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

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Chinese Science Bulletin 2014年第16期59卷 1845-1855页

作者： Zenghui Xu Chuanyin Shi qijun Qian Laboratory of Viral and Gene Therapy Eastern Hepatobiliary Surgery HospitalThe Second Military Medical University Department of Biotherapy Eastern Hepatobiliary Surgery HospitalThe Second Military Medical University Xinyuan Institute of Medicine and Biotechnology College of Life ScienceZhejiang Sci-Tech University

Adeno-associated virus(AAV)is a promising viral vector and meets most requirements of being a safe biological ***,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 *** recent years,progresses in scalable manufacturing of AAV have dramatically improved AAVbased clinical researches,and have assisted the development of investigational drug *** AAV1-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 production process involves a scalable baculovirus-insect cell ***,many problems still need to be solved to improve the productivity and quality of *** present review gives critical insights into current state-of-the-art scalable producing methodologies of AAV,such as baculovirus-insect cell system,HSV complementation system,and Ad complementation system,along with a discussion on the problems,solutions,and developmental *** AAV-producing platforms in Saccharomyces cerevisiae and vaccinia virus complementation system will also be discussed.

关键词：腺相关病毒制造方法基础可伸缩临床试验基因治疗昆虫细胞大规模生产

川中地区大安寨段页岩热演化史及油气地质意义

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新疆石油地质 2024年第3期45卷 262-270页

作者：蒋奇君李勇肖正录路俊刚秦春雨张少敏西南石油大学地球科学与技术学院成都610500 西南石油大学天然气地质四川省重点实验室成都610500 中国石油西南油气田分公司勘探开发研究院成都610051

下侏罗统自流井组大安寨段为四川盆地陆相页岩油开发的最有利层段,页岩油勘探潜力巨大,然而对该地层的热演化史缺乏系统研究。利用含油气盆地模拟系统,对比分析了川中地区北部与中部大安寨段页岩热演化及生烃差异,并探讨其对页岩油富集... 详细信息

下侏罗统自流井组大安寨段为四川盆地陆相页岩油开发的最有利层段,页岩油勘探潜力巨大,然而对该地层的热演化史缺乏系统研究。利用含油气盆地模拟系统,对比分析了川中地区北部与中部大安寨段页岩热演化及生烃差异,并探讨其对页岩油富集的影响。研究区大安寨段页岩现今热演化程度由西南向东北逐渐增高,平面上可分为高成熟区和成熟区。高成熟区位于研究区北部,镜质体反射率为1.3%~1.7%,主要发育Ⅲ型有机质,在晚侏罗世早期进入早期生油阶段,晚侏罗世末达到生烃高峰,存在2.生烃作用;成熟区位于研究区中—南部,镜质体反射率为0.9%~1.3%,主要发育Ⅱ1型—Ⅱ2.有机质,侏罗系沉积厚度相对较小,有机质成熟时期较晚,晚侏罗世末进入早期生油阶段,早白垩世进入生烃高峰,仅有1期生烃过程。相较于北部地区,中部地区沉积了大套的富有机质页岩,是大安寨段页岩油坚实的物质基础,但古近纪以来的构造抬升与地层剥蚀,对该区的油气保存具有一定的破坏作用。

关键词：四川盆地下侏罗统自流井组大安寨段热演化史生烃能力保存条件页岩油气

基于能量-相角的无线电能传输系统建模与验证

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武汉大学学报（工学版） 2024年第1期57卷 96-103页

作者：董帅良邓其军刘曾洋陈晶朱傲刘志勇武汉大学电气与自动化学院湖北武汉430072

为了解决无线电能传输系统中电流和电压的变化频率较快且不能直接反映负载上的电压有效值的问题,采用基于能量-相角的建模法为全桥逆变器的无线电能传输系统建模,同时避免了相较于d-q分解法系统阶数较高的情况。首先分析了由全桥逆变器... 详细信息

