Scalable manufacturing methodologies for improving adeno-associated virus-based pharmaprojects

Adeno-associated virus （AAV） is a promising viral vector and meets most requirements of being a safe biological agent. However, the commercialization of AAV has been hampered due to the limitation of large-scale production, and only a small number of clinical trials have been launched. In recent years, progresses in scalable manufacturing of AAV have dramatically improved AAV- based clinical researches, and have assisted the develop- ment of investigational drug products. An AAVl-based investigational product, Glybera, has been formally approved by European Commission for the treatment of lipoprotein lipase deficiency （LPLD）. Glybera was the first gene therapy product in the western world, and the pro- duction process involves a scalable baculovirus-insect cell system. However, many problems still need to be solved to improve the productivity and quality of AAV. The present review gives critical insights into current state-of-the-art scalable producing methodologies of AAV, such as bacu-lovirus-insect cell system, HSV complementation system, and Ad complementation system, along with a discussion on the problems, solutions, and developmental trends.Novel AAV-producing platforms in Saccharomyces cere- visiae and vaccinia virus complementation system will also be discussed.     

级数逼近法求解一类R-L分数阶积分方程

采用泰勒级数将分数阶积分方程转化为线性方程组,利用Cramer法则求得原方程的数值解.并以数值算例验证了该算法的有效性.     

大黄鱼消化系统的组织学和组织化学研究

为探讨大黄鱼消化系统的结构与功能,用组织学和组织化学方法对各主要消化器官进行了研究.胃前段粘膜上皮由柱状细胞和粘液细胞组成;胃中后段粘膜上皮仅有柱状细胞,固有层含有发达的胃腺,胃腺上皮由Ⅰ型和Ⅱ型细胞构成.幽门盲囊与肠粘膜形成发达的皱襞和绒毛,粘膜上皮由柱状细胞和粘液细胞组成.胰腺为弥散性腺体.胃中后段粘膜柱状细胞呈现脂酶和非特异性酯酶活性;胃前段粘膜粘液细胞及胃腺Ⅰ型细胞分泌中性和酸性混合粘液,胃腺Ⅱ型细胞呈现强蛋白酶活性.幽门盲囊与肠粘膜粘液细胞分泌酸性粘液,柱状细胞呈现蛋白酶、脂酶和非特异性酯酶活性,其游离端质膜和胞质还分别具有碱性磷酸酶和酸性磷酸酶活性.肝细胞和胰腺细胞呈现非特异性酯酶和弱蛋白酶活性,肝细胞还贮存糖原.     

面向高光谱影像分类的改进局部切空间排列降维

提出多策略提升的局部切空间排列算法来解决常规局部切空间排列降维在高光谱影像分类中计算复杂度高的问题.通过引入随机映射来预先减少高光谱影像波段数,降低后续k-邻域和局部切空间构建的计算复杂度;采用递归兰索斯切分算法快速构建近似k-邻域,降低常规k-邻域构建的计算时间;采用快速近似奇异值分解算法提高全局排列矩阵的本征分解计算速度.利用两个不同的高光谱数据集,设计4组实验来分析多策略速度提升的局部切空间排列算法的计算性能和分类效果.实验证明,相比常规局部切空间排列方法,多策略提升的局部切空间排列方法损失约1%左右的总体分类精度却能够提高至少3倍的计算速度.     

糯米酒发酵工艺优化

以优质糯米为原料对糯米酒发酵工艺参数进行优化,比较了3种酒曲的发酵性能,通过正交试验优化糯米酒生产工艺.结果表明,甜酒曲为最佳发酵酒曲,糯米酒生产的最佳工艺为糯米蒸煮15 min,酒曲量0.5%,发酵时间为48 h,料水比为10∶3（g∶m L）,在30℃下恒温发酵生产的糯米酒口感适宜,香气浓郁.     

