈低;在微生物活性温度范围内,环境温度愈高,E2降解速率愈高。好氧条件下,湖泊沉积物中E2降解反应的k值为0.002~0.120h^-1·g^-1·L;厌氧条件下,k值为0.002~0.057h^-1·g^-1·L。由于诱导驯化及有机物竞争关系减小等原因,向反应体系中再次添加E2后,其k值增大约34%。湖泊沉积物中硝化细菌的存在对E2降解具有促进作用。 相似文献
39.
以薄膜水化法制备的阴离子脂质体的平均粒径为(180±2.3)nm.Zeta电位为-33.9mV.分别以脂质体中钙黄绿素的泄露量和紫外分光光度法测定蛋白含量,以表征羟丙基书-环糊精(HP-β-CD)对脂质体和真核微生物蓝色犁头霉(Absidiacoerulea)细胞通透性的影响.结果表明:在HP-f1.CD作用下,两者的通透性变化趋势一致.分析比较HP-β-CD作用下的甾体化合物17a,21-二羟基孕甾-4-烯-3,20-二酮(RS)在脂质体和菌体细胞中的通量变化的相关性,表明脂质体与细胞通量变化的拟合度达到97.9%,相关性显著(P〈0.05).由此说明,本研究建立的脂质体制备方法以及获得的脂质体能够模拟真核细胞,应用于真核微生物的生物学研究. 相似文献
40.
《地基处理规范》(JGJ79-2002)和该规范2010年征求意见稿中有关CFG长短桩复合地基承载力计算公式的不同,以及征求意见稿公式中发挥系数和桩间土承载力特征值的取值在实际设计中的注意事项,所表述与各实际地基中桩和桩间土的承载性状是不相符的。2010稿公式(7.1.5-2)中各发挥系数的引入使公式与复合地基中桩和桩间土的承载性状较为一致,但在刚性基础下,一般中、硬土层中,桩间土承载力发挥系数β均大于1,现场测试和室内试验也已得到验证。2010稿中λ和β的取值推荐范围偏低。由于增强体(CFG桩)的作用,桩间土的承载能力比天然地基承载力会有一定程度的提高,两者的差异随地基土的工程特性、增强体的性质、增强体的设置方法不同而不同,通过对桩间土承载力的提高主要所受影响因素的分析,桩间土无试验资料时可取天然地基承载力特征值,而在其它系数中又没有体现桩间土承载力的提高,这也造成了复合地基承载力计算值偏低。 相似文献