Comprehensive Biotechnology, Second Edition

Editor-In-Chief......Page 1
Copyright......Page 3
Volume Editors......Page 4
Secction Editors......Page 7
General Preface......Page 9
6.49.1 Introduction: BES in the Context of Industrial and Environmental Biotechnology......Page 12
6.40.1 Introduction......Page 13
6.40.2.1 Electricity Requirements......Page 14
Permission Acknowledgments......Page 16
Introduction......Page 17
References......Page 18
Amino Acid Metabolism......Page 19
1.02.2 General Properties, Classification, and Structure of Amino Acids......Page 20
6.40.2.2 Excess Sludge Production......Page 22
6.40.3 Sustainability in Wastewater Treatment......Page 23
6.40.3.3.1 Nitrification......Page 24
6.40.3.3.2 OLAND: Partial nitritation and anammox......Page 25
6.40.4 Overall Technology Ranking......Page 26
References......Page 27
6.09.5.4 Chemotactic Bacteria......Page 28
References......Page 29
6.52.6 Conclusion......Page 30
1.03.2 Enzyme Kinetics......Page 31
1.03.3 Enzyme Engineering......Page 35
6.21.2.2 Leachate Release......Page 36
1.03.5 Immobilized Enzymes......Page 38
1.03.6 Enzyme Applications......Page 39
References......Page 40
1.04.1 Introduction: Definitions and Scope......Page 41
1.04.2.1 Application of Immobilized Enzymes as Industrial Catalysts......Page 42
1.04.2.2 Other Applications of Immobilized Enzymes......Page 43
1.04.3.1.1 Carrier-bound immobilized enzymes......Page 44
1.04.3.1.2 Carrier free immobilized enzymes......Page 45
1.04.3.2.2 Membrane retention......Page 46
1.04.5 Evaluation of Enzyme Immobilization......Page 47
1.04.5.1 Immobilization Yields......Page 48
1.04.5.4 Optimization of Enzyme Immobilization......Page 49
6.49.6.4 Perchlorate......Page 50
1.04.6.2.2 Internal diffusional restrictions......Page 52
References......Page 54
1.05.2 Structure of Fatty Acids......Page 56
1.05.3 Nomenclature......Page 58
1.05.5 What Do Lipids Do?......Page 59
1.05.6.1 Classical Synthesis......Page 61
1.05.6.2 Polyketide Route......Page 64
1.05.7 Biochemistry of Lipid Accumulation......Page 65
References......Page 67
1.06.1 Introduction......Page 68
1.06.2 Cloning Vectors: Replication Origins and Partition Regions......Page 70
1.06.3 Cloning Vectors: Selection Markers......Page 71
1.06.4 Preparing DNA Fragments for Ligation......Page 72
1.06.5 Ligation Systems......Page 73
1.06.6 Methods of Bacterial and Yeast Transformation......Page 75
1.06.7 Exploitation of Bacteriophage Packaging for DNA Cloning in Plasmid Vectors......Page 76
1.06.8 Screening of Plasmid Clones in Bacteria for the Desired Recombinant Plasmids......Page 77
1.06.9 Vector-Implemented Systems for the Direct Selection of Recombinant Plasmids......Page 78
1.06.10 Direct Selection of Recombinant Plasmids Involving Restriction Enzyme Digestion of the Ligation Mixture......Page 80
6.48.3.2.2.1 Biohydrogen from hydrolyzed cellulose......Page 81
1.06.14 Instability of Recombinant Plasmids......Page 82
1.06.15 DNA Cloning Using Site-Specific Recombination......Page 83
1.06.18 Conclusion......Page 84
References......Page 85
Relevant Websites......Page 86
1.07.1 Introduction......Page 87
1.07.2.2 Stereochemical Projections of Carbohydrates......Page 89
1.07.2.4 Anomericity......Page 90
1.07.2.5 Stereoelectronic Effects......Page 91
1.07.3.1 Torsion Angles of Glycosidic Linkages......Page 93
1.07.3.2 Oligosaccharide Nomenclature......Page 94
1.07.4.1 N-Linked Glycans: Glycoprotein Folding and Processing......Page 96
1.07.4.2 O-Linked Glycans: Glycoprotein Folding and Processing......Page 99
1.07.5.1 Overview......Page 100
1.07.5.2 Case Study: Structure of Therapeutic Antibody Glycoforms......Page 102
Relevant Websites......Page 104
1.08.1 Introduction......Page 105
1.08.2 Synthesis of Phosphoribosyl Diphosphate (PRPP)......Page 106
1.08.3.1 The Formation of IMP......Page 107
1.08.4.1 The Formation of UMP......Page 111
1.08.6 Deoxyribonucleotide Biosynthesis......Page 112
1.08.7.1 Salvage Pathways......Page 113
1.08.7.2 Uptake of Nucleosides and Nucleobases......Page 115
1.08.9.1 Nucleotide Regulation at the Mechanistic Level......Page 116
1.08.9.2 Nucleotide Regulation at the Systems Level......Page 119
6.31.4.2 Kinetics and Modeling......Page 120
1.09.1 Introduction......Page 122
1.09.2 Citric Acid......Page 123
1.09.2.1 Biochemistry of Citric Acid Accumulation......Page 124
1.09.2.2.1 Factors that influence fermentation......Page 125
6.15.3.2 (Bio)degradation Pathways of Nitramine Explosives......Page 127
1.09.3.1 Biochemistry of Gluconic Acid Accumulation......Page 128
1.09.4 Lactic Acid......Page 129
1.09.5 Itaconic Acid......Page 130
6.27.5 Conclusions......Page 131
References......Page 132
Peptides and Glycopeptides......Page 134
1.10.1 Introduction......Page 135
1.10.2.1 Angiotensin II and Bradykinin......Page 136
1.10.3.2 Neuropeptide Y......Page 137
1.10.4 Antibacterial Peptides......Page 138
1.10.5 Glycosylation Is a Common and Important Post-Translational Modification of Peptides......Page 139
1.10.6.2.1 Threonine O-glycosylation in drosocin......Page 140
1.10.7 Peptide Synthesis......Page 141
1.10.7.1 Solid-Phase Peptide Synthesis......Page 142
1.10.8.1 Controlling Regio- and Stereoselectivity......Page 143
1.10.8.3 Strategies for Glycopeptide Synthesis......Page 144
1.10.9.1 Mucin Glycoprotein Model Peptides......Page 145
1.10.9.3 Collagen Glycoprotein Model Peptides......Page 146
1.10.10.1 A Peptide-Based Malaria Vaccine......Page 147
1.10.10.2.2 A glycopeptide vaccine based on the MUC1 glycoprotein......Page 148
References......Page 150
1.11.1 Introduction......Page 152
6.04.3 Community Fingerprinting......Page 153
1.11.2.2 Protein Crystallization......Page 154
6.09.1.4 Bioavailability versus Chemical Activity......Page 155
1.11.2.4 Structure Determination......Page 156
1.11.2.6 Applications of Protein Crystallography to Biology......Page 157
1.11.3.1 Principles of NMR Spectroscopy......Page 158
6.31.3.2 Kinetics......Page 159
1.11.3.4 Beyond High-Resolution Structure......Page 161
1.11.4.1 Overview......Page 162
1.11.4.3 Instrumentation......Page 163
1.11.4.5 Tryptophan Fluorescence as Probe of Protein Structure......Page 164
1.11.4.6 Tryptophan Fluorescence as Probe of Ligand Binding......Page 165
References......Page 166
1.12.1 Introduction......Page 167
1.12.2 Antibiotics......Page 168
1.12.2.1 β-Lactam Antibiotics......Page 169
1.12.2.4 Macrolides and Other Polyketides......Page 170
1.12.2.6 Other Peptides......Page 171
1.12.2.8 Synthetic Antimicrobials......Page 172
1.12.2.11 The Need for New Antibiotics......Page 173
1.12.3.1 Anticancer Agents......Page 175
1.12.3.2 Immunosuppressants......Page 176
1.12.3.3 Hypocholesterolemic Compounds......Page 177
1.12.3.5 Other Applications......Page 178
References......Page 179
1.13.1 Introduction......Page 180
1.13.2.2.1 Robotic colony picking......Page 181
1.13.2.2.2 Flow cytometry and fluorescence-activated cell sorting......Page 183
1.13.3.2.1 Microbioreactors......Page 184
1.13.4.1 Regulatory Considerations......Page 185
1.13.4.4 Classical Cell Line Development......Page 186
1.13.4.6 Host Cell Engineering: The New Frontier......Page 187
References......Page 188
1.14.1 Introduction......Page 190
1.14.3 Hypothermic Continuum......Page 191
1.14.4 Cryopreservation......Page 192
1.14.5.1 Apoptosis......Page 193
6.41.3.2.3 Filter function and performance......Page 195
1.14.8 Targeted Control of Molecular-Based Death......Page 196
References......Page 197
Further Reading......Page 198
1.15.1 Introduction......Page 202
1.15.2.2 Dimeric Myosins......Page 203
1.15.2.3 Monomeric Myosins......Page 204
1.15.2.4 The ATPase Cycle of Myosins and Their Interaction with Their Actin Tracks......Page 206
1.15.2.5 Regulation of Myosins......Page 208
1.15.3.1 The Anatomy of Migrating Cells......Page 209
6.03.10 Translating Biodegradation Knowledge into Predictive Power......Page 210
1.15.3.3 Actin Polymerization Is Important in Protrusion of the Leading Edge......Page 211
1.15.3.6 Myosins and Cell Polarity......Page 213
1.15.4 Involvement of Unconventional Myosins in Cell Migration and Trafficking......Page 214
6.20.3 Transgenic Plants and Bacteria for Phytoremediation......Page 215
1.16.1 Introduction......Page 216
1.16.2.2 Amino Acids......Page 217
6.20.2.1.2 Rhizofiltration: Adsorption of contaminants on roots......Page 218
1.16.3.1 Basic Research......Page 219
1.16.3.2.1 Growing cells for cell therapy applications......Page 220
1.16.4.1 Design of Experiment-based Methods......Page 221
1.16.5 Manufacturing of the Designed Medium......Page 223
1.16.7 Quality Control Testing......Page 224
References......Page 225
1.17.1 Introduction: Protein Folding......Page 227
1.17.3.1 BiP/GRP78......Page 229
1.17.5 PDI: Redox-Dependent Folding and Disulfide Bond Formation......Page 231
1.17.7 Quality Control and ER-Associated Degradation......Page 232
1.17.10.1 PERK Signaling and Attenuation of Protein Translation......Page 233
1.17.11 UPR and Apoptosis......Page 234
References......Page 236
1.18.1 Introduction......Page 238
1.18.2 The Diversity......Page 239
1.18.3.1 Background......Page 240
6.08.1.3 Objectives and Organization......Page 241
1.18.3.4 Biomass Conversion......Page 243
1.18.4.2 Cold-Active Enzymes......Page 244
1.18.4.3 Bioremediation......Page 245
1.18.5.1 Background......Page 246
1.18.5.3 Biomining–Bioleaching......Page 247
1.18.6.1 Background......Page 248
1.18.6.2 Detergent Proteases......Page 249
1.18.7 Conclusion......Page 250
References......Page 251
1.19.1 Introduction......Page 252
1.19.2 Classical Mutagenesis......Page 253
1.19.4 Recombinant DNA Technology and First-Generation Metabolic Engineering......Page 254
1.19.5 Quantitative Approaches for Metabolic Design......Page 258
6.10.3.3 Anaerobic Metabolism of Aromatic Hydrocarbons......Page 261
1.19.7 Synthetic Biology: Parts, Devices, and Circuits......Page 262
References......Page 263
Relevant Websites......Page 264
Microbial Growth Dynamics......Page 265
1.20.2.1 State Variables and Growth Parameters......Page 266
1.20.2.2 Exponential Growth......Page 268
1.20.2.3 Monod Model: Explanation of Growth Limitation by Availability of Substrate......Page 270
1.20.2.4 Modifications of the Monod Models......Page 273
1.20.2.5 Structured Models......Page 276
1.20.2.6 Genome-Scale Metabolic Network Models, Flux Balance Analysis......Page 277
1.20.2.7 Dynamic Models of Intermediate Complexity, Synthetic Chemostat Model......Page 278
1.20.3.1 Yield Variation as Dependent on Nutrient Substrates: Catabolic Substrates......Page 280
1.20.3.2 Yield Variation as Dependent on Nutrient Substrates: Anabolic Substrates......Page 281
1.20.3.3 Effect of Environmental Factors......Page 282
1.20.3.4 Self-Inhibition of Growth: Metabolic Acidification and Alkalization......Page 285
1.20.3.6 Growth and Production of Antibiotics and Other Secondary Metabolites......Page 287
1.20.3.7 Population Dynamics: Mutations, Autoselection, and Plasmid Transfer......Page 288
References......Page 290
1.21.1 Introduction......Page 292
1.21.2 Batch Culture: The Basis for All Cell Culture Systems......Page 295
1.21.2.1 Batch Culture Kinetics......Page 296
1.21.2.2 Bioreactor and Process Control......Page 297
1.21.3 Fed-Batch Culture: Dominator of Industrial-Scale Processes......Page 298
1.21.3.1 Feed Medium Design......Page 299
1.21.3.3 Process and Bioreactor Control......Page 300
1.21.4.1 Kinetics......Page 301
1.21.4.2.1 Cell retention through immobilization......Page 302
1.21.4.2.2 Cell retention systems for suspension culture......Page 303
1.21.4.3 Scale-Up and Optimization......Page 305
1.21.5 Concluding Remarks on the Selection of Culture Mode......Page 306
References......Page 308
6.31.4 Anaerobic Biotransformation Processes......Page 309
1.22.2 Modes of Microbial Culture......Page 310
1.22.2.1 Batch Cultures......Page 311
1.22.2.1.1 Batch culture variations......Page 312
1.22.2.2.1 Chemostat variations......Page 313
1.22.3.1 Harvesting Microbes and Wall Growth......Page 314
1.22.3.2.1 Serial transfer......Page 315
1.22.3.2.2 Continuous cultures......Page 317
1.22.3.2.3 New variations on long-term culture......Page 318
References......Page 320
1.23.1 Introduction......Page 322
1.23.2 Energy Absorption, Trapping, Conversion, and Storage......Page 324
1.23.3 Photostasis and Cellular Energy Imbalance......Page 325
1.23.4 Photoacclimation Tailors the Photosynthetic Apparatus......Page 326
1.23.5 Acclimation to Low Temperature Mimics Photoacclimation......Page 327
1.23.6 Conclusions......Page 328
References......Page 329
Protein Expression in Insect Cells......Page 330
1.24.1 Historical Background and General Introduction......Page 331
1.24.2.1 Genomics and Phylogeny......Page 332
1.24.2.3.3 Very late gene expression......Page 333
1.24.3.2 Linear Virus DNA and Recombinant Virus Production......Page 335
1.24.3.4.1 BacPAK6 transfer plasmids......Page 336
1.24.3.5.1 Bac-N-Blue transfer plasmids......Page 337
1.24.4.2 MultiBac – Protein Production from Multiple Genes......Page 338
1.24.6.1 BaculoDirect......Page 339
1.24.7.3 Insect Cell-Free expression......Page 340
1.24.8.3.2 Mimic cells......Page 341
1.24.10.1 Cloning Genes into Baculovirus Transfer Plasmids......Page 342
References......Page 343
1.24.10.4 High Throughput (HTP) Baculovirus Expression......Page 345
1.24.11 Concluding Summary......Page 346
Relevant Websites......Page 347
Stem Cells......Page 348
6.13.1 Introduction......Page 349
1.25.2.2 Sources and Methods of Deriving hESCs......Page 350
1.25.2.4 Differentiation Capabilities......Page 351
1.25.3.1 Discovery of Reprogramming......Page 352
1.25.3.2 Characterization to Authenticate hiPSCs......Page 353
1.25.3.4.1 Sources of cells......Page 354
1.25.4.1 Initial Discovery......Page 355
1.25.4.2 Sources and Niche of NSCs......Page 356
1.25.4.4 Differentiation Capabilities......Page 357
1.25.5.2 Sources and Niches of MSCs......Page 359
1.25.5.3 Characteristics......Page 360
1.25.5.5.1 Immune-modulatory therapy......Page 361
1.25.5.6 Conclusion......Page 363
1.25.6.4.1 Osteoblastic niche......Page 364
1.25.6.5.2 Common lymphoid progenitors......Page 365
1.25.6.7.1 HLA-matching of HSC sources......Page 367
1.25.6.8 Conclusion......Page 368
References......Page 369
Structural Organization of Cells – The Cytoskeleton......Page 373
1.26.2.2.1 Microfilaments......Page 374
1.26.2.2.3 Intermediate filaments......Page 375
1.26.2.3 Polymerization, Polarity, and Treadmilling......Page 376
1.26.2.4 Associated Proteins......Page 377
1.26.3 Cytoskeletal Arrays and Their Structural Functions......Page 378
6.45.6 Concluding Remarks......Page 379
1.26.4.2.1 Actin microfilament-based molecular motors: Myosins......Page 380
1.26.4.2.2 Microtubule-based molecular motors: Kinesins and dyneins......Page 381
1.26.4.3.2 Cell locomotion......Page 382
1.26.4.3.3 Contractility......Page 384
1.26.5.2 Microtubule-Related Diseases......Page 386
Relevant Websites......Page 387
1.27.1 Introduction......Page 388
1.27.3 Types of Growth Flasks......Page 389
1.27.4.3 Cell Density......Page 393
1.27.4.4 Media pH......Page 394
1.27.5.1 Gradient Ultracentrifugation......Page 395
1.27.5.2 Ultrafiltration......Page 397
6.48.4.2 Metabolic Shift by End-Product Inhibition......Page 398
1.28.1 Introduction......Page 399
1.28.2.2 Chemical Methods......Page 400
1.28.2.2.3 PEI–DNA condensation method......Page 401
1.28.3 Advances in Large-Scale Transfection Technology......Page 403
References......Page 404
1.34.1 Introduction......Page 406
1.34.2.1 Peptide Ionization......Page 407
1.34.3.1 Gel-Based Proteomics......Page 408
1.34.3.3 LC or Gel Based?......Page 409
1.34.4.2 Quantitative Methods in LC–MS Proteomics......Page 410
References......Page 411
1.34.5 Data Processing......Page 412
1.34.6 Applications in Biotechnology......Page 413
References......Page 414
1.29.2 Translational Machinery......Page 415
1.29.3 Manipulation of mRNA for Optimal Translational Efficiency......Page 418
1.29.5 mRNA Translation Shutdown......Page 419
References......Page 420
1.30.2 Cell Influences on Protein Expression......Page 422
1.30.4 Improving the Protein Folding and Secretory Pathways......Page 423
1.30.7 Cell Clearance of Misfolded Proteins......Page 424
1.30.9 Analytical Techniques for Protein Aggregate Detection......Page 425
6.46.2.3.4 Filamentous fungi......Page 427
Relevant Websites......Page 428
1.35.1 Introduction and Scope......Page 429
6.09.1.1 Biovailability as a Prerequisite for Bioremediation......Page 430
1.35.2.2.2 In silico approach......Page 431
1.35.2.2.3(i) Amino acid production......Page 432
1.35.2.2.3(ii) Lycopene production......Page 433
1.35.2.3.2 Synthetic pathway optimization......Page 434
1.35.2.3.3(i) Algorithm for synthetic pathway reconstruction......Page 435
1.35.2.3.3(ii) Synthetic pathway reconstruction......Page 436
1.35.2.3.3(iii) Synthetic pathway optimization......Page 437
1.35.2.4.3(ii) Synthetic genome......Page 438
1.35.3 Summary......Page 439
References......Page 440
1.31.1 Introduction......Page 441
6.35.2 Sludge Production and Characterization......Page 442
1.31.3 Engineering the Regulation of Protein Folding and Assembly: The Unfolded Protein Response......Page 443
1.31.5 Engineering of the Secretory Apparatus......Page 444
