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.     

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。     

贝母组培物提取物的质量标准研究

目的:研究贝母组培物提取物的质量控制方法.方法:采用薄层色谱法,紫外分光光度法进行定性鉴别和定量鉴别,通过测定总灰分、酸不溶灰分对提取物所含杂质的量进行控制,采用热浸法对水溶性浸出物和醇溶性浸出物的含量进行测定.结果:定性鉴别薄层色谱特征明显,专属性强;水溶性浸出物不少于72.69%,醇溶性浸出物不少于75.95%,总灰分的检查限度为不超过11.89%.建立了贝母组培物提取物中西贝母碱的含量测定方法,回归方程为Y=7.7591X+0.0437(R~2=0.9991).平均加样回收率为98.7541%,回收率RSD=1.3067%.结论:定性鉴别和含量测定方法操作简便,重复性好,可有效控制贝母组培物提取物的质量.     

K近邻隶属度的P-PHD滤波多目标状态提取

在P-PHD滤波多目标状态提取中,传统的K-Means聚类方法存在需要提取峰值、聚类时间长、类簇边缘易被侵蚀等问题。针对此问题,在对一般聚类算法的研究的基础上,进一步提出了一种基于K近邻隶属度P-PHD滤波多目标状态提取算法。该算法首先通过量测与粒子的关联性,根据距离来进行量测筛选剔除虚警量测信息,估计真实目标量测类别,然后利用K近邻隶属度将粒子分配给各个估计的真实量测类别,重新分配粒子集,在新粒子集直接提取目标状态信息,从而避免粒子峰值提取过程,降低了算法的时间复杂度。仿真实验表明,所提算法与传统P-PHD滤波以及其它改进聚类算法的P-PHD滤波相比,具有状态提取精度高以及运算时间短的优点。     

基于Linux的S3C6410核心唯一性信息采集终端的研发

针对基层部队配发的各类野战通讯装备在实际应用中效率低、便携性和可靠性较差, 无法适应野外环境下通信保障需求的问题, 设计了基于Linux 平台S3C6410 核心的唯一性信息采集终端。将嵌入式处理器、GPS(Global Positioning System)数据采集模块、图像采集模块、RFID(Ratio Frequency Identification)模块及WiFi(Wireless Fidelity)相结合, 实现了将采集的地理位置信息、身份认证信息以及图像信息整合于一体的唯一性数据信息的显示。通过WiFi 快速连接实时传送数据信息, 并给出了整体方案。经过编程调试证明, 系统运行稳定, 唯一性数据信息传输速度较快, 信息完整可靠, 达到了预期效果。