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  • 1
    Online Resource
    Online Resource
    Newark :John Wiley & Sons, Incorporated,
    Keywords: Biochemical engineering. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (653 pages)
    Edition: 1st ed.
    ISBN: 9783527800605
    Series Statement: Advanced Biotechnology Series
    Language: English
    Note: Cover -- Title Page -- Copyright -- Contents -- List of Contributors -- Chapter 1 Introduction -- 1.1 Introduction -- 1.2 Enzyme Technology -- 1.3 Microbial Process Engineering -- 1.3.1 Bioreactor Development -- 1.3.2 Measurement and Monitoring -- 1.3.3 Modeling and Control -- 1.3.4 Solid-State Fermentation -- 1.4 Plant Cell Culture -- 1.5 Animal Cell Culture -- 1.6 Environmental Bioengineering -- 1.7 Composition of the Volume -- References -- Part I Enzyme Technology -- Chapter 2 Enzyme Technology: History and Current Trends -- 2.1 The Early Period up to 1890 -- 2.1.1 Observations and Empirical Results -- 2.1.2 Theoretical Approaches -- 2.2 The Period from 1890 to 1940 -- 2.2.1 Scientific Progress -- 2.2.2 Theoretical Developments -- 2.2.3 Technological Developments -- 2.3 A New Biocatalyst Concept - Immobilized Enzymes -- 2.3.1 Fundamental Research -- 2.3.2 Examples of Industrial Development: The Case of Penicillin Amidase (PA) - Penicillin Hydrolysis and Derivatives -- 2.3.3 Examples of Industrial Development: The Case of Sugar Isomerization -- 2.4 Expanding Enzyme Application after the 1950s -- 2.5 Recombinant Technology - A New Era in Biocatalysis and Enzyme Technology -- 2.5.1 New Enzymes - A Key to Genetic Engineering -- 2.5.2 Analytical and Diagnostic Enzymes -- 2.5.3 Expanding Market of Industrial Enzymes -- 2.6 Current Strategies for Biocatalyst Search and Tailor Design -- 2.6.1 Enzyme Discovery from the Metagenome or Protein Databases -- 2.6.2 Protein Engineering of Enzymes -- 2.6.3 Enzyme Cascade Reactions -- 2.6.4 Metabolic Engineering -- 2.7 Summary and Conclusions -- Acknowledgment -- Abbreviations -- References -- Chapter 3 Molecular Engineering of Enzymes -- 3.1 Introduction -- 3.2 Protein Engineering: An Expanding Toolbox -- 3.2.1 From Sequence to Fold and Function. , 3.2.2 Improving Enzyme Properties by Rational Design and Directed Evolution -- 3.2.3 Designing Smart Libraries -- 3.2.4 In Vivo Continuous Directed Evolution -- 3.2.5 Diversification of Enzyme Functionalities by Recombination -- 3.3 High-Throughput Screening Systems -- 3.4 Engineered Enzymes for Improved Stability and Asymmetric Catalysis -- 3.4.1 Stability -- 3.4.1.1 Cellulases -- 3.4.1.2 Lipases -- 3.4.2 Asymmetric Biocatalysis -- 3.5 De Novo Design of Catalysts: Novel Activities within Common Scaffolds -- 3.6 Conclusions -- References -- Chapter 4 Biocatalytic Process Development -- 4.1 A Structured Approach to Biocatalytic Process Development -- 4.2 Process Metrics -- 4.2.1 Reaction Yield -- 4.2.2 Productivity -- 4.2.3 Biocatalyst Yield -- 4.2.4 Product Concentration -- 4.3 Technologies for Implementation of Biocatalytic Processes -- 4.3.1 Biocatalyst Engineering -- 4.3.1.1 Protein and Genetic Engineering -- 4.3.1.2 Biocatalyst Immobilization -- 4.3.2 Reaction Engineering -- 4.3.2.1 Reactant Supply -- 4.3.2.2 Product Removal -- 4.3.2.3 Two-Phase Systems -- 4.4 Industrial Development Examples -- 4.4.1 Development of a Biocatalytic Route to Atorvastatin (Developed by Codexis Inc., USA) -- 4.4.2 Development of a Biocatalytic Route to Sitagliptin (Developed by Codexis Inc., USA and Merck and Co., USA) -- 4.5 Future Outlook -- 4.6 Concluding Remarks -- References -- Chapter 5 Development of Enzymatic Reactions in Miniaturized Reactors -- 5.1 Introduction -- 5.2 Fundamental Techniques for Enzyme Immobilization -- 5.2.1 Enzyme Immobilization by Adsorption -- 5.2.1.1 Monoliths and Particles -- 5.2.1.2 Synthetic Polymer Membranes and Papers -- 5.2.1.3 Adsorption to Channel Walls -- 5.2.2 Enzyme Immobilization by Entrapment -- 5.2.2.1 Silica-Based Matrices -- 5.2.2.2 Non-Silica-based Matrices -- 5.2.3 Enzyme Immobilization by Affinity Labeling. , 5.2.3.1 His-Tag/Ni-NTA System -- 5.2.3.2 GST-Tag/Glutathione System -- 5.2.3.3 Avidin/Biotin System -- 5.2.3.4 DNA Hybridization System -- 5.2.3.5 Other Techniques Using Nucleotides for Enzyme Immobilization -- 5.2.4 Enzyme Immobilization by Covalent Linking -- 5.2.4.1 Immobilization to Solid Supports -- 5.2.4.2 Direct Immobilization to a Channel Wall -- 5.2.4.3 Enzyme Polymerization -- 5.2.5 Enzyme Immobilization by Other Techniques Using Organisms -- 5.2.6 Application of Immobilized Enzymes in Microfluidics -- 5.3 Novel Techniques for Enzyme Immobilization -- 5.3.1 Polyketone Polymer: Enzyme Immobilization by Hydrogen Bonds -- 5.3.2 Thermoresponsive Hydrogels -- 5.3.3 Immobilization Methods Using Azide Chemistry -- 5.3.3.1 Staudinger Ligation -- 5.3.3.2 Click Chemistry -- 5.3.4 Graphene-Based Nanomaterial as an Immobilization Support -- 5.3.5 Immobilization Methods Using Proteins Modified with Solid-Support-Binding Modules -- 5.4 Conclusions and Future Perspectives -- Abbreviations -- References -- Part II Microbial Process Engineering -- Chapter 6 Bioreactor Development and Process Analytical Technology -- 6.1 Introduction -- 6.2 Bioreactor Development -- 6.2.1 Parallel Bioreactor Systems for High-Throughput Processing -- 6.2.1.1 Microtiter Plate Systems -- 6.2.1.2 Stirred-Tank Reactor Systems -- 6.2.1.3 Microfluidic Microbioreactor Systems -- 6.2.1.4 Bubble Column Systems -- 6.2.1.5 Comparison of Various Parallel-Use Micro-/Mini-Bioreactor System -- 6.2.2 Single-Use Disposable Bioreactor Systems -- 6.2.2.1 Features of Single-Use Bioreactors -- 6.2.2.2 Sensors and Monitoring -- 6.2.2.3 Single-Use Bioreactors in Practical Use -- 6.3 Monitoring and Process Analytical Technology -- 6.3.1 Monitoring and State Recognition -- 6.3.1.1 Sensors for Monitoring Bioprocesses -- 6.3.1.2 Spectrometry -- 6.3.2 Process Analytical Technology (PAT). , 6.3.2.1 PAT Tools -- 6.3.2.2 PAT Implementations -- 6.4 Conclusion -- Abbreviations -- References -- Chapter 7 Omics-Integrated Approach for Metabolic State Analysis of Microbial Processes -- 7.1 General Introduction -- 7.2 Transcriptome Analysis of Microbial Status in Bioprocesses -- 7.2.1 Introduction -- 7.2.2 Microbial Response to Stress Environments and Identification of Genes Conferring Stress Tolerance in Bioprocesses -- 7.2.3 Transcriptome Analysis of the Ethanol-Stress-Tolerant Strain Obtained by Evolution Engineering -- 7.3 Analysis of Metabolic State Based on Simulation in a Genome-Scale Model -- 7.3.1 Introduction -- 7.3.2 Reconstruction of GSMs and Simulation by FBA -- 7.3.3 Using Prediction of Metabolic State for Design of Metabolic Modification -- 7.4 13C-Based Metabolic Flux Analysis of Microbial Processes -- 7.4.1 Introduction -- 7.4.2 Principles of 13C-MFA -- 7.4.3 Examples of 13C-MFA in Microbial Processes -- 7.5 Comprehensive Phenotypic Analysis of Genes Associated with Stress Tolerance -- 7.5.1 Introduction -- 7.5.2 Development of a High-Throughput Culture System -- 7.5.3 Calculation of Specific Growth Rate -- 7.5.4 Results of Comprehensive Analysis of Yeast Cells Under Conditions of High Osmotic Pressure and High Ethanol Concentration -- 7.5.5 Identification of Genes Conferring Desirable Phenotypes Based on Integration with the Microarray Analysis Method -- 7.6 Multi-Omics Analysis and Data Integration -- 7.7 Future Aspects for Developing the Field -- Acknowledgments -- References -- Chapter 8 Control of Microbial Processes -- 8.1 Introduction -- 8.2 Monitoring -- 8.2.1 Online Measurements -- 8.2.2 Filtering, Online Estimation, and Software Sensors -- 8.2.3 Algorithm of Extended Kalman Filter and Its Application to Online Estimation of Specific Rates -- 8.3 Bioprocess Control -- 8.3.1 Control of Fed-Batch Culture. , 8.3.2 Online Optimization of Continuous Cultures -- 8.3.3 Cascade Control for Mixed Cultures -- 8.3.4 Supervision and Fault Detection -- 8.4 Recent Trends in Monitoring and Control Technologies -- 8.4.1 Sensor Technologies and Analytical Methods -- 8.4.2 Control Technologies -- 8.5 Concluding Remarks -- Abbreviations -- References -- Part III Plant Cell Culture and Engineering -- Chapter 9 Contained Molecular Farming Using Plant Cell and Tissue Cultures -- 9.1 Molecular Farming - Whole Plants and Cell/Tissue Cultures -- 9.2 Plant Cell and Tissue Culture Platforms -- 9.2.1 Cell Suspension Cultures -- 9.2.2 Tissue Cultures -- 9.2.3 Light-Dependent Expression Platforms -- 9.3 Comparison of Whole Plants and In Vitro Culture Platforms -- 9.4 Technical Advances on the Road to Commercialization -- 9.4.1 Improving the Quantity of Recombinant Proteins Produced in Cell Suspension Cultures -- 9.4.2 Improving the Quality and Consistency of Recombinant Proteins Produced in Cell Suspension Cultures -- 9.5 Regulatory and Industry Barriers on the Road to Commercialization -- 9.6 Outlook -- Acknowledgments -- References -- Chapter 10 Bioprocess Engineering of Plant Cell Suspension Cultures -- 10.1 Introduction -- 10.2 Culture Development and Maintenance -- 10.3 Choice of Culture System -- 10.4 Engineering Considerations -- 10.4.1 Cell Growth and Morphology -- 10.4.2 Gas Requirements -- 10.4.3 Aggregation -- 10.4.4 Medium Rheology -- 10.4.5 Shear Sensitivity -- 10.5 Bioprocess Parameters -- 10.5.1 Medium Composition and Optimization -- 10.5.2 Temperature and pH -- 10.5.3 Agitation -- 10.5.4 Aeration -- 10.6 Operational Modes -- 10.7 Bioreactors for Plant Cell Suspensions -- 10.7.1 Conventional Bioreactors -- 10.7.1.1 Stirred-Tank Reactors -- 10.7.1.2 Pneumatic Bioreactors -- 10.7.2 Disposable Bioreactors -- 10.8 Downstream Processing. , 10.8.1 Specialized Metabolite Extraction and Purification.