为了解决无线电能传输系统中电流和电压的变化频率较快且不能直接反映负载上的电压有效值的问题,采用基于能量-相角的建模法为全桥逆变器的无线电能传输系统建模,同时避免了相较于d-q分解法系统阶数较高的情况。首先分析了由全桥逆变器驱动的无线电能传输系统的等效电路模型,然后将能量和相角作为变量对等效电路模型进行小信号建模,接着将小信号模型在工作点附近线性化,得到系统的线性模型及其传递函数,最后开发全桥逆变器原型机并应用于无线电能传输系统。实验结果与小信号建模得到的幅相特性曲线在中低频段基本一致,在1 000 rad/s及以下频率情况下的吻合度达到90%,验证了建模方法和模型的准确性。

关键词：无线电能传输能量-相角建模法相移控制

Molecular Structure and Electronic Spectra of CoS under the Radiation Fields

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Computers, Materials & Continua 2018年第6期55卷 393-403页

作者： qijun Wu Limin Han Lingxuan Wang Xun Gong School of Chemical Engineering Guizhou Institute of TechnologyGuiyang550003P.R.China Department of Physics and State Key Laboratory of Low-Dimensional Quantum Physics Tsinghua UniversityBeijing100084P.R.China School of Food and Pharmaceutical Engineering Guizhou Institute of TechnologyGuiyang550003P.R.China

We optimized the ground-state stable configuration of CoS molecule in different external radiation fields(0-0.04 atomic units(a.u.))at the basis set level of 6-311G++(d,p)using the B3LYP density functional *** this basis,the molecular structure,total energy,energy gap,and the intensities of infrared ray(IR)spectra,Raman spectra,and ultraviolet-visible(UV-Vis)absorption spectra of CoS molecule were computed using the same *** results showed that the molecular structure changed greatly under the effect of the external radiation fields and had significant dependency on the radiation *** total energy of CoS molecule grew slightly at first and then significantly decreased in a monotonous *** bond length,dipole moment,and energy gap of the molecule all reduced at first and then increased,with the turning point all at F=0.02. *** the radiation *** absorption peak of IR spectra and Raman optical activity both had maximums at F=0.03 *** significant red *** the external radiation field of F=0.030 a.u.,the absorption wavelength of the UV-Vis absorption spectra showed large blue shift,and a strong absorption peak was observed.

关键词： CoS density functional theory molecular structure radiation field spectra

One-step synthesis of fluorescent smart thermo- responsive copper clusters： A potential nanothermometer in living cells

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Nano Research 2015年第6期8卷 1975-1986页

作者： Chan Wang Lin Ling Yagang Yao qijun Song Key Laboratory of Food Colloids and Biotechnology Ministry of Education School of Chemical & Material Engineering Jiangnan University Wuxi 214122 China Suzhou Institute of Nano-Tech and Nano-Bionics Chinese Academy of Sciences Suzhou 215123 China State Key Laboratory of Materials-Oriented Chemical Engineering College of Chemistry and Chemical Engineering Nanjing Tech University Nanjing 210009 China

Temperature measurement in biology and medical diagnostics, along with sensitive temperature probing in living cells, is of great importance; however, it still faces significant challenges. Metal nanoclusters （NCs） with attractive luminescent properties may be promising candidates to overcome such challenges. Here, a novel one-step synthetic method is presented to prepare highly fluorescent copper NCs （CuNCs） in ambient conditions by using glutathione （GSH） as both the reducing agent and the protective layer preventing the aggregation of the as-formed NCs. The resultant CuNCs, with an average diameter of 2.3 nm, contain 1-3 atoms and exhibit red fluorescence （A^m = 610 nm） with high quantum yields （QYs, up to 5.0%）. Interestingly, the fluorescence signal of the CuNCs is reversibly responsive to the environmental temperature in the range of 15-80 ℃. Furthermore, as the CuNCs exhibit good biocompatibility, they can pervade the MC3T3-E1 cells and enable measurements over the physiological temperature range of 15-45 ℃ with the use of the confocal fluorescence imaging method. In view of the facile synthesis method and attractive fluorescence properties, the as-prepared CuNCs may be used as photoluminescence thermometers and biosensors.