1.31.6 Mathematical Modeling of Recombinant Protein Synthesis and Secretion......Page 445
References......Page 446
1.32.1 Introduction......Page 449
1.32.2.1 HPLC-Based High-Throughput Analysis......Page 450
1.32.2.2 Mass Spectrometry......Page 452
6.12.2.3 Benzene Dioxygenase Enzymology......Page 453
1.32.3 Glycomics in Bioproduction......Page 454
1.32.3.1.1 Hormones: FSH......Page 455
1.32.3.1.2 Growth factors: EPO......Page 456
1.32.3.1.3 Enzyme replacement therapies for lysosomal storage diseases......Page 457
1.32.3.1.5 Antibody-derived therapeutics......Page 458
1.32.3.2 Engineering Glycosylation for Improved Glycoprotein Function......Page 459
1.32.3.2.3 The bisecting β(1,4)-N-acetylglucosamine influences ADCC......Page 460
6.08.4 Future Directions......Page 461
1.32.3.3.3 Restructuring of yeast N-linked glycan biosynthesis......Page 462
1.32.3.3.5 Murine-derived N-linked glycosylation......Page 463
1.32.5 Summary......Page 464
References......Page 465
1.36.1 Introduction......Page 469
1.36.3 Apoptotic Pathways......Page 470
1.36.3.1 Intrinsic Pathway......Page 471
1.36.3.2 ER Stress Pathway......Page 472
1.36.4 Apoptosis and Autophagy......Page 473
1.36.5 Inhibition of Apoptosis......Page 475
1.36.6 Apoptosis affects Metabolic Pathways......Page 476
References......Page 477
1.33.1 Introduction......Page 481
1.33.2.1 GS Coupled to MS......Page 482
6.55.2.2 Case History 2: Bioconversion of Palladium- and Platinum-Containing Industrial and Automotive Catalyst Wastes into Catalysts for (1) Treatment of Environmental Contaminants and (2) Clean Electricity Generation......Page 483
1.33.4 Bioinformatics: What Can It Do......Page 484
1.33.5 What Does the Informatician Need to Analyze the High-Density Data?......Page 485
1.33.6 Data Preprocessing: From Raw to Sense......Page 486
1.33.6.1 Normalization and Data Transformation......Page 487
1.33.6.1.2 Median......Page 489
Relevant Websites......Page 490
1.33.7.2.3 Hierarchical cluster analysis......Page 491
1.33.8 Conclusions......Page 492
References......Page 493
1.37.1 Introduction......Page 494
1.37.2.2 Ionic Complementarity......Page 495
1.37.2.2.2 Physical/biochemical properties......Page 496
1.37.2.2.3 Peptide self-assembly and control......Page 497
1.37.2.3 Hydrogen Bonding Complementarity......Page 498
1.37.2.4 Amino Acid Pairing......Page 499
1.37.3.1 Peptide-Mediated Drug Delivery......Page 500
1.37.3.1.1 Complexation of ellipticine with self-assembling peptides and its release into a cell membrane mimic......Page 501
1.37.3.1.2 Cellular toxicity and uptake of EAK16-II–ellipticine complexes......Page 502
1.37.3.2 Peptide-Mediated siRNA Delivery......Page 505
1.37.3.3 Tissue Engineering......Page 506
1.37.3.4 Biosensors......Page 507
6.31.3.3.2 Structured models......Page 508
1.38.1 Introduction......Page 509
1.38.2 Fundamentals of Metabolic Control Analysis......Page 510
1.38.2.1 Metabolic Modeling......Page 511
1.38.3.1 MCA for the Identification of Drug Targets in Human Parasitic Diseases......Page 512
6.50.6 Non-Cereal-Based Processes......Page 514
1.38.3.2.2 OxPhos inhibitors......Page 515
1.38.3.3 Enhanced Production of Amino Acids......Page 516
1.38.3.3.2 Metabolic engineering for l-phenylalanine production......Page 518
1.38.3.4 Enhanced Production of the Biogas Methane......Page 519
References......Page 522
Unfolded Protein Response......Page 523
1.39.2 Molecular Mechanism of the UPR......Page 524
1.39.2.1 ER Chaperones......Page 525
1.39.2.2 ER-Associated Degradation......Page 526
1.39.2.3.1 ATF6 pathway......Page 528
1.39.2.3.2 IRE1 pathway......Page 529
1.39.2.3.3 PERK pathway......Page 531
1.39.2.3.5 Apoptotic pathways......Page 532
1.39.3.3 Mitochondrial Unfolded Protein Response......Page 533
1.39.4 Concluding Remarks......Page 534
References......Page 535
1.40.1 Introduction......Page 536
1.40.2.3 Gradient Sensing and Chemotaxis......Page 537
1.40.3.1 Cell Migration in the Immune System......Page 539
1.40.3.3 Cell Migration in Wound Healing......Page 540
1.40.4.1 In Vitro Cell Migration Assays......Page 541
1.40.5 Summary and Outlook......Page 542
References......Page 543
1.41.1 Introduction......Page 544
1.41.2 Model Systems for Growing and Analyzing Biofilms......Page 545
1.41.2.2 Growth and Microscopic Analysis of Biofilms Formed in Continuous-Culture (Flowing) Systems......Page 546
1.41.4 Stages of Biofilm Development......Page 548
1.41.4.3 Step 3: Mature Biofilm Formation......Page 549
1.41.5.1 Quorum Sensing......Page 550
1.41.5.1.2(iii) QS inhibition as a means of attenuating virulence and biofilm formation......Page 551
6.24.6.1.1 Classification of wetlands......Page 552
1.41.7.1 Restricted Penetration......Page 553
1.41.8 Antibiotics Act as Signals that Stimulate Biofilm Formation......Page 554
References......Page 555
1.42.1 Introduction......Page 556
6.37.2 Phthalic Acid Esters (Phthalates), PAEs......Page 557
1.42.3 Data Representation......Page 559
1.42.4.3 Cell Physiology......Page 565
1.42.4.3.3 Cytosolic Ca2+ Concentrations......Page 566
1.42.4.3.4 Ros Generation......Page 567
1.42.4.4 Membrane Integrity, Apoptosis, and Necrosis......Page 568
1.42.4.5 Cell Cycle, DNA, and RNA Analysis......Page 569
1.42.4.7 Cell Sorting......Page 572
1.42.4.8 Imaging Flow Cytometer......Page 573
References......Page 574
Relevant Websites......Page 575
1.43.1 Introduction......Page 576
1.43.2 The Case for Superresolution Microscopy Techniques......Page 577
1.43.3 Near-Field Scanning Optical Microscopy......Page 579
1.43.4 Stimulated Emission Depletion......Page 580
1.43.5 Superresolution Structured Illumination Microscopy......Page 581
1.43.6 Photoactivation Localization Microscopy, Fluorescence Photoactivation Localization Microscopy, and’Stochastic’Optical Reconstruction’Microscopy......Page 583
References......Page 585
Relevant Websites......Page 586
1.44.1 Introduction......Page 587
1.44.3 Tissue/Organ Preservation......Page 588
1.44.6.2 Enzymatic Dissociation......Page 589
6.52.3.1.2 Encapsulation......Page 590
1.44.7.1 Regular Centrifugation......Page 591
1.44.8.2 Cell Viability......Page 592
References......Page 593
1.45.1 Introduction......Page 595
1.45.3.1 Nanoparticles for Molecular Diagnostics......Page 598
1.45.3.3 Paramagnetic and Superparamagnetic Nanoparticles......Page 599
1.45.4.1 Role of Nanobiotechnology in Drug Discovery and Development......Page 600
1.45.4.3 Nanobiotechnology and Drug Delivery Devices......Page 601
6.31.3.2.2 Fermentation and anaerobic oxidation of hydrolysis products......Page 602
1.45.5.5 Role of Nanobiotechnology in RNA Interference......Page 603
1.45.6 Clinical Nanomedicine......Page 604
1.45.7.2 Combination of Diagnosis and Therapy in Cancer......Page 605
1.45.8.1 Role of Nanobiotechnology in Diagnosis of Neurological Disorders......Page 606
6.41.4.4 Sessile Biomass Quantification......Page 607
1.45.11 Nanorobotics......Page 608
1.45.13.1 Fate of Nanoparticles in the Human Body......Page 609
References......Page 610
1.46.1 Introduction......Page 611
1.46.2 Shear Stress......Page 612
1.46.3.2 Integrin-Mediated Signaling......Page 613
1.46.3.4.4 Primary cilia......Page 614
1.46.4.1 Role of Shear in Leukocyte Rolling and Arrest on ECs......Page 615
1.46.5.2 Cardiovascular Development......Page 616
1.46.5.4 VEGF Signaling......Page 617
References......Page 618
Viruses and Virus-Like Particles in Biotechnology: Fundamentals and Applications......Page 620
1.47.2.2 Virus with RNA......Page 621
1.47.2.2.3 Group V: (−) ssRNA viruses......Page 622
1.47.3.1 VLPs of Structurally Simple Viruses......Page 623
1.47.4.1 Cell Lines for Virus Production......Page 626
1.47.4.1.1 Cell lines used to produce adenovirus......Page 627
1.47.4.2.1 Bacteria and yeast cells......Page 629
1.47.4.2.2 Baculovirus/insect cell system......Page 630
1.47.5.1.2 Gene therapy......Page 631
1.47.5.2 VLP Applications......Page 632
1.47.5.2.4 Drug delivery......Page 633
1.47.6.3 The Downstream Processing......Page 634
1.47.6.5 The Key Process-Related Parameters......Page 635
1.47.7 Concluding Remarks and Future Trends......Page 636
References......Page 637
1.48.1 Introduction......Page 645
1.48.2 Metabolic Network Models and Flux Balance Analysis......Page 646
1.48.3 Reverse Engineering of Gene Regulatory Networks......Page 647
1.48.4 Continuous Ordinary Differential Equation-Based Dynamic Models......Page 648
1.48.7 Conclusion......Page 650
References......Page 651
1.49.1 Introduction......Page 653
1.49.1.2.1 Hapten design......Page 654
1.49.2 Immunoassay Formats......Page 655
1.49.2.3 Format Considerations......Page 656
1.49.2.5 Microarrays......Page 657
1.49.2.7 Immunosensors......Page 658
1.49.3.3 Proteomics......Page 659
References......Page 660
Relevant Websites......Page 661
1.50.1 Introduction......Page 662
1.50.2.3 Matrix-Assisted Laser Desorption/Ionization......Page 663
1.50.3.1 Quadrupoles......Page 664
1.50.3.3 Time-of-Flight Analyzers......Page 665
1.50.4.1 HPLC/MS......Page 666
1.50.4.3 Capillary electrophoresis......Page 667
1.50.6 Concluding Remarks......Page 668
References......Page 669
Relevant Websites......Page 670
1.51.1 Introduction......Page 671
1.51.2 Production Strain Development......Page 672
1.51.3.1 Inoculum Generation......Page 674
1.51.3.3 Production Fermentation......Page 675
1.51.4 Product Recovery and Purification......Page 676
1.51.4.2 Product Purification......Page 677
1.51.5.2 Inoculum Generation......Page 678
1.51.5.3 Intermediate Fermentation......Page 679
1.51.5.4 Production Fermentation......Page 680
1.51.6 Process Documentation......Page 681
Relevant Websites......Page 682
vol2......Page 683
Introduction......Page 684
2.02.2 The Impact of Science and Technology on Society......Page 687
2.02.3 Roots and Development of Evolutionary Biology and of Genetics......Page 688
2.02.5 Molecular Mechanisms and Natural Strategies of Spontaneous Genetic Variation......Page 689
2.02.8 Prospects of Bioengineering......Page 690
2.02.9 Public Perception of Genetics, Biological Evolution, and Bioengineering......Page 691
References......Page 692
2.03.1 Introduction......Page 693
2.03.2.1.1 E. coli for heterologous protein production......Page 694
2.03.2.1.5 1,3-Propanediol......Page 695
6.23.4.2 Mesocosm Studies......Page 696
2.03.2.6 Lactic Acid Bacteria......Page 697
2.03.3.1.1 Saccharomyces cerevisiae......Page 698
2.03.3.2 Aspergillus......Page 699
2.03.4.1.1 Algae for biodiesel......Page 700
2.03.4.2 Other Plant Cells......Page 701
2.03.6 Human Stem Cells......Page 702
2.03.7 Artificial Cells......Page 704
References......Page 705
2.04.1.1 Overview......Page 706
6.39.2.3 Toxicity Monitoring Biosensors......Page 707
2.04.2.2 Models of Mixed Cultures......Page 708
2.04.2.4 Population Models Based on Single-Cell Models (Segregated and Chemically Structured Models)......Page 709
2.04.2.6 Cybernetic Models......Page 710
2.04.2.8 Models Specific to Animal Cells......Page 711
References......Page 712
2.05.1 Introduction......Page 714
2.05.2.1 Michaelis–Menten Equation......Page 715
2.05.2.3 Experimental Determination of Kinetic Parameters in the Michaelis–Menten Equation......Page 716
2.05.2.4.1 Allosteric enzyme......Page 717
2.05.2.4.2 Two substrate reactions......Page 718
6.12.8 Degradation of Naphthalene......Page 719
2.05.3.1.2 Substrate inhibition......Page 720
2.05.3.2 Deactivation of enzyme......Page 721
2.05.3.3 pH Dependency of Reaction Rate......Page 722
2.05.4 Biochemical Reaction Rate Related to Cellular Systems......Page 723
2.05.4.2 Substrate Uptake Rate......Page 724
2.05.5.1 Yield Coefficient based on Mass......Page 725
2.05.5.2 Biochemical Stoichiometry......Page 726
References......Page 727
Mixing in Bioreactor Vessels......Page 728
2.07.1.1 The Ideal Stirred Vessel......Page 729
2.07.2 Characterization of Mixing......Page 730
2.07.3 Mixing Models......Page 731
2.07.3.1 Bulk Flow Model......Page 732
2.07.3.2 Turbulence Models......Page 733
2.07.4.1 Inherent Variations in Measured Mixing Times......Page 734
2.07.4.2.2.(i) Single phase mixing time equation......Page 735
2.07.4.3 Two-Phase Stirred Tanks......Page 737
2.07.4.4 Bubble Column......Page 739
2.07.5 The Airlift......Page 740
2.07.6 Comparison of the Reactor Types......Page 741
2.07.7.3 Airlift......Page 742
2.07.8.3 C-Substrate......Page 743
2.07.8.6 Oxygen Depletion in Bubble Column......Page 744
Relevant Website......Page 745
2.06.1 Introduction......Page 746
6.18.2 Selection of the Plant Species Offering the Best Performance......Page 747
2.06.4 Flow around Single Bubbles......Page 749
2.06.5 Flow around Impeller Blades......Page 751
2.06.7 Flow Patterns in Stirred Tanks......Page 753
2.06.8 Flow Patterns in Bubble Columns......Page 755
References......Page 761
2.08.1 Introduction to Genetic Engineering......Page 762
2.08.2 Molecular Cloning and Recombinant DNA Technology......Page 763
2.08.3 Molecular Manipulations......Page 766
2.08.4.1 Chromosomal Engineering......Page 768
2.08.4.2 Application to Metabolic Engineering and Synthetic Biology......Page 770
References......Page 771
2.09.1 Common Feedstocks......Page 773
2.09.2.1 Lignocellulose Pretreatment......Page 775
2.09.2.3 Fermentation of Lignocellulosic Hydrolysates......Page 776
2.09.3 Use of Perennial Grasses......Page 777
6.30.2.1 Ammonia, Iron, and Manganese Removal from Potable Water......Page 778
2.09.4 Methane, Methanol, Syngas......Page 779
References......Page 780
Substrate Hydrolysis: Methods, Mechanism, and Industrial Applications of Substrate Hydrolysis......Page 782
2.10.1.1 Nature of Hydrolysis Reaction......Page 783
2.10.2 Substrate for Hydrolysis......Page 784
2.10.3.2 Hydrolysis Using Subcritical and Supercritical Water......Page 785
2.10.3.2.3 Hydrolysis of lignocellulosic waste......Page 786
2.10.4.1 Mechanism of Acid-Catalyzed Hydrolysis of Esters......Page 787
2.10.4.2 Mechanism of Base-Catalyzed Hydrolysis of Esters......Page 788
2.10.5.1 Biochemical Significance of Enzymatic Hydrolysis......Page 789
2.10.5.3.3 Limitation of enzymatic hydrolysis......Page 791
2.10.5.4.1 Enzymatic hydrolysis of starch......Page 793
2.10.5.4.4 Enzymatic hydrolysis of beta-lactam antibiotics......Page 795
2.10.6 Concluding Remarks......Page 796
References......Page 797
2.11.1 Introduction......Page 798
2.11.2.1 Complex Media......Page 799
2.11.3.1 General Aspects......Page 800
2.11.3.2.1 Identification of important media components (screening)......Page 802
2.11.3.2.3 Identification of the optimum (optimum search)......Page 803
2.11.3.3 Stochastic Search Strategies......Page 805
6.34.4.3 Effect of Sulfide......Page 806
2.11.4.4 Crossover and Mutation......Page 807
2.11.4.6 Artificial Neural Networks......Page 808
2.11.5.1 Shake Flasks......Page 810
References......Page 811
Sterilization in Biotechnology......Page 814
2.12.2 Sterilization of Gases......Page 815
2.12.2.2 Fibrous Filters......Page 816
2.12.2.5 Stainless Steel Filters......Page 817
2.12.2.7.1 Polypropylene depth filter cartridges......Page 818
6.34.5 Bioreactor Types Used for Sulfate Reduction......Page 819
2.12.3.2 Sterilization by Heat......Page 820
2.12.3.3.2 Continuous sterilization principle......Page 821
2.12.3.3.3 Plate heat exchanger......Page 822
2.12.3.5 Sterilization of liquids by high pressure......Page 823
2.12.4.1 Microbicidal Gases and Chemical Agents......Page 824
2.12.5 Sterilization of Large Equipment......Page 825
2.12.5.2.3 Elimination of Condensate......Page 826
2.12.7 Conclusions......Page 827
References......Page 828
Inoculum Preparation......Page 830
2.13.2.1 Physiology and Morphology......Page 831
2.13.2.6 Culture Medium......Page 832
2.13.3.1.1 Mutation......Page 833
2.13.3.2 Immobilization of Cells in Inoculum Preparation......Page 834
2.13.3.3 Preparation of the Inoculum......Page 835
2.13.4 Monitoring Inoculum Development......Page 836
2.13.6.1 Bacterial......Page 837
2.13.6.1.2 Inoculum size......Page 838
2.13.6.2.1 Use of a mathematical model......Page 839
2.13.8.5 Feces......Page 840
2.13.11 Conclusion......Page 841
References......Page 842
Bioreactor Engineering......Page 844
6.36.1 Background......Page 845
2.14.2.3 Pneumatically Agitated Bioreactors......Page 846
2.14.2.4 Membrane Bioreactors......Page 847
2.14.2.7 Wave Bioreactors......Page 848
2.14.3.1 Temperature......Page 849
6.29.3.4 Heavy Metals Removal......Page 850
2.14.4.1 Fed-Batch Culture......Page 851
2.14.5.2 Multiscale Study of Industrial Bioreactors and Bioprocesses......Page 852
2.14.6.1 Microbioreactor......Page 853
2.14.6.2 Cell as a Super Bioreactor......Page 854
References......Page 855
Nomenclature......Page 857
2.15.2 Mass and Energy Balances......Page 858
2.15.3.2 Oxygen Transfer and Oxygen Uptake......Page 863
2.15.4 Case in Study: Xanthan Gum Production......Page 865
2.15.4.1 Design of an STBR in Batch Operation......Page 867
2.15.4.1.1 Simulation of a BSTBR for xanthan gum production......Page 868
2.15.4.1.2 Volume determination of a BSTBR......Page 871
2.15.4.2 Design of an STBR in Continuous Operation......Page 872
References......Page 875
2.16.2 Reactor Configurations......Page 877
2.16.4.1 Gas Holdup......Page 878
2.16.4.2 Liquid Circulation Velocity......Page 882
2.16.4.3 Gas–liquid separators......Page 883
2.16.5.1 Gas/Liquid Mass Transfer......Page 885