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  • 2
    Online Resource
    Online Resource
    Newark :John Wiley & Sons, Incorporated,
    Keywords: Cyanobacteria-Biotechnology. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (563 pages)
    Edition: 1st ed.
    ISBN: 9783527824922
    Series Statement: Advanced Biotechnology Series
    DDC: 579.39
    Language: English
    Note: Cover -- Title Page -- Copyright -- Contents -- Foreword: Cyanobacteria Biotechnology -- Acknowledgments -- Part I Core Cyanobacteria Processes -- Chapter 1 Inorganic Carbon Assimilation in Cyanobacteria: Mechanisms, Regulation, and Engineering -- 1.1 Introduction - The Need for a Carbon‐Concentrating Mechanism -- 1.2 The Carbon‐Concentrating Mechanism (CCM) Among Cyanobacteria -- 1.2.1 Ci Uptake Proteins/Mechanisms -- 1.2.2 Carboxysome and RubisCO -- 1.3 Regulation of Ci Assimilation -- 1.3.1 Regulation of the CCM -- 1.3.2 Further Regulation of Carbon Assimilation -- 1.3.3 Metabolic Changes and Regulation During Ci Acclimation -- 1.3.4 Redox Regulation of Ci Assimilation -- 1.4 Engineering the Cyanobacterial CCM -- 1.5 Photorespiration -- 1.5.1 Cyanobacterial Photorespiration -- 1.5.2 Attempts to Engineer Photorespiration -- 1.6 Concluding Remarks -- Acknowledgments -- References -- Chapter 2 Electron Transport in Cyanobacteria and Its Potential in Bioproduction -- 2.1 Introduction -- 2.2 Electron Transport in a Bioenergetic Membrane -- 2.2.1 Linear Electron Transport -- 2.2.2 Cyclic Electron Transport -- 2.2.3 ATP Production from Linear and Cyclic Electron Transport -- 2.3 Respiratory Electron Transport -- 2.4 Role of Electron Sinks in Photoprotection -- 2.4.1 Terminal Oxidases -- 2.4.2 Hydrogenase and Flavodiiron Complexes -- 2.4.3 Carbon Fixation and Photorespiration -- 2.4.4 Extracellular Electron Export -- 2.5 Regulating Electron Flux into Different Pathways -- 2.5.1 Electron Flux Through the Plastoquinone Pool -- 2.5.2 Electron Flux Through Fdx -- 2.6 Spatial Organization of Electron Transport Complexes -- 2.7 Manipulating Electron Transport for Synthetic Biology Applications -- 2.7.1 Improving Growth of Cyanobacteria -- 2.7.2 Production of Electrical Power in BPVs -- 2.7.3 Hydrogen Production -- 2.7.4 Production of Industrial Compounds. , 2.8 Future Challenges in Cyanobacterial Electron Transport -- References -- Chapter 3 Optimizing the Spectral Fit Between Cyanobacteria and Solar Radiation in the Light of Sustainability Applications -- 3.1 Introduction -- 3.2 Molecular Basis and Efficiency of Oxygenic Photosynthesis -- 3.3 Fit Between the Spectrum of Solar Radiation and the Action Spectrum of Photosynthesis -- 3.4 Expansion of the PAR Region of Oxygenic Photosynthesis -- 3.5 Modulation and Optimization of the Transparency of Photobioreactors -- 3.6 Full Control of the Light Regime: LEDs Inside the PBR -- 3.7 Conclusions and Prospects -- References -- Part II Concepts in Metabolic Engineering -- Chapter 4 What We Can Learn from Measuring Metabolic Fluxes in Cyanobacteria -- 4.1 Central Carbon Metabolism in Cyanobacteria: An Overview and Renewed Pathway Knowledge -- 4.1.1 Glycolytic Routes Interwoven with the Calvin Cycle -- 4.1.2 Tricarboxylic Acid Cycling -- 4.2 Methodologies for Predicting and Quantifying Metabolic Fluxes in Cyanobacteria -- 4.2.1 Flux Balance Analysis and Genome‐Scale Reconstruction of Metabolic Network -- 4.2.2 13C‐Metabolic Flux Analysis -- 4.2.3 Thermodynamic Analysis and Kinetics Analysis -- 4.3 Cyanobacteria Fluxome in Response to Altered Nutrient Modes and Environmental Conditions -- 4.3.1 Autotrophic Fluxome -- 4.3.2 Photomixotrophic Fluxome -- 4.3.3 Heterotrophic Fluxome -- 4.3.4 Photoheterotrophic Fluxome -- 4.3.5 Diurnal Metabolite Oscillations -- 4.3.6 Nutrient States' Impact on Metabolic Flux -- 4.4 Metabolic Fluxes Redirected in Cyanobacteria for Biomanufacturing Purposes -- 4.4.1 Restructuring the TCA Cycle for Ethylene Production -- 4.4.2 Maximizing Flux in the Isoprenoid Pathway -- 4.4.2.1 Measuring Precursor Pool Size to Evaluate Potential Driving Forces for Isoprenoid Production -- 4.4.2.2 Balancing Intermediates for Increased Pathway Activity. , 4.4.2.3 Kinetic Flux Profiling to Detect Bottlenecks in the Pathway -- 4.5 Synopsis and Future Directions -- Acknowledgments -- References -- Chapter 5 Synthetic Biology in Cyanobacteria and Applications for Biotechnology -- 5.1 Introduction -- 5.2 Getting Genes into Cyanobacteria -- 5.2.1 Transformation -- 5.2.2 Expression from Episomal Plasmids -- 5.2.3 Delivery of Genes to the Chromosome -- 5.3 Basic Synthetic Control of Gene Expression in Cyanobacteria -- 5.3.1 Quantifying Transcription and Translation in Cyanobacteria -- 5.3.2 Controlling Transcription with Synthetic Promoters -- 5.3.2.1 Constitutive Promoters -- 5.3.2.2 Regulated Promoters that Are Sensitive to Added Compounds (Inducible) -- 5.3.2.3 CRISPR Interference for Transcriptional Repression -- 5.3.3 Controlling Translation -- 5.3.3.1 Ribosome Binding Sites (Cis‐Acting) -- 5.3.3.2 Riboswitches (Cis‐Acting) -- 5.3.3.3 Small RNAs (Trans‐Acting) -- 5.4 Exotic Signals for Controlling Expression -- 5.4.1 Oxygen -- 5.4.2 Light Color -- 5.4.3 Cell Density or Growth Phase -- 5.4.4 Engineering Regulators for Altered Sensing Properties: State of the Art -- 5.5 Advanced Regulation: The Near Future -- 5.5.1 Logic Gates and Timing Circuits -- 5.5.2 Orthogonal Transcription Systems -- 5.5.3 Synthetic Biology Solutions to Increase Stability -- 5.5.4 Synthetic Biology Solutions for Cell Separation and Product Recovery -- 5.6 Conclusions -- Acknowledgments -- References -- Chapter 6 Sink Engineering in Photosynthetic Microbes -- 6.1 Introduction -- 6.2 Source and Sink -- 6.3 Regulation of Sink Energy in Plants -- 6.3.1 Sucrose and Other Signaling Carbohydrates -- 6.3.2 Hexokinases -- 6.3.3 Sucrose Non‐fermenting Related Kinases -- 6.3.4 TOR Kinase -- 6.3.5 Engineered Pathways as Sinks in Photosynthetic Microbes -- 6.3.6 Sucrose -- 6.3.7 2,3‐Butanediol -- 6.3.8 Ethylene -- 6.3.9 Glycerol. , 6.3.10 Isobutanol -- 6.3.11 Isoprene -- 6.3.12 Limonene -- 6.3.13 P450, an Electron Sink -- 6.4 What Are Key Source/Sink Regulatory Hubs in Photosynthetic Microbes? -- 6.5 Concluding Remarks -- Acknowledgment -- References -- Chapter 7 Design Principles for Engineering Metabolic Pathways in Cyanobacteria -- 7.1 Introduction -- 7.2 Cofactor Optimization -- 7.2.1 Recruiting NADPH‐Dependent Enzymes Wherever Possible -- 7.2.2 Engineering NADH‐Specific Enzymes to Utilize NADPH -- 7.2.3 Increasing NADH Pool in Cyanobacteria Through Expression of Transhydrogenase -- 7.3 Incorporation of Thermodynamic Driving Force into Metabolic Pathway Design -- 7.3.1 ATP Driving Force in Metabolic Pathways -- 7.3.2 Increasing Substrate Pool Supports the Carbon Flux Toward Products -- 7.3.3 Product Removal Unblocks the Limitations of Product Titer -- 7.4 Development of Synthetic Pathways for Carbon Conserving Photorespiration and Enhanced Carbon Fixation -- 7.5 Summary and Future Perspective on Cyanobacterial Metabolic Engineering -- References -- Chapter 8 Engineering Cyanobacteria for Efficient Photosynthetic Production: Ethanol Case Study -- 8.1 Introduction -- 8.2 Pathway for Ethanol Synthesis in Cyanobacteria -- 8.2.1 Pyruvate Decarboxylase and Type II Alcohol Dehydrogenase -- 8.2.2 Selection of Better Enzymes in the Pdc-AdhII Pathway -- 8.2.3 Systematic