A Novel Docetaxel-Biotin Chemical Conjugate for Prostate Cancer Treatment

A novel conjugate of docetaxel and biotin (designated as IDD-1010) was designed and chemically synthesized via an ester linkage at position 2’ carbon in docetaxel. The synthesized pure IDD-1010 exhibits a potent anti-cancer activity in in vitro and in vivo studies. At 10 nM, IDD-1010 has induced increased apoptosis and mitotic arrest of PC3-Luc prostate cancer cells, causing aneuploidy and cell death at higher concentrations. Toxicology studies indicate that the maximal tolerated dose (MTD) of IDD-1010 is 150 mg/kg in mice; equivalent to about 12.2 mg/kg of body weight, or to about an 850 mg dose for a patient weighing 70 kg. The MTD-treated mice exhibited weight gain similar to that of the control group, with no gross pathological signs at 14 days post-dosing. At a lower dose, IDD-1010 treatment did not lead to any significant weight loss in mice, although decreased the tumor volume stemming from injecting cancer cells into the dorsal loop of mouse prostate, and it was found to be more potent than Paclitaxel (reference drug). Similarly, IDD-1010 treatment significantly reduced tumor weight and thereby increased the percentage of mice survival as compared to reference drug-treated and control groups. To summarize, the described experiments using IDD-1010, as compared to the reference drug, strongly suggest a potential treatment utility with a wider therapeutic window for prostate cancer. Henceforth, clinical research on such a novel drug candidate would be greatly worthwhile.     

Meshless acoustic analysis using a weakly singular Burton-Miller boundary integral formulation

The Burton-Miller boundary integral formulation is solved by a complex variable boundary element-free method (CVBEFM) for the boundary-only meshless analysis of acoustic problems with arbitrary wavenumbers. To regularize both strongly singular and hypersingular integrals and to avoid the computation of the solid angle and its normal derivative, a weakly singular Burton-Miller formulation is derived by considering the normal derivative of the solid angle and adopting the singularity subtraction procedures. To facilitate the implementation of the CVBEFM and the approximation of gradients of the boundary variables, a stabilized complex variable moving least-square approximation is selected in the meshless discretization procedure. The results show the accuracy and efficiency of the present CVBEFM and reveal that the method can produce satisfactory results for all wavenumbers, even for extremely large wavenumbers such as k = 10 000.     

水下对转螺旋桨流致辐射噪声机理与预报方法*

水下对转螺旋桨流致辐射噪声的预报对于水下目标的特征提取和分类识别具有重要意义。由桨叶的旋转引起的湍流场是水下对转螺旋桨流致辐射噪声的源场。分述了水下对转螺旋桨湍流边界层脉动、旋转干涉效应和空化效应引发的水动力噪声机制和研究进展,比较了目前工程应用中的3种对转螺旋桨流致辐射噪声预报方法的特点。在分析对转螺旋桨流致辐射噪声数值预报难点的基础上,综述了对转螺旋桨流致辐射噪声计算方法的研究进展,指出间接数值模拟方法是工程中进行对转螺旋桨流致辐射噪声预报的有效方法。     

浅谈黄原胶及其在农药制剂加工中的应用

黄原胶是极具发展潜力的生物多糖,独特的分子结构使其具有良好的增稠、乳化和稳定作用,已被广泛应用于日用化工、石油开采、纺织印染、食品、医药、涂料、农药等众多工业领域,拥有广阔的市场前景。本文对黄原胶的结构、特性、生产工艺以及主要应用领域等进行了简单综述,总结了黄原胶在农药制剂加工中的应用现状,指出黄原胶优越的流变特性对悬浮剂、水乳剂、悬乳剂等农药制剂悬浮稳定性的提高具有重大意义,最后展望了黄原胶未来的发展前景。     

Development of a competitive ELISA for the quantification of F5 conjugate in HER2-targeted STEALTH immunoliposome doxorubicin in plasma samples