2.16.5.2 Liquid–Solid and Liquid–Liquid Mass Transfer......Page 886
2.16.7 Mixing......Page 887
2.16.9 Conclusions......Page 889
References......Page 890
2.17.1 Introduction......Page 891
2.17.2 Specific Power Input in Shake Flasks......Page 892
2.17.3.2 Calculation of Out-of-Phase Conditions......Page 894
2.17.4.2 Calculation of the Maximum Local Energy Dissipation Rate in Shake Flasks......Page 895
2.17.5.3 Influence of Operation Conditions on Oxygen Transfer......Page 896
2.17.5.4 Mass Transfer Resistance of Sterile Plugs......Page 897
2.17.6.1 Specific Power Input in Baffled Shake Flasks......Page 898
2.17.6.3 Maximum Energy Dissipation Rate in Baffled Shake Flasks......Page 899
2.17.7.3 Scale-Up of Ventilation from Shake Flask to Stirred-Tank Reactor......Page 900
2.17.9.1 Online Measuring Techniques of the OTR and Carbon Dioxide Transfer Rate......Page 901
2.17.9.3 Online Measurement of the pH Value......Page 902
References......Page 903
2.19.1 Introduction......Page 905
2.19.2 Types of Single-Use Bioreactors with Disposable Bags......Page 906
2.19.2.1.1 Wave Bioreactor™......Page 907
2.19.2.1.2 CELL-tainer® bioreactor......Page 908
2.19.2.2.1 Cultivation of CHO cells in various rocking-type bioreactors......Page 910
2.19.2.2.2 Fed-batch culture of PER.C6® – cells in the CELL-tainer® single-use bioreactor compared with a stirred bioreactor......Page 911
2.19.2.3 Stirred Single-Use Bioreactors......Page 912
2.19.2.4.2 PER.C6® culture in single-use bioreactor (fed-batch)......Page 913
2.19.3 Conclusions......Page 916
Relevant Websites......Page 917
2.20.1 Introduction......Page 918
2.20.2 Basic Concepts in Membrane Bioreactors......Page 919
2.20.3 Membrane Bioreactors for Production and Separation of Bioactive Molecules......Page 925
2.20.3.1.1 Effect of immobilization......Page 927
6.53.6 Concluding Remarks......Page 928
2.20.3.1.3 Influence of reaction microenvironment on enzyme enantioselectivity......Page 929
2.20.3.2 Applications......Page 930
2.20.4 Membrane Bioreactors for Bioartificial Organs and Engineered-Tissue Culture......Page 931
2.20.4.1 Design Issues of Membrane Bioartificial Organs......Page 932
2.20.4.2 Membrane BAP......Page 933
2.20.4.3 Membrane Bioartificial Liver......Page 936
2.20.4.4 Cytocompatibility of Membranes in Bioartificial Organs......Page 939
2.20.4.5 Membrane Biocompatibility......Page 941
References......Page 942
2.21.1 Introduction......Page 944
2.21.2.1.1 Decrease of physical size......Page 945
2.21.2.2 Fluid Flow at the Microscale......Page 946
2.21.3 Microbioreactors for Cell Culturing......Page 948
6.34.3.3.3 Methane as e-donor......Page 949
2.21.3.3 Microfluidic Chips with Culture Chambers......Page 950
2.21.3.4 Miniature Bioreactors......Page 951
2.21.4 Enzymatic Microreactors......Page 953
2.21.4.3 Biotransformations in Microreactors......Page 954
References......Page 955
2.18.1 Introduction......Page 957
2.18.3 Mathematical Representation of Photosynthesis......Page 958
2.18.4 Modeling and Interpretation of Irradiance......Page 959
2.18.5 The Kinetic Model......Page 961
2.18.7 Photosynthesis in the Bioreactor......Page 963
2.18.8 Simulated Illumination–Darkness Cycles......Page 964
2.18.9 Experimental Evaluation of Illumination–Darkness Cycles......Page 973
References......Page 976
2.22.1 Introduction......Page 978
2.22.2.1 Bioscrubbers......Page 979
2.22.2.3 Biotrickling Filter......Page 980
2.22.2.4 Trickling Filter......Page 981
2.22.2.6 Fluidized Bed Reactor......Page 982
2.22.3 Filter Media......Page 983
2.22.5 Factors Affecting BF Performance......Page 985
2.22.5.3 Oxygen Content......Page 986
2.22.5.7 Waste Stream Composition......Page 987
6.52.3.3.1 Extrusion......Page 988
6.30.3.1 Cr(VI) Reduction......Page 989
2.22.6.2.1 Terminology......Page 991
2.22.6.2.2 Design and operational features......Page 992
References......Page 993
2.23.1 Introduction......Page 994
2.23.2.1 Adsorption......Page 995
2.23.2.2 Covalent Binding......Page 996
2.23.2.4 Membrane Confinement......Page 997
2.23.3.1 Stirred-Tank Reactor......Page 998
2.23.3.2 Packed-Bed Reactor......Page 999
2.23.3.4 Membrane Reactor......Page 1000
2.23.4.2 Choice of Enzyme Reactors......Page 1001
2.23.5.1 Enzyme Reactors with Cofactor Regeneration......Page 1002
2.23.5.3 Enzyme Reactors with Multienzyme Reactions......Page 1003
References......Page 1004
2.24.1 Introduction......Page 1005
6.35.3 Theory of Anaerobic Digestion......Page 1006
2.24.2.1.2 Entrapment......Page 1008
2.24.2.1.3 Aggregation......Page 1009
2.24.3.1 Stirred Tank Bioreactors......Page 1010
2.24.3.2 Fixed-Bed Bioreactors......Page 1011
2.24.3.3 Fluidized-Bed Bioreactors......Page 1012
2.24.3.4 Gas-Agitated Bioreactors......Page 1013
2.24.3.5 Membrane Bioreactors......Page 1014
2.24.4 Mass Transfer and Biokinetics in Immobilized Cell Bioreactors......Page 1015
2.24.5.1 Biological Stability......Page 1017
2.24.5.4.1 Improved yield......Page 1018
2.24.6.3 Substrate Limitation......Page 1019
References......Page 1020
Bioreactors for Solid-State Fermentation......Page 1021
2.25.1.2 Processes for Which We Need SSF Bioreactors: Past, Present, and Future......Page 1022
2.25.1.4 An Engineering-Based Approach......Page 1023
2.25.2.2 General Considerations about Bioreactor Performance......Page 1024
2.25.3.1 Basic Features of Tray Bioreactors......Page 1025
2.25.3.2 Design, Operation, and Scale-Up of Tray Bioreactors......Page 1026
2.25.4.1 Basic Features of Packed-Bed Bioreactors......Page 1027
2.25.4.2.3 Strategies for scale-up of packed-bed bioreactors......Page 1028
6.52.3.3.2 Fluidized-bed granulation......Page 1029
2.25.5.2.1 Key considerations in designing and operating rotating and stirred drums......Page 1030
2.25.6.2.1 Key considerations in designing forcefully aerated agitated bioreactors......Page 1031
2.25.6.3 Current Challenges in Design, Operation, and Scale-Up of Forcefully Aerated Agitated Bioreactors......Page 1032
2.25.8.2 Automated Control......Page 1033
References......Page 1034
2.26.1 Introduction......Page 1035
2.26.2.2 Medium Component......Page 1036
2.26.2.4 Genetic Transformation of Plant Cells......Page 1037
2.26.3.2 Bubble Beds......Page 1038
2.26.3.4 Reactors for Hairy Root Culture......Page 1039
2.26.3.5 Reactors with Product Separation......Page 1041
2.26.4.1 Preparation of Plant Cells......Page 1042
2.26.4.2 Operating Condition of Reactors......Page 1043
2.26.4.4 Recovery of Products......Page 1044
2.26.5.2 Somatic Embryo Production......Page 1045
References......Page 1046
2.27.1 Introduction......Page 1047
2.27.3 Bioreactors for High Cell Density Cultures......Page 1048
2.27.3.1 Radial Flow Bioreactor Systems......Page 1049
2.27.3.2 Bioreactor for Manufacturing Mechanical Substitutes......Page 1052
2.27.4 Automation of Cell Processing toward Clinical Application......Page 1053
References......Page 1055
2.29.1 Introduction......Page 1057
2.29.2 Mammalian Expression Vectors......Page 1058
2.29.4 Cells......Page 1059
2.29.6 Generation of Recombinant Cell Lines......Page 1060
2.29.7 Transient Gene Expression......Page 1061
Relevant Websites......Page 1062
Bioreactors for Tissue Engineering: Design, Applications, and’Monitoring......Page 1063
2.28.2.1 Mass Transfer Requirements......Page 1064
2.28.2.2 Oxygen Mass Transfer......Page 1065
2.28.3 Reactor Designs for Tissue Engineering......Page 1068
2.28.3.2 Perfusion Bioreactors......Page 1069
2.28.3.3 Biaxial Bioreactors......Page 1071
2.28.3.4 Strain Bioreactors......Page 1072
2.28.3.5.1 Rotating bed bioreactor from Z®RP Technology (Glen Mills, USA)......Page 1073
2.28.3.5.3 The Flexcell tissue train culture system......Page 1074
2.28.4.3 Positron Emission Tomography......Page 1075
2.28.4.5 Perspectives......Page 1076
2.28.5 Conclusions......Page 1077
References......Page 1078
Nomenclature......Page 1080
2.30.1 Introduction......Page 1082
2.30.2.1 Reduction of the Formation of Acetate Byproduct......Page 1084
6.47.2.2 Hydrolysis and Fermentation......Page 1085
6.52.2.3.1 Leaching of organic material and active sites......Page 1087
2.30.4 Global Regulators in Relation to the Cultural Environment......Page 1088
2.30.5 The Systems Biology Approach......Page 1091
2.30.6 Conclusion......Page 1092
References......Page 1093
Proteomics, Protein Engineering......Page 1094
2.31.1 Introduction......Page 1095
2.31.1.2 Why Proteomics? Applications and Benefits......Page 1096
2.31.2 Mass Spectrometry-Based Proteome Profiling Techniques......Page 1097
2.31.2.2.1 1D SDS-PAGE and 2D-GE......Page 1098
2.31.2.2.2 Gel-free and gel-based shotgun methods......Page 1099
2.31.2.3.2 Toward trypsin digestion optimization......Page 1100
2.31.2.4 Mass Spectrometric Protein Identification......Page 1101
2.31.2.4.2 Acquisition of mass spectra: MS and tandem MS......Page 1102
2.31.2.5 Protein Quantitation......Page 1105
2.31.3.2 Microfluidics in Proteomics: Chip Formats......Page 1107
2.31.3.2.1 Protein and peptide fractionation on a chip......Page 1108
2.31.3.2.4 Toward a total proteomic analytical system in a chip......Page 1109
2.31.4 Current Challenges in Proteomics......Page 1110
References......Page 1112
2.32.1 Introduction......Page 1113
2.32.2 Heterologous Protein Expression in Bacterial Cultures......Page 1114
2.32.4 Heterologous Protein Expression in Insect Cell Culture......Page 1116
2.32.5 Heterologous Protein Expression in Mammalian Cell culture......Page 1117
2.32.6 Heterologous Protein Expression in Plant Cell Culture......Page 1118
2.32.8 Heterologous Protein Expression in Moss Culture......Page 1119
References......Page 1120
2.33.1 Introduction......Page 1122
2.33.2 Enzymes versus Whole Cells......Page 1123
2.33.2.1.1 Engineered and directed evolution of enzymes......Page 1124
2.33.3 Extremophiles as a Source of New Enzymes......Page 1125
2.33.4 Biotransformations as a Source of Chiral Compounds......Page 1126
2.33.5.1 Organic Systems......Page 1127
2.33.5.3 Gas–Solid systems......Page 1128
2.33.5.5 Freely Suspended versus Immobilized Biocatalysts......Page 1129
2.33.6 Industrial Processes – Overview on Present and Prospective Trends......Page 1130
References......Page 1131
2.34.1 Introduction......Page 1132
2.34.4 Approaches toward Robust Immobilized Enzymes......Page 1134
2.34.4.1 Rational versus Trial–Error......Page 1135
2.34.4.2 Diversity versus Versatility......Page 1136
2.34.4.4 Modification versus Immobilization......Page 1138
2.34.4.4.2 Post-immobilization improvements......Page 1139
2.34.5.1 Enhanced Stability......Page 1140
6.47.4 Conclusions......Page 1141
2.34.5.3 Improved Selectivity......Page 1142
2.34.6 Prospectives and Future Developments......Page 1143
References......Page 1144
2.36.1 Introduction: Development and Main Application Fields of Immobilized Cell Cultures......Page 1148
2.36.2 Original Motivation of Viable IC Technology......Page 1149
2.36.3.2 Biocatalytic Efficiency and Enzyme Expression......Page 1151
2.36.3.3 Stress Resistance......Page 1152
2.36.4 Proteomic Approach and Biofilm Phenotype......Page 1154
2.36.5 Conclusion......Page 1158
References......Page 1159
Immobilization Technology: Cells......Page 1163
2.35.2 Strategies for Cell Immobilization......Page 1164
2.35.2.2.1 Advantages of self-immobilized cells......Page 1165
2.35.2.3 Encapsulation of Cells......Page 1166
6.21.4.1 Phytoremediation Approach for Landfill Soils......Page 1167
6.12.8.2 NDO Substrate Specificity......Page 1168
2.35.3.5 Biologics......Page 1169
2.35.4 Immobilized-Cell Bioreactors......Page 1170
2.35.4.2 Suspended-Bed Bioreactors......Page 1171
2.35.4.3 Airlift Bioreactors......Page 1173
2.35.4.4 Membrane Bioreactors......Page 1174
References......Page 1175
2.37.1 Introduction......Page 1176
2.37.2 Microbial Growth and Stoichiometry......Page 1177
2.37.3 Autocatalytic Nature of Microbial Growth......Page 1179
2.37.4 Cell Yields......Page 1180
2.37.5 Product Yields......Page 1181
References......Page 1182
2.38.1 Introduction......Page 1183
2.38.2 Different Types of Fed-Batch Cultivations......Page 1184
2.38.2.1 Fixed-Volume Fed-Batch Cultivation......Page 1185
2.38.2.2.1 Repeated or cyclic fed-batch cultivation......Page 1186
2.38.4 Control Techniques for Fed-Batch Fermentation......Page 1187
2.38.4.1 Indirect Control of Substrate Feed......Page 1188
2.38.6.2 Startup of Feed During the Exponential Phase of Growth......Page 1189
2.38.6.3 Generalized Feeding Profile for Simple (Growth-Associated) Fermentations......Page 1190
2.38.6.6 Time of Feeding......Page 1191
2.38.7.2 Byproduct Concentration......Page 1192
References......Page 1193
2.39.1 Introduction......Page 1195
2.39.2 Homogeneous System......Page 1197
2.39.3 Heterogeneous Systems......Page 1200
References......Page 1203
2.41.1 Introduction......Page 1204
2.41.2 Integration Methodology for Reducing Process Step......Page 1205
2.41.3 Cross-Sectional Technologies through Integration Methodology......Page 1206
2.41.3.3 Membrane Separation......Page 1207
6.23.3.4 Oxygen Limitations......Page 1208
2.41.6.2 Two-Liquid-Phase Systems......Page 1210
2.41.6.4 Complex Formation......Page 1211
2.41.7.1 Secretion of Intracellular Proteins......Page 1212
2.41.8 Perspective for the Process Integration......Page 1213
References......Page 1214
2.42.1 Introduction......Page 1216
2.42.3 Modular Unit Operations in Downstream Processing......Page 1217
2.42.3.1 Recovery of Solids and Liquids......Page 1218
6.13.3.1.1 Environmental significance of PCBs......Page 1219
2.42.3.9 Membrane Filtration......Page 1220
2.42.4.2 Reaction and Solvent Extraction......Page 1221
2.42.4.7 Reaction and Chromatography......Page 1222
2.42.5.1 Metabolite Purification......Page 1223
2.42.5.5 Carbohydrate Biopolymer Purification......Page 1224
2.42.7 Conclusion......Page 1225
References......Page 1226
Multistage Continuous High Cell Density Culture......Page 1227
2.40.2.1 Fermentation History......Page 1228
2.40.2.2.3 Oxygen transfer rate......Page 1229
2.40.2.3.1 Substrates......Page 1232
2.40.2.3.4 Major products (petroleum based)......Page 1233
2.40.2.3.5 Performance index......Page 1234
2.40.3.2.1 Normal cell density......Page 1235
2.40.3.2.3 Separation of hydraulic retention time and solid retention time......Page 1236
2.40.3.4 Cell-Recycle Techniques for HCDC......Page 1238
2.40.3.4.3 Immobilization on solid carrier surfaces......Page 1239
2.40.3.4.6 Self-aggregation and flocculation......Page 1241
2.40.3.4.7 Upflow anaerobic sludge blanket......Page 1242
2.40.3.5.1 Methods of cell separation......Page 1243
2.40.3.5.4 Filtration......Page 1244
2.40.3.5.5 Hollow-fiber-based HCDC......Page 1245
2.40.3.5.6 Depth filter perfusion system......Page 1247
2.40.3.6.1 Kinetics of HCDC......Page 1248
2.40.4.1 Characteristics of MSC-HCDC......Page 1249
2.40.4.2.3 Dilution rate......Page 1250
2.40.4.3.2 Two-stage DFPS for mAb......Page 1252
2.40.4.3.3 Two-stage continuous ethanol production......Page 1254
2.40.4.3.5 Multistage continuous ethanol production with cell recycle......Page 1255
2.40.4.4.1 Background......Page 1256
2.40.4.4.2 Simulation for mAb production......Page 1257
2.40.4.5 Industrial Applications......Page 1259
2.40.4.5.1 MBRs (wastewater treatment, GE)......Page 1260
2.40.4.5.2 Halobacteria (Bitop, Germany)......Page 1261
2.40.4.5.3 Animal cell culture......Page 1262
2.40.5 Summary......Page 1263
References......Page 1264
Membrane Systems and Technology......Page 1268
2.43.1 Introduction......Page 1269
2.43.3 Membrane Configurations......Page 1270
2.43.4.1 Microfiltration Membranes......Page 1271
2.43.5.1 Concentration Polarization......Page 1272
2.43.5.3 Fouling......Page 1273
2.43.6 Membrane Cleaning......Page 1274
2.43.7.1 Sterile Filtration......Page 1275
2.43.7.4 Other Applications......Page 1276
2.43.8.1 Configurations......Page 1277
2.43.8.4 Membrane Bioreactors with Immobilized Enzymes......Page 1278
2.43.9.2 Purification of Biological Products......Page 1279
2.43.10.1 Configurations......Page 1280
2.43.10.3 Reaction......Page 1281
References......Page 1282
Relevant Websites......Page 1283
2.45.1 Introduction......Page 1284
2.45.2 Yeast Autolysis Mechanism......Page 1285
2.45.2.1 Biochemical and Morphological Changes......Page 1286
2.45.3.1 Evolution of Nitrogen Compounds during Autolysis......Page 1288
2.45.3.3 Polysaccharides......Page 1289
2.45.3.5 Nucleic Acids......Page 1290
References......Page 1291
2.44.1 Introduction......Page 1293
2.44.2.1 Bacterial Cell Envelope......Page 1294
2.44.2.2 Yeast Cell Walls......Page 1295
2.44.3 Approaches to Microbial Cell Disruption......Page 1297
6.48.3.1 Introduction......Page 1298
2.44.4.2 High-Speed Bead Mills......Page 1302
6.27.3.2.4 Integration of anammox in the main liquid-stream treatment train......Page 1303
2.44.5.2.2 Hydrodynamic cavitation......Page 1304
2.44.5.4 Enzymatic Attack......Page 1305
2.44.5.6 Thermal Treatment......Page 1306
2.44.6 Selective Product Release......Page 1307
2.44.8 Integration of Biomass Formation and Product Release......Page 1309
2.44.10 Closing Remarks......Page 1311
References......Page 1312
2.46.1 Introduction......Page 1315
6.04.2 Detection of Degradative Genes......Page 1316
2.46.2.2 Characterizing the Equilibrium: Ternary Phase Diagrams......Page 1317
2.46.3 Modeling of Solid–Liquid Equilibrium......Page 1318
2.46.4 Crystallization of Proteins......Page 1321
