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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

Mineralogy,Fluid Inclusion and H-O-C-S Stable Isotopes of Mengqiguer Uranium Deposit in the Southern Yili Basin,Xinjiang:Implication for Ore Formation

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Acta Geologica Sinica(English Edition) 2020年第5期94卷 1488-1503页

作者： DING Bo LIU Hongxu ZHANG Chuang LIU Hongjun LI Ping ZHANG Bin CNNC Key Laboratory of Uranium Resources Exploration and evaluation Techniques Beijing Research Institute of Uranium GeologyBeijing 100029China China institute of Nuclear Information and Economics Beijing 100048China

The Mengqiguer deposit in the southern Yili basin Ili Basin is a large interlayer-oxidation-zone type uranium *** this paper,we applied multiple methods including microscopic observation,scanning electron microscope and electronic probe,to analyze the systematical alteration characteristics of the ore-bearing sandstone *** inclusion and stable isotope studies on the ore-bearing sandstone have also been carried out to discuss the internal relations between fluid activities,epigenetic alteration and the uranium *** epigenetic alteration include clay alteration,carbonatization and pyritization,of which biogenetic pyritization is most closely related to the uranium *** suggests the existence of microorganism during the uranium mineralization *** mineralization fluids of low temperature,medium density but varied salinities are suggested to be derived from multi-source,including the meteoric water and organic acidic vapor components from coal-bearing *** mineralization,grain-dispersed kaolinite,limonite,colloidal pyrite,and the carbonate cements associated with sulfate-reducing bacteria were formed by meteoric water and vermicular-shaped kaolinite,autologous pyrite,and the carbonate cementation associated with the dehydroxylation of organic matter was formed by organic *** on these results,we consider that the uranium mineralization and epigenetic alteration both resulted from the reciprocity of organic–inorganic fluid and fluid–rock during the formation of the interlayer oxidation zone.

关键词： Metallogenic fluid Epigenetic alteration Uranium metallogenic Mengqiguer sandstone type uranium deposit

Development of methods for establishing nutrient criteria in lakes and reservoirs: A review

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Journal of Environmental Sciences 2018年第5期30卷 54-66页

作者： Shouliang Huo Chunzi Ma Beidou Xi Yali Zhang Fengchang Wu Hongliang Liu State Key Laboratory of Environmental Criteria and Risk assessment Chinese Research Academy of Environmental Sciences

Nutrient criteria provide a scientific foundation for the comprehensive evaluation, prevention,control and management of water eutrophication. In this review, the literature was examined to systematically evaluate the benefits, drawbacks, and applications of statistical analysis,paleolimnological reconstruction, stressor-response model, and model inference approaches for nutrient criteria determination. The developments and challenges in the determination of nutrient criteria in lakes and reservoirs are presented. Reference lakes can reflect the original states of lakes, but reference sites are often unavailable. Using the paleolimnological reconstruction method, it is often difficult to reconstruct the historical nutrient conditions of shallow lakes in which the sediments are easily disturbed. The model inference approach requires sufficient data to identify the appropriate equations and characterize a waterbody or group of waterbodies, thereby increasing the difficulty of establishing nutrient criteria. The stressor-response model is a potential development direction for nutrient criteria determination, and the mechanisms of stressor-response models should be studied further. Based on studies of the relationships among water ecological criteria, eutrophication, nutrient criteria and plankton, methods for determining nutrient criteria should be closely integrated with water management requirements.

关键词： Nutrient criteria Statistical analysis approach Paleolimnological reconstructionapproach Stressor-response model Model inference approach

Dependence of the sediment delivery ratio on scale and its fractal characteristics

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International Journal of Sediment research 2015年第04期30卷 338-343页

作者： Xiaoming Zhang Sihong Wu Wenhong Cao Jianchao Guan Zhaoyan Wang State Key Laboratory of Simulation and Regulation of Water Cycle in River Basin China Institute of Water Resources and Hydropower Research National Center of Science and Technology evaluation China institute of Water Resources and Hydropower research

The sediment delivery ratio(SDR) is an indicator used to determine the capacity for eroded sediment to be delivered to the outlet of a particular *** on systematic reviews of SDR studies in China and abroad during the last 50 years,this study analyzes whether the SDR has scale-dependent characteristics and discusses the fractal characteristics of the *** addition,the SDR in various watersheds in China and abroad showed correlations with temporal and spatial scales,which means that the SDR depends on watershed ***,the SDR can be quantitatively expressed and scaled using fractal dimension under certain temporal and spatial *** a nested watershed,a proposed SDR scale transfer model was constructed using the SDR at a typical watershed unit scale with an area of approximately1 km2(SDR) and a fractal dimension of the SDR at a nested watershed scale(D).This research also points out that the study and calculation of the SDR cannot be correct without considering its scale *** is a valid and useful approach to construct SDR scaling models by using fractal dimension,which could be an interesting research topic regarding SDR scaling in the future.