HER2 (human epidermal growth factor receptor 2, erbB2, or neu) is overexpressed by a large number of tumor types and has been identified as an important target for cancer therapy. F5 is a single-chain human antibody fragment that recognizes HER2 receptor and is covalently conjugated to PEGylated lipid to form F5 conjugate (F5CG) in the product HER2 targeted STEALTH immunoliposome doxorubicin. Here we described the method development of a competitive enzyme-linked immunosorbent assay (ELISA) for the determination of total concentration of F5 conjugate in plasma samples. The method involved the biotinylation of F5CG, detergent treatment of plasma sample to solubilize F5CG into monomeric form, and competitive ELISA for solubilized F5CG competitively binding to anti-F5CG antibody with biotinylated F5CG for the determination of total F5CG in plasma. The detection range of this method was from 0.2 ng/mL to 125 ng/mL for F5CG in plasma. The lower limit of quantification (LLOQ) was 0.2 ng/mL. This method was established and used for the measurement of F5CG concentration to provide information about F5CG circulation after the administration of immunoliposome in preclinical studies.      

Electrochemical Behaviour and Rapid Determination of L‐Dopa at Electrochemically Pretreated Screen Printed Carbon Electrode

A simple and rapid voltammetric method based on a disposable electrochemically pretreated screen‐printed carbon electrode is proposed for the determination of L ‐dopa. Under optimum differential pulse voltammetry conditions a limit of detection of 3.6×10^?7 M for L ‐dopa was obtained. The method was successfully applied to the determination of L ‐dopa in a commercial pharmaceutical formulation.     

新型Poisson括号意义下的无穷维Lie代数

本文首先针对ＫｄＶ方程的Ｈａｍｉｌｔｏｎ形式，建立一种比较容易验证的新型Ｐｏｉｓｓｏｎ括号和无穷维Ｌｉｅ代数．其次，研究ＫｄＶ方程的Ｈａｍｉｌｔｏｎ形式的第一积分与新型Ｐｏｉｓｏｎ括号的关系，得到判定第一积分的充分必要条件．最后，构造ＫｄＶ方程的第一积分．     

弹塑性摩擦接触问题形状设计灵敏度分析

提出了一种计算二维有限变形弹塑性摩擦接触问题形状设计灵敏度的算法. 采用主动集策略和mortar方法处理接触边线上的约束条件. 在mortar接触边线的切线和法线方向上采用相同的名义罚函数,提出基于名义罚函数的移动摩擦锥算法来正则化接触约束条件,发展了一种新的二维多体有限变形摩擦接触算法. 在此基础上, 通过将离散形式的摩擦接触问题控制方程对形状设计变量微分,得到了该路径相关问题的直接微分法解析设计灵敏度计算格式, 其节点位移灵敏度方程在每个增量步不用迭代、直接求解. 与国际上现有的二维多体有限变形摩擦接触问题的解析设计灵敏度算法相比,本算法不需分解为法向和切向推导,表达式较简洁,便于编程实现. 数值算例验证了算法的精度和有效性.      

非饱和土壤水流问题基于POD 方法的降阶有限体积元格式及外推算法实现

利用特征投影分解(proper orthogonal decomposition, 简记为POD) 方法对非饱和土壤水流问题的经典有限体积元格式做降阶处理, 建立一种具有足够高精度维数较低的降阶有限体积元格式, 并给出这种降阶有限体积元解的误差估计和外推算法的实现, 最后用数值例子说明数值结果与理论结果是相吻合的. 进一步表明了基于POD 方法的降阶有限体积元格式对求解非饱和土壤水流问题数值解是可靠和有效的.     

健脾八珍颗粒的研制

为筛选出最佳的健脾八珍颗粒处方,以其成型性、溶解性为筛选指标,筛选出处方中加入辅料的品种及配比。结果表明,健脾八珍颗粒的原粉中加入2倍量的糊精和25%的蔗糖,并以2%的CMC-Na作为助悬剂、15%的自制变性淀粉胶(SWJ)为黏合剂为最佳处方。所得产品溶解性、成型性能均较好。