2.46.4.1 Solubility and Supersaturation......Page 1322
2.46.4.2 Nucleation......Page 1323
2.46.4.3 Crystal Growth......Page 1324
2.46.4.5 Protein Crystallization in the Biotechnology Industry......Page 1325
2.46.5 Developing a Protein Crystallization Process......Page 1326
References......Page 1327
Adsorption and Chromatography......Page 1328
2.47.2.2 Hydrophobic Interaction......Page 1329
6.17.10 Conclusion and Final Remarks......Page 1330
6.38.3.3 Bioaccumulation and Biological Effects......Page 1331
2.47.3.1.3 Hydrophobic interaction chromatography......Page 1332
2.47.3.1.5 Displacement chromatography......Page 1333
2.47.3.3 Electrochromatography......Page 1334
2.47.4.1 Adsorption Equilibria......Page 1335
2.47.4.2 Uptake Kinetics......Page 1336
2.47.5.1.1 Flow-through media......Page 1337
2.47.5.2.2 Rational design......Page 1338
2.47.5.4 Displacer Screening and Design......Page 1339
2.47.5.5 Molecular Insight into Protein Adsorption......Page 1340
References......Page 1341
Modeling Chromatographic Separation......Page 1343
2.48.1 Introduction......Page 1344
2.48.2.1.1 Pore diffusion......Page 1345
2.48.2.2 Particle Concentration Profile Development......Page 1346
2.48.3 Models for Chromatography......Page 1347
2.48.3.1 Formulation of the Models......Page 1348
2.48.3.1.3 The transport dispersive model......Page 1349
2.48.3.2 Alternative Method for the Numerical Solution of the GR Model with Nonlinear Isotherms......Page 1350
2.48.4.1 Case Study 1......Page 1352
2.48.4.3 Case Study 3......Page 1353
2.48.4.5 Case Study 5......Page 1354
2.48.5 Summary......Page 1355
References......Page 1356
2.49.1 Introduction......Page 1358
2.49.2.1 Phase Formation, Binodal Curves, Tie-Line Length, Volume Ratio, and Phase Separation......Page 1359
6.46.2.1.3 Geobacillus thermoglucosidasius......Page 1362
6.51.3.1 Main Objectives of the Culture Selection Stage......Page 1363
2.49.2.3.4 Specific affinity-dependent partition......Page 1364
2.49.3.2 Process Integration Using ATPSs......Page 1365
2.49.3.3 Bioaffinity-Enhanced Partitioning on ATPSs......Page 1367
6.51.4 How Can Mixed Culture Processes Convert Organic Byproducts into PHAs?......Page 1368
2.49.3.4.3 Virus, virus-like particles, and other bionanoparticles......Page 1371
2.49.3.5 Other Applications of ATPSs......Page 1372
References......Page 1373
Foam Separations......Page 1375
2.50.1 Introduction......Page 1376
2.50.2.2 Enrichment of Biological Solutions......Page 1377
2.50.3.1 Foam Dynamics......Page 1378
2.50.3.2.2 Adsorption of proteins and enzymes......Page 1380
2.50.3.4 Mass Balance......Page 1381
2.50.4.2.3 Dissolved air foam fractionation......Page 1382
2.50.4.5.1 Foam recovery......Page 1383
2.50.5.1 Multiple Physical Stages......Page 1384
2.50.5.2 The ‘Foam Riser’......Page 1385
References......Page 1386
6.22.1 Introduction......Page 1387
2.51.3.1 Air Drying......Page 1388
2.51.3.3 Vacuum Drying......Page 1389
2.51.3.4 Spray Drying......Page 1390
2.51.3.6 Drum Drying......Page 1392
2.51.4 Other Drying Technologies......Page 1393
References......Page 1395
Chiral Separations......Page 1396
2.52.1 General Introduction......Page 1397
2.52.2.2 Preferential Crystallization......Page 1398
2.52.2.3 Resolution by Diastereomeric Salt Formation......Page 1400
6.34.3.3.1 Hydrogen as e-donor......Page 1401
2.52.3.3 Chiral Stationary Phases......Page 1402
2.52.3.5 Preparative Chiral Chromatography......Page 1403
2.52.4.2 Principles......Page 1404
2.52.5.1 Introduction......Page 1405
2.52.5.2 Principles......Page 1406
2.52.6.1 Introduction......Page 1407
2.52.6.3 Liquid Enantioselective Membranes......Page 1408
2.52.7.1 Introduction......Page 1409
References......Page 1410
2.53.1 Introduction......Page 1411
2.53.2.1 Microfabrication......Page 1412
2.53.2.2.3 Centrifugal force......Page 1414
2.53.3.1 Sample Introduction and Treatment......Page 1415
2.53.3.2.1 Capillary electrophoresis......Page 1416
2.53.3.3.1 Laser-induced fluorescence......Page 1417
2.53.4.1 Centrifugal Forces for Microimmunoassays......Page 1418
2.53.4.3 Liquid Chromatography–MS on a Chip......Page 1419
References......Page 1421
Relevant Websites......Page 1422
Protein Refolding/Renaturation......Page 1423
2.54.2 Inclusion Bodies......Page 1424
2.54.3 Isolation and Purification of Inclusion Bodies......Page 1425
2.54.4 Solubilization of Inclusion Bodies......Page 1426
2.54.5 Mechanism of Protein Aggregation......Page 1427
2.54.6.1 Construction of Refolding Buffer......Page 1428
2.54.6.2.1 Artificial chaperone-assisted refolding......Page 1430
2.54.6.3 Refolding by Dialysis or Diafiltration......Page 1431
2.54.6.4.1 Refolding using size-exclusion chromatography......Page 1432
2.54.6.4.3 Refolding using hydrophobic interaction chromatography......Page 1434
2.54.6.4.6 Affinity chromatography for protein refolding......Page 1435
References......Page 1437
Biogas Production......Page 1443
2.55.1 Introduction......Page 1444
2.55.2 Advantages of the AD Processes......Page 1445
2.55.3.3 Metanogenesis......Page 1446
2.55.4.1.3 Deoxyribonucleic acid......Page 1447
6.14.4.5 Aerobic Oxidation of PCBs......Page 1448
2.55.4.3.1 Gas production and composition......Page 1449
2.55.5 Types of Anaerobic Reactors......Page 1450
2.55.5.2 Anaerobic Filter......Page 1451
2.55.5.6 Anaerobic Sequencing Batch Reactors......Page 1452
2.55.7 Biogas Utilization......Page 1453
2.55.8.2 Water Removal......Page 1454
References......Page 1455
Purification Process Design and the Influence of Product and’Technology Platforms......Page 1457
6.11.4 Monocyclic and Low-Molecular-Weight Aromatic Hydrocarbons......Page 1458
2.56.2.4 Virus Removal and Inactivation......Page 1459
2.56.3.4 Filtration......Page 1460
2.56.3.7 Normal Flow Virus Filtration......Page 1461
2.56.4.1.1 Intracellular versus extracellular expression......Page 1462
2.56.4.1.4 Sanitary processing......Page 1463
2.56.4.2.3 Capture (primary purification) and concentration......Page 1464
2.56.4.3 Sequence of and Transitions between Unit operations......Page 1465
2.56.5.2 Antibiotics......Page 1466
2.56.5.4 Recombinant Antibodies......Page 1467
References......Page 1468
2.57.1 Introduction......Page 1469
6.46.2 Fermenting Microorganisms......Page 1470
References......Page 1471
2.58.1 Introduction......Page 1473
2.58.2.1.1 Cassava......Page 1474
2.58.2.2 Lignocellulosic Biomass......Page 1476
2.58.3.1 Development of Fermenting Organisms and Techniques......Page 1478
2.58.3.3 Syngas......Page 1481
2.58.3.4 Bioprocess Integration......Page 1482
2.58.4.1 Biorefinery of Sweet Sorghum......Page 1483
2.58.4.3 Microbial Lipid Production from Sugar-Containing Wastewater......Page 1484
References......Page 1485
2.59.1 Introduction......Page 1487
2.59.2 Physical Process Parameters......Page 1488
2.59.3 Cell Mass Measurements......Page 1489
6.42.3.2 Composting......Page 1490
2.59.3.2.3 Online optical loss measurement......Page 1491
2.59.4.1 Flow Injection Analysis (FIA) and Biosensors......Page 1492
2.59.5.2 Raman Spectroscopy......Page 1494
6.29.5.2 Pollutant Reduction Models......Page 1495
References......Page 1496
Life Cycle Assessment in Biotechnology......Page 1497
2.60.1 Introduction......Page 1498
2.60.2.2 Inventory Analysis......Page 1499
2.60.3 LCA: Utility and Limitations......Page 1500
2.60.4.2 LCA of Industrial Food Products and Processes......Page 1501
2.60.5 Application of LCA in Pharmaceutical Biotechnology......Page 1502
2.60.6.1 LCA of PLA......Page 1503
2.60.7 Application of LCA in Biofuels......Page 1504
2.60.7.2 LCA of Transportation Biofuels: Bioethanol and Biodiesel......Page 1505
2.60.8 Application of LCA in Biodegradable Waste Management......Page 1506
2.60.9.2 LCA Indicators......Page 1507
References......Page 1508
Relevant Websites......Page 1509
2.61.1 Introduction......Page 1510
2.61.3 Control of Biological Systems......Page 1511
2.61.4.2 Branch Point Classification......Page 1512
2.61.6 Metabolic Control Analysis......Page 1513
2.61.6.2 Concentration Control Coefficient......Page 1514
2.61.6.4 Connectivity Theorem......Page 1515
2.61.7 Determination of the Flux Control Coefficients......Page 1516
2.61.9 Conclusion......Page 1517
References......Page 1518
Fuzzy Control of Bioprocess......Page 1519
2.62.1.1 Feed Rate......Page 1520
2.62.2 Determination of Process Variables Based on Identification of Culture Phase......Page 1522
2.62.2.1 Pravastatin Precursor Production......Page 1523
2.62.2.2 Vitamin B2 Production......Page 1525
6.31.3 Kinetics and Modeling......Page 1526
2.62.4 Conclusion......Page 1527
References......Page 1528
2.63.1 Introduction......Page 1530
2.63.2.2 Closed-Loop Control Based on At- or Online Measurements......Page 1531
2.63.3.1.1 Gain scheduling......Page 1532
2.63.3.1.2 Self-tuning controller......Page 1533
2.63.3.2 Linearization-based control......Page 1534
2.63.4 Concluding Remarks......Page 1535
References......Page 1536
2.64.2 Review of the Most Relevant Optimization Techniques......Page 1538
2.64.3.1 A Small-Scale Case Study Based on Literature Data......Page 1540
2.64.3.2 A Large-Scale Application Case Study......Page 1543
References......Page 1545
Micro-Biochemical Engineering: Using Small-Scale Devices to’Predict Industry-Scale Downstream Performance......Page 1546
2.65.2.2 Extreme Scale-Down Techniques......Page 1547
2.65.3.1.1 Precipitation......Page 1548
2.65.3.1.2 Recovery of precipitates by centrifugation......Page 1549
2.65.3.1.3 Recovery of cells and secreted products by centrifugation......Page 1550
2.65.3.1.4 Filtration......Page 1551
2.65.3.1.7 Packed bed chromatography......Page 1552
2.65.3.2.2 Precipitation and centrifugation......Page 1554
2.65.3.2.4 Precipitation and centrifugation......Page 1555
2.65.5 Conclusions......Page 1556
References......Page 1557
2.66.1 Introduction......Page 1559
2.66.2 About Sustainability......Page 1560
2.66.3 Spatial and Temporal Dimensions of Sustainability......Page 1561
2.66.5 Indicators of Sustainability......Page 1562
2.66.6.2 Eco-Efficiency......Page 1567
2.66.6.4 Design for Environment......Page 1568
2.66.6.5.1 Industrial sustainability......Page 1569
2.66.6.7 Life Cycle Analysis......Page 1570
2.66.6.9 Extended Producer Responsibility......Page 1571
2.66.7 Biotechnology and Sustainability......Page 1572
2.66.8.1 Renewable Resources......Page 1575
2.66.8.3 Renewable and Sustainable Energy......Page 1576
Relevant Websites......Page 1577
2.67.2 Nonaqueous Enzymatic Catalysis......Page 1578
6.36.4 The Attainment of Representative Values for B0......Page 1579
2.67.4.2.1 The pH of the acryloylation reaction......Page 1580
2.67.5.1 Assembly of Monomers around the Enzyme in Aqueous Solution......Page 1581
2.67.5.3 Experimental Validation of Enhanced Enzyme Stability......Page 1582
2.67.6.3 Lipase Nanogel-Catalyzed Synthesis of Polyester......Page 1584
References......Page 1585
2.68.1 Introduction......Page 1586
2.68.3.1 Equipment Design......Page 1589
2.68.3.2 Use of Disposables......Page 1590
2.68.3.5 Seed Expansion Considerations......Page 1591
2.68.4.2 Considerations for Applying Disposable Technology to Purification......Page 1592
2.68.5.1 Sterilization Considerations......Page 1593
2.68.5.3 Sanitary Cleaning Issues......Page 1594
2.68.6.1 Procedures Used for Process Sampling......Page 1595
2.68.6.3 Criteria for Contaminated Samples......Page 1596
References......Page 1597
Oxygen Mass Transfer in Bioreactors......Page 1599
2.69.2.1.1 Effect of baffles and indentations......Page 1600
References......Page 1601
2.69.2.2.2 Effect of salt in the medium......Page 1602
2.69.2.2.5 Effect of biomass concentration and biomass particle size......Page 1603
2.69.2.3.1 Effect of various types and size of closures......Page 1604
2.69.2.3.2 Effect of flask size and filling volume......Page 1605
2.69.2.4.2 Effect of gas sparger and bubble properties......Page 1606
References......Page 1607
2.70.1 Introduction......Page 1609
6.10.2 The Nature of Aromatic Compounds and Their Sources......Page 1610
2.70.2.2 Hydrodynamic Cavitation Reactors......Page 1611
2.70.3.2 Microbial Disinfection......Page 1613
6.24.4.2 Nitrification......Page 1615
2.70.3.7 Concluding Remarks......Page 1616
References......Page 1617
Flow Cytometry: A High-Throughput Technique for Microbial Bioprocess Characterization......Page 1618
2.71.1 Introduction......Page 1619
6.31.2.1.1 Hydrolysis......Page 1620
2.71.2.2 Data Acquisition and Processing......Page 1621
2.71.2.3.2 Fluorescence signals: Use of fluorochromes......Page 1622
2.71.3.1.1 Cell growth......Page 1623
2.71.3.1.3 Membrane potential......Page 1624
2.71.3.2 Combination of Different Structural and Functional Criteria......Page 1625
2.71.4.3 Alcoholic Beverage Production......Page 1626
2.71.5 Monitoring and Control of Biotransformations......Page 1627
2.71.5.2 Bacteria......Page 1628
2.71.6 Theoretical Applications: Kinetic Modeling......Page 1629
2.71.7 Devices of Practical Use and Automation of FC Equipments......Page 1630
References......Page 1631
Relevant Websites......Page 1632
Cleaning in Place......Page 1633
2.72.1 Introduction......Page 1634
2.72.2.2 Disinfection and Disinfectants......Page 1635
2.72.3 Overview of CIP Systems......Page 1637
2.72.3.1.1 Single use and partial recovery......Page 1638
2.72.3.1.2 Full recovery......Page 1639
2.72.3.2 Automatic Tank Cleaning......Page 1640
2.72.4.1 Fouling: Types and Mechanisms......Page 1641
2.72.4.2.1 Effect of variables......Page 1642
2.72.4.2.3 Kinetic models......Page 1643
2.72.5.2 Recovery of Cleaning Solutions......Page 1645
References......Page 1646
Relevant Websites......Page 1647
2.73.1 Introduction......Page 1648
6.35.3.2 Process Microbiology......Page 1649
2.73.2.3 Lipases and the Use of Ionic Liquids......Page 1651
2.73.3 Environmental Impact of Ionic Liquids......Page 1652
References......Page 1653
Relevant Websites......Page 1655
6.15.1 Introduction......Page 1656
2.74.2 Pure Substances as Supercritical Fluids......Page 1657
2.74.4 Modifiers......Page 1659
2.74.5 Solubility in a Supercritical Fluid......Page 1660
2.74.5.2 Solubility and Chemical Structure......Page 1661
2.74.7 Supercritical Fluid Extraction......Page 1662
2.74.7.1.1 Analytical scale SFE......Page 1663
2.74.7.2.2 Pilot and industrial scale liquid SFE plants......Page 1664
2.74.7.3 Analytical Scale SFE......Page 1665
2.74.7.3.1 Analytical scale SFE method development......Page 1666
2.74.7.3.2 SFE cleanup procedures......Page 1667
2.74.8 Supercritical Fluid Chromatography......Page 1669
2.74.9.2 Supercritical Antisolvent......Page 1670
2.74.9.4 Particles from Gas-Saturated Solution......Page 1671
2.74.10.1 Supercritical Fluid Gas Foaming......Page 1672
2.74.11 Supercritical Fluids as Alternative Enzymatic Reaction Solvents......Page 1673
2.74.12 Sterilization Using SF-CO2......Page 1674
References......Page 1675
Computational Fluid Dynamics......Page 1676
2.75.2.1 Transport Equations......Page 1677
2.75.2.2 Turbulent Flow Modeling......Page 1678
2.75.2.3 Numerical Solution of Transport Equations......Page 1680
2.75.2.3.1 Finite volume method......Page 1681
2.75.2.3.2 Grid types......Page 1682
2.75.3 Single-Phase Flow Simulations......Page 1683
2.75.4.2 Solid–Liquid Systems......Page 1684
2.75.4.3 Liquid–Gas–Solid Systems......Page 1685
6.49.3.4 Photomicrobial Solar and Fuel Cells......Page 1686
References......Page 1687
Vol3......Page 1688
Introduction......Page 1689
3.02.1 Introduction......Page 1691
3.02.2 Protease......Page 1693
3.02.3 Lipase......Page 1694
3.02.4 Amylase......Page 1695
3.02.6 Pectinases......Page 1696
6.26.2.2.1 Experimental measurement of influent COD fractions in MBR studies......Page 1698
3.02.10 Phytase......Page 1699
6.45.5 The Role of White-Rot Fungi and Their Enzymes on Second-Generation Bioethanol......Page 1700
3.04.1 Introduction......Page 1702
3.04.2.1 Sugarcane......Page 1703
3.04.2.3 Sugar Beets......Page 1704
3.04.4.1 Sugarcane Ethanol......Page 1705
3.04.4.1.1 Sugar extraction......Page 1706
3.04.4.4 Molasses Ethanol......Page 1709
References......Page 1710
3.03.1 Introduction......Page 1711
3.03.2.1 Cellulase–Cellulase......Page 1712
3.03.2.3 Cellulase–Hemicellulase......Page 1714
3.03.3 Inter- and Intra Molecular Synergism......Page 1715
3.03.4 Intra Molecular Synergism: Clues from Three-Dimensional Structures......Page 1716
3.03.5 Artificial Chimeras......Page 1718
3.03.5.2 Challenges of Multifunctional Enzyme Chimeras......Page 1719
References......Page 1720
Relevant Website......Page 1721
Ethanol from Starch-Based Feedstocks......Page 1722
3.05.2 Biochemistry of the Ethanol Process......Page 1723
3.05.3.1 Yeast......Page 1724
3.05.4.2 Enzymatic Processing and Cooking......Page 1725
3.05.4.3.2 VHG fermentation......Page 1726
3.05.5.1 pH......Page 1728
3.05.5.3 Aeration......Page 1729
6.51.4.3 Stoichiometric and Kinetic Parameters of Waste/Surplus Feedstocks Conversion into PHA......Page 1731
3.05.6.4 Net Rate Expression in Continuous Fermentations......Page 1732
3.05.8 Summary......Page 1733
References......Page 1734
Biofuels from Cellulosic Feedstocks......Page 1735
3.06.2 Cellulosic Biomass......Page 1736
3.06.3 Conversion of Cellulosic Biomass into Ethanol......Page 1737
3.06.3.2 Enzymatic Hydrolysis......Page 1738