Characterization of the PdcZM-Slr1192 Pathway -- 8.3 Selection of Optimal Cyanobacteria "Chassis," Strain for Ethanol Production -- 8.3.1 Synechococcus PCC 6803 and Synechococcus PCC 7942 -- 8.3.2 Synechococcus PCC 7002 -- 8.3.3 Anabaena PCC 7120 -- 8.3.4 Nonconventional Cyanobacteria Species -- 8.4 Metabolic Engineering Strategies Toward More Efficient and Stable Ethanol Production -- 8.4.1 Enhancing the Carbon Flux via Overexpression of Calvin Cycle Enzymes -- 8.4.2 Blocking Pathways that Are Competitive to Ethanol. , 8.4.3 Arresting Biomass Formation -- 8.4.4 Engineering Cofactor Supply -- 8.4.5 Engineering Strategies Guided by In Silico Simulation -- 8.4.6 Stabilizing Ethanol Synthesis Capacity in Cyanobacterial Cell Factories -- 8.5 Exploring the Response in Cyanobacteria to Ethanol -- 8.5.1 Response of Cyanobacterial Cells Toward Exogenous Added Ethanol -- 8.5.2 Response of Cyanobacteria to Endogenous Synthesized Ethanol -- 8.6 Metabolic Engineering Strategies to Facilitate Robust Cultivation Against Biocontaminants -- 8.6.1 Engineering Cyanobacteria Cell Factories to Adapt for Selective Environmental Stresses -- 8.6.2 Engineering Cyanobacteria Cell Factories to Utilize Uncommon Nutrients -- 8.7 Conclusions and Perspectives -- References -- Chapter 9 Engineering Cyanobacteria as Host Organisms for Production of Terpenes and Terpenoids -- 9.1 Terpenoids and Industrial Applications -- 9.2 Terpenoid Biosynthesis in Cyanobacteria -- 9.2.1 Methylerythritol‐4‐Phosphate Pathway -- 9.2.2 Formation of Terpene Backbones -- 9.3 Natural Occurrence and Physiological Roles of Terpenes and Terpenoids in Cyanobacteria -- 9.4 Engineering Cyanobacteria for Terpenoid Production -- 9.4.1 Metabolic Engineering -- 9.4.1.1 Terpene Synthases -- 9.4.1.2 Increasing Supply of Terpene Backbones -- 9.4.1.3 Engineering the Native MEP Pathway -- 9.4.1.4 Implementing the MVA Pathway -- 9.4.1.5 Enhancing Precursor Supply -- 9.4.2 Optimizing Growth Conditions for Production -- 9.4.3 Product Capture and Harvesting -- 9.5 Summary and Outlook -- Acknowledgments -- References -- Chapter 10 Cyanobacterial Biopolymers -- 10.1 Polyhydroxybutryate -- 10.1.1 Introduction -- 10.1.2 PHB Metabolism in Cyanobacteria -- 10.1.3 Industrial Applications of PHB -- 10.1.3.1 Physical Properties of PHB and Its Derivatives -- 10.1.3.2 Biodegradability -- 10.1.3.3 Application of PHB as a Plastic. , 10.1.3.4 Reactor Types.
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  • 3
    Online Resource
    Online Resource
    Newark :John Wiley & Sons, Incorporated,
    Keywords: Metabolites. ; Genomics. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (339 pages)
    Edition: 1st ed.
    ISBN: 9780470105504
    Series Statement: Wiley Series on Mass Spectrometry Series ; v.24
    DDC: 572.8/6
    Language: English
    Note: Intro -- METABOLOME ANALYSIS -- CONTENTS -- PREFACE -- LIST OF CONTRIBUTORS -- PART I: CONCEPTS AND METHODOLOGY -- 1 Metabolomics in Functional Genomics and Systems Biology -- 1.1 From genomic sequencing to functional genomics -- 1.2 Systems biology and metabolic models -- 1.3 Metabolomics -- 1.4 Future perspectives -- 2 The Chemical Challenge of the Metabolome -- 2.1 Metabolites and metabolism -- 2.2 The structural diversity of metabolites -- 2.2.1 The chemical and physical properties -- 2.2.2 Metabolite abundance -- 2.2.3 Primary and secondary metabolism -- 2.3 The number of metabolites in a biological system -- 2.4 Controlling rates and levels -- 2.4.1 Control by substrate level -- 2.4.2 Feedback and feedforward control -- 2.4.3 Control by "pathway independent" regulatory molecules -- 2.4.4 Allosteric control -- 2.4.5 Control by compartmentalization -- 2.4.6 The dynamics of the metabolism-the mass flow -- 2.4.7 Control by hormones -- 2.5 Metabolic channeling or metabolons -- 2.6 Metabolites are arranged in networks that are part of a cellular interactome -- 3 Sampling and Sample Preparation -- 3.1 Introduction -- 3.2 Quenching-the first step -- 3.2.1 Overview on metabolite turnover -- 3.2.2 Different methods for quenching -- 3.2.3 Quenching microbial and cell cultures -- 3.2.4 Quenching plant and animal tissues -- 3.3 Obtaining metabolites from biological samples -- 3.3.1 Release of intracellular metabolites -- 3.3.2 Structure of the cell envelopes-the main barrier to be broken -- 3.3.3 Cell disruption methods -- 3.3.4 Nonmechanical disruption of cell envelopes -- 3.3.5 Mechanical disruption of cell envelopes -- 3.4 Metabolites in the extracellular medium -- 3.4.1 Metabolites in solution -- 3.4.2 Metabolites in the gas phase -- 3.5 Improving detection via sample concentration -- 4 Analytical Tools -- 4.1 Introduction. , 4.2 Choosing a methodology -- 4.3 Starting point-samples -- 4.4 Principles of chromatography -- 4.4.1 Basics of chromatography -- 4.4.2 The chromatogram and terms in chromatography -- 4.5 Chromatographic systems -- 4.5.1 Gas chromatography -- 4.5.2 HPLC systems -- 4.6 Mass spectrometry -- 4.6.1 The mass spectrometer-an overview -- 4.6.2 GC-MS-the EI ion source -- 4.6.3 LC-MS-the ESI ion source -- 4.6.4 Mass analyzer-the quadrupole -- 4.6.5 Mass analyzer-the ion-trap -- 4.6.6 Mass analyzer-the time-of-flight -- 4.6.7 Detection and computing in MS -- 4.7 The analytical work-flow -- 4.7.1 Separation by chromatography -- 4.7.2 Mass spectrometry -- 4.7.3 General analytical considerations -- 4.8 Data evaluation -- 4.8.1 Structure of data -- 4.8.2 The chromatographic separation -- 4.8.3 Mass spectral data -- 4.8.4 Exporting data for processing -- 4.9 Beyond the core methods -- 4.9.1 Developments in chromatography -- 4.9.2 Capillary electrophoresis -- 4.9.3 Tandem MS and advanced scanning techniques -- 4.9.4 NMR spectrometry -- 4.10 Further reading -- 5 Data Analysis -- 5.1 Organizing the data -- 5.2 Scales of measurement -- 5.2.1 Qualitative data -- 5.2.2 Quantitative data -- 5.3 Data structures -- 5.4 Preprocessing of data -- 5.4.1 Calibration of data -- 5.4.2 Combining profile scans -- 5.4.3 Filtering -- 5.4.4 Centroid calculation -- 5.4.5 Internal mass scale correction -- 5.4.6 Binning -- 5.4.7 Baseline correction -- 5.4.8 Chromatographic profile matching -- 5.5 Deconvolution of spectroscopic data -- 5.6 Data standardization (normalization) -- 5.7 Data transformations -- 5.7.1 Principal component analysis -- 5.7.2 Fisher discriminant analysis -- 5.8 Similarities and distances between data -- 5.8.1 Continuous functions -- 5.8.2 Binary functions -- 5.9 Clustering techniques -- 5.9.1 Hierarchical clustering -- 5.9.2 k-means clustering. , 5.10 Classification techniques -- 5.10.1 Decision theory -- 5.10.2 k-nearest neighbor -- 5.10.3 Tree-based classification -- 5.11 Integrated tools for automation, libraries, and data evaluation -- PART II-CASE STUDIES AND REVIEWS -- 6 Yeast Metabolomics: The Discovery of New Metabolic Pathways in Saccharomyces cerevisiae -- 6.1 Introduction -- 6.2 Brief description of the methodology used -- 6.2.1 Sample preparation -- 6.2.2 The analysis -- 6.3 Early discoveries -- 6.4 Yeast stress response gives evidence of alternative pathway for glyoxylate biosynthesis in S. cerevisiae -- 6.5 Biosynthesis of glyoxylate from glycine in S. cerevisiae -- 6.5.1 Stable isotope labeling experiment to investigate glycine catabolism in S. cerevisiae -- 6.5.2 Data leveraged for speculation -- 7 Microbial Metabolomics: Rapid Sampling Techniques