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Real time monitoring of bioreactor mAb IgG3 cell culture process dynamics via Fourier transform infrared spectroscopy： Implications for enabling cell culture process analytical technology

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Frontiers of Chemical Science and Engineering 2015年第3期9卷 386-406页

作者： Huiquan Wu Erik Read maury white Brittany Chavez Kurt Brorson Cyrus Agarabi Mansoor Khan Division of Product Quality Research (DPQR HFD-940) Office of Testing and Research (OTR) Office of Pharmaceutical Quality (OPQ) Center for Drug Evaluation and Research (CDER) US Food and Drug Administration (FDA) Federal Research Center at White Oak 10903 New Hampshire Ave Silver Spring MD 20993 USA Process Assessment Branch II Division of Process Assessment 1 (DPA 1) Office of Process and Facilities (OPF) Office of Pharmaceutical Quality (OPQ) Center for Drug Evaluation and Research (CDER) US Food and Drug Administration (FDA) Federal Research Center at White Oak 10903 New Hampshire Ave Silver Spring MD 20993 USA Division of Biotechnology Review and Research II (DBRRII) Office of Biotechnology Products (OBP) Office of Pharmaceutical Quality (OPQ) Center for' Drug Evaluation and Research (CDER) US Food and Drug Administration (FDA) Federal Research Center at White Oak 10903 New Hampshire Ave Silver Spring MD 20993 USA

Compared to small molecule process analytical technology （PAT） applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufac- turing biotechnology drug products. However, the use of inline Fourier transform infrared （FTIR） spectroscopic techniques for bioreactor cell culture process monitoring has not been reported. In this work, real time inline FTIR Spectroscopy was applied to a lab scale bioreactor mAb IgG3 cell culture fluid biomolecular dynamic model. The technical feasibility of using FTIR Spectroscopy for real time tracking and monitoring four key cell culture metabolites （including glucose, glutamine, lactate, and ammonia） and protein yield at increasing levels of complexity （simple binary system, fully formulated media, actual bioreactor cell culture process） was evaluated via a stepwise approach. The FTIR fingerprints of the key metabolites were identified. The multivariate partial least squares （PLS） calibration models were established to correlate the process FTIR spectra with the concentrations of key metabolites and protein yield of in-process samples, either individually for each metabolite and protein or globally for all four metabolites simultaneously. Applying the 2＇ld derivative pre-processing algorithm to the FTIR spectra helps to reduce the number of PLS latent variables needed significantly and thus simplify the interpretation of the PLS models. The validated PLS models show promise in predicting the concentration profiles of glucose, glutamine, lactate, and ammonia and protein yield over the course of the bioreactor cell culture process. Therefore, this work demonstrated the t

关键词： process analytical technology (PAT) Fouriertransform infrared (FTIR) spectroscopy partial least squares (PLS) regression mouse IgG3 bioreactor cell culture process real time process monitoring

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Redox Regulation of Glycogen Biosynthesis in the Cyanobacterium Synechocystis sp. PCC 6803： Analysis of the AGP and Glycogen Synthases

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Molecular Plant 2014年第1期7卷 87-100页

作者： Sandra Diaz-Troya Luis Lopez-maury Ana Maria Sanchez-Riego Miguel Roldan Francisco J. Florencio Instituto de Bioquimica Vegetal y Fotosintesis Universidad de Sevilla-CSIC Americo Vespucio 49 E-41092 Sevilla Spain

Glycogen constitutes the major carbon storage source in cyanobacteria, as starch in algae and higher plants. Glycogen and starch synthesis is linked to active photosynthesis and both of them are degraded to glucose in the dark to maintain cell metabolism. Control of glycogen biosynthesis in cyanobacteria could be mediated by the regulation of the enzymes involved in this process, ADP-glucose pyrophosphorylase （AGP） and glycogen synthase, which were identified as putative thioredoxin targets. We have analyzed whether both enzymes were subjected to redox modification using purified recombinant enzymes or cell extracts in the model cyanobacterium Synechocystis sp. PCC 6803. Our results indicate that both AGP and glycogen synthases are sensitive to copper oxidation. However, only AGP exhibits a decrease in its enzymatic activity, which is recovered after reduction by DTT or reduced thioredoxin （TrxA）, suggesting a redox control of AGP. In order to elucidate the role in redox control of the cysteine residues present on the AGP sequence （C45, C185, C320, and C337）, they were replaced with serine. All AGP mutant proteins remained active when expressed in Synechocystis, although they showed different electrophoretic mobility profiles after copper oxidation, reflecting a complex pattern of cysteines interaction.

关键词： cyanobacteria glycogen Synechocystis thioredoxin redox regulation.