Properties and Morphology of TiN Films Deposited by Atomic Layer Deposition

In this study,TiN films were deposited on SiO2 substrates by Atomic Layer Deposition(ALD) using TiCl4and NH3 as precursors. Properties and morphology of the TiN films were characterized by different methods.Using Grazing Incidence X-Ray Diffraction(GIXRD),TiN films demonstrated polycrystalline structure with(111)preferred orientation. Film thickness was measured by Spectroscopic Ellipsometry(SE) and a stable growth rate of 0.0178 nm/cycle was reached after 500 deposition cycles,which was consistent with the essence of ALD as a surface-saturated self-limiting reaction. Film resistivity measured by a four-point probe continuously decreased with increasing deposition cycles until it reached the minimum value of 300μΩ cm at 5000 deposition cycles with a thickness of 87.04 nm. The surface roughness and morphology of the TiN films at different deposition cycles ranging from 50 to 400 were analyzed by Atomic Force Microscopy(AFM). The AFM results indicated that the initial film growth follows the Stranski-Krastanov mode.     

地方高校中外合作办学本科项目教学机制研究——以湖北工程学院为例

在我国高等教育体系中,中外合作办学有了较快的发展,一些地方高校都进行了中外合作办学的实践。以湖北工程学院为例,地方高校中外合作办学本科项目的现状及问题是:地方高校中外合作办学有重视外语教学和利用外方教学资源与教学理念的优势,存在着语言课程与专业课程融合不够,中外双方缺乏深度合作等问题。地方高校应当在中外合作办学本科项目的人才培养机制、教学管理机制、资源配置机制、教学质量保障机制等方面加以改进,以最大限度地发挥中外合作教育的独特功效。     

多同性源激发极化法超前预报仪的设计与实验

多同性源激发极化法的出现与应用,是激发极化法在方法的上的突破,但与之相适应的预报仪器是制约该方法的瓶颈。通过基于MSP430逆变、整流以及逆变整流控制模块实现4路可控输出,采用FPGA实现对电压、电流的4路同步采集与信号传输,设计量程自动切换模块与软硬件相结合的信号去噪方法,实现多同性源激发极化超前地质预报仪的设计;对设计预报仪的信号采集精度与运行稳定性进行室内定性与定量实验。结果表明,该仪器能够达到工程探测的准确性、实用性与可行性要求。     

被动式太阳能结合相变墙在苏北自然通风环境下的应用研究

通过建立实体的模型房间,选择寒冷的冬季和炎热的夏季两种环境,对被动式太阳能建筑结合相变墙体的综合应用状态进行了模拟研究,获得了太阳能集热墙、相变墙体等结构的表面温度及室内温度参数,利用动态热网络分析法,建立综合考虑建筑内部舒适度的4种运行工况,通过对比分析的方法,验证了由被动式太阳能建筑结合相变墙体的实验房具有冬暖夏凉的功能。在炎热的夏季,相变墙发挥了蓄冷作用,同时太阳能集热墙的被动通风,使得实验房内白天温度较普通房有所下降;在寒冷的冬季,白天太阳能集热墙的吸热与相变材料的蓄热,使得实验房内夜晚温度较普通房有所上升,从而实现实验房冬暖夏凉的功能。     

矩形盾构管片拼装机同步控制系统的设计

针对矩形盾构管片拼装机拼装拱顶块和拱底块时需要同步控制两台机械手的问题,设计了基于CAN(Controller Area Network)总线的同步控制系统并采用同步PID(Proportion Integral Derivative)算法实现对同步误差的控制.对同步控制系统的工作原理以及系统的网络架构做了分析.建立了矩形盾构管片拼装机两台机械手沿径向的立柱同步升降和沿轴向的同步拼装头移动同步控制系统的仿真模型,并对这两个动作的同步PID控制性能进行仿真分析.通过矩形盾构管片同步立柱升降和同步拼装头移动的实验对同步控制性能进行验证,结果表明,同步PID算法可减小同步误差并将立柱升降同步误差控制在±3 mm之间,拼装头移动同步误差控制在不超过±1 mm,显示了同步PID控制在矩形盾构管片拼装过程中的有效性与可实现性.