关键词： fluorescence copper nanoclusters cellular imaging nanothermometer

Stealth performance evaluation of helicopter against airborne early warning radar considering trimming control

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Chinese Journal of Aeronautics 2023年第11期36卷 204-220页

作者： Zhongyang FEI Xiangwen JIANG qijun ZHAO Zhuangzhuang CUI Yan YANG National Key Laboratory of Rotorcraft Aeromechanics College of Aerospace EngineeringNanjing University of Aeronautics and AstronauticsNanjing 210016China

Airborne pulse Doppler radar is a key threat to the military helicopter,and assessing the stealth performance of helicopter against airborne early warning radar is helpful to the helicopter’s stealth design and operational *** this paper,the Shooting and Bouncing Ray(SBR)and Uniform Theory of Diffraction(UTD)based high-frequency algorithms are used to calculate the Radar Cross Section(RCS)of helicopter,and the radar range equations are used to evaluate the stealth *** order to account for the effects of rotor flapping motions during actual flight,the aerodynamics model of whole helicopter is established and the attitudes and controls of helicopter at different flight states are trimmed and input into the RCS calculation *** effects of helicopter flight speed,flying direction and operational environment on radar stealth performance are studied in *** is demonstrated by the results that the trimming control does have a great influence of more than 5 dB on the RCS of helicopter,and the introduction of the trim calculation brings the helicopter’s returns calculation closer to the *** in flight speed lead to the changes in the stealth performance of helicopter against Early Warning Aircraft(EWA),and the helicopter flight speed can be planned according to the operational requirements to minimize exposure distance or exposure *** in flying direction mainly affect the detection properties of helicopter returns,and flying in the same direction with EWA usually gives the helicopter better low-observability than flying *** in operational environment mainly affect the radar detection performance and the sensitivity of the detection performance to external factors;the same amount of change in some external factor causes a different amount of change in the helicopter’s detectability in different environments.

关键词： Helicopters Trimming Airborne early warning radar Stealth performance High-frequency algorithm Radar range equation

^(18)F-FDG PET在颞叶外癫痫术前评估中的作用

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中华核医学与分子影像杂志 2024年第4期44卷 207-212页

作者：郭瑞杰李奇骏金丽日窦万臣崔瑞雪中国医学科学院、北京协和医学院北京协和医院核医学科、疑难重症及罕见病全国重点实验室、中国医学科学院罕见病研究中心、核医学分子靶向诊疗北京市重点实验室北京100730 中国医学科学院、北京协和医学院北京协和医院神经内科北京100730 中国医学科学院、北京协和医学院北京协和医院神经外科北京100730

目的分析^(18)F-FDG PET在颞叶外癫痫(ETLE)患者术前评估中的应用价值,并探讨提高其定位准确性的改进方法。方法纳入2.06年1月至2.2.年11月间于北京协和医院行手术治疗、最终证实致痫灶位于颞叶外的41例患者[男2.例、女16例,年龄(2..7±... 详细信息

目的分析^(18)F-FDG PET在颞叶外癫痫(ETLE)患者术前评估中的应用价值,并探讨提高其定位准确性的改进方法。方法纳入2.06年1月至2.2.年11月间于北京协和医院行手术治疗、最终证实致痫灶位于颞叶外的41例患者[男2.例、女16例,年龄(2..7±7.5)岁],采用视觉及半定量方法回顾性分析其术前独立^(18)F-FDG PET显像,以及^(18)F-FDG PET与MRI联合应用对致痫灶检出的准确性,及对治疗决策的影响。采用Fisher确切概率法分析数据。结果41例患者中,独立^(18)F-FDG PET视觉分析发现40例颞叶外脑部代谢异常,其中2.例为单一部位的局灶性代谢异常,定位为致痫灶;14例为多灶性代谢异常,其中8例经半定量分析进一步明确致痫灶。有1例PET视觉分析阴性的患者发现其MRI异常信号部位存在微小代谢增高灶。在13例独立MRI阅片结果为阴性的患者中,9例在^(18)F-FDG PET所示代谢减低脑区发现存在微小结构异常。^(18)F-FDG PET帮助18例(43.9%,18/41)患者改善临床决策。73.2.(30/41)的患者术后无癫痫发作,其中局灶性与多灶性^(18)F-FDG PET代谢异常患者间预后无明显差异[73.1%(19/2.)和10/14,P=1.000]。结论^(18)F-FDG PET对于ETLE患者是一种有用的术前评估工具。半定量分析有助于在多灶性代谢异常中检出致痫灶。^(18)F-FDG PET和MRI联合评估可提高颞叶外致痫灶定位的准确性。