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Cell-matrix reciprocity in 3D culture models with nonlinear elasticity

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Bioactive Materials 2022年第3期7卷 316-331页

作者： Kaizheng Liu maury Wiendels Hongbo Yuan Changshun Ruan Paul H.J.Kouwer Research Center for Human Tissue and Organs Degeneration Institute of Biomedicine and BiotechnologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055PR China Radboud University Institute for Molecules and MaterialsHeyendaalseweg 1356525 AJNijmegenthe Netherlands Institute of Biophysics Hebei University of TechnologyTianjin300401PR China Molecular Imaging and Photonics Chemistry DepartmentKU LeuvenCelestijnenlaan 200F3001HeverleeBelgium

Three-dimensional(3D)matrix models using hydrogels are powerful tools to understand and predict cell *** interactions between the cell and its matrix,however is highly complex:the matrix has a profound effect on basic cell functions but simultaneously,cells are able to actively manipulate the matrix ***(mechano)reciprocity between cells and the extracellular matrix(ECM)is central in regulating tissue functions and it is fundamentally important to broadly consider the biomechanical properties of the in vivo ECM when designing in vitro matrix *** manuscript discusses two commonly used biopolymer networks,*** and fibrin gels,and one synthetic polymer network,polyisocyanide gel(PIC),which all possess the characteristic nonlinear mechanics in the biological stress *** start from the structure of the materials,then address the uses,advantages,and limitations of each material,to provide a guideline for tissue engineers and biophysicists in utilizing current materials and also designing new materials for 3D cell culture purposes.

关键词： Artificial extracellular matrices Mechanical reciprocity Collagen Fibrin Polyisocyanides

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A de novo germline MLH1 mutation in a Lynch syndrome patient with discordant immunohistochemical and molecular biology test results

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World Journal of Gastroenterology 2012年第39期18卷 5635-5639页

作者： Fabrice Airaud Sébastien Küry Isabelle Valo Ingrid maury Dominique Bonneau Olivier Ingster Stéphane Bezieau CHU Nantes Service de Génétique Médicale9 quai Moncousu44093 Nantes Cedex 1France Institut de Cancérologie de l'Ouest Service d'Anatomie et Cytologie Pathologique2 rue Moll49933 Angers Cedex 9France CHU Angers Service de Génétique Médicale4 rue Larrey49933 AngersFrance

We describe a patient with a Homo sapiens mutL homolog 1 (MLH1)-associated Lynch syndrome with previous diagnoses of two distinct primary cancers:a sigmoid colon cancer at the age of 39 years, and a right colon cancer at the age of 50 years. The mutation identified in his blood and buccal cells, c.1771delG, ***591Ilefs*25, appears to be a de novo event, as it was not transmitted by either of his parents. This type of de novo event is rare in MLH1 as only three cases have been reported in the literature so far. Further-more, the discordant results observed between repli-cation error phenotyping and immunohistochemistry highlight the importance of the systematic use of both pre-screening tests in the molecular diagnosis of Lynch syndrome.

关键词： Lynch syndrome Homo sapiens mutL ho-molog 1 De novo mutation Replication error pheno- type Immunohistochemistry

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Hiding on jagged karst pinnacles:A new microendemic genus and species of a limestone-dwelling agamid lizard(Squamata:Agamidae:Draconinae)from Khammouan Province,Laos

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Zoological Research 2023年第6期44卷 1039-1051页

作者： Saly Sitthivong Peter Brakels Santi Xayyasith Nathanaël maury Sabira Idiiatullina Parinya Pawangkhanant Kai Wang Tan Van Nguyen Nikolay A.Poyarkov Faculty of Forestry National University of LaosVientiane 01170Lao PDR IUCN Laos PDR Vientiane 01160Lao PDR Faculty of Environmental Sciences National University of LaosVientiane 01170Lao PDR Chelonian Conservation Center Laos World Encyclopedia of HerpetofaunaVientiane 01000Lao PDR Department of Vertebrate Zoology Biological FacultyLomonosov Moscow State UniversityMoscow 119234Russia Rabbit in the Moon Foundation(RIM) SuanphuengRatchaburi 70180Thailand State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Southeast Asia Biodiversity Research Institute Chinese Academy of SciencesYezinNay Pyi Taw 05282Myanmar Institute for Research and Training in Medicine Biology and PharmacyDuy Tan UniversityDa Nang 550000Vietnam College of Medicine&Pharmacy Duy Tan UniversityDa Nang 550000Vietnam Joint Russian-Vietnamese Tropical Research and Technological Center Nghia DoCau GiayHanoi 122000Vietnam

We describe a unique new species and genus of agamid lizard from the karstic massifs of Khammouan Province,central *** carsticola *** *** an elusive medium-sized lizard(maximum snout-vent length101 mm)specifically adapted to life on limestone rocks and *** assess the phylogenetic position of the new genus amongst other agamids,we generated DNA sequences from two mitochondrial gene fragments(16S rRNA and ND2)and three nuclear loci(BDNF,RAG1 and c-mos),with a final alignment comprising 7418 base pairs for 64 agamid *** analyses unambiguously place the new genus in the mainland Asia subfamily Draconinae,where it forms a clade sister to the genus Diploderma from East Asia and the northern part of Southeast ***,the new genus is distinguished from all other genera in Draconinae by possessing a notably swollen tail base with enlarged scales on its dorsal and ventral *** work provides further evidence that limestone regions of Indochina represent unique“arks of biodiversity”and harbor numerous relict *** date,Laodracon carsticola *** *** known from only two adult male specimens and its distribution seems to be restricted to a narrow limestone massif on the border of Khammouan and Bolikhamxai provinces of *** studies are required to understand its life history,distribution,and conservation status.