3.06.4 Development of Microorganisms for Fermenting Cellulosic Biomass Hydrolyzates to Ethanol......Page 1739
3.06.4.1.1 Saccharomyces yeast......Page 1741
3.06.4.1.2 E. coli and Klebsiella oxytoca......Page 1743
References......Page 1745
3.07.1 Introduction......Page 1747
3.07.4.1 Alkali-Catalyzed Transesterification......Page 1748
3.07.5 Transesterification – Supercritical Fluids......Page 1749
3.07.6.2 Immobilized Whole-Cell Catalysis......Page 1750
3.07.6.2.2 Molecular characterization of whole-cell biocatalysts......Page 1751
3.07.6.2.4 Comparative study of lipase and whole-cell biocatalysts......Page 1752
3.07.8 Packed-Bed Reactors Containing Whole-Cell Biocatalysts......Page 1753
References......Page 1754
Biofuels and Bioenergy: Acetone and Butanol......Page 1755
3.08.1 Introduction......Page 1756
3.08.2.6 AB Fermentation Decline since the 1950s......Page 1757
3.08.4.1 Metabolic Pathways......Page 1758
3.08.5.1.1 Protoplast production and transformation......Page 1760
3.08.5.2.2 Group II intron......Page 1761
3.08.5.4.2 Engineering solvent pathways......Page 1762
3.08.6.1 Genomics Study......Page 1763
3.08.6.3 Proteomics Study......Page 1764
3.08.7.1 Substrates......Page 1765
3.08.7.2 Butanol Toxicity and Tolerance......Page 1766
3.08.7.3 Strain Improvement and In Situ Recovery Technology......Page 1767
3.08.8 Development of Fermentation Technology......Page 1768
References......Page 1769
3.09.1 Introduction......Page 1770
3.09.3 Microorganisms Producing 2,3-Butanediol......Page 1771
3.09.4.1 Metabolic Pathway for 2,3-BDL Formation......Page 1772
3.09.4.2 Biological Role of 2,3-Butanediol......Page 1773
3.09.4.3 Pathway Engineering......Page 1774
3.09.5.2 Aeration......Page 1775
3.09.6 Recovery of 2,3-Butanediol......Page 1777
References......Page 1779
Biogas......Page 1781
3.10.2 Fundamentals......Page 1782
3.10.2.1.2 Methanogens......Page 1783
3.10.2.2.3 Raw materials......Page 1784
3.10.3.2 Household AD Process......Page 1785
6.25.6.5 Validation......Page 1786
3.10.3.3.2 Types of digesters......Page 1787
3.10.4.1 Modes of Biogas Plants......Page 1790
3.10.4.2 Farm biogas plant......Page 1791
3.10.4.3 Organic Municipal Solid Waste Treatment Biogas Plant......Page 1793
3.10.5 Utilization of Biogas......Page 1794
References......Page 1795
Relevant Websites......Page 1796
3.11.1 Introduction......Page 1797
3.11.2.1 General......Page 1798
6.22.2.2 Catalytic Properties of MMOs......Page 1799
3.11.2.3 Limitations for Practical Application......Page 1800
3.11.3.2 Factors Affecting the Nitrogenase-Mediated Hydrogen Evolution......Page 1801
6.42.4 Wastewaters......Page 1802
3.11.4.2 Factors Affecting Dark Fermentation......Page 1803
3.11.5.1 General......Page 1805
3.11.5.3 Gas–Liquid Mass Transfer Problem......Page 1806
References......Page 1807
3.12.1 Introduction and Scope......Page 1808
3.12.3.1 Biogas......Page 1809
3.12.4.1 Algal Physiology and Genetic Engineering......Page 1810
3.12.4.2 Mass Algal Culture......Page 1811
3.12.4.3 Algae Harvesting and Dewatering......Page 1812
3.12.4.5 Conversion of Algal Oil into Biodiesel......Page 1813
References......Page 1814
3.13.2 Properties and Applications of Citric Acid......Page 1815
3.13.3 Historical Background of Citric Acid Production......Page 1816
3.13.4 Microorganisms and Biosynthesis of Citric Acid......Page 1817
3.13.5 Factors Affecting Citric Acid Production by’A. niger......Page 1818
3.13.6.3 Solid Fermentation Process (Koji Process)......Page 1819
3.13.7 Product Recovery......Page 1820
6.08.2.4 Munitions Plants – Nitroaromatic Compounds, Explosives......Page 1821
3.14.2 d-Gluconic Acid......Page 1823
3.14.2.3 Microorganisms......Page 1824
3.14.3 Itaconic Acid......Page 1825
6.49.3 Microbial BES Generating Electricity: MFCs......Page 1826
References......Page 1827
Organic Acids: Succinic and Malic Acids......Page 1828
3.15.2.1 Traditional Petrochemical Process......Page 1829
6.10.3.1 Fundamentals......Page 1830
3.15.2.3.5 Escherichia coli......Page 1832
3.15.3.2.1 Chemical route......Page 1833
3.15.3.3.1 Chemical routes......Page 1834
3.15.4 Malic Acid Production......Page 1835
3.15.4.1 l-Malic Acid Production from Fumarate......Page 1836
3.15.5.2.1 Derivatives synthesized through monomalonaldehyde......Page 1837
3.15.6 Conclusion......Page 1838
References......Page 1839
3.16.1 Introduction......Page 1841
3.16.2 Properties and Applications......Page 1842
3.16.3.1 Isomerization of Maleic Acid to Fumaric Acid......Page 1844
3.16.3.2 Fermentation of Sugar to Fumaric Acid......Page 1845
6.45.3.1 Use of Laccase in Bleaching Processes......Page 1846
6.20.2.1.6 Phytostabilization: Stabilization in soil or incorporation into plant structures......Page 1847
3.16.4.4 Metabolic Engineering and Systems Biology for Strain Development......Page 1848
3.16.5 Fermentation Process Development and Optimization......Page 1849
3.16.5.1.2 Cell immobilization on solid carriers......Page 1850
3.16.5.2 Medium Formulation......Page 1851
3.16.5.3 Effects of pH and Neutralizing Agent......Page 1852
3.16.5.5 Simultaneous Fermentation and Separation......Page 1853
3.16.6 Conclusion and Future Prospects......Page 1854
6.26.3.3.1 Stand-alone EPS models......Page 1855
3.17.1 Introduction......Page 1856
3.17.3 Biological Production of Lactic Acid......Page 1857
3.17.4 The Cargill Yeast......Page 1859
3.17.5 Fermentation Carbon Sources......Page 1862
3.17.6.4 Extraction (Both Solid and Liquid Phase)......Page 1863
References......Page 1864
Acetic and Propionic Acids......Page 1866
3.18.3.1 History......Page 1867
3.18.3.2.2 Metabolic pathways......Page 1868
3.18.3.2.3 Process development......Page 1869
3.18.3.3.3 Process development......Page 1870
3.18.3.4 Comparison of Aerobic and Anaerobic Fermentation Processes......Page 1871
3.18.3.6.3 Metabolic pathways......Page 1872
3.18.3.6.4 Production improvement......Page 1873
3.18.4 Product Recovery and Purification......Page 1874
References......Page 1875
3.19.1 Introduction......Page 1877
3.19.2.2.1 Direct reduction pathway......Page 1878
3.19.3.1 Proposed Metabolic Pathways......Page 1880
3.19.3.2 Proposed Industrial Production Process......Page 1881
References......Page 1882
3.20.1 Introduction......Page 1883
6.30.1.1.1 Biofilm formation......Page 1884
3.20.4.1 Metabolic Pathway......Page 1886
3.20.4.2 Genetic Engineering of Clostridia......Page 1887
3.20.5.3 Solvent Extraction......Page 1888
3.20.5.6 Membrane Techniques......Page 1889
3.20.6 Summary......Page 1890
References......Page 1891
3.21.1 Introduction......Page 1892
6.46.2.1 Gram-Positive Thermophilic Bacteria......Page 1894
3.21.3.1 Metabolic Engineering of Microorganisms for the Production of PHAs......Page 1895
3.21.3.2 Metabolic Engineering for the Production of Unnatural Polymers......Page 1897
3.21.3.3 Future Perspectives of Systems Metabolic Engineering for Polymer Production......Page 1899
3.21.4.3 PHA/PHB as Medical Implant Materials......Page 1900
3.21.4.4 PHA as Drug Delivery Carriers......Page 1901
References......Page 1902
3.22.1 Introduction......Page 1903
3.22.2 Polytrimethyleneterephthalate......Page 1904
3.22.4 Metabolic Pathways and Engineering of PDO Formation......Page 1905
3.22.4.2 Metabolic Pathways......Page 1906
3.22.4.3 Yield and Productivity of PDO......Page 1907
3.22.5 Fermentation Conditions and Operation Modes......Page 1909
3.22.6.1 Route 1: Conventional Route......Page 1910
3.22.6.2 Route 2: Liquid Extraction......Page 1912
3.22.7 Production Costs and Biorefinery Concept......Page 1913
References......Page 1915
3.23.2 The Miracle of Antibiotics......Page 1917
3.23.3 The Golden Era of Antibiotic Discovery......Page 1919
3.23.4 Microbial Genomics and the Failure of Antibiotic Discovery Research......Page 1920
3.23.5 Medical Need, Antimicrobial Resistance, and the Anti-Infective Marketplace......Page 1921
3.23.6 The Regulatory Environment for Antibacterials......Page 1922
3.23.7 Large Pharmaceutical Companies Exit and Biotechnology Enters......Page 1925
3.23.8 Conclusions......Page 1927
References......Page 1928
3.24.1 Introduction to Penicillins and Cephalosporins......Page 1929
3.24.2 Structure and Mechanism of Action of Penicillins and Cephalosporins......Page 1930
3.24.3.1 Penicillin and Cephalosporin Biosynthetic Pathways......Page 1931
3.24.3.2 Organization and Expression of Penicillin and Cephalosporin Biosynthetic Genes......Page 1933
3.24.3.3 Compartmentalization of the Penicillin Biosynthetic Pathway......Page 1934
3.24.3.4 Compartmentalization of the Cephalosporin Biosynthetic Pathway......Page 1936
3.24.4.1.1 Industrial strain improvement and genetic engineering......Page 1937
3.24.4.1.2 Production of semisynthetic penicillins......Page 1938
6.16.5 Practical Approach......Page 1939
3.24.4.2.3 Semisynthetic cephalosporins......Page 1940
References......Page 1941
Relevant Websites......Page 1942
3.25.1 Introduction and Scope......Page 1943
3.25.3.1 The Tetracycline Biosynthesis Pathway......Page 1945
3.25.3.1.1 Tetracyclines derived from other actinomycetes and microorganisms......Page 1946
3.25.4.2 Minimal Structural Requirements for Antibacterial Activity in Tetracycline Derivatives......Page 1947
3.25.5.1.1 A-ring C2 modifications of the tetracyclines......Page 1948
3.25.5.2.1 Lower periphery derivatives and antibacterial activity......Page 1949
3.25.5.3.2 The synthesis and antibacterial activity of methacycline and second-generation tetracyclines......Page 1950
3.25.5.3.4 Synthesis and antibacterial activity of doxycycline......Page 1951
3.25.5.4.1 Minocycline semisynthesis......Page 1952
3.25.6 Semisynthesis of Third-Generation Tetracyclines: Derivatives of Minocycline, Sancycline, and Doxycycline......Page 1953
3.25.6.1 Semisynthesis of the Glycylcyclines and Tygacil®......Page 1954
3.25.8 Antibacterial and General Chemical Properties of the Tetracyclines: Uptake and Membrane Activity......Page 1955
3.25.10 Conclusions......Page 1956
References......Page 1957
3.26.1 Introduction......Page 1958
3.26.3 Overview of Bioactivities......Page 1959
3.26.5.1 Fermentation......Page 1960
3.26.5.2 Strain Improvement......Page 1961
3.26.6.1 Antibacterial Antibiotics......Page 1962
3.26.6.2 Antifungal Antibiotics......Page 1964
3.26.6.3 Antitumor Antibiotics......Page 1965
3.26.6.4 Immunosuppressant Agents......Page 1967
3.26.6.5 Statins......Page 1968
3.26.7 Conclusions......Page 1969
References......Page 1970
3.27.1 Plants and Secondary Metabolites......Page 1971
3.27.2 Heterogeneity of Plant Secondary Metabolites......Page 1972
3.27.3 Secondary Metabolite Production by Plant Cell Culture......Page 1974
3.27.4.2 Calcium Ion......Page 1975
3.27.4.5 Nitric Oxide......Page 1976
3.27.5.2 Metabolic Engineering......Page 1977
3.27.6 Conclusions and Perspectives......Page 1979
References......Page 1980
3.28.1 Introduction......Page 1981
3.28.2.2 Lactic Acid......Page 1982
6.19.3 Removal of Heavy Metals......Page 1983
3.28.2.6 Aromas from Natural Products......Page 1984
3.28.2.7 Sesquiterpenes, Diterpenes, and Other High Terpenes......Page 1985
3.28.3.1 Redox Biotransformations......Page 1987
3.28.3.1.1 Whole cell-catalyzed oxidations......Page 1988
3.28.3.1.2 Whole cell-catalyzed reductions......Page 1993
3.28.4.1 Reactions Catalyzed by Oxidoreductases......Page 1998
3.28.4.2.2 Reactions catalyzed by proteases......Page 1999
3.28.4.2.4 Reactions catalyzed by acylases......Page 2000
3.28.4.4 Reactions Catalyzed by d-Hydantoinase/d-N-Carbamoylase......Page 2001
References......Page 2002
Relevant Websites......Page 2003
3.29.1 Introduction......Page 2004
3.29.3 Systems for Producing Recombinant Proteins......Page 2005
3.29.3.1.1 Escherichia coli......Page 2006
3.29.3.1.2 Bacillus......Page 2007
6.55.2.5 Case History 5: Bioconversion of Fe(III)-Oxide Waste into a Nanoscale Magnetic Material......Page 2008
3.29.3.4 Insect Cells......Page 2010
3.29.3.5 Mammalian Cells......Page 2011
3.29.3.7 Transgenic Plants......Page 2012
3.29.4 Conclusions......Page 2013
References......Page 2014
3.30.1 Introduction......Page 2017
3.30.2 Smallpox Vaccine and Other Vaccines of the Nineteenth Century......Page 2018
6.45.2.2 Laccases as Green Agents in the Transformation of Pollutants......Page 2019
3.30.3.2.2 Pneumococcal disease and vaccines......Page 2020
3.30.3.2.5 International importance of vaccination......Page 2021
3.30.4.2.1 Poliovirus vaccines......Page 2022
6.24.5.2 Coupled Enzyme Kinetics and Bacterial Growth......Page 2023
References......Page 2024
3.31.1 Introduction......Page 2026
3.31.3 Improved Recovery of High-Producing Cell Lines......Page 2027
3.31.4 High-Throughput Bioprocess Development......Page 2028
3.31.7 Conclusions......Page 2029
References......Page 2030
6.29.1 Introduction......Page 2032
3.32.2 Characterization of mAb Quality Attributes......Page 2033
3.32.4.1 Fusion Proteins......Page 2034
3.32.5 Engineering Enhanced mAb Domain Functionality......Page 2035
6.27.3.2.1 Single-reactor anammox processes......Page 2036
3.32.6.3 Product Aggregates......Page 2037
3.32.7 Comparability Considerations......Page 2038
3.32.8 New Analytics......Page 2039
3.32.9 Platform Technologies......Page 2040
3.32.10.2 Disposable Product Equipment......Page 2041
3.32.10.5 High-Protein Formulations......Page 2042
References......Page 2043
6.37.1 Introduction......Page 2045
3.33.2.1 Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome)......Page 2046
3.33.3 Enzyme Kinetics......Page 2047
3.33.4 Substrate Considerations......Page 2049
3.33.5 Complex Heterodisperse Natural Substrates......Page 2054
3.33.6 Application of Cell-Based Activity Assays to Qualification of Non-Biomimetic Substrates......Page 2056
References......Page 2057
3.34.1 Introduction......Page 2058
3.34.3 Advantages of Cell-Free Protein Production......Page 2059
3.34.5.1 Display Technologies and Directed Evolution......Page 2060
3.34.7.1 Selection of Cell-Free System......Page 2061
3.34.7.4 Reactor Format......Page 2062
References......Page 2063
3.35.1 Introduction and Definitions......Page 2065
3.35.2 FDA’s Organization and the Office of Combination Products......Page 2067
3.35.3 Request for Designation, Primary Mode of Action, and Assignment of Jurisdiction......Page 2068
3.35.4 How Things Work – Differences in Processes between Centers......Page 2069
3.35.4.4 Meetings......Page 2070
3.35.4.6 Nonclinical Studies......Page 2071
3.35.4.8 Manufacturing and Compliance......Page 2072
3.35.4.9 Postmarket Reporting......Page 2073
3.35.6 The Future......Page 2074
Relevant Websites......Page 2075
Cellular Therapies......Page 2076
3.36.2 Sources of Cells and Clinical Applications of Cell Therapy......Page 2077
3.36.3.3 Products under Development......Page 2078
3.36.4 Cellular Vaccines......Page 2079
3.36.5 Adoptive Cell Therapies......Page 2080
3.36.6.2 Umbilical Cord and Peripheral Blood-Derived Stem Cell Therapies......Page 2081
3.36.6.6 Ethical Considerations......Page 2084
3.36.7.1 Physical Methods......Page 2085
3.36.7.6 Magnetic Bead Separation......Page 2087
3.36.8 Summary......Page 2088
References......Page 2089
3.37.1 Introduction and Scope......Page 2090
3.37.3 Challenges Pertinent to the Development of Gene Therapy Products......Page 2091
3.37.4 Regulatory Issues and Standardization Activities Pertinent to Gene Therapy Products......Page 2093
3.37.5.3.1 Cell banks......Page 2094
6.45.4.2 Production of Laccases by Fungi on Agriculture Residues......Page 2095
References......Page 2096
3.37.7.3 Bioproduction and Purification of Nonviral (Plasmid) Vectors......Page 2097
3.37.8.1 Safety Issues Pertinent to Gene Therapy Products – Replication-Competent Viruses......Page 2098
3.37.8.3 Determination of Purity and Identity......Page 2099
3.37.10 Product Administration of Gene Therapy Products......Page 2100
References......Page 2101
Relevant Websites......Page 2102
3.38.1 Introduction......Page 2103
3.38.2.1 Phase 1 INDs......Page 2104
3.38.2.1.1 Current good manufacturing practices at Phase 1......Page 2105
3.38.3 Biologic License Application......Page 2106
3.38.3.1 Quality by Design......Page 2110
3.38.4 Comparability Testing......Page 2111
6.19.6 Concluding Remarks......Page 2112
3.38.6 Conclusions......Page 2114
References......Page 2115
3.39.2 Regulations on Raw Materials......Page 2117
3.39.3.3 Raw Material Qualification......Page 2118
3.39.5 Control of the Quality of Raw Materials......Page 2119
3.39.8 Controlling the Risk of Introducing Raw Materials......Page 2120
References......Page 2121
3.40.1 Assessment of Product Characteristics......Page 2123
3.40.2 Biotechnology Product Characterization, Comparability, Release, and Stability Tool Kits......Page 2125
3.40.3 Selection of Analytical Methods......Page 2126
3.40.4 Analytical Method Lifecycle Issues......Page 2127
References......Page 2129
Immunogenicity Assay Development and Validation......Page 2131
3.42.2 Development of Binding Antibody Methods......Page 2132
3.42.3.1 System Suitability Controls (Quality Controls)......Page 2133
3.42.3.2.1 Screening method cut-point......Page 2134
3.42.3.3 Sensitivity and ADA Dilutability......Page 2135
3.42.3.7 Study-Phase Acceptance Criteria for the System Suitability Controls......Page 2136
3.42.4 Development of NAb Methods......Page 2137
3.42.4.2 Non-Cell-Based NAb Assays......Page 2138