to Investigate Intracellular Metabolite Dynamics-An Overview -- 7.1 Introduction -- 7.2 Starting with a simple sampling device proposed by Theobald et al. (1993) -- 7.3 An improved device reported by Lange et al. (2001) -- 7.4 Sampling tube device by Weuster-Botz (1997) -- 7.5 Fully automated device by Schaefer et al. (1999) -- 7.6 The stopped-flow technique by Buziol et al. (2002) -- 7.7 The BioScope: a system for continuous-pulse experiments -- 7.8 Conclusions and perspectives -- 8 Plant Metabolomics -- 8.1 Introduction -- 8.2 History of plant metabolomics -- 8.3 Plants, their metabolism and metabolomics -- 8.3.1 Plant structures -- 8.3.2 Plant metabolism -- 8.4 Specific challenges in plant metabolomics -- 8.4.1 Light dependency of plant metabolism -- 8.4.2 Extraction of plant metabolites -- 8.4.3 Many cell types in one tissue -- 8.4.4 The dynamical range of plant metabolites -- 8.4.5 Complexity of the plant metabolome -- 8.4.6 Development of databases for metabolomics-derived data in plant science. , 8.5 Applications of metabolomics approaches in plant research -- 8.5.1 Phenotyping -- 8.5.2 Functional genomics -- 8.5.3 Fluxomics -- 8.5.4 Metabolic trait analysis -- 8.5.5 Systems biology -- 8.6 Future perspectives -- 9 Mass Profiling of Fungal Extract from Penicillium Species -- 9.1 Introduction -- 9.2 Methodology for screening of fungi by DiMS -- 9.2.1 Cultures -- 9.2.2 Extraction -- 9.2.3 Analysis by direct infusion mass spectrometry -- 9.3 Discussion -- 9.3.1 Initial data processing -- 9.3.2 Metabolite prediction -- 9.3.3 Chemical diversity and similarity -- 9.4 Conclusion -- 10 Metabolomics in Humans and Other Mammals -- 10.1 Introduction -- 10.2 A brief history of mammalian metabolomics -- 10.3 Sample preparation for mammalian metabolomics studies -- 10.3.1 Working with blood -- 10.3.2 Working with urine -- 10.3.3 Working with cerebrospinal fluid -- 10.3.4 Working with cells and tissues -- 10.4 Sample analysis -- 10.4.1 GC-MS analysis of urine, plasma, and CSF -- 10.4.2 LC-MS analysis of urine, blood, and CFS -- 10.4.3 NMR analysis of CSF, urine, and blood -- 10.5 Applications -- 10.5.1 Identification and classification of metabolic disorders -- 10.6 Future outlook -- INDEX.
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  • 4
    Online Resource
    Online Resource
    Newark :John Wiley & Sons, Incorporated,
    Keywords: Microorganisms. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (768 pages)
    Edition: 1st ed.
    ISBN: 9783527807789
    Series Statement: Advanced Biotechnology Series
    DDC: 660.62
    Language: English
    Note: Cover -- Title Page -- Copyright -- Dedication -- Contents -- List of Contributors -- About the Series Editors -- Preface -- Volume 1 -- Part I Industrial Biotechnology: From Pioneers to Visionary -- Chapter 1 History of Industrial Biotechnology -- 1.1 The Beginning of Industrial Microbiology -- 1.2 Primary Metabolites and Enzymes -- 1.3 The Antibiotic Era -- 1.4 The Biotechnology Era Between 1970 and 2015 -- 1.5 How Pioneering Developments Led to Genetic Engineering -- References -- Chapter 2 Synthetic Biology: An Emerging Approach for Strain Engineering -- 2.1 Introduction -- 2.2 Basic Elements -- 2.3 Functional and Robust Modules -- 2.4 Microbial Communities -- 2.5 Conclusions and Future Prospects -- Acknowledgments -- References -- Chapter 3 Toward Genome-Scale Metabolic Pathway Analysis -- 3.1 Introduction -- 3.2 DD Method -- 3.3 Calculating Short EFMs in Genome-Scale Metabolic Networks -- 3.4 Conclusions -- Acknowledgments -- References -- Chapter 4 Cell-Free Synthetic Systems for Metabolic Engineering and Biosynthetic Pathway Prototyping -- 4.1 Introduction -- 4.2 Background -- 4.3 The Benefits of Cell-Free Systems -- 4.4 Challenges and Opportunities in Cell-Free Systems -- 4.5 Recent Advances -- 4.6 Summary -- Acknowledgments -- References -- Part II Multipurpose Bacterial Cell Factories -- Chapter 5 Industrial Biotechnology: Escherichia coli as a Host -- 5.1 Introduction -- 5.2 E. coli Products -- 5.3 Rewiring Central Metabolism -- 5.4 Alternative Carbon Sources -- 5.5 E. coli Techniques and Concerns -- 5.6 Conclusions -- References -- Chapter 6 Industrial Microorganisms: Corynebacterium glutamicum -- 6.1 Introduction -- 6.2 Physiology and Metabolism -- 6.3 Genetic Manipulation of Corynebacterium glutamicum -- 6.4 Systems Biology of Corynebacterium glutamicum -- 6.5 Application in Biotechnology -- 6.6 Conclusions and Perspectives. , References -- Chapter 7 Host Organisms: Bacillus subtilis -- 7.1 Introduction and Scope -- 7.2 Identification of Genetic Traits Pertinent to Enhanced Biosynthesis of a Value Product -- 7.3 Traits to Be Engineered for Enhanced Synthesis and Secretion of Proteinaceous Products -- 7.4 Engineering of Genetic Traits in Bacillus subtilis -- 7.5 Genome Reduction -- 7.6 Significance of Classical Strain Improvement in Times of Synthetic Biology -- 7.7 Resource-Efficient B. subtilis Fermentation Processes -- 7.8 Safety of Bacillus subtilis -- 7.9 Bacillus Production Strains on the Factory Floor: Some Examples -- Acknowledgments -- References -- Chapter 8 Host Organism: Pseudomonas putida -- 8.1 Introduction -- 8.2 Physiology and Metabolism -- 8.3 Genetic Manipulation -- 8.4 Systems Biology -- 8.5 Application in Biotechnology -- 8.6 Future Outlook -- References -- Part III Exploiting Anaerobic Biosynthetic Power -- Chapter 9 Host Organisms: Clostridium acetobutylicum/Clostridium beijerinckii and Related Organisms -- 9.1 Introduction -- 9.2 Microorganisms -- 9.3 Bacteriophages -- 9.4 ABE Fermentation of Solvent-Producing Clostridium Strains -- 9.5 Genome-Based Comparison of Solvent-Producing Clostridium Strains -- 9.6 Regulation of Solvent Formation in C. acetobutylicum -- 9.7 Genetic Tools for Clostridial Species -- 9.8 Industrial Application of ABE Fermentation -- Acknowledgments -- References -- Chapter 10 Advances in Consolidated Bioprocessing Using Clostridium thermocellum and Thermoanaerobacter saccharolyticum -- 10.1 Introduction -- 10.2 CBP Organism Development Strategies -- 10.3 Plant Cell Wall Solubilization by C. thermocellum -- 10.4 Bioenergetics of C. thermocellum Cellulose Fermentation -- 10.5 Metabolic Engineering -- 10.6 Summary and Future Directions -- Acknowledgments -- References -- Chapter 11 Lactic Acid Bacteria -- 11.1 Introduction. , 11.2 Fermented Foods -- 11.3 Industrially Relevant Compounds -- 11.4 Conclusions -- Conflict of Interest -- References -- Volume 2 -- Part IV Microbial Treasure Chests for High-Value Natural Compounds -- Chapter 12 Host Organisms: Myxobacterium -- 12.1 Introduction into the Myxobacteria -- 12.2 Phylogeny and Classification -- 12.3 Physiology -- 12.4 Growth and Nutritional Requirements -- 12.5 Genetics and Genomics -- 12.6 Secondary Metabolism -- 12.7 Myxococcus -- 12.8 Sorangium -- 12.9 Outlook -- References -- Chapter 13 Host Organism: Streptomyces -- 13.1 Introduction -- 13.2 Streptomyces Genome Manipulation Toolkits -- 13.3 Hosts for Heterologous Production of Natural Products -- Acknowledgments -- References -- Part V Extending the Raw Material Basis for Bioproduction -- Chapter 14 Extreme Thermophiles as Metabolic Engineering Platforms: Strategies and Current Perspective -- 14.1 Introduction -- 14.2 Bioprocessing Advantages for Extremely Thermophilic Hosts -- 14.3 Biobased Chemicals and Fuels: Targets and