关键词： Biodiversity Endemism Indochina Karstic landscape Laodracon carsticola Phylogeny Southeast Asia Taxonomy

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Shepherding Public Discourse Practices： Homiletic Form Aligned to the Logic Operative in Racial Rhetoric and Public Theological Discourse for Secular Liberal Democracies

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Cultural and Religious Studies 2016年第9期4卷 576-588页

作者： maury Jackson Horace Crogman La Sierra University HMS Richards Divinity School Riverside USA The Institute of Effective Thinking Riverside USA College of the Desert Palm Spring USA

Given that preaching is the primary mode of public theological discourse for most Christian ministers, an intellectual virtue of verbal restraint is required when practicing public theology and it is wise to address the ways that homilies can shepherd public discourse practices. A theology of rhetoric includes the homilist＇s moral purpose. Homilies either enhance public discourse or pervert it. This essay sketches a pattern of sermon movement that respects the logic operative in public theology, given the social context of America. Homilies can help cultivate the pastoral care of public rhetoric by modeling discourse that nurtures the politics of accountability. While many call for a public ethos where divergent moral voices engage each other in highly contested arenas, a precondition to practicing effective public theology requires that one exercises discourse in a way that respects the social limits on the free exercise of religion. It is important that a public theology of rhetoric clarifies the original social agreement for acceptable religious discourse in the public arena. Homiletics, as a dimension of practical theology, can teach preachers methods of pastoral care for public discourse. The social agreement in liberal democracies to contain the combative nature of religious discourse assumes a logic that is circumscribed by commitments to （1） religious pluralism, （2） theological agnosticism, and （3） epistemological pragmatism. Here we propose that a sermon＇s form, which implicitly touches upon these commitments, can tap into the basic modes of persuasion in secular liberal societies. This respects the moral purposes previously agreed upon and expected of partisans during highly contestable times. This calls for incarnational humility on the part of the Christian public theologian and it guides her/his practice.

关键词： homiletics liberal democracy secularization Bonhoeffer radical theology rhetoric

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矢量自动网络分析仪的3.5mm和7mm两端口检验标准

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宇航计测技术 1989年第5期8卷 33-38,27页

作者： M.A.maury 张明睿

为了提高微波测量的准确度,需要研制检验标准并利用检验标准来检查测量的准确度。文中介绍了3.5mm和7mm两端口检验标准的设计和注意事项、使其准确度、重复性和通用性均达到最佳状态。文中还阐明了使用检验标准所必须完成的四个重要步骤... 详细信息

为了提高微波测量的准确度,需要研制检验标准并利用检验标准来检查测量的准确度。文中介绍了3.5mm和7mm两端口检验标准的设计和注意事项、使其准确度、重复性和通用性均达到最佳状态。文中还阐明了使用检验标准所必须完成的四个重要步骤,检查测试端口、比较实测数据和校准数据的方法,以及对测试结果进行统计分析的方法。

关键词：网络分析仪毫米波部件微波连接器微波测量设计

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织构对先进锆合金蠕变性能各向异性的影响

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稀有金属 2008年第1期32卷 1-6页

作者：彭继华李文芳 Jean-Luc Bechade R.maury 华南理工大学机械工程学院广东广州510640 SMRA/DEN/CEA/Saclay 91191Gif-Sur-Yvette CedexFrance

研究了两种组织形貌相似的先进锆合金M5TM和N36锆合金核燃料包壳管材的单轴拉伸和内压蠕变性能。利用X射线衍射仪分析了它们的织构。试验发现两种先进锆合金包壳材料的蠕变性能表现出明显的各向异性。根据试验条件下的蠕变机理,结合弹... 详细信息

研究了两种组织形貌相似的先进锆合金M5TM和N36锆合金核燃料包壳管材的单轴拉伸和内压蠕变性能。利用X射线衍射仪分析了它们的织构。试验发现两种先进锆合金包壳材料的蠕变性能表现出明显的各向异性。根据试验条件下的蠕变机理,结合弹性粘塑性自洽模型定性地分析了织构对锆合金管材蠕变各向异性的影响,解释了先进锆合金各向异性随应力指数变化的共性规律。揭示了织构与先进锆合金管材蠕变各向异性的定性关系。由于成分和织构因素的共同作用,在研究的试验条件下,N36合金的初始蠕变应变、稳态蠕变速率低于M5合金。织构是合金蠕变行为产生各向异性的主要原因,对于再结晶状态的先进锆合金包壳管,具有(0002)织构特征时,应力指数越高(即施加的应力水平越高),其蠕变的各向异性值越大。

关键词：先进锆合金织构蠕变各向异性

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