3.42.5.1 System Suitability Controls (Quality Controls)......Page 2139
3.42.5.7 Study-Phase Acceptance Criteria for System Suitability Controls......Page 2140
3.42.6.5 Efficient Experimental Conduct......Page 2141
3.42.7 Concluding Remarks......Page 2142
References......Page 2143
Protein Glycosylation......Page 2144
3.41.1.1 Glycoanalytical Methods......Page 2145
3.41.3 Analysis of Free Glycans......Page 2146
3.41.3.2 Glycan Release......Page 2147
3.41.3.2.2 Enzymatic release......Page 2148
3.41.3.3 Glycan Labeling and Purification......Page 2149
3.41.3.4.1 Anion exchange chromatography and separation by charge......Page 2151
3.41.3.4.4 High-pH anion exchange chromatography......Page 2152
3.41.3.5.1 Glycan analysis......Page 2154
3.41.3.5.2 Applications of oligosaccharide sequencing in glycan analysis of therapeutic glycoproteins......Page 2155
3.41.3.6 High-Throughput Glycan Analysis Based on a Robotics Platform......Page 2156
3.41.3.7 Data Analysis and Glycobioinformatics......Page 2157
3.41.3.8 Mass Spectrometry......Page 2158
3.41.4.2 Analysis of Sialic Acids......Page 2159
3.41.5 Glycan Analysis Design for Therapeutic Glycoproteins......Page 2160
References......Page 2161
Process Analytical Technology in Bioprocess Development and’Manufacturing......Page 2164
3.43.1 Introduction and Scope......Page 2165
3.43.1.1 Bioprocess Development......Page 2166
3.43.1.3 Development of Design and Control Spaces......Page 2167
3.43.2.2 Multivariate Data Analysis......Page 2169
3.43.2.3 Online Batch Monitoring, Supervision, and Control......Page 2170
3.43.3 Concluding Remarks......Page 2171
References......Page 2172
3.44.1 Introduction and Scope......Page 2173
3.44.2.3 Equipment, Facilities, Utilities, and Strategy......Page 2174
6.07.3 Saturated Zone Treatment Methods......Page 2175
3.44.3.6 Design of Experiments......Page 2176
3.44.3.7.2 Cell culture......Page 2177
3.44.3.7.4 Downstream processing......Page 2178
3.44.4.1 Utilization of Risk Assessments......Page 2179
3.44.4.7 Process Monitoring after Approval......Page 2180
References......Page 2181
3.45.1 Introduction......Page 2182
3.45.2 Unique challenges associated with protein products......Page 2183
3.45.3 Impact of the manufacturing process on product quality......Page 2184
3.45.4 Impact of product quality on clinical performance......Page 2186
3.45.5 Conclusions......Page 2187
References......Page 2188
6.19.2.1 Production of Oil-Enriched Microalgae Using Wastewater and CO2......Page 2191
3.46.2.2 l-Glutamic Acid......Page 2192
3.46.2.3 l-Lysine......Page 2193
3.46.2.4 l-Threonine......Page 2195
3.46.2.5 l-Serine......Page 2196
3.46.3.1 l-Aspartic Acid......Page 2198
References......Page 2199
Lysine: Industrial Uses and Production......Page 2200
3.47.1 Introduction......Page 2201
3.47.2.1 d-Lysine......Page 2202
3.47.3.1 Classical Methods for Development of l-Lysine Overproducers......Page 2203
3.47.5 Fermentation Is the Dominant Method for Industrial l-Lysine Production......Page 2204
3.47.5.3.1 Batch fermentations......Page 2205
3.47.6.1 Key Genes and Enzymes Controlling the l-Lysine Biosynthetic Pathway......Page 2206
3.47.6.2 Feedback Regulation by Allosteric Inhibition and Transcriptional Repression......Page 2207
3.47.7.1 Manipulations with Key Genes of the Aspartate Pathway......Page 2208
3.47.7.6 Impact of Osmotic Stress......Page 2209
3.47.8.1 Lignocellulose......Page 2210
3.47.8.2.3 Bacillus methanolicus......Page 2211
References......Page 2212
Relevant Websites......Page 2213
3.48.1 Introduction......Page 2214
3.48.2 Sources of Food-Grade Enzymes......Page 2215
3.48.3.1.1 Amylases......Page 2216
3.48.3.1.4 β-Galactosidases......Page 2219
3.48.3.2 Proteases......Page 2220
3.48.4.1.1 Lysozymes......Page 2221
3.48.4.2.1 Lactoperoxidases......Page 2222
3.48.5.1 Screening of Food-Grade Enzymes in Wild Stains......Page 2223
3.48.5.2 Expression of Food-Grade Enzymes in Engineered Strains......Page 2224
3.48.5.4 Immobilization of Food-Grade Enzymes......Page 2225
3.48.6.3 Purification of Food-Grade Enzymes......Page 2226
3.48.8 Safety Concerns with Food-Grade Enzymes......Page 2227
References......Page 2228
3.49.1 Introduction......Page 2229
3.49.2 Protease Types......Page 2233
3.49.3.2 Production of Microbial Proteases......Page 2234
3.49.3.3 Impact of Recombinant Technology on Microbial Protease Production......Page 2235
3.49.4.2.1 Brewing and cereal processing......Page 2236
3.49.4.3 Proteases in Leather and Fabric Processing......Page 2237
3.49.4.5 Proteases in Organic Synthesis......Page 2238
3.49.5 Protease Inhibitors......Page 2239
References......Page 2240
3.50.1 Introduction and Scope......Page 2241
3.50.2 Riboflavin – Vitamin B2......Page 2242
3.50.3 Niacin – Vitamin B3......Page 2245
3.50.4 R-Pantothenic Acid and R-Panthenol – Vitamin B5 and Provitamin B5......Page 2246
3.50.5 Biotin – Vitamin B7......Page 2247
3.50.6 Cobalamin – Vitamin B12......Page 2248
3.50.7 l-Ascorbic Acid – Vitamin C......Page 2251
3.50.8 Phylloquinones and Menaquinones – Vitamin K......Page 2253
6.35.4.2 Two-Phased Anaerobic Digestion......Page 2255
3.50.11 l-Carnitine......Page 2257
3.50.12 Outlook......Page 2258
References......Page 2259
3.51.1 Introduction......Page 2261
3.51.3 Use of Fruiting Body......Page 2262
3.51.4.3 Use of Yeast Cells in Food and Fodder......Page 2265
3.51.5.3 Production of Bakery and Cheese Products......Page 2266
3.51.7 Fungal Enzymes Used in Feed......Page 2267
3.51.8 Commercial Recombinant Enzymes from Fungi......Page 2269
3.51.11 Symbiotic Fungus Termitomyces: A Filamentous Basidiomycota......Page 2270
3.51.14 Concluding Remarks and Future Prospects......Page 2271
References......Page 2272
3.52.1 Introduction: Evolution of Metabolic Engineering......Page 2274
3.52.2.1 Host Selection Overview......Page 2275
3.52.2.3.1 Bacteria......Page 2276
3.52.2.3.4 Animalia......Page 2277
3.52.3.1 Amino Acids......Page 2278
3.52.3.2 Biofuels......Page 2279
3.52.3.3 Secondary Metabolites......Page 2280
3.52.3.5 Polymers......Page 2281
3.52.4.2 Rational Metabolic Engineering......Page 2282
3.52.5 Future Perspectives......Page 2283
References......Page 2284
3.53.1 Introduction......Page 2286
3.53.2 Historical Foundation......Page 2287
3.53.3.3 Genetic Parts (BioBricks) and Circuits......Page 2288
3.53.4.3 Consultancies and BioFabs......Page 2289
3.53.5.2 DIYbio......Page 2290
3.53.6.1 Industrial Synthetic Biology......Page 2291
3.53.7 Regulatory Debate......Page 2292
3.53.8 Synbioethics......Page 2293
3.53.9.1 Patents and Synthetic Biology......Page 2294
3.53.9.2 Open Source Synthetic Biology......Page 2295
6.30.3.1.3 Sequencing batch reactor (SBR) operation with recirculation......Page 2296
Relevant Websites......Page 2297
3.55.1 Introduction......Page 2298
3.55.2 Classifications of Bioreactors......Page 2299
6.49.2.1 Thermodynamic Fundamentals......Page 2300
3.55.4 Bioreactors and Sustainability......Page 2301
References......Page 2303
3.54.1 Introduction......Page 2304
3.54.2.1 Mixing......Page 2305
3.54.2.2 Cell Culture......Page 2306
3.54.2.3 Cell Harvest......Page 2307
3.54.3.1 Purification......Page 2308
3.54.3.2 Filling......Page 2309
3.54.4.1 Liquid Hold Bags......Page 2310
3.54.4.2 Filtration......Page 2311
3.54.4.3 Fluid Transfer......Page 2312
6.16.5.1 Bioremediation of Wastewater and Wastewater Sludge......Page 2313
References......Page 2315
3.56.1 Introduction......Page 2316
3.56.2.1 Mimicking Large-Scale Process Conditions......Page 2317
3.56.2.5 Monitoring of Glutamine......Page 2318
3.56.3 Integrating PSDs with Bench-Scale Devices by Developing a Scale-Up Strategy......Page 2319
3.56.4.1 Static Devices......Page 2321
3.56.5 Future Developments......Page 2322
References......Page 2323
Overview of Downstream Processing in the Biomanufacturing Industry......Page 2325
3.57.1 Introduction and Scope......Page 2326
3.57.3.1 Centrifugation......Page 2327
3.57.3.2 Microfiltration......Page 2328
3.57.3.3.2 Precipitation......Page 2330
3.57.4.1 General Principles of Process Chromatography......Page 2331
3.57.4.3.1 Ion exchange chromatography......Page 2333
3.57.4.3.2 Hydrophobic interaction chromatography......Page 2334
3.57.5.1 Principles of UF and DF......Page 2335
3.57.6 Crystallization as a Low-Technology Polishing Method......Page 2336
References......Page 2337
Nanotechnology......Page 2339
3.58.1 Introduction......Page 2340
3.58.2.1.2 Liposomes......Page 2343
6.39.3 Biosensors for Control of Anaerobic Digestion......Page 2344
3.58.2.2.5 Nanorobotics and nanomachines......Page 2345
3.58.3 Bionanotechnology and Nanobiotechnology......Page 2346
3.58.3.2 Nanomedicine......Page 2347
3.58.4.2 Nucleotide Delivery for Genetic Control......Page 2348
3.58.4.4 Risk Assessment......Page 2349
3.58.4.5.3 Self-assembly......Page 2350
3.58.4.5.5 Molecular nanotechnology......Page 2351
3.58.4.6 Commercialization of Bionanotechnology......Page 2352
Relevant Websites......Page 2353
Biosurfactants......Page 2354
3.59.2.1 Low-Molecular-Weight Biosurfactants......Page 2355
3.59.2.2 High-Molecular-Weight Biosurfactants......Page 2359
3.59.2.2.1 Genetic organization and regulation......Page 2360
3.59.2.2.3 Natural role for emulsan......Page 2361
3.59.3.2.2 Polysaccharide–protein interactions......Page 2363
3.59.3.3.2 Biodegradation and bioremediation of hydrocarbon substrates......Page 2365
3.59.4 Perspectives and Future Development......Page 2366
3.59.4.2.1 EEP technology......Page 2367
3.59.5.1.2 Engineering overproducers and new products......Page 2368
References......Page 2369
3.61.2 Biological Control......Page 2371
3.61.4.1 Biochemical Pesticides......Page 2372
3.61.4.2.2 Bacillus thuringiensis......Page 2373
3.61.4.3.2 Production of toxins......Page 2374
3.61.4.4 Entomopathogenic Viruses......Page 2375
3.61.4.6 Entomopathogenic Nematodes......Page 2376
3.61.7 Engineering Biological Control Agents......Page 2377
3.61.10 Conclusion......Page 2378
References......Page 2379
3.60.1 Introduction......Page 2380
3.60.2 Microorganisms Involved in Biomining......Page 2381
3.60.3 Industrial Biomining of Ores......Page 2382
3.60.4 Environmental Impact of Biomining Activities......Page 2383
3.60.5.1 Main Bacteria–Mineral Interactions......Page 2384
3.60.5.2 Mechanisms of Oxidation of Minerals......Page 2385
3.60.5.3 Microbial Resistance to Acid and Metals......Page 2386
3.60.6.2 Genomics and Metagenomics......Page 2387
3.60.6.4 Proteomics and Metaproteomics......Page 2390
References......Page 2391
vol4......Page 2393
Introduction......Page 2394
Plant Biotechnology and GMOs......Page 2401
4.02.2.1 Increasing Food and Feed Demand......Page 2402
4.02.3.1 Population Growth in the Twentieth Century......Page 2403
4.02.3.2 Yield Per Acre of Corn......Page 2404
6.12.7 Degradation of Biphenyl......Page 2405
4.02.4.4.1 No-till farming......Page 2406
4.02.4.5 Consumer Response......Page 2407
4.02.5.3 The Ability to Turn Genes On and Off......Page 2408
4.02.5.4.2 Genetic engineering of drought tolerance......Page 2409
4.02.5.4.4 Developing crops tolerant to high temperatures......Page 2410
4.02.5.5.2 Omega-3 fatty acid formation in plants......Page 2411
4.02.5.7 Biofuels......Page 2412
Relevant Websites......Page 2413
4.03.1 Introduction......Page 2415
4.03.2.1.1 Photosystem II inhibitors......Page 2416
4.03.2.1.2 Photosystem I electron diverters......Page 2418
6.36.8 A Case Study: AD as a Service Technology for the Territory......Page 2419
4.03.3.1 Cell Wall Synthesis......Page 2420
4.03.3.2.2 Very-long-chain fatty acid elongases......Page 2421
4.03.3.3.2 Acetolactate synthase......Page 2423
4.03.4.1 Auxinic Herbicides......Page 2424
4.03.4.3 7,8-Dihydropteroate Synthase......Page 2425
References......Page 2426
Relevant Websites......Page 2427
Starch Biosynthesis in Higher Plants: The Starch Granule......Page 2428
4.04.2 Overview of Starch Structure......Page 2429
4.04.4 Control of Starch Granule Size......Page 2431
4.04.7 High-Amylose Starches......Page 2432
References......Page 2433
Starch Biosynthesis in Higher Plants: The Enzymes of Starch Synthesis......Page 2437
4.05.3 The Pathway of Starch Biosynthesis......Page 2438
4.05.4 The Formation of ADP-glucose by ADP-glucose Pyrophosphorylase......Page 2439
4.05.6 Amylose Biosynthesis......Page 2441
References......Page 2442
4.05.11 Starch Synthase IV......Page 2443
4.05.12 Branching of the Glucan Chain......Page 2444
4.05.14.1 d-Enzyme......Page 2445
4.05.15 Coordination of Enzyme Activities during Starch Granule Synthesis......Page 2446
4.05.17 Summary and Future Prospects......Page 2448
References......Page 2449
4.06.1 Introduction......Page 2456
6.23.2 Fate (Weathering) of Oil Spills......Page 2457
4.06.3 Industrial Uses of Plant Oils......Page 2458
4.06.4 Seed Oil Biosynthesis......Page 2460
4.06.5 Oils for Biodiesel Production......Page 2462
4.06.7 Oils Enriched in VLCFAs......Page 2464
4.06.9 Increasing Functionality: FA Modification in Membrane Lipids......Page 2466
4.06.10.1 Targeting Specific Enzyme-Catalyzed Reactions in Carbon Flow......Page 2467
4.06.10.2 Altering the Action of TFs......Page 2469
4.06.10.3 Production of TAG in Vegetative Tissue......Page 2471
4.06.13 Closing Comments......Page 2472
References......Page 2473
Biodiesel – An Integrated Approach for a Highly Efficient Biofuel......Page 2475
6.16.3 Oxidative Fungal Enzymes......Page 2476
4.07.3.1 Plant Breeding......Page 2477
4.07.4.1 Plant Growth-Promoting Rhizobacteria as Biofertilizers......Page 2478
4.07.4.2.1 Lipo-chitooligosaccharides (LCOs)......Page 2479
6.07.5 Monitoring Methods......Page 2480
4.07.5.2.1 Choice of lipase......Page 2481
4.07.7 Fuel Quality and Use in Engines......Page 2482
References......Page 2485
4.08.1 Introduction......Page 2488
4.08.2.1 Biopolymers from Agricultural Resources......Page 2489
4.08.2.2.1 Wheat-fiber-based composites......Page 2490
4.08.2.2.6 Miscanthus-fiber-based composites......Page 2491
4.08.3 Manufacturing Bioproducts......Page 2492
4.08.3.2 Thermoset Processing......Page 2493
4.08.4 Applications of Bioproducts......Page 2494
6.16.5.3 Bioremediation of Contaminated Wood......Page 2495
6.14.5 Engineered Systems for Bacterial Degradation of PCBs......Page 2496
4.09.1 Introduction......Page 2497
6.07.2.1 Natural Attenuation......Page 2498
4.09.3.1.3 Nanocarbon......Page 2499
4.09.3.2.1 Electrospun biofibers......Page 2500
4.09.3.2.2 Cellulose nanostructures......Page 2501
4.09.3.2.4 Plant leaf extract-mediated synthesis of silver nanoparticles......Page 2503
4.09.4.3 Advanced Electronics......Page 2504
References......Page 2505
4.10.1 Introduction......Page 2506
4.10.2.1 Weeds and Weed Control......Page 2507
4.10.2.3 Impacts of the Use of RR and Other HT Crops......Page 2508
4.10.3.1 Insects and Insect Control......Page 2510
4.10.3.3 Impacts of the Use of Bt Maize and Other Bt Crops......Page 2511
4.10.4.2 Isolation and Transfer of PRSV-Resistance Gene......Page 2512
4.10.5.2 Development and Maintenance of Male-Sterile Female Line......Page 2513
4.10.5.3 Development and Maintenance of Fertility Restorer Male Line......Page 2514
4.10.5.5 Impact of Hybrid Canola in Canada......Page 2515
References......Page 2516
4.11.1 Introduction......Page 2517
4.11.2.1 History......Page 2518
4.11.2.3.1 Anther culture......Page 2519
4.11.2.3.5 Microspore isolation......Page 2520
4.11.2.5 Advantages and Application of DHs......Page 2521
6.24.5.1 Coupling of Water Circulation and Microbiology......Page 2522
4.11.3 Molecular Markers......Page 2523
4.11.4 Quantitative Trait Loci......Page 2524
4.11.4.3 Linkage Disequilibrium......Page 2525
4.11.5 Strengths and Weaknesses of LD Mapping......Page 2526
4.11.6.1 Variations in MAS......Page 2527
4.11.6.2 Application of MAS in Industry......Page 2528
4.11.7 Conclusions and Perspectives on Using DH and Molecular Markers in Plant Breeding......Page 2529
References......Page 2530
4.12.1 Introduction......Page 2532
4.12.2.1 An Overview of Microarrays and Microarray Hybridizations......Page 2533
4.12.2.2 Background Correction and Normalization of Array Data......Page 2535
4.12.2.3 Sequencing cDNA to Assay Gene Expression......Page 2536
4.12.3.1 Identifying Differentially Expressed Genes......Page 2537
4.12.3.3 Software for Differential Expression......Page 2538
4.12.4.2 Distances......Page 2539
4.12.4.3.1 Hierarchical clustering......Page 2540
4.12.4.3.3 Two-way clusters......Page 2542
4.12.4.3.4 What clustering method is right for my data?......Page 2544
Relevant Websites......Page 2545
4.13.1 Introduction......Page 2547
4.13.2.1 Effects of Enzymatic Properties of RuBisCO on Leaf Photosynthesis......Page 2548
4.13.2.2 Site-Directed Mutation......Page 2550
4.13.2.3 Directed Evolution of RuBisCO......Page 2551
4.13.2.4 Improvement of RuBisCO in Plants......Page 2552
4.13.3 Engineering Regulation of RuBisCO Activation......Page 2553
4.13.3.2 Enhancement of RuBP Regenerative Capacity......Page 2554
4.13.4.2 C4-Ization of C3 Crop Plants......Page 2555
6.42.4.4 Winery Wastewater......Page 2556
References......Page 2557
4.14.1 Introduction......Page 2559
6.42.2 Guidelines for the Valorization of Agriculture and Agro-Industrial Wastes and Wastewaters......Page 2561
4.14.2.2.1 Leaf source strength of natural variants......Page 2562
4.14.2.2.2 Temperature and source strength: Photosynthesis and export......Page 2564