关键词： Sediment delivery ratio Soil erosion Sediment delivery Scale Typical watershed unit

Synergistic effect of polyoxometalate solution and TiO_2 under UV irradiation to catalyze formic acid degradation and their application in the fuel cell and hydrogen evolution

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Green Energy & Environment 2017年第4期2卷 436-441页

作者： Congmin Liu Zhe Zhang Wei Liu Xu Du Shi Liu Yong Cui Guodian New Energy Technology research institute School of Chemical & Biomolecular Engineering and RBI at Georgia Tech Georgia Institute of Technology Key Laboratory of Nuclear Materials and Safety assessment Division of Materials for Special Environments Institute of Metal Research Chinese Academy of Sciences

The synergistic effect of H_3PMo_(12)O_(40) or H_3PW_(12)O_(40) polyoxometalate solution(POM) and TiO_2 to catalyze formic acid oxidation was investigated. Under UV irradiation, hole and electron were photogenerated by TiO_2. Formic acid was oxided by the photogenerated hole and photogenerated electron was transferred to reduce polyoxometalate. With this design, formic acid can be converted into electricity in the fuel cell and hydrogen can be generated in the electrolysis cell without noble metal catalyst. Unlike other noble metal catalysts applied in the fuel cells and electrolysis cell, POM and TiO_2 are stable and low cost. The maximum output power density of liquid formic acid fuel cell after 12 h UV irradiation is 5.21 mW/cm^2 for phosphmolybdic acid and 22.81 m W/cm^2 for phosphotungstic acid respectively. The applied potential for the hydrogen evolution is as low as 0.8 V for phosphmolybdic acid and 0.6 V for phosphotungstic acid.

关键词： TiO2 UV Polyoxometalate solution(POM) Fuel cell Hydrogen evolution

Flexible Graphene Field‑Effect Transistors and Their Application in Flexible Biomedical Sensing

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Nano-Micro Letters 2025年第2期17卷 252-313页

作者： Mingyuan Sun Shuai Wang Yanbo Liang Chao Wang Yunhong Zhang Hong Liu Yu Zhang Lin Han institute of Marine Science and Technology Shandong UniversityQingdao 266237ShandongPeople’s Republic of China State Key Laboratory of Crystal Materials Shandong UniversityJinan 250100ShandongPeople’s Republic of China School of Integrated Circuits Shandong UniversityJinan 250100ShandongPeople’s Republic of China Shandong Engineering research Center of Biomarker and Artificial Intelligence Application Jinan250100ShandongPeople’s Republic of China

Flexible electronics are transforming our lives by making daily activities more *** to this innovation are field-effect transistors(FETs),valued for their efficient signal processing,nanoscale fabrication,low-power consumption,fast response times,and ***,known for its exceptional mechanical properties,high electron mobility,and biocompatibility,is an ideal material for FET channels and *** combination of graphene and FETs has given rise to flexible graphene field-effect transistors(FGFETs),driving significant advances in flexible electronics and sparked a strong interest in flexible biomedical ***,we first provide a brief overview of the basic structure,operating mechanism,and evaluation parameters of FGFETs,and delve into their material selection and patterning *** ability of FGFETs to sense strains and biomolecular charges opens up diverse application *** specifically analyze the latest strategies for integrating FGFETs into wearable and implantable flexible biomedical sensors,focusing on the key aspects of constructing high-quality flexible biomedical ***,we discuss the current challenges and prospects of FGFETs and their applications in biomedical *** review will provide valuable insights and inspiration for ongoing research to improve the quality of FGFETs and broaden their application prospects in flexible biomedical sensing.

关键词： Flexible Graphene Field-effect transistor Wearable Implantable Biosensor

Dietary supplementation of zinc oxide modulates intestinal functionality during the post-weaning period in clinically healthy piglets

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Journal of Animal Science and Biotechnology 2024年第1期15卷 313-328页

作者： Dirkjan Schokker Soumya K.Kar Els Willems Alex Bossers Ruud A.Dekker Alfons J.M.Jansman Wageningen Bioveterinary research LelystadThe Netherlands Wageningen Livestock research Wageningen University&ResearchWageningenThe Netherlands Royal Agrifirm Group ApeldoornThe Netherlands institute for Risk assessment Sciences Utrecht UniversityUtrechtThe Netherlands