Opportunities -- 14.4 Considerations for Selecting an Extremely Thermophilic Host -- 14.5 General Strategies for Genetic Manipulation of Extreme Thermophiles -- 14.6 Limitations and Barriers to Genetic Modification of Extreme Thermophiles -- 14.7 Current Status of Metabolic Engineering Efforts and Prospects in Extreme Thermophiles -- 14.8 Metabolic Engineering of Extreme Thermophiles - Tool Kit Needs -- 14.9 Conclusions and Future Perspectives -- Acknowledgments -- References -- Chapter 15 Cyanobacteria as a Host Organism -- 15.1 Introduction and Relevance: Cyanobacteria as a Host Organism -- 15.2 General Description of Cyanobacteria -- 15.3 Genetic Tools -- 15.4 Improving Photosynthetic Efficiency -- 15.5 Direct Conversion of CO2 into Biofuels and Chemicals -- 15.6 Conclusions -- References -- Chapter 16 Host Organisms: Algae. , 16.1 Introduction to Algae as an Industrial Organism -- 16.2 Algal Genetic Engineering -- 16.3 Therapeutic and Nutraceutical Applications -- 16.4 Bioenergy Applications -- 16.5 Other Industrial Applications -- 16.6 Industrial-Scale Algal Production -- 16.7 Conclusions and Potential of Algal Platforms -- References -- Part VI Eukaryotic Workhorses: Complex Cells Enable Complex Products -- Chapter 17 Host Organisms: Mammalian Cells -- 17.1 Introduction -- 17.2 Basics of Cellular Structure and Metabolism -- 17.3 The Genome of CHO Cells -- 17.4 Molecular Biology Tools -- 17.5 Kinetics of Growth and Product Formation -- 17.6 Intracellular Metabolome Analysis -- 17.7 Proteome and Gene Expression Analysis -- 17.8 Improving Cellular Performance by Genetic and Metabolic Engineering -- 17.9 Outlook -- References -- Chapter 18 Industrial Microorganisms: Saccharomyces cerevisiae and other Yeasts -- 18.1 Industrial Application of Yeasts -- 18.2 Baker's Yeast as Versatile Host for Metabolic Engineering -- 18.3 Protein Production in Yeasts -- 18.4 Lipid Production in Yeasts -- 18.5 Pentose-Utilizing Yeasts -- 18.6 Conclusions -- Conflict of Interest -- References -- Chapter 19 Industrial Microorganisms: Pichia pastoris -- 19.1 Physiology and Genetics of Pichia pastoris -- 19.2 Methylotrophic Metabolism -- 19.3 Application for the Production of Recombinant Proteins -- 19.4 Application of P. pastoris for Metabolite Production -- 19.5 Conclusion -- References -- Index -- EULA.
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  • 5
    Online Resource
    Online Resource
    Newark :John Wiley & Sons, Incorporated,
    Keywords: Systems biology. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (512 pages)
    Edition: 1st ed.
    ISBN: 9783527696178
    Series Statement: Advanced Biotechnology Series
    DDC: 570.285
    Language: English
    Note: Intro -- Related Titles -- Title Page -- Copyright -- Table of Contents -- List of Contributors -- About the Series Editors -- Chapter 1: Integrative Analysis of Omics Data -- Summary -- 1.1 Introduction -- 1.2 Omics Data and Their Measurement Platforms -- 1.3 Data Processing: Quality Assessment, Quantification, Normalization, and Statistical Analysis -- 1.4 Data Integration: From a List of Genes to Biological Meaning -- 1.5 Outlook and Perspectives -- References -- Chapter 2: 13C Flux Analysis in Biotechnology and Medicine -- 2.1 Introduction -- 2.2 Theoretical Foundations of 13C MFA -- 2.3 Metabolic Flux Analysis in Biotechnology -- 2.4 Metabolic Flux Analysis in Medicine -- 2.5 Emerging Challenges for 13C MFA -- 2.6 Conclusion -- Acknowledgments -- Disclosure -- References -- Chapter 3: Metabolic Modeling for Design of Cell Factories -- Summary -- 3.1 Introduction -- 3.2 Building and Refining Genome-Scale Metabolic Models -- 3.3 Strain Design Algorithms -- 3.4 Case Studies -- 3.5 Conclusions -- Acknowledgments -- References -- Chapter 4: Genome-Scale Metabolic Modeling and In silico Strain Design of Escherichia coli -- 4.1 Introduction -- 4.2 The COBRA Approach -- 4.3 History of E. coli Metabolic Modeling -- 4.4 In silico Model-Based Strain Design of E. coli Cell Factories -- 4.5 Future Directions of Model-Guided Strain Design in E. coli -- References -- Chapter 5: Accelerating the Drug Development Pipeline with Genome-Scale Metabolic Network Reconstructions -- Summary -- 5.1 Introduction -- 5.2 Metabolic Reconstructions in the Drug Development Pipeline -- 5.3 Species-Level Microbial Reconstructions -- 5.4 The Human Reconstruction -- 5.5 Community Models -- 5.6 Personalized Medicine -- 5.7 Conclusion -- References -- Chapter 6: Computational Modeling of Microbial Communities -- Summary -- 6.1 Introduction -- 6.2 Ecological Models. , 6.3 Genome-Scale Metabolic Models -- 6.4 Concluding Remarks -- References -- Chapter 7: Drug Targeting of the Human Microbiome -- Summary -- 7.1 Introduction -- 7.2 The Human Microbiome -- 7.3 Association of the Human Microbiome with Human Diseases -- 7.4 Drug Targeting of the Human Microbiome -- 7.5 Future Perspectives -- 7.6 Concluding Remarks -- Acknowledgments -- References -- Chapter 8: Toward Genome-Scale Models of Signal Transduction Networks -- 8.1 Introduction -- 8.2 The Potential of Network Reconstruction -- 8.3 Information Transfer Networks -- 8.4 Approaches to Reconstruction of ITNs -- 8.5 The rxncon Approach to ITNWR -- 8.6 Toward Quantitative Analysis and Modeling of Large ITNs -- 8.7 Conclusion and Outlook -- Acknowledgments -- References -- Chapter 9: Systems Biology of Aging -- Summary -- 9.1 Introduction -- 9.2 The Biology of Aging -- 9.3 The Mathematics of Aging -- 9.4 Future Challenges -- Conflict of Interest -- References -- Chapter 10: Modeling the Dynamics of the Immune Response -- 10.1 Background -- 10.2 Dynamics of NF-κB Signaling -- 10.3 JAK/STAT Signaling -- 10.4 Conclusions -- Acknowledgments -- References -- Chapter 11: Dynamics of Signal Transduction in Single Cells Quantified by Microscopy -- 11.1 Introduction -- 11.2 Single-Cell Measurement Techniques -- 11.3 Microscopy -- 11.4 Imaging Signal Transduction -- 11.5 Conclusions -- References -- Chapter 12: Image-Based In silico Models of Organogenesis -- Summary -- 12.1 Introduction -- 12.2 Typical Workflow of Image-Based In silico Modeling Experiments -- 12.3 Application: Image-Based Modeling of Branching Morphogenesis -- 12.4 Future Avenues -- References -- Chapter 13: Progress toward Quantitative Design Principles of Multicellular Systems -- Summary -- 13.1 Toward Quantitative Design Principles of Multicellular Systems. , 13.2 Breaking Multicellular Systems into Distinct Functional and Spatial Modules May Be Possible -- 13.3 Communication among Cells as a Means of Cell-Cell Interaction -- 13.4 Making Sense of the Combinatorial Possibilities Due to Many Ways that Cells Can Be Arranged in Space -- 13.5 From Individual Cells to Collective Behaviors of Cell Populations -- 13.6 Tuning Multicellular Behaviors -- 13.7 A New Framework for Quantitatively Understanding Multicellular Systems -- Acknowledgments -- References -- Chapter 14: Precision Genome Editing for Systems Biology - A Temporal Perspective -- Summary -- 14.1 Early Techniques in DNA Alterations -- 14.2 Zinc-Finger Nucleases -- 14.3 TALENs -- 14.4 CRISPR-Cas9 -- 14.5 Considerations of Gene-Editing Nuclease Technologies -- 14.6 Applications -- 14.7 A Focus on the Application of Genome-Engineering Nucleases on Chromosomal Rearrangements -- 14.8 Future Perspectives -- References -- Index -- End User License Agreement.