4.14.3.1 Plant Biomass Gain of Photosynthetic Variants under High CO2......Page 2565
4.14.3.3 Scaling from Leaf Photosynthesis and Export Traits to Whole-Plant Growth Traits......Page 2566
4.14.4.1 Greenhouses as Bioreactors for Vascular Plants......Page 2567
4.14.4.2 Elevated CO2 Levels in Field Production Scenarios......Page 2568
6.31.3.2.3 Methanogenesis......Page 2569
References......Page 2570
4.15.1 Introduction......Page 2572
4.15.2 Genetic Modification of Glycolytic Enzymes......Page 2574
4.15.4 Genetic Modification of TCA Cycle Enzymes......Page 2582
4.15.4.1 A Case Study: Enhanced Sink Activity and Productivity in Arabidopsis Lines with Increased mtPDH Complex Activity under Elevated CO2......Page 2583
4.15.5.2 Cyanide-Resistant Pathway Enzymes......Page 2584
4.15.7 Conclusion......Page 2585
References......Page 2587
4.16.2 What Is NUE?......Page 2589
4.16.3 Agronomic Approaches for Improving NUE......Page 2590
4.16.4.1 NUE – Transgenic Approach......Page 2591
4.16.4.5 Manipulating Genes of C Metabolism......Page 2592
4.16.4.6 Manipulating Signaling Targets......Page 2594
4.16.6 Improving NUE: A Systems Biology Approach......Page 2595
4.16.7 Global Status of NUE......Page 2596
References......Page 2597
Circadian Clocks/Photoperiodism and Crop Quality......Page 2599
4.17.1 Introduction and Scope......Page 2600
4.17.2 Introduction to Biological Rhythms and the Plant Circadian Clock......Page 2602
4.17.3.2 The Input Pathway......Page 2603
4.17.3.3 The Core Oscillator......Page 2605
4.17.5 Adaptive Significance of Plant Circadian Rhythms......Page 2606
4.17.6.2 Relationship between the Photoperiodic Flowering Response and the Plant Circadian Clock......Page 2607
4.17.7.2 Genetic Modification of Photoperiod-Sensitive Flowering in Crop Plants......Page 2608
4.17.8.2 Temperature Stress......Page 2609
4.17.8.5 Biotic Stress......Page 2610
4.17.10 Nitrogen Acquisition and Assimilation......Page 2611
References......Page 2612
6.48.1 Introduction......Page 2615
4.18.4 Micropropagation and Bioreactor Production of Breadfruit......Page 2616
4.18.4.2 Stage 1: Establishment of Aseptic Culture and Confirmation of Bacterial Indexing......Page 2617
6.25.3.3 Sedimentation Tank Models......Page 2618
Relevant Websites......Page 2619
4.19.1 Introduction......Page 2620
4.19.2 Grape Cultivars......Page 2621
4.19.4 Grape and Wine Genomics......Page 2622
4.19.4.1 Improved Quality in Grapevine for Wine Production......Page 2623
4.19.4.2.3 Possible roles of hydroxycinnamic acid glucose esters......Page 2624
4.19.4.2.4 Biosynthesis of flavonoids and anthocyanins......Page 2625
4.19.4.2.5 Foxy methyl anthranilate biosynthesis is linked to the production of 3,5 anthocyanin diglucosides......Page 2626
4.19.4.2.6 R2R3 MYB transcription factors that activate and control pigment formation......Page 2627
4.19.4.2.8 Terpenoids and their variation in grapes......Page 2628
4.19.4.3 Grapevine Disease Resistance......Page 2629
4.19.4.4 Grapevine Transformation and Genetic Engineering......Page 2630
4.19.6 GMO Grapevines and Fermentation Organisms in Grape and Wine Production......Page 2631
4.19.6.2 Historical and Cultural Issues That Impede Adoption of the New Technology......Page 2632
References......Page 2633
4.20.1 Introduction......Page 2635
6.11.3 Proteomic Applications to the Study of Bacterial Degradation of Aromatic Hydrocarbons......Page 2636
4.20.2.1.2 Glutathione and methionine biosynthesis......Page 2637
4.20.3 Sulfur-Containing Secondary Metabolite in Plants/Microbes and Their Importance/Role......Page 2638
6.51.3.2 Factors That Govern Culture Selection in Mixed Cultures Operated under FF Conditions......Page 2643
4.20.4.2 Removal of Hydrogen Sulfide from Gas Stream......Page 2644
4.20.4.5 Wastewater Treatment......Page 2646
4.20.4.7 Mining Metallurgy Industry – Extraction of Metals......Page 2647
4.20.4.9 Food and Dairy Industry: Improving Cheese Flavor......Page 2648
Relevant Websites......Page 2649
4.21.1 Introduction to Plant Terpenoids and Scope......Page 2650
4.21.1.1 The Pathways......Page 2651
4.21.2.1 Roles of Carotenoid Pigments......Page 2653
6.48.2.3 Hydrogen Production by Photofermentations......Page 2655
4.21.2.3.2 Strigolactones and canopy development......Page 2656
4.21.3 Isoprene Emission......Page 2657
4.21.5 Taxol......Page 2658
4.21.6 Iridoid Glycosides......Page 2660
References......Page 2662
Relevant Websites......Page 2663
4.22.1 Introduction......Page 2664
4.22.2.1.1 Agrobacterium-Mediated Stable Transformation......Page 2666
4.22.2.1.2 Direct Gene Transfer......Page 2667
4.22.2.1.4 Magnifection (magnICON® System)......Page 2668
4.22.2.2 Model Plant Systems......Page 2669
4.22.2.3 Glycosylation......Page 2670
4.22.3.2 Clarification and Enrichment......Page 2671
4.22.3.4 SemBioSys Oilbody Platform......Page 2672
6.25.6.6 Application......Page 2673
4.22.4.2.2 Immunopurification......Page 2674
4.22.4.3.2 Bacterial Infections......Page 2675
References......Page 2676
Relevant Websites......Page 2677
4.23.1 Introduction......Page 2678
4.23.2 C. reinhardtii as Protein Expression Platforms......Page 2679
4.23.3 Pharmaceutically Relevant Proteins Produced in Transplastomic C. reinhardtii......Page 2680
4.23.4.1 Promoter and UTR Combinations......Page 2681
4.23.4.4 Chloroplast Codon Optimization......Page 2682
References......Page 2683
4.24.1 Introduction......Page 2685
4.24.2 Chemostat Design......Page 2687
6.24.2.2 The Microbial Community......Page 2688
4.24.6 Toxin Studies Using Chemostats......Page 2689
References......Page 2690
Relevant Websites......Page 2691
4.25.1 Introduction......Page 2692
4.25.2 Plant Growth Characteristics......Page 2693
4.25.2.1 Ginseng Phytochemicals of Medicinal Importance......Page 2694
4.25.2.3 Traditional Propagation......Page 2695
4.25.3.2 Somatic Embryogenesis......Page 2696
4.25.4 In Vitro Growth Requirements of Panax Species......Page 2697
4.25.4.5 Genetic Modification......Page 2700
References......Page 2701
4.26.1 Introduction......Page 2705
6.23.3.1 Water-Soluble Inorganic Nutrients......Page 2706
4.26.3 Gas Exchange between the PPM and Its Surroundings......Page 2707
4.26.3.2 Active Botanical Biofiltration......Page 2708
4.26.4 Effluent Quality......Page 2710
References......Page 2711
4.27.1 Introduction......Page 2713
4.27.2 Model Systems for Fruit Development......Page 2714
4.27.3 Ethylene Synthesis and Fruit Ripening......Page 2715
4.27.4 Ethylene Perception and Fruit Ripening......Page 2716
4.27.5 Cell-Wall Metabolism and Fruit Ripening......Page 2717
4.27.6 The Role of Light in Fruit Ripening......Page 2718
4.27.7 Insights into Developmental Control from Ripening Mutants......Page 2719
References......Page 2720
Pre- and Postharvest Treatments Affecting Nutritional Quality......Page 2722
4.28.2 Inhibition of Ethylene Biosynthesis......Page 2723
4.28.3 Inhibition of Ethylene Action......Page 2724
4.28.5 Effects of Pre- and Postharvest Treatments on Firmness......Page 2726
4.28.6 Effects of Pre- and Postharvest Treatments on Color and Phenolics......Page 2727
6.46.2.3.1 Saccharomyces cerevisiae......Page 2728
References......Page 2729
Relevant Websites......Page 2730
4.29.1 Introduction......Page 2731
4.29.2 Decoding the Genome of Livestock......Page 2732
4.29.4 The Single Gene Phenotypes......Page 2734
4.29.4.1 The Complex Phenotypes......Page 2735
4.29.5.2 Gender Determination......Page 2736
4.29.5.7 Transgenesis......Page 2737
4.29.7 The Emerging Role of Epigenetics......Page 2738
4.29.8 The DNA-Based Tools for the Study of Gene Expression......Page 2739
4.29.9 Microarray versus Deep Sequencing......Page 2740
References......Page 2741
Relevant Websites......Page 2742
4.30.1 Introduction......Page 2743
4.30.2.1 Understanding the Genome Repeat Structures......Page 2744
4.30.2.5 Scaffolding Using BAC-Based Physical Maps......Page 2745
4.30.3.1 EST Resources......Page 2746
4.30.4 Whole Genome Sequencing......Page 2747
4.30.5.2 Important Catfish Traits and the Need for Genome-Based Tools for Selection......Page 2748
References......Page 2749
Epigenetics and Animal Health......Page 2753
4.31.2.2 PTM of Histones and Remodeling of Chromatin......Page 2754
4.31.3.1 Highlights in the Epigenetic Regulation of the NEI......Page 2755
4.31.3.1.3 Epigenetic regulation of T-cell development and differentiation......Page 2756
4.31.4.1.1 The high-fat diet......Page 2757
4.31.4.2.3 Bacteria......Page 2758
4.31.4.3.1 Heavy metals......Page 2759
6.34.5.6 Membrane Bioreactor......Page 2760
4.31.5.1.1 DNA methylation analysis using methylation-sensitive restriction endonucleases......Page 2761
4.31.5.1.2 DNA methylation analysis relying on chemical modifications......Page 2762
4.31.5.2.2 ChIP for genome-wide analyses......Page 2763
4.31.5.3.4 Identification through artificial preparation of intronic miRNAs for targeting known gene sequences......Page 2764
References......Page 2765
4.32.1 Introduction and Scope......Page 2767
4.32.2.1 Muscle Hypertrophy......Page 2768
4.32.2.2 Myogenesis......Page 2769
4.32.2.3 Regulation of Myogenesis......Page 2771
4.32.3 Identification of Markers of Beef Tenderness......Page 2773
References......Page 2776
From Stem Cell to Gamete......Page 2778
4.33.2.1 Germ Cell Specification......Page 2779
4.33.2.3.1 Oct4......Page 2780
4.33.2.3.7 Dazl......Page 2781
4.33.2.5 Sex Determination and Entry into Meiosis......Page 2782
4.33.3.1 Similarities between Stem Cells and PGCs......Page 2783
4.33.3.2 PGCs from ESCs......Page 2784
4.33.3.3 Female Gametes from ESCs......Page 2785
4.33.3.4 Germ Cells Generated from Somatic-Derived Stem Cells......Page 2786
Relevant Websites......Page 2787
4.34.1 Introduction......Page 2788
4.34.2.1 Canine......Page 2790
4.34.2.2 Ovine......Page 2791
4.34.2.4 Bovine......Page 2792
4.34.2.5 Equine......Page 2793
4.34.3 Summary and Perspectives......Page 2795
References......Page 2796
Relevant Websites......Page 2798
Flow Cytometric Sorting of Mammalian Sperm for Predetermination’of Sex......Page 2799
4.35.2.1 Reasons for Sex Predetermination......Page 2800
4.35.3.1 Principles of Flow Cytometric Sorting......Page 2801
4.35.3.2 Constraints of Flow Cytometry......Page 2802
4.35.3.3.3 In vivo fertility of sorted sperm......Page 2803
4.35.4.1.2 Site of insemination......Page 2804
4.35.5.1 Reasons for Sorting Frozen–Thawed Sperm......Page 2805
4.35.5.2.2 Sorting frozen–thawed bull sperm......Page 2806
4.35.6 Concluding Remarks......Page 2808
References......Page 2809
6.52.1 Introduction......Page 2811
4.36.2 Technical Aspects of Animal Cloning by NT......Page 2812
4.36.2.1.1 Oocyte maturation......Page 2813
4.36.2.1.2 Oocyte micromanipulation......Page 2814
4.36.2.2 Donor Cell Preparation and Oocyte–Cell Fusion......Page 2816
4.36.2.3 Oocyte Activation and Culture......Page 2817
4.36.3.1 Cloning for Rescuing Endangered Species......Page 2818
4.36.3.3 Cloning to Produce Transgenic Animals......Page 2819
4.36.3.4.2 Cloning for animal pharming......Page 2820
4.36.3.4.4 Cloning for xenotransplantation......Page 2821
4.36.4 Problems of SCNT Cloning......Page 2822
4.36.5 Nuclear Reprogramming in SCNT Embryos......Page 2823
4.36.7 Effects of Cell Cycle Coordination on SCNT Cloning......Page 2824
4.36.10 Concluding Remarks......Page 2825
References......Page 2826
Transgenesis......Page 2827
4.37.2 SCNT: Current Methodology for Transgenic Animal Production......Page 2828
4.37.3.1 Lentiviral-Mediated Transgenesis......Page 2829
4.37.3.4 Use of Dna-Specific Enzymes......Page 2830
4.37.3.8 Use of Pluripotent Stem Cells......Page 2831
6.25.6.2 Configuration......Page 2832
4.37.4.2.4 Xenotransplantation of porcine organs to human patients......Page 2833
4.37.4.3 Transgenic Animals in Agriculture......Page 2834
4.37.4.3.5 Transgenic strategies to increase disease resistance......Page 2835
4.37.6 Safety Aspects and Outlook......Page 2836
References......Page 2837
4.38.2 Survival of the Early Embryo......Page 2838
4.38.3.1 Possible Ways to Reduce EEM......Page 2839
6.33.3.2 Alternative Electron Acceptors for AnMO......Page 2840
6.05.2.5 Functional Gene Arrays......Page 2841
4.38.5 Metabolomic Signatures: Markers for Embryo Health......Page 2842
References......Page 2843
4.39.1 Introduction – the Impact of Heat Stress on Animal Production......Page 2846
4.39.2 Homeothermy......Page 2847
4.39.3.1 Crossbreeding......Page 2848
4.39.3.2 Genetic Selection......Page 2849
4.39.3.3 Introgression of Specific Genes Conferring Thermotolerance via Crossbreeding......Page 2850
4.39.4.1 Biologically Active Molecules to Enhance Thermoregulation or Overcome Effects of Heat Stress on Cellular Function......Page 2852
6.05.3 Future Perspectives......Page 2853
Relevant Websites......Page 2854
4.40.1 Introduction......Page 2855
4.40.2 Bioactive Compounds Used in Functional Foods and Dietary Supplements......Page 2856
4.40.3.1 Anthocyanins......Page 2857
4.40.4 Omega-3 Fatty Acids and Conjugated Linoleic Acid (CLA)......Page 2858
4.40.6 Phytosterols......Page 2859
4.40.8 Vitamins......Page 2860
4.40.9 Glucosamine......Page 2861
4.40.12.1 Ginkgo......Page 2862
4.40.12.4 Ginseng......Page 2863
4.40.13 Conclusions......Page 2864
References......Page 2865
Relevant Websites......Page 2867
Plant Derived Bioactives......Page 2868
4.41.1 Introduction......Page 2869
4.41.2.1.2 Soluble fibers......Page 2870
6.34.3.3.2 Synthesis gas as e-donor......Page 2871
4.41.4.1.1 Lunasin......Page 2872
4.41.4.1.5 Protein hydrolysates and peptides......Page 2873
4.41.5 Polyphenolic Compounds......Page 2874
4.41.5.2 Phytosterols......Page 2876
4.41.5.3.1 PAs and UTIs......Page 2877
4.41.5.4 Tea Polyphenols......Page 2878
4.41.6.1 Lycopene......Page 2879
References......Page 2880
4.42.1 Introduction......Page 2883
4.42.2.1 Cellulose and Lignin......Page 2884
4.42.2.5 Mucilages......Page 2885
4.42.4 Functional Properties of Dietary Fiber......Page 2886
4.42.4.3 Gel-Forming Capacity......Page 2887
4.42.5.1 Application in Bread Making......Page 2888
4.42.5.4 Fat Replacement......Page 2889
References......Page 2890
4.43.1 Introduction......Page 2892
4.43.3.1 Type 1 RS......Page 2893
4.43.3.3 Type 3 RS......Page 2894
4.43.3.4 Type 4 RS......Page 2895
4.43.4.2 Englyst Method......Page 2896
4.43.5 Future Directions......Page 2897
References......Page 2898
4.44.1 Introduction......Page 2900
4.44.3 Metabolism of Plant Sterols......Page 2901
4.44.4.1 Hypolipidemic Effects......Page 2902
4.44.4.2 Cholesterol-Lowering Mechanisms of Plant Sterols......Page 2903
4.44.5 Plant Sterols and Coronary Heart Disease Risk......Page 2904
4.44.6.2 Subject-Specific Factors Affecting Plant Sterol Efficacy......Page 2905
4.44.9 Conclusion......Page 2906
References......Page 2907
4.45.1 Introduction......Page 2908
6.55.2 Case Histories Illustrating Bioconversion of Wastes into New Materials......Page 2909
4.45.3 Adsorption of Soy Proteins at Interfaces: Emulsifying Properties......Page 2910
4.45.4 Gelling Properties of Soy Protein......Page 2913
References......Page 2915
4.46.1 Introduction......Page 2917
4.46.3 Pathogenesis of Cardiovascular Diseases......Page 2918
4.46.4.1 Defatted Egg Preparation Effects on Human Health......Page 2920
4.46.5.2 Effects of n-3 PUFA-Enriched Egg on Serum Lipid Profile......Page 2921
4.46.6.1 Production of ACEI Peptides from Egg......Page 2922
4.46.6.3 Mode of Action of Antihypertensive Peptides......Page 2923
4.46.7.1 Antioxidant Activities of Egg Components......Page 2924
4.46.8.1 Inhibitory Effect on Platelet Aggregation and Blood Coagulation......Page 2926
4.46.8.4 Egg Consumption Improves Metabolic Syndrome......Page 2927
References......Page 2928
4.47.1 Introduction......Page 2930
4.47.2.1 Alkaline Phosphatase (EC 3.1.3.1)......Page 2931
4.47.2.3 Plasmin (EC 3.4.21.7)......Page 2932
6.28.4.2 Microbiology of EBPR......Page 2933
4.47.3.3 Lipases (Triacylglycerol Acylhydrolase; EC 3.1.1.3) and Pregastric Esterases......Page 2935
4.47.3.4 Phospholipases (A1, EC 3.1.1.32; A2, EC 3.1.14; C, EC 3.1.4.11; D, EC 3.1.4.4)......Page 2936
References......Page 2937
Gut Microbiology – A Relatively Unexplored Domain......Page 2938
4.48.2 Diversity of the Gut Microbiota......Page 2939
4.48.2.1 The Colonic Fermentation......Page 2940
4.48.2.3 Response of the Microbiota to Diet......Page 2943
4.48.3 Immunomodulatory Effects of Gut Microbes......Page 2945
4.48.3.2 Host Compartmentalization of the Gut Microbiota......Page 2946
4.48.3.4 Role of the Gut Microbiota in Disease......Page 2947
4.48.3.5 Perturbations to the Intestinal Microbiota and Its Relation to Disease......Page 2948
4.48.4 Complementation of the Gut Microbiota......Page 2949
4.48.5 Use of Animal Models to Study the Microbiota–Host Interaction......Page 2950
References......Page 2951
4.49.1 Introduction......Page 2954
4.49.2.1 Lactobacilli......Page 2955
4.49.2.2 Bifidobacteria......Page 2956
4.49.3 Probiogenomics......Page 2957
4.49.4 Selection of Probiotic Strains......Page 2958
4.49.5 Technology......Page 2959
4.49.6 Probiotic Food Products......Page 2960
4.49.7 The Probiotic Concept......Page 2961
6.33.4 Concluding Remarks......Page 2962
References......Page 2963
4.50.1 Introduction......Page 2966
4.50.2 Traditional Fat Crystal Networks......Page 2967
4.50.3 Novel Lipid Substitutes......Page 2968
