pH‐Triggered Charge‐Reversal Polyurethane Micelles for Controlled Release of Doxorubicin

A series of pH‐triggered charge‐reversal polyurethane copolymers (PS‐PUs) containing methoxyl‐poly(ethylene glycol) (mPEG), carboxylic acid groups, and piperazine groups is presented in this work. The obtained PS‐PUs copolymers can form into stable micelles at pH 7.4, which response to a narrow pH change (5.5–7.5) and show a tunable pH‐triggered charge‐reversal property. Doxorubicin (DOX) is encapsulated into the PS‐PU micelles as a model drug. The drug release of DOX‐loaded PS‐PU micelles shows an obviously stepped‐up with reducing the pH. Meanwhile, it is found that the charge‐reversal property can improve the cellular uptake behavior and intracellular drug release in both HeLa cells and MCF‐7 cells. Additionally, the time‐dependent cytotoxicity of the DOX‐loaded PS‐PU micelles is confirmed by MTT assay. Attributed to the tunable charge‐reversal property through changing the molar ratio of piperazine/carboxyl, the PS‐PU micelles will be a potential candidate as an intelligent drug delivery system in future studies.

     

多重时滞富营养化生态模型的稳定性与分支分析

本文研究了多重时滞富营养化生态模型的稳定性与分支问题.利用特征值方法,分别研究了具有单时滞和双时滞模型的线性稳定性.发现当模型中的时滞经过一系列临界值时,模型在平衡点附近经历了Hopf分支和Hopf-zero分支,并给出Hopf分支和Hopf-zero分支存在的充分条件.最后数值模拟验证了理论结果.     

Protonation‐Driven Membrane Insertion of a pH‐Low Insertion Peptide

The pH‐low insertion peptide (pHLIP) inserts into membranes and forms a transmembrane (TM) α‐helix in response to slight acidity, and has shown great potential for cancer diagnosis and treatment. As a lead, pHLIP is challenging to optimize because the mechanism of its pH‐dependent membrane interactions is not completely understood. Within pHLIP there are multiple D/E residues which could sense the pH change, the particular role played by each of them in the protonation‐driven insertion process is not clear. The precise location of the TM helix within the pHLIP sequence is also unknown. In this work, solid‐state NMR spectroscopy is used to address these central questions. Tracing backbone conformations revealed that the TM helix spans from A10 to D33 with a break at T19 to P20. Residue‐specific pK_a values of D31, D33, D25, and D14 were determined to be 6.5, 6.3, 6.1, and 5.8, respectively, and define the sequence of protonations which lead to insertion. Furthermore, possible intermediate states which disrupt membranes at pH 6.4 were proposed based on tryptophan fluorescence quenching and NMR data.     

Site‐Selective Disulfide Modification of Proteins: Expanding Diversity beyond the Proteome

The synthetic transformation of polypeptides with molecular accuracy holds great promise for providing functional and structural diversity beyond the proteome. Consequently, the last decade has seen an exponential growth of site‐directed chemistry to install additional features into peptides and proteins even inside living cells. The disulfide rebridging strategy has emerged as a powerful tool for site‐selective modifications since most proteins contain disulfide bonds. In this Review, we present the chemical design, advantages and limitations of the disulfide rebridging reagents, while summarizing their relevance for synthetic customization of functional protein bioconjugates, as well as the resultant impact and advancement for biomedical applications.     

Magnetically and Near‐Infrared Light‐Powered Supramolecular Nanotransporters for the Remote Control of Enzymatic Reactions

Cancer is one of the primary causes of death worldwide. A high‐precision analysis of biomolecular behaviors in cancer cells at the single‐cell level and more effective cancer therapies are urgently required. Here, we describe the development of a magnetically‐ and near infrared light‐triggered optical control method, based on nanorobotics, for the analyses of cellular functions. A new type of nanotransporters, composed of magnetic iron nanoparticles, carbon nanohorns, and liposomes, was synthesized for the spatiotemporal control of cellular functions in cells and mice. Our technology will help to create a new state‐of‐the‐art tool for the comprehensive analysis of “real” biological molecular information at the single‐cell level, and it may also help in the development of innovative cancer therapies.     

Psyllium Arabinoxylan: A Versatile Biomaterial for Potential Medicinal and Pharmaceutical Applications

Psyllium (PS), a water-swellable dietary fiber from seeds of widely distributed plant, Plantago ovata (PO) is esteemed for its medicinal and nutraceutical values. PS has been attributed to its broad range of pharmacological activities like anti-tumor, anti-inflammatory, anti-diabetic, hypolipidemic, laxative, anti-obesity, anti-diarrheal, anti-amoebic, and anti-nociceptive, and has been employed for sustained/delayed/targeted drug delivery due to its biocompatible and biodegradable nature. Interestingly, PS can be utilized for the absorption of toxic materials from industrial waste and is also used as substituent of gluten in breads for better acceptance. This review focuses upon the utilization of PS in drug delivery systems, medicinal uses, and pharmacological attributes to explore its potential in the nutraceutical industry.     

Stability prediction for milling process with multiple delays using an improved semi‐discretization method

Milling chatter leads to a poor surface finish, premature tool wear, and potential damage to the machine or tool. Thus, it is desirable to predict and avoid the onset of this instability. Considering that the stability of milling with variable pitch cutter or tool runout case is characterized by multiple delays, in this paper, an improved semi‐discretization method is proposed to predict the stability lobes for milling processes with multiple delays. Taking the variable pitch milling, for example, a comparisonwith prior methods is conducted to verify the accuracy and efficiency of the proposed approach for the stability prediction both in low and high radial immersion ratios. In addition, the rate of convergence of the proposed method is also evaluated. The results show that the proposed method has high computational efficiency. Copyright © 2015 John Wiley & Sons, Ltd.     

多聚焦极栅控电子模拟源的研究

采用电子光学软件设计模拟了一种长焦距多聚焦级的电子枪结构.利用电子透镜原理分析多聚焦极电子枪的电子束斑产生,依据不同栅控电压,分析零场模式、拒斥场模式和肖特基场模式3种阴极电子发射方式下电子聚焦情况.模拟结果表明:拒斥场模式和肖特基场模式对电子束流密度分别有减弱和增强的作用;当聚焦极电压比U1∶U2∶U3∶U4∶U5=5∶8∶15∶70∶100时,能量为30keV的电子束焦斑最小,在10m处焦斑大小为160mm.     

基于半监督稀疏多流形嵌入的高光谱影像分类

提出了一种半监督稀疏多流形嵌入方法,并应用于高光谱影像分类.该方法充分利用少量标记和大量无标记样本,采用稀疏表示方法得到样本的稀疏系数,并选取来自同一流形的点作为近邻点,然后构建相似图来表征多流形结构,得到样本在每个流形上低维鉴别特征,增加来自同一流形的数据点聚集性,进而提升分类性能.本文方法在PaviaU和Salinas两个高光谱数据集上的总体分类准确度分别达到84.91%和89.74%,相较于其他方法明显提高了地物分类性能.     

基于STAF自动化测试框架的研究与应用

随着软件功能实现技术越来越复杂,软件测试领域迫切需要具有自动化、多平台、开销小的自动化测试框架,STAF的出现很好地解决了这个问题。提出一种基于STAF的自动化测试框架,并进行模拟实践,采用ATT工具设计自动测试引擎,通过模拟实验测试,构建基于STAF的自动化测试框架。测试结果显示：在不同环境下,该框架均具有软件测试自动化程度高、测试效率高,易于管理、维护和可扩展等优点。