关键词：癫痫正电子发射断层显像术氟脱氧葡萄糖F18 磁共振成像脑电描记术

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圆形截面凝汽器布管设计及换热性能分析

山东电力技术 2024年第5期51卷 56-62页

作者：秦启君周旭陈令章清洁燃烧与烟气净化四川省重点实验室四川成都611731 东方电气集团东方锅炉股份有限公司四川自贡643001

凝汽器是蒸汽动力系统重要的设备之一,其换热性能直接影响整个系统的运行效率。多领域对更高效凝汽器的需求不断涌现,针对凝汽器的结构设计迭代与换热性能优化的研究具有重要意义。文中在FLUENT计算平台中,基于多孔介质模型通过自定义... 详细信息

凝汽器是蒸汽动力系统重要的设备之一,其换热性能直接影响整个系统的运行效率。多领域对更高效凝汽器的需求不断涌现,针对凝汽器的结构设计迭代与换热性能优化的研究具有重要意义。文中在FLUENT计算平台中,基于多孔介质模型通过自定义函数嵌入管间换热模型、质量汇与阻力模型,分析了一种圆形截面凝汽器布管方式的换热性能。结果表明,相比于管内冷却水工况的变化,蒸汽流速变化引起的管外热阻变化更大程度地影响平均换热系数。依据实际运行工况参数范围,入口蒸汽流速为30~70 m/s,冷却水流速为0.72.2.15 m/s,冷却水温度为2.~2.℃,平均换热系数最大可达3562.W(/m^(2.·K),同时压降范围为2.1~52. kPa。该结构设计表现出较好的换热性能和较低的压力损失,但局部不凝结气体的积聚表明该结构仍有进一步改进的空间。

关键词：凝汽器管束布置数值模拟多孔介质

基于多特征融合结合深度学习模型的药材切片鉴别

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世界科学技术-中医药现代化 2024年第1期26卷 211-217页

作者：周丽媛高红梅赵启军高定国西藏大学信息科学技术学院拉萨850000 藏文信息技术创新人才培养示范基地拉萨850000 四川大学计算机学院成都610065

目的针对现有复杂背景药材切片自动鉴别准确率较低的问题,实现复杂背景下药材切片图像的准确识别。方法基于整理的藏药材切片图像数据集进行实验,分析切片的RGB、HOG、LBP特征,使用改进的HOG算法进行多特征融合,最后使深度学习网络对任... 详细信息

目的针对现有复杂背景药材切片自动鉴别准确率较低的问题,实现复杂背景下药材切片图像的准确识别。方法基于整理的藏药材切片图像数据集进行实验,分析切片的RGB、HOG、LBP特征,使用改进的HOG算法进行多特征融合,最后使深度学习网络对任务图像进行识别。结果本文提出的多特征融合结合深度学习方法对32.复杂背景下藏药材切片的3610张图像识别准确率达到91.68%,同时该方法对川贝母、山楂及半夏等2.种常见中药饮片的平均鉴别准确率达到98.00%,优于其他现有的复杂背景下的中药饮片识别方法,说明该方法对其他中药材鉴定也同样具有可行性,应用范围较广泛。结论多特征融合能够较好地提取复杂背景下药材切片的区分特征,对于背景复杂且堆积遮挡严重的藏药材切片识别率较高,可有效应用于自然场景下的中药材、藏药材切片与其他中药饮片识别,具有较好的应用前景。

关键词：特征融合深度学习藏药材图像识别药材切片注意力机制