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  • 6
    Online Resource
    Online Resource
    Newark :John Wiley & Sons, Incorporated,
    Keywords: Biotechnology industries. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (642 pages)
    Edition: 1st ed.
    ISBN: 9783527807826
    Series Statement: Advanced Biotechnology Series
    Language: English
    Note: Cover -- Title Page -- Copyright -- Dedication -- Contents -- List of Contributors -- About the Series Editors -- Preface -- Part I Enabling and Improving Large-Scale Bio-production -- Chapter 1 Industrial-Scale Fermentation -- 1.1 Introduction -- 1.2 Industrial-Scale Fermentation Today -- 1.3 Engineering and Design Aspects -- 1.4 Industrial Design Examples -- 1.5 Cost Analysis for the Manufacture of Biotechnological Products -- 1.6 Influence of Process- and Facility-Related Aspects on Cost Structure -- Acknowledgments -- References -- Chapter 2 Scale-Down: Simulating Large-Scale Cultures in the Laboratory -- 2.1 Introduction -- 2.2 Heterogeneities at Large Scale and the Need for Scaling Down -- 2.3 Bioreactor Scale-Down -- 2.4 Tools to Study Cell Responses to Environmental Heterogeneities -- 2.5 Physiological Effects of Environmental Heterogeneities -- 2.6 Improvements Based on Scale-Down Studies: Bioreactor Design and Cell Engineering -- 2.7 Perspectives -- Acknowledgment -- References -- Chapter 3 Bioreactor Modeling -- 3.1 Large-Scale Industrial Fermentations: Challenges for Bioreactor Modeling -- 3.2 Bioreactors -- 3.3 Compartment and Hybrid Multizonal/Computational Fluid Dynamics Approaches for the Description of Large-Scale Bioreactor Phenomena -- 3.4 Computational Fluid Dynamics Modeling: Unstructured Continuum Approach (Euler-Euler) -- 3.5 Computational Fluid Dynamics Modeling: Structured Segregated Approach (Euler-Lagrange) -- 3.6 Conclusion -- 3.7 Outlook -- References -- Chapter 4 Cell Culture Technology -- 4.1 Introduction -- 4.2 Overview of Applications for Cell Culture Products and Tissue Engineering -- 4.3 Fundamentals -- 4.4 Bioreactors for Cell Culture -- 4.5 Downstream -- 4.6 Regulatory and Safety Issues -- 4.7 Conclusions and Outlook -- References -- Part II Getting Out More: Strategies for Enhanced Bioprocessing. , Chapter 5 Production of Fuels and Chemicals from Biomass by Integrated Bioprocesses -- 5.1 Introduction -- 5.2 Utilization of Starchy Biomass -- 5.3 Utilization of Lignocellulosic Biomass -- 5.4 Conclusions and Perspectives -- Acknowledgment -- References -- Chapter 6 Solid-State Fermentation -- 6.1 Introduction -- 6.2 Fundamentals Aspects of SSF -- 6.3 Factors Affecting Solid-State Fermentation -- 6.4 Scale-Up -- 6.5 Product Recovery -- 6.6 Bioreactor Designing -- 6.7 Kinetics and Modeling -- 6.8 Applications -- 6.9 Challenges in SSF -- 6.10 Summary -- References -- Chapter 7 Cell Immobilization: Fundamentals, Technologies, and Applications -- 7.1 Introduction -- 7.2 Fundamentals of Cell Immobilization -- 7.3 Immobilization with Support Materials -- 7.4 Self-Immobilization -- 7.5 Immobilized Cells and their Applications -- 7.6 Bioreactors for Cell Immobilization -- 7.7 Challenges and Recommendations for Future Research -- 7.8 Conclusions -- References -- Part III Molecules for Human Use: High-Value Drugs, Flavors, and Nutraceuticals -- Chapter 8 Anticancer Drugs -- 8.1 Natural Products as Anticancer Drugs -- 8.2 Anticancer Drug Production -- 8.3 Important Anticancer Natural Products -- 8.4 Prospects -- References -- Chapter 9 Biotechnological Production of Flavors -- 9.1 History -- 9.2 Survey on Today's Industry -- 9.3 Regulations -- 9.4 Flavor Production -- 9.5 Biotechnological Production of Flavors -- 9.6 Vanillin -- 9.7 2-Phenylethanol -- 9.8 Benzaldehyde -- 9.9 Lactones -- 9.10 Raspberry Ketone -- 9.11 Green Notes -- 9.12 Nootkatone -- 9.13 Future Perspectives -- References -- Chapter 10 Nutraceuticals (Vitamin C, Carotenoids, Resveratrol) -- 10.1 Introduction -- 10.2 Vitamin C -- 10.3 Carotenoids -- 10.4 Resveratrol -- 10.5 Future Perspectives -- References -- Part IV Industrial Amino Acids. , Chapter 11 Glutamic Acid Fermentation: Discovery of Glutamic Acid-Producing Microorganisms, Analysis of the Production Mechanism, Metabolic Engineering, and Industrial Production Process -- 11.1 Introduction -- 11.2 Discovery of the Glutamic Acid-Producing Bacterium C. glutamicum -- 11.3 Analysis of the Mechanism of Glutamic Acid Production by C. glutamicum -- 11.4 Metabolic Engineering of C. glutamicum for Glutamic Acid Production -- 11.5 Glutamic Acid Fermentation by Other Microorganisms -- 11.6 Industrial Process of Glutamic Acid Production -- 11.7 Future Perspectives -- References -- Chapter 12 l-Lysine -- 12.1 Uses of l-Lysine -- 12.2 Biosynthesis and Production of l-Lysine -- 12.3 The Chassis Concept: Biotin Prototrophy and Genome Reduction -- 12.4 l-Lysine Biosensors for Strain Selection and on-Demand Flux Control -- 12.5 Perspective -- References -- Part V Bio-Based Monomers and Polymers -- Chapter 13 Diamines for Bio-Based Materials -- 13.1 Introduction -- 13.2 Diamine Metabolism in Bacteria -- 13.3 Putrescine - 1,4-Diaminobutane -- 13.4 Cadaverine - 1,5-Diaminopentane -- 13.5 Conclusions and Perspectives -- References -- Chapter 14 Microbial Production of 3-Hydroxypropionic Acid -- 14.1 Introduction -- 14.2 3-HP Obtained from Native Producers -- 14.3 Synthesis of 3-HP from Glucose -- 14.4 Synthesis of 3-HP from Glycerol -- 14.5 Bridging the Gap Between Glucose and Glycerol in 3-HP Production -- 14.6 Other Strains for 3-HP Production from Glycerol -- 14.7 Limitations of 3-HP Synthesis -- 14.8 Conclusions and Future Prospects -- Acknowledgments -- References -- Chapter 15 Itaconic Acid - An Emerging Building Block -- 15.1 Background, History, and Economy -- 15.2 Biosynthesis of Itaconic Acid -- 15.3 Production Conditions for Itaconic Acid -- 15.4 Physiological Effects and Metabolism of Itaconic acid. , 15.5 Metabolic Engineering for Itaconic Acid Production -- 15.6 Outlook -- Acknowledgments -- References -- Part VI Top-Value Platform Chemicals -- Chapter 16 Microbial Production of Isoprene: Opportunities and Challenges -- 16.1 Introduction -- 16.2 The Milestones of Isoprene Production -- 16.3 Microbial Production of Isoprene: Out of the Laboratory -- 16.4 Main Challenges for Bioisoprene Production -- 16.5 Future Prospects -- Acknowledgments -- References -- Chapter 17 Succinic Acid -- 17.1 Introduction -- 17.2 Development of Succinic Acid Producers and Fermentation Strategies -- 17.3 Succinic Acid Recovery and Purification -- 17.4 Summary -- Acknowledgments -- References -- Part VII Biorenewable Fuels -- Chapter 18 Ethanol: A Model Biorenewable Fuel -- 18.1 Introduction -- 18.2 Metabolic Engineering: Design, Build, Test, Learn -- 18.3 Biomass Deconstruction -- 18.4 Closing Remarks -- Acknowledgments -- References -- Chapter 19 Microbial Production of Butanols -- 19.1 Introduction -- 19.2 A Historical Perspective of n-Butanol Production -- 19.3 ABE Fermentation -- 19.4 n-Butanol Production in Non-native Producers -- 19.5 Isobutanol Production -- 19.6 Summary and Outlook -- Acknowledgments -- References -- Index -- EULA.