Background To improve our understanding of host and intestinal microbiome interaction,this research investigated the effects of a high-level zinc oxide in the diet as model intervention on the intestinal microbiome and small intestinal functionality in clinically healthy post-weaning *** study 1,piglets received either a high concentration of zinc(Zn)as zinc oxide(Zn O,Zn,2,690 mg/kg)or a low Zn concentration(100 mg/kg)in the diet during the post weaning period(d 14–23).The effects on the piglet's small intestinal microbiome and functionality of intestinal tissue were *** study 2,the impact of timing of the dietary zinc intervention was investigated,i.e.,between d 0–14 and/or d 14–23 post weaning,and the consecutive effects on the piglet's intestinal functionality,here referring to microbiota composition and diversity and gene expression *** Differences in the small intestinal functionality were observed during the post weaning period between piglets receiving a diet with a low or high concentration Zn O content.A shift in the microbiota composition in the small intestine was observed that could be characterized as a non-pathological change,where mainly the commensals *** the immediate post weaning period,i.e.,d 0–14,the highest number of differentially expressed genes(DEGs)in intestinal tissue were observed between animals receiving a diet with a low or high concentration Zn O content,i.e.,23 DEGs in jejunal tissue and 11 DEGs in ileal *** genes are involved in biological processes related to immunity and inflammatory *** example,genes CD59 and REG3G were downregulated in the animals receiving a diet with a high concentration Zn O content compared to low Zn O content in both jejunum and ileum *** the second study,a similar result was obtained regarding the expression of genes in intestinal tissue related to immune pathways when comparing piglets receiving a diet with a high concentration Zn O con

关键词： Immune system Intestinal functionality Microbiota Piglets Zinc oxide

Effects of sgRNA length and number on gene editing efficiency and predicted mutations generated in rice

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The Crop Journal 2022年第2期10卷 577-581页

作者： Xiaojing Liu Jiangtao Yang Yaya Song Xiaochun Zhang Xujing Wang Zhixing Wang Biotechnology research institute Chinese Academy of Agricultural Sciences/MARA Key Laboratory on Safety Assessment(Molecular)of Agri-GMOBeijing 100081China

CRISPR-Cas9 is a common tool for gene editing, and appropriate sg RNAs are the key factor for successful editing. In this study, the effect of sg RNA length and number on editing efficiency was analyzed in rice using CYP81 A6 as the target gene. A series of CRISPR-Cas9 plant expression vectors containing single sg RNAs with different lengths(17, 18, 19, 20, 21, 22, 23 nt) or two sg RNAs were constructed and introduced into rice cultivar Zhonghua11 by Agrobacterium-mediated transformation. Analysis of the editing status of 1283 transgenic rice plants showed that 371 were successfully edited with base *** A or T insertions were the most frequent among the six edited types. The editing efficiency of transgenic rice with two sg RNAs was higher than that with a single sg RNA. Editing efficiency and sg RNA length showed a normal distribution with 20 nt sg RNA(25%) being the most efficient. The editing efficiency decreased slightly with decreases of 1–2 bases(19 nt 20%, 18 nt 21%), but decreased significantly with a decrease of 3 bases(17 nt 4.5%). Editing efficiency was significantly reduced by adding 1 to 3 bases(21 nt 16.8%, 22 nt 13%, 23 nt 13%) to the sg RNA. These results provide data for successful gene editing or rice by CRISPR-Cas9.

关键词： CRISPR-Cas9 sgRNA number sgRNA length Editing efficiency

Impacts of Global Warming on Hydrological Cycles in the Asian Monsoon Region

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Advances in Atmospheric Sciences 2008年第6期25卷 960-973页

作者： Koji DAIRAKU Seita EMORI Toru NOZAWA Storm Flood and Landslide Research Department National Research Institute for Earth Science and Disaster Prevention Climate Risk assessment research Section Center for Global Environmental Research National Institute for Environmental Studies Atmospheric Physics Section Atmospheric Environment Division National Institute for Environmental Studies

The hydrologic changes and the impact of these changes constitute a fundamental global-warmingrelated concern. Faced with threats to human life and natural ecosystems, such as droughts, floods, and soil erosion, water resource planners must increasingly make future risk assessments. Though hydrological predictions associated with the global climate change are already being performed, mainly through the use of GCMs, coarse spatial resolutions and uncertain physical processes limit the representation of terrestrial water/energy interactions and the variability in such systems as the Asian monsoon. Despite numerous studies, the regional responses of hydrologic changes resulting from climate change remains inconclusive. In this paper, an attempt at dynamical downsealing of future hydrologic projection under global climate change in Asia is addressed. The authors conducted present and future Asian regional climate simulations which were nested in the results of Atmospheric General Circulation Model （AGCM） experiments. The regional climate model could capture the general simulated features of the AGCM. Also, some regional phenomena such as orographic precipitation, which did not appear in the outcome of the AGCM simulation, were successfully produced. Under global warming, the increase of water vapor associated with the warmed air temperature was projected. It was projected to bring more abundant water vapor to the southern portions of India and the Bay of Bengal, and to enhance precipitation especially over the mountainous regions, the western part of India and the southern edge of the Tibetan Plateau. As a result of the changes in the synoptic flow patterns and precipitation under global warming, the increases of annual mean precipitation and surface runoff were projected in many regions of Asia. However, both the positive and negative changes of seasonal surface runoff were projected in some regions which will increase the flood risk and cause a mismatch between water

关键词： hydrologic change dynamical downscaling regional climate model Asian monsoon region