Preparation of AChE Inhibitors From Jujubogenin

The advanced medical technology has lengthened the life expectancy of human beings.This makes some previously ignored diseases prominent, such as Alzheimer disease(AD). The low level of acetylcholine (ACh) in brain is considered to be one of mainreasons for suffering such memory loss disease. Thereby, how to elevate ACh level inbrain and enhance the cognition has become a main issue l'2. One of the approaches is toinvestigate acetylcholinesterase (AChE) inhibitors, which can prevent the hy…     

AD590设计数字温度计的原理分析与改进

利用AD590特性设计数字温度计，分析实验的原理，并提出改进的措施，以达到更高的实验精度，而且不需要添加任何仪器。     

Enantiomeric impurity determination of levetiracetam using capillary electrochromatography

CEC was used to develop a method for the enantiomeric excess determination of levetiracetam, an antiepileptic drug. Different types of calibration curve were evaluated for use in the range between 0.01 and 1 mg/mL when aniracetam was used as an internal standard. The method gave comparable results when only the areas of the impurity were used in the calibration curve. The predicted detection and quantification limits from the S/N were 1.1 and 3.6 microg/mL, respectively. However, experimental results showed that LOD and LOQ were underestimated. Repeatability of injection was demonstrated by the RSD values obtained for retention time, resolution, ratios of the areas impurity/internal standard, and areas of impurity and internal standard individually, which were below or equal to 9.30%. The between-days variability experiments indicated that it is better to make a calibration curve daily. The finally selected calibration curves were used to test the accuracy of the developed method on bulk samples and Keppra tablets containing 250 mg levetiracetam. Both selected calibration curves performed similarly. The one using the internal standard information gave overall recoveries between 88 and 118%, while the one using areas gave results between 84 and 118%.     

Characterizing the Memory Effect on the amylose tris(3,5-dimethylphenyl) carbamate stationary phase

Acid/base modifiers are sometimes used as additives in normal phase elution on columns packed with CHIRALPAK^® AD^®. They affect enantioseparations in ways that are not understood for the lack of systematic studies, which makes the scale-up of preparative separations difficult to predict. Once a column has been exposed to these modifiers, the selectivity of certain pairs of enantiomers may change, for the better or the worse. Numerous molecules that are affected by this phenomenon are listed in the literature. We selected five of them, the selectivity of which changes as more acidic or basic solutions are percolated through the column. The selectivity of ketoprofen, 4-chlorophenylalanine methyl and ethyl esters improves as a solution of Ethanesulfonic Acid is percolated through the column. The selectivity of Propranolol HCl and Tröger’s base increases as a solution of diisopropylamine is percolated through the column. Each one of these five compounds is inversely affected by the percolation of the opposite acid/base solution. We used trans-Stilbene Oxide (tso) as a “standard” to determine the columns stability because no Memory Effect is observed for it (its retention, enantioselectivity, and resolution remain constant). Karl Fisher titrations showed that only slight changes in the water content of the mobile phase occurred, and that a unique water to polymer moiety ratio is important. Analytical studies of the stationary phase suggest that slow protonation/deprotonation of water attached to the carbamate moiety may be responsible for the acid/base Memory Effect. Finally, we showed that the Memory Effect can be minimized by percolating through the column a sufficiently concentrated solution of the appropriate acid or base. Thus, columns that were unreliable for method development, due to the Memory Effect, can now be used. As a result, the need to store several CHIRALPAK AD columns, specific for each condition of the Memory Effect, is eliminated.     

采用移动极差统计合并技术来监控ICP-AES测量系统的不确定度

采用ICP AES(电感耦合等离子体 原子发射光谱法 )测定金属硅中铁杂质含量进行不确定度评估时 ,提出了平均移动极差 (MR)合并统计动态监控技术。研究认为 ,采用该技术来进行ICP AES测量系统的不确定度评估 ,其贡献量分别是由控制样品 (QC)和线性拟合两部分合成。这一结论的得出能最大限度合成各种变异因素的影响 ,避免了相关性的复杂计算 ,有利于ICP AES测量系统的不确定度评估     

对不良导体导热系数测量实验的改进

对稳态法测量导热系数的实验进行改进,用AD590温度传感器代替热电偶,实现了计算机对数据的采集和处理     

研究蛋白质相互作用的新系统——酵母双杂交系统

自酵母双杂交系统创建以来,已经成为研究蛋白质相互作用的重要手段,被广泛用于各个生物学研究领域,揭示了大量未知蛋白质之间的相互作用. 近来,在经典的酵母双杂交系统基础上,又相继提出许多新的研究方法,如:三杂交系统,单杂交系统,逆向双杂交系统,SOS富集系统等等. 酵母双杂交及其衍生系统已经成功地运用于蛋白质之间,蛋白质与DNA、RNA、配体之间的相互作用的研究     

All-atom molecular dynamics studies of the full-length β-amyloid peptides

β-Amyloid peptides are believed to play an essential role in Alzheimer’s disease (AD), due to their sedimentation in the form of β-amyloid aggregates in the brain of AD-patients, and the in vitro neurotoxicity of oligomeric aggregates. The monomeric peptides come in different lengths of 39–43 residues, of which the 42 alloform seems to be most strongly associated with AD-symptoms. Structural information on these peptides to date comes from NMR studies in acidic solutions, organic solvents, or on shorter fragments of the peptide. In addition X-ray and solid-state NMR investigations of amyloid fibrils yield insight into the structure of the final aggregate and therefore define the endpoint of any conformational change of an Aβ-monomer along the aggregation process. The conformational changes necessary to connect the experimentally known conformations are not yet understood and this process is an active field of research.     

Aβ蛋白分泌酶抑制剂研究进展

Aβ蛋白是淀粉样前体蛋白的代谢产物,它在脑组织中含量的异常增加可能是诱发AD的主要因素.应用分泌酶抑制剂可有效减少Aβ的生成,缓解患者症状.本文综述了其中的β分泌酶抑制剂的研究进展.     

Concentration Effect,Structural Properties,and Driving Force on Aβ28 Dimerization with and without Zn2+ Cooperation: Learning from Replica Exchange Sampling**

Zn²⁺ is a very important factor in promoting the formation of amyloid beta (Aβ) aggregates and amyloid plaques. The Zn²⁺-bound Aβ species generate amorphous or low molecular-weight oligomers. However, it is a lack of studies to approach the starting structural features (dimerization) in Aβ nucleation processes with and without Zn²⁺, which is the key point in understanding Zn²⁺-induced nucleation mechanisms. To better understand the effect of concentration, structural properties, and the driving force, 14 independent replica exchange molecular dynamics simulations were performed in Aβ₂₈ dimerization with and without Zn²⁺ (zAβ₂₈) cooperation. Our scanning results show that the aggregation propensity is easier in Aβ₂₈-Aβ₂₈ and Aβ₂₈-zAβ₂₈ systems than zAβ₂₈-zAβ₂₈ system. In binding property, the Aβ₂₈-Aβ₂₈ model (−61.5 kcal mol⁻¹) is stronger than zAβ₂₈-zAβ₂₈ (−26.6 kcal mol⁻¹) and Aβ₂₈-zAβ₂₈ (−7.24 kcal mol⁻¹) models. Further analysis confirmed that H13 and H14 residues play specific roles in the three systems. The key point is the orientation of N atom of the imidazole ring in histidine residues. Furthermore, we discovered different driving forces for each system. Our current study contributes to the understanding of how the Aβ₂₈ dimer interacts with Zn²⁺, which could lead to new insights into Zn²⁺-induced nucleation mechanisms.