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  • 7
    Online Resource
    Online Resource
    Newark :John Wiley & Sons, Incorporated,
    Keywords: Recombinant proteins. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (439 pages)
    Edition: 1st ed.
    ISBN: 9783527811380
    Series Statement: Advanced Biotechnology Series
    Language: English
    Note: Cover -- Title Page -- Copyright -- Contents -- About the Series Editors -- Chapter 1 Platform Technology for Therapeutic Protein Production -- 1.1 Introduction -- 1.2 Overall Trend Analysis -- 1.2.1 Mammalian Cell Lines -- 1.2.2 Brief Introduction of Advances and Techniques -- 1.3 General Guidelines for Recombinant Cell Line Development -- 1.3.1 Host Selection -- 1.3.2 Expression Vector -- 1.3.3 Transfection/Selection -- 1.3.4 Clone Selection -- 1.3.4.1 Primary Parameters During Clone Selection -- 1.3.4.2 Clone Screening Technologies -- 1.4 Process Development -- 1.4.1 Media Development -- 1.4.2 Culture Environment -- 1.4.3 Culture Mode (Operation) -- 1.4.4 Scale‐up and Single‐Use Bioreactor -- 1.4.5 Quality Analysis -- 1.5 Downstream Process Development -- 1.5.1 Purification -- 1.5.2 Quality by Design (QbD) -- 1.6 Trends in Platform Technology Development -- 1.6.1 Rational Strategies for Cell Line and Process Development -- 1.6.2 Hybrid Culture Mode and Continuous System -- 1.6.3 Recombinant Human Cell Line Development for Therapeutic Protein Production -- 1.7 Conclusion -- Acknowledgment -- Conflict of Interest -- References -- Chapter 2 Cell Line Development for Therapeutic Protein Production -- 2.1 Introduction -- 2.2 Mammalian Host Cell Lines for Therapeutic Protein Production -- 2.2.1 CHO Cell Lines -- 2.2.2 Human Cell Lines -- 2.2.3 Other Mammalian Cell Lines -- 2.3 Development of Recombinant CHO Cell Lines -- 2.3.1 Expression Systems for CHO Cells -- 2.3.2 Cell Line Development Process Using CHO Cells Based on Random Integration -- 2.3.2.1 Vector Construction -- 2.3.2.2 Transfection and Selection -- 2.3.2.3 Gene Amplification -- 2.3.2.4 Clone Selection -- 2.3.3 Cell Line Development Process Using CHO Cells Based On Site‐Specific Integration -- 2.4 Development of Recombinant Human Cell Lines -- 2.4.1 Necessity for Human Cell Lines. , 2.4.2 Stable Cell Line Development Process Using Human Cell Lines -- 2.5 Important Consideration for Cell Line Development -- 2.5.1 Clonality -- 2.5.2 Stability -- 2.5.3 Quality of Therapeutic Proteins -- 2.6 Conclusion -- References -- Chapter 3 Transient Gene Expression‐Based Protein Production in Recombinant Mammalian Cells -- 3.1 Introduction -- 3.2 Gene Delivery: Transient Transfection Methods -- 3.2.1 Calcium Phosphate‐Based Transient Transfection -- 3.2.2 Electroporation -- 3.2.3 Polyethylenimine‐Based Transient Transfection -- 3.2.4 Liposome‐Based Transient Transfection -- 3.3 Expression Vectors -- 3.3.1 Expression Vector Composition and Preparation -- 3.3.2 Episomal Replication -- 3.3.3 Coexpression Strategies -- 3.4 Mammalian Cell Lines -- 3.4.1 HEK293 Cell‐Based TGE Platforms -- 3.4.2 CHO Cell‐Based TGE Platforms -- 3.4.3 TGE Platforms Using Other Cell Lines -- 3.5 Cell Culture Strategies -- 3.5.1 Culture Media for TGE -- 3.5.2 Optimization of Cell Culture Processes for TGE -- 3.5.3 qp‐Enhancing Factors in TGE‐Based Culture Processes -- 3.5.4 Culture Longevity‐Enhancing Factors in TGE‐Based Culture Processes -- 3.6 Large‐Scale TGE‐Based Protein Production -- 3.7 Concluding Remarks -- References -- Chapter 4 Enhancing Product and Bioprocess Attributes Using Genome‐Scale Models of CHO Metabolism -- 4.1 Introduction -- 4.1.1 Cell Line Optimization -- 4.1.2 CHO Genome -- 4.1.2.1 Development of Genomic Resources of CHO -- 4.1.2.2 Development of Transcriptomics and Proteomics Resources of CHO -- 4.2 Genome‐Scale Metabolic Model -- 4.2.1 What Is a Genome‐Scale Metabolic Model -- 4.2.2 Reconstruction of GEMs -- 4.2.2.1 Knowledge‐Based Construction -- 4.2.2.2 Draft Reconstruction -- 4.2.2.3 Curation of the Reconstruction -- 4.2.2.4 Conversion to a Computational Format -- 4.2.2.5 Model Validation and Evaluation -- 4.3 GEM Application. , 4.3.1 Common Usage and Prediction Capacities of Genome‐Scale Models -- 4.3.2 GEMs as a Platform for Omics Data Integration, Linking Genotype to Phenotype -- 4.3.3 Predicting Nutrient Consumption and Controlling Phenotype -- 4.3.4 Enhancing Protein Production and Bioprocesses -- 4.3.5 Case Studies -- 4.4 Conclusion -- Acknowledgments -- References -- Chapter 5 Genome Variation, the Epigenome and Cellular Phenotypes -- 5.1 Phenotypic Instability in the Context of Mammalian Production Cell Lines -- 5.2 Genomic Instability -- 5.3 Epigenetics -- 5.3.1 DNA Methylation -- 5.3.2 Histone Modifications -- 5.3.3 Downstream Effectors -- 5.3.4 Noncoding RNAs -- 5.4 Control of CHO Cell Phenotype by the Epigenome -- 5.5 Manipulating the Epigenome -- 5.5.1 Global Epigenetic Modification -- 5.5.1.1 Manipulating Global DNA Methylation -- 5.5.1.2 Manipulating Global Histone Acetylation -- 5.5.2 Targeted Epigenetic Modification -- 5.5.2.1 Targeted Histone Modification -- 5.5.2.2 Targeted DNA Methylation -- 5.6 Conclusion and Outlook -- References -- Chapter 6 Adaption of Generic Metabolic Models to Specific Cell Lines for Improved Modeling of Biopharmaceutical Production and Prediction of Processes -- 6.1 Introduction -- 6.1.1 Constraint‐Based Models -- 6.1.2 Limitations of Flux Balance Analysis -- 6.1.2.1 Thermodynamically Infeasible Cycles -- 6.1.2.2 Genetic Regulation -- 6.1.2.3 Limitation of Intracellular Space -- 6.1.2.4 Multiple States in the Solution -- 6.1.2.5 Biological Objective Function -- 6.1.2.6 Kinetics and Metabolite Concentrations -- 6.2 Main Source of Optimization Issues with Large Genome‐Scale Models: Thermodynamically Infeasible Cycles -- 6.2.1 Definition of Thermodynamically Infeasible Fluxes -- 6.2.2 Loops Involving External Exchange Reactions -- 6.2.2.1 Reversible Passive Transporters from Major Facilitator Superfamily (MFS). , 6.2.2.2 Reversible Passive Antiporters from Amino Acid‐Polyamine‐organoCation (APC) Superfamily -- 6.2.2.3 Na+‐linked Transporters -- 6.2.2.4 Transport via Proton Symport -- 6.2.3 Tools to Identify Thermodynamically Infeasible Cycles -- 6.2.3.1 Visualizing Fluxes on a Network Map -- 6.2.3.2 Algorithms Developed -- 6.2.4 Methods Available to Remove Thermodynamically Infeasible Cycles -- 6.2.4.1 Manual Curation -- 6.2.4.2 Software and Algorithms Developed for the Removal of Thermodynamically Infeasible Loops from Flux Distributions -- 6.3 Consideration of Additional Biological Cellular Constraints -- 6.3.1 Genetic Regulation -- 6.3.1.1 Advantages of Considering Gene Regulation in Genome‐Scale Modeling -- 6.3.1.2 Methods Developed to Take into Account a Feedback of FBA on the Regulatory Network -- 6.3.2 Context Specificity -- 6.3.2.1 What Are Context‐Specific Models (CSMs)? -- 6.3.2.2 Methods and Algorithms Developed to Reconstruct Context‐Specific Models (CSMs) -- 6.3.2.3 Performance of CSMs -- 6.3.2.4 Cautions About CSMs -- 6.3.3 Molecular Crowding -- 6.3.3.1 Consequences on the Predictions -- 6.3.3.2 Methods Developed to Account for a Total Enzymatic Capacity into the FBA Framework -- 6.4 Conclusion -- References -- Chapter 7 Toward Integrated Multi‐omics Analysis for Improving CHO Cell Bioprocessing -- 7.1 Introduction -- 7.2 High‐Throughput Omics Technologies -- 7.2.1 Sequencing‐Based Omics Technologies -- 7.2.1.1 Historical Developments of Nucleotide Sequencing Techniques -- 7.2.1.2 Genome Sequencing of CHO Cells -- 7.2.1.3 Transcriptomics of CHO Cells -- 7.2.1.4 Epigenomics of CHO Cells -- 7.2.2 Mass Spectrometry‐Based Omics Technologies -- 7.2.2.1 Mass Spectrometry Techniques -- 7.2.2.2 Proteomics of CHO Cells -- 7.2.2.3 Metabolomics/Lipidomics of CHO Cells -- 7.2.2.4 Glycomics of CHO Cells -- 7.3 Current CHO Multi‐omics Applications. , 7.3.1 Bioprocess Optimization -- 7.3.2 Cell Line Characterization -- 7.3.3 Engineering Target Identification -- 7.4 Future Prospects -- References -- Chapter 8 CRISPR Toolbox for Mammalian Cell Engineering -- 8.1 Introduction -- 8.2 Mechanism of CRISPR/Cas9 Genome Editing -- 8.3 Variants of CRISPR‐RNA‐guided Endonucleases -- 8.3.1 Diversity of CRISPR/Cas Systems -- 8.3.2 Engineered Cas9 Variants -- 8.4 Experimental Design for CRISPR‐mediated Genome Editing -- 8.4.1 Target Site Selection and Design of gRNAs -- 8.4.2 Delivery of CRISPR/Cas9 