Helices on Interdomain Interface Couple Catalysis in the ATPPase Domain with Allostery in Plasmodium falciparum GMP Synthetase

GMP synthetase catalyses the conversion of XMP to GMP through a series of reactions that include hydrolysis of Gln to generate ammonia in the glutamine amidotransferase (GATase) domain, activation of XMP to adenyl-XMP intermediate in the ATP pyrophosphatase (ATPPase) domain and reaction of ammonia with the intermediate to generate GMP. The functioning of GMP synthetases entails bidirectional domain crosstalk, which leads to allosteric activation of the GATase domain, synchronization of catalytic events and tunnelling of ammonia. Herein, we have taken recourse to the analysis of structures of GMP synthetases, site-directed mutagenesis and steady-state and transient kinetics on the Plasmodium falciparum enzyme to decipher the molecular basis of catalysis in the ATPPase domain and domain crosstalk. Our results suggest an arrangement at the interdomain interface, of helices with residues that play roles in ATPPase catalysis as well as domain crosstalk enabling the coupling of ATPPase catalysis with GATase activation. Overall, the study enhances our understanding of GMP synthetases, which are drug targets in many infectious pathogens.     

制药企业在2010版药品GMP实施过程中召回管理现状与常见问题分析

总结制药企业在2010版药品GMP实施过程中召回管理的现状,并分析存在问题,包括对产品召回持消极态度,召回管理方面培训不到位,操作规程缺乏可操作性,有效性评估不足等。建议制药企业必须重视产品召回的管理,严格按照2010版药品GMP的要求积极建立召回系统。     

基于弱监督的改进型GoogLeNet在DR检测中的应用

针对糖尿病视网膜病变分级检测中标定样本少、多目标检测的问题，提出了一种基于改进型GoogLeNet的弱监督目标检测网络。首先，对GoogLeNet网络进行改进，去掉最后一个全连接层并保留检测目标的位置信息，添加全局最大池化层，以sigmoid交叉熵作为训练的目标函数以获得带有多种特征位置信息的特征图；然后，基于弱监督方法仅使用类别标签对网络进行训练；其次，设计一种连通区域算法来计算特征连通区域边界坐标集合；最后在待测图片中使用边界框定位病灶。实验结果表明，在小样本条件下，改进模型准确率达到了94.5%，与SSD算法相比，准确率提高了10%。改进模型实现了小样本条件下端到端的病变识别，同时该模型的高准确率保证了模型在眼底筛查中具有应用价值。     

医药行业新版GMP实行后的节能技术探讨

针对新版GMP关注点，分析目前医药厂房能耗通病并提出解决方案。     

在线悬浮物(MLSS)/浊度分析仪的最新动态观察与探讨

以美国哈希公司研制生产的Txpro-2在线悬浮物(MLSS)/浊度分析仪为例,介绍了目前制药工业废水质量控制和监测方面的最新技术动向,并探讨其应用。     

新版药品GMP中的变更控制

新版药品GMP引入了变更控制这一先进的质量管理体系。作为制药企业如何贯彻法规要求,建立变更控制管理体系是企业面对的主要问题。阐述变更控制的概念、范围和变更的分类,分析变更控制管理流程和管理过程中的难点,期望为药品生产企业的变更控制管理提供参考。     

药品GMP与ISO9000质量管理标准

通过对药品GMP与国际标准化组织制定的ISO9000标准比较。使制药企业在实施GMP过程中自愿地引入ISO9000的思想和办法。在保证达到GMP要求的基础上,进一步吸收ISO9000有关内容形成一个更完整的质量管理体系。     

Antoni Gaudí and Frei Otto: Essential Precursors to the Parametricism Manifesto

As Senior Architect to the Basilica of the Sagrada Família in Barcelona, Mark Burry has been ‘thinking parametrically’ for almost his entire career. Here he describes how his longstanding role overseeing the completion of Antoni Gaudí's masterpiece has afforded unique insights into the work of a great geometer and parametric thinker. Burry places the contribution of Gaudí alongside that of Frei Otto – the other eminent 20th-century Proto-Parametricist.     

Effect of gamma-irradiation on flavour 5′-nucleotides,tyrosine, and phenylalanine in mushrooms (Agaricus bisporus)

The impact of gamma-irradiation on 5′-nucleotides and on the free amino acids tyrosine and phenylalanine in fresh mushrooms was studied. After irradiation the samples were freeze-dried to avoid enzyme induced chemical changes. Three 5′-nucleotides could be detected using HPLC–UV and LC–ESI-MS: adenosine 5′-monophosphate (AMP), guanosine 5′-monophosphate (GMP) and guanosine 5′-diphosphate (GDP). Irradiation significantly reduced (p = 0.05) the GDP concentration (22%). AMP showed a marked reduction (46%) only at 5 kGy. GMP, tyrosine, and phenylalanine were not affected by gamma-irradiation.     

通用管理模型在高校实验过程管理中的应用

运用过程方法、PDCA原理等通用的管理模型建立一套行之有效的实验过程管理规范和管理制度。从实验过程操作规范方面着手引进了GMP（良好操作规范）管理模型及理念,对实验过程进行管理分析,从而建立一套实验过程管理程序,可使实验过程管理更加系统化、规范化、科学化、实用化。