Components -- 8.5 Development of CRISPR/Cas9 Tools -- 8.5.1 CRISPR/Cas9‐mediated Gene Editing -- 8.5.1.1 Gene Knockout -- 8.5.1.2 Site‐Specific Gene Integration -- 8.5.2 CRISPR/Cas9‐mediated Genome Modification -- 8.5.2.1 Transcriptional Regulation -- 8.5.2.2 Epigenetic Modification -- 8.5.3 RNA Targeting -- 8.6 Genome‐Scale CRISPR Screening -- 8.7 Applications of CRISPR/Cas9 for CHO Cell Engineering -- 8.8 Conclusion -- Acknowledgment -- References -- Chapter 9 CHO Cell Engineering for Improved Process Performance and Product Quality -- 9.1 CHO Cell Engineering -- 9.2 Methods in Cell Line Engineering -- 9.2.1 Overexpression of Engineering Genes -- 9.2.2 Gene Knockout -- 9.2.3 Noncoding RNA‐mediated Gene Silencing -- 9.3 Applications of Cell Line Engineering Approaches in CHO Cells -- 9.3.1 Enhancing Recombinant Protein Production -- 9.3.2 Repression of Cell Death and Acceleration of Growth -- 9.3.3 Modulation of Posttranslational Modifications to Improve Protein Quality -- 9.4 Conclusions -- References -- Chapter 10 Metabolite Profiling of Mammalian Cells -- 10.1 Value of Metabolic Data for the Enhancement of Recombinant Protein Production -- 10.2 Technologies Used in the Generation of Metabolic Data Sets -- 10.2.1 Targeted and Untargeted Metabolic Analysis. , 10.2.2 Analytical Technologies Used in the Generation of Metabolite Profiles.
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  • 8
    ISSN: 1522-9602
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Mathematics
    Notes: Abstract The paper presents a mathematical analysis of the criteria for gene therapy of T helper cells to have a clinical effect on HIV infection. The analysis indicates that for such a therapy to be successful, it must protect the transduced cells against HIV-induced death. The transduced cells will not survive as a population if the gene therapy only blocks the spread of virus from transduced cells that become infected. The analysis also suggests that the degree of protection against disease-related cell death provided by the gene therapy is more important than the fraction of cells that is initially transduced. If only a small fraction of the cells can be transduced, transduction of T helper cells and transduction of haematopoietic progenitor cells will result in the same steady-state level of transduced T helper cells. For gene therapy to be efficient against HIV infection, our analysis suggests that a 100% protection against viral escape must be obtained. The study also suggests that a gene therapy against HIV infection should be designed to give the transduced cells a partial but not necessarily total protection against HIV-induced cell death, and to avoid the production of viral mutants insensitive to the gene therapy.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1570-7458
    Keywords: Automatic area estimation ; image processing ; shrinkage correction ; insect plant relationships ; feeding assays ; flea beetle ; Phyllotreta armoraciae ; Phyllotreta nemorum ; horseradish ; radish ; Cruciferae ; glucosinolates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Blattscheiben-Tests haben viele Anwendungs-Möglichkeiten in Studien über Frass-Verhalten von pflanzenfressenden Insekten. Aufnahme von solche Versuche geschieht am Meisten durch visuelle Aufzählung von konsumierten Arealen in einer Präparations-Mikroskop. Diese Aufzählung ist langweilig und zeitraubend. Deshalb ist eine neue automatische Methode entwickelt, die diese aufzählungen ausführen. Mit der neuen Methode wird die Blattscheiben mit einer Videokamera fotografiert, die Bilder werden digitalisiert, und die Aufzählungen geschehen mittels einen Computer. Die neue Methode ausgleicht Veränderungen im Areal der Blattscheiben. Solche veränderungen geschehen oft im Laufe der Tests (24 Stunden Versuchsdauer) nach den Abschneiden der Blattscheiben. Die neue Methode zeigte sich als sehr zeitsparend und ausreichend präzis für viele Zwecke. Kalibrierung mit früheren Methoden, die auch visuelles Zählen beinhalteten wurde ausgeführt. Die neue und die frühere Methode wurden in einer Studie über die relative Akzeptanz von Meerrettich (Armoracia rusticana G., M. & Sch.), Radieschen (Raphanus sativus L.) und Erbsen (Pisum sativum L.) bei zwei kreuzblütlerfressenden Erdfloharten verglichen: Phyllotreta armoraciae (Koch) und P. nemorum L. (Coleoptera: Chrysomelidae: Alticinae). Erbsenblattscheiben wurden mit Sinigrin behandelt, ein bekanntes Frass-Stimulanz für beide Arten. Sowohl Wahl als auch Nicht-Wahl-Tests ergaben das gleiche Resultat, unabhängig von der Methode, die für die Schätzung der konsumierten Fläche benutzt wurde. Beide Arten zogen es in Wahl-Tests vor, an ihren Wirtspflanzen zu fressen, P. armoraciae an Meerrettisch und P. nemorum an Radieschen. Die relativen Mengen, die an Nicht-Wirtspflanzen konsumiert wurden, waren in Nicht-Wahl-Tests grösser als in Wahl-Tests. Unerfahrene P. armoraciae konsumierten gleiche Mengen von Meerrettich und sinigrinbehandelten Erbsen in den Nicht-Wahl-Tests.
    Notes: Abstract An automatic method is described which can measure areas consumed from leaf discs by insects. The method is based on digital image processing and is able to compensate for changes in areas which occur during the feeding experiments after the leaf discs have been cut. Calibration with previous methods involving visual counting has been made. The new method proved to be very time-saving and sufficiently accurate for many purposes. The new and the previous method were compared in a study of the relative acceptability of horseradish (Armoracia rusticana G., M. & Sch.), radish (Raphanus sativus L.) and pea (Pisum sativum L.) to two crucifer feeding flea beetle species, Phyllotreta armoraciae (Koch) and P. nemorum L. (Coleoptera: Chrysomelidae: Alticinae). Pea leaf discs were treated with sinigrin, a known feeding stimulant for both species. Choice as well as non-choice tests yielded the same results independant of the method used for estimation of consumed areas. Both species preferred to feed on their host plants in choice tests, P. armoraciae on horseradish and P. nemorum on radish. Relative amounts consumed from non-host plants were higher in non-choice than in choice tests. Inexperienced P. armoraciae consumed similar amounts of horseradish and pea treated with sinigrin in the non-choice tests.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 91 (1999), S. 359-368 
    ISSN: 1570-7458
    Keywords: Barbarea vulgaris ssp. arcuata ; Cruciferae ; Phyllotreta nemorum ; Chrysomelidae ; Alticinae ; flea beetle ; plant defence ; host plant range ; near-isogenic ; Y-linkage ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract A Y-linked gene (R-gene) in the flea beetle Phyllotreta nemorum L. (Coleoptera: Chrysomelidae: Alticinae) confer the ability of larvae to survive on types of the plant Barbarea vulgaris R.Br. (Brassicaceae) which are immune to attack by susceptible conspecifics. Two near-isogenic flea beetle lines were developed. The YE-line contained the Y-linked R-gene, and male larvae from this line survived on B. vulgaris. The ST-line did not contain the gene and did not survive on the plant. The YE-line had been developed through 8–9 generations of backcrosses (YE-males with ST-females) and the two lines were considered to be isogenic except for genes located on the Y-chromosome. A single copy of the Y-linked gene is sufficient to transfer a susceptible genotype (ST) into a resistant genotype (YE) which is able to utilize a plant that is immune to attack by specimens without R-genes. The Y-linked gene had no effects on survival on other plant species tested. The gene did not have any effect on developmental times and weights of adult beetles reared on other plants than B. vulgaris. Developmental times of larvae with the Y-linked gene were longer on B. vulgaris than on normal host plants, R. sativus and S. arvensis, but the adults obtained the same size on these plant species. No trade-offs of the Y-linked gene were discovered. The results suggest that the occurrence of the Y-linked gene is a derived trait which has enabled the flea beetle to expand its host plant range. The evolution of a host shift to B. vulgaris seems not to be favoured by the presence of this single gene.
    Type of Medium: Electronic Resource
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