4.50.3.1.2 Carbohydrate-based caloric reducers......Page 2969
4.50.3.2.1 Lipid-based trans and saturated fat substitutes......Page 2970
4.50.3.2.2 Nonlipid-based trans and saturated fat substitutes......Page 2973
4.50.4 Modifying the Crystal Structure of Novel Lipid Substitutes......Page 2975
References......Page 2978
4.51.1 Introduction......Page 2980
4.51.2.1 Dielectric Properties......Page 2982
4.51.2.3 Dielectric Breakdown or Arcing......Page 2983
4.51.3.1 MultiMode Resonant Cavity......Page 2984
6.23.4 Bioaugmentation......Page 2985
4.51.4 Microwave Dehydration......Page 2986
4.51.5.1 Microwave-Assisted Vacuum Drying (MVD)......Page 2987
4.51.6 Microwave-Assisted Freeze-Drying......Page 2989
4.51.7 Food Culture and Probiotics......Page 2990
References......Page 2991
4.52.1 Introduction......Page 2992
4.52.2.1 Controlled Release of Volatile Antimicrobial Agent from a Carrier......Page 2993
4.52.2.1.2 Allyl isothiocyanate emitter......Page 2994
4.52.2.2.1 Coating and immobilization of antimicrobials on package surface......Page 2996
4.52.2.2.2 Antimicrobial polymer......Page 2997
4.52.3 Vapor and Gas Scavengers......Page 2998
4.52.3.2 Ethylene Scavenger......Page 2999
4.52.3.3 Controlled Release of Food Preservatives......Page 3000
4.52.4.1 Oxygen Indicator with Controlled Activation......Page 3001
4.52.4.2.2 Indicator for detecting meat spoilage......Page 3003
4.52.4.2.3 Ripeness indicator technologies for fruits......Page 3004
References......Page 3005
Antimicrobials from Plants – Food Preservation and Shelf-Life Extension......Page 3008
4.53.2.1 Terpenoids......Page 3009
4.53.2.5 Sulfur-Containing Compounds......Page 3012
4.53.2.6 Other Antimicrobial Compounds......Page 3013
4.53.3.1 Terpenes......Page 3014
4.53.3.4 Peptides......Page 3015
4.53.4 Mechanisms......Page 3016
4.53.5 Applications......Page 3017
References......Page 3018
4.54.1 Introduction......Page 3022
4.54.2 Target Microbes......Page 3023
4.54.4.3 Bacteriophages......Page 3025
4.54.4.6 Peptide Nucleic Acid......Page 3026
4.54.5.2 Immunocapture......Page 3027
4.54.6.2 Amperometric Biosensors......Page 3029
4.54.6.3 Impedimeteric Biosensors......Page 3031
4.54.6.5 Optical Sensors......Page 3032
4.54.6.7 Raman Spectroscopy......Page 3033
4.54.6.8 Luminescence-Based Pathogen Sensors......Page 3034
4.54.6.10 Mass Sensors......Page 3035
References......Page 3036
4.55.1 Literature Review......Page 3038
4.55.1.1.2 The aqueous phase......Page 3039
4.55.1.1.4 Co-surfactants......Page 3040
6.45.5.1 Biological Pretreatment of Lignocellulose for Ethanol Production......Page 3041
Relevant Websites......Page 3042
4.55.2.1.2 Protection against oxidation/light......Page 3043
References......Page 3044
4.57.1 Introduction......Page 3046
4.57.2 Alcohol......Page 3047
4.57.4 Dietary Fat......Page 3048
4.57.5 Fruits and Vegetables......Page 3050
6.42.3.3 Use As Multifunctional Food Ingredients and Fine-Chemical Recovery......Page 3051
4.57.7 Conclusions......Page 3052
References......Page 3053
4.58.1 Introduction: Plant Nutrient Management and Agricultural Productivity......Page 3056
4.58.2 Endophyte Nutrient Uptake......Page 3057
4.58.3 Enhancing Root Growth......Page 3058
4.58.4 Nitrogen Fixation......Page 3060
4.58.5 Other Endophytic Mechanisms Affecting Plant Nutrient Status......Page 3062
4.58.6 Application of Endophytes to Agriculture......Page 3063
6.14.3.1 Biotransformation of PCBs by Mammals......Page 3066
Relevant Websites......Page 3070
4.56.1 Introduction......Page 3071
4.56.2 Unique Animal Bio-Processed Foods......Page 3072
4.56.2.1 Kopi Luwak Coffee......Page 3073
4.56.2.2 Bird’s Nest......Page 3081
4.56.3 Conclusions......Page 3089
References......Page 3090
Disease Resistance/Pathology/Fusarium......Page 3091
4.59.3 Economic Impacts of Fusarium Infections and Their Toxins......Page 3092
4.59.4 Plant–Pathogen Interactions and Plant Resistance Mechanisms......Page 3093
4.59.6.1 Introduction......Page 3095
4.59.6.2 Modes of Infection and Genetics of Resistance......Page 3096
4.59.6.3.4 Biological control of disease......Page 3097
4.59.7.2 Modes of Infection and Genetics of Resistance......Page 3098
4.59.7.3.2 Transgenic approaches to resistance......Page 3099
4.59.8.2 Modes of Infection and Genetics of Resistance......Page 3100
4.59.8.3.1 MAS for resistance......Page 3101
4.59.8.3.4 Biological control of disease......Page 3102
4.59.9.3.1 MAS for resistance......Page 3103
4.59.9.3.4 Biological Control of Disease......Page 3104
Relevant Websites......Page 3105
Plant Biochemistry: Antifungal Proteins Protecting Plants from Fungal Pathogens......Page 3106
4.60.2.1.2 Hypogin, an antifungal peptide with sequence similarity to peanut allergen......Page 3107
4.60.2.4.1 Chitinase-like antifungal protein......Page 3108
4.60.2.8.1 Peptides from red bean and pinto bean......Page 3109
4.60.2.10.1 The gene encoding EPGIP......Page 3110
4.60.2.10.2 TLP from French bean legumes......Page 3111
4.60.2.11.2 Miraculin-like protein from sugar snap P. sativum var. macrocarpon......Page 3112
4.60.2.13.1 Cyclophilin-like protein......Page 3113
4.60.3 Nonleguminous Antifungal Proteins......Page 3114
References......Page 3115
4.61.1 Introduction......Page 3118
4.61.5 Biocontrol of Insect, Mite, and Nematode Pests......Page 3119
4.61.6 Biocontrol of Vertebrate Pests......Page 3120
6.38.2.4 Endocrine Disrupting Effects......Page 3121
6.31.3.2 Kinetics......Page 3122
4.62.1 Introduction......Page 3123
4.62.2.2 Nosema apis and’N. ceranae......Page 3124
4.62.3.3 Grooming Behavior......Page 3125
4.62.4 Conclusion......Page 3126
References......Page 3127
4.63.1 Introduction......Page 3128
4.63.1.1 Tell Stories......Page 3130
4.63.2 Use New Media......Page 3131
References......Page 3132
4.64.1 Introduction......Page 3133
4.64.2.2 The Cost of Food in Canada......Page 3134
4.64.3.5 The Influence of the Mass Media......Page 3135
4.64.6.1 Calorie Labeling on Menus......Page 3136
4.64.7 Conclusion......Page 3137
Relevant Websites......Page 3138
6.26.1.1 General Overview......Page 3139
6.43.6 Modification of Phenol Derivatives......Page 3140
4.65.4 Specific Legislations Governing Food Products Derived from Biotechnology-Derived Animals......Page 3141
References......Page 3143
Vol5......Page 3144
Introduction......Page 3145
5.02.1 Introduction......Page 3146
5.02.2 Current Use of Materials in Medicine......Page 3147
5.02.2.2 Ceramics in Medicine......Page 3148
5.02.3 Functionality in Biomaterials......Page 3149
5.02.3.1 Mechanical Influences of Relevance to Biomaterials......Page 3150
5.02.3.2.1 Tailoring biomaterial physicochemical properties......Page 3151
5.02.4 Conclusions......Page 3152
References......Page 3153
5.03.1 Introduction......Page 3154
5.03.2 Production of Cryogels in Semi-Frozen Systems......Page 3155
5.03.3 Cryogel Characterization......Page 3156
5.03.4 Cryogel Properties......Page 3157
5.03.5 Composite Cryogel Materials: Inherent Features and Applications......Page 3160
5.03.6 Cryogels in Biomedicine and Biotechnology......Page 3161
References......Page 3164
5.04.1 Introduction......Page 3166
5.04.2 Principle of Electrospinning......Page 3167
6.03.3 What Is in a Genome......Page 3170
5.04.4 Applications of Electrospun Biomaterials......Page 3171
5.04.4.1 Tissue-Engineering Scaffold......Page 3172
5.04.5 Biocompatibility of Electrospun Biomaterials......Page 3173
5.04.5.3 Degradation......Page 3174
5.04.6 Electrospun Biomaterials for 3D Tissue Regeneration......Page 3175
5.04.7.6 Collector......Page 3176
5.04.8 Conclusion......Page 3177
References......Page 3178
5.05.2 Two Application Streams for Engineered Tissues......Page 3180
5.05.3 Which Cell Support Materials to Use: Indirect and Direct TE?......Page 3181
5.05.4 Interstitial Cell Seeding: Cell-Matrix Embedding from the Start......Page 3182
5.05.5 Structure of Collagen – A Raw Material for Weavers?......Page 3183
5.05.6 Collagen Materials: Engineering the Basics......Page 3184
5.05.7 Building Blocks......Page 3185
5.05.9 Collagen Purity (and Antigenicity)......Page 3186
5.05.10 Bottom-Up Collagen Engineering, Where Is the Bottom – Amino Acids or Tropocollagen?......Page 3187
5.05.10.1 Controlling Fibril Density......Page 3188
5.05.10.2 Controlling Fibril Diameter......Page 3189
5.05.11 Conclusion......Page 3190
References......Page 3191
5.06.1 Introduction......Page 3193
5.06.2.1 Temperature-Responsive Hydrophobic Interaction Chromatography......Page 3194
5.06.2.2 Temperature-Responsive Ionic Interaction Chromatography......Page 3196
5.06.2.4 Temperature-Responsive Affinity Chromatography......Page 3199
5.06.3.1 Preparation of Temperature-Responsive Cell Culture Surfaces......Page 3200
5.06.3.2 Temperature-Responsive Cell Culture Surfaces for Rapid Cell Sheet Detachment......Page 3202
5.06.3.3 Carrier for Transplanting and Layering the Cell Sheets......Page 3203
5.06.3.4 Cell Sheet Engineering for Regenerative Medicine......Page 3204
References......Page 3206
5.07.1 Introduction......Page 3207
5.07.2 Surface Events, Interactions, and Material Characteristics......Page 3208
5.07.3.1 Self-Assembled Monolayers......Page 3210
5.07.3.2 Brush Polymers......Page 3211
5.07.3.3 Polymers and Block Polymers......Page 3213
5.07.3.4 Coatings......Page 3216
5.07.3.7 Inspiration from Nature......Page 3217
5.07.4 Future......Page 3221
References......Page 3222
5.08.1 Introduction......Page 3224
5.08.2.1 Freezing–Thawing versus Vitrification......Page 3225
5.08.2.2 CPA Transportation in Tissues......Page 3226
5.08.2.3 Outcome Assessment of Tissue Cryopreservation......Page 3227
5.08.3.1 Embryo Cryopreservation......Page 3228
6.12.6 Degradation of Styrene......Page 3229
5.08.3.2.2 Vitrification......Page 3230
5.08.3.2.5 Detection in clinic......Page 3231
5.08.3.4 Blood Vessel Cryopreservation......Page 3232
6.16.5.4 Bioreactors......Page 3233
5.08.4.1 Tissue-Engineered Bone Cryopreservation......Page 3234
References......Page 3236
Relevant Websites......Page 3239
5.09.1 Introduction......Page 3240
5.09.2.1 Alginate......Page 3241
5.09.2.4 Agarose......Page 3242
5.09.3.1 Permeability and Mass Transport......Page 3243
5.09.3.2 Microcapsule Mechanical Stability......Page 3244
5.09.3.3 Biocompatibility......Page 3245
5.09.4.1 Encapsulated Primary Cells for Artificial Organ Research......Page 3246
5.09.4.2 Encapsulated Genetically Modified Cells for Gene Therapy......Page 3247
5.09.4.3 Encapsulated Stem Cells for Tissue Engineering and Regenerative Medicine......Page 3250
5.09.5 Conclusions and Future Considerations......Page 3251
References......Page 3252
5.10.1 The Cellular Composition of Bone Marrow......Page 3256
5.10.2 Why Isolate MSC Populations?......Page 3257
5.10.3.2 Cell-Surface Markers for Bone Marrow Populations......Page 3258
5.10.3.4.1 Flow cytometry......Page 3260
5.10.3.5.1 Field-flow fractionation......Page 3261
Reference......Page 3262
Nanoimprint Lithography and Its Application in Tissue Engineering and Biosensing......Page 3265
5.11.1 Introduction......Page 3266
5.11.2.1.1 Propagating SPR and Localized SPR......Page 3267
5.11.2.1.2 Extraordinary optical transmission biosensor......Page 3268
6.25.3.2 Hydraulic Models......Page 3269
5.11.2.2 Nonplasmonic Optical Biosensors......Page 3271
5.11.2.3 Electrical and Electrochemical Biosensors......Page 3272
5.11.2.4 NIL Application in NEMS-Based Biosensor......Page 3273
5.11.2.5 Fabrication of Micro-Nanofluidics Using NIL......Page 3274
5.11.3.3 Examples of Application of NIL in Tissue Engineering......Page 3275
5.11.4.1 Additional References for Biosensors......Page 3277
References......Page 3278
Relevant Websites......Page 3279
5.13.1 Introduction......Page 3280
5.13.2 Biomolecule Immobilization......Page 3281
5.13.3.1.1 Enzyme-based substrate analysis......Page 3282
5.13.3.2 Immunodetection of Antigen......Page 3283
5.13.3.3 Nucleic Acid Detection......Page 3284
5.13.4.2 Ion-Selective Field Effective Transistors......Page 3285
5.13.4.4 Impedimetric Devices......Page 3286
5.13.5.2 Planar Waveguide Optical Platforms......Page 3287
5.13.6 Nanowire Arrays......Page 3289
5.13.8 Recent Developments......Page 3291
References......Page 3292
Relevant Websites......Page 3293
5.12.1 Introduction......Page 3294
5.12.2.2 Characteristics of Microfluidic Systems......Page 3295
5.12.2.3 Materials and Microfabrication......Page 3296
5.12.3.1 Micropumps......Page 3297
5.12.3.2.1 Passive micromixers......Page 3300
5.12.3.3 Microvalves......Page 3301
5.12.3.4 Microthermal Control System......Page 3302
5.12.3.5 Integrated Microfluidic System......Page 3303
5.12.4.1 Sample Pretreatment......Page 3304
5.12.4.2.2 ODEP force......Page 3305
5.12.4.3 Microflow Cytometer......Page 3306
5.12.4.3.1 Driving force for the microflow cytometer......Page 3307
5.12.4.4 Micro-Scale Cell Culture......Page 3308
References......Page 3310
5.14.2 Existing Options for Treating Intracranial Aneurysms......Page 3311
5.14.3 Cerebral Stents for Direct Treatment of Intracranial Aneurysms......Page 3313
References......Page 3315
RNA Interference (RNAi) Technology......Page 3316
5.15.3.1 The Discovery of Short-Interfering RNA......Page 3317
5.15.4.2 miRNA Pathway and Functional Characterization of miRNA......Page 3318
5.15.5.1 Generation of siRNA through Biological Process......Page 3319
6.48.4 Strategies to Increase Biohydrogen Yields......Page 3320
5.15.7.3 siRNA Delivery Issues and Solutions......Page 3321
References......Page 3322
5.16.1 Introduction......Page 3325
5.16.2.2 Oscillatory Rotational......Page 3327
5.16.3.2 Shear Thinning......Page 3328
5.16.4.1 Linear versus Nonlinear Rheology......Page 3329
5.16.4.3 Microrheology......Page 3330
5.16.4.4 Constitutive Models......Page 3331
5.16.5.1 Measuring Rheology for Clinical Characterization......Page 3332
5.16.5.1.2 Mucus rheology......Page 3333
5.16.5.1.3 Cell rheology......Page 3334
5.16.5.4.1 Scaffold production......Page 3335
5.16.5.4.5 Image registration......Page 3336
Relevant Websites......Page 3337
5.17.1 Introduction......Page 3338
5.17.2.1.1 Thrombosis......Page 3339
5.17.2.2 Heart Valves Diseases......Page 3340
5.17.2.3 Aortic Coarctation and Dissection......Page 3341
5.17.2.4 Intracranial Aneurysms......Page 3342
5.17.3.1 Computational Fluid Dynamics......Page 3343
5.17.3.1.2 Patient-derived morphology and meshing considerations......Page 3344
5.17.3.2.1 Wall shear stress......Page 3345
6.29.5 Models for Constructed Wetland Performance Determination......Page 3346
5.17.3.3 Coupled Mass-Transport Models......Page 3347
5.17.4 Evolving to Multiscale, Multiphysics Models......Page 3348
5.17.5 Epilogue......Page 3350
References......Page 3351
Mechanobiology of Bone......Page 3352
5.18.2 Fundamental Cell Mechanics......Page 3353
5.18.4.1 Organ Level......Page 3354
5.18.5.1 Ultrastructure......Page 3355
5.18.5.3 Soma......Page 3356
5.18.6 Basic Mechanics of Solid Materials......Page 3357
5.18.7.1 A Stride Subjects the Human Leg to Strain......Page 3358
5.18.7.2 Osteon Strain......Page 3359
5.18.8.4 Color scheme......Page 3360
5.18.10 Intracellular Signaling Downstream of Mechanical Deformation......Page 3362
5.18.12 How BMUs Remodel Bone......Page 3364
5.18.13.2 How to Decrease Bone Mass......Page 3365
5.18.14.3 Implants and tissue engineering......Page 3366
References......Page 3367
5.19.1 Introduction......Page 3372
5.19.2.1 Cell–Wall Interaction in Stationary Flow......Page 3373
5.19.2.3 Effect of the Glycocalyx on Cell–Wall Interaction......Page 3375
5.19.2.4 Stress on the Endothelial Cell Membrane Mediated by the Glycocalyx......Page 3376
5.19.3 Transcapillary Exchange of Fluid and Solute......Page 3377
5.19.3.1 Oxygen Transport in Outer Layers of the Skin......Page 3378
5.19.3.2 Inert Gas Clearance from the Tissue......Page 3380
5.19.3.3 Countercurrent Exchange in Renal Medulla......Page 3381
5.19.3.4 Transcapillary Exchange of Plasma Proteins......Page 3382
5.19.4 Transport of HA across the Synovial Lining of Joint Cavities......Page 3383
5.19.5 Summary and Future Perspective......Page 3384
References......Page 3385
5.20.1 Introduction......Page 3386
5.20.2.1 Decellularized ECMs......Page 3387
5.20.2.2 Tissue-Engineering Scaffolds......Page 3388
5.20.3 Microscale Technologies......Page 3390
5.20.4 Bioreactors......Page 3391
5.20.5 Translation into Clinical Applications......Page 3392
5.20.6 Cell Sourcing......Page 3393
5.20.7 Future Directions......Page 3394
5.20.8 Conclusion......Page 3395
References......Page 3396
5.21.1 Introduction and Scope......Page 3399
5.21.3.1 Drugs and Surgical Procedures......Page 3400
5.21.4.2 Condensation and Sox9......Page 3401
5.21.4.4 Hypertrophy and Endochondal Ossification......Page 3402
5.21.5.2 Stem Cells and Cartilage Tissue Engineering......Page 3404
5.21.6.3 Direct ESC Chondrogenic Differentiation......Page 3405
5.21.7 Conclusions......Page 3406
References......Page 3407
Tissue Engineering: Bone......Page 3408
5.22.2 Clinical Need......Page 3409
5.22.3.1 Skeletal Stem Cell......Page 3410
5.22.3.2 Skeletal Stem Cells for Bone Tissue Engineering......Page 3411
6.04.3.3 Single-Strand Conformation Polymorphism......Page 3413
5.22.4.4.3 Platelet-derived growth factor......Page 3414
5.22.5.1 Cell-Matrix Interactions During Bone Development and Repair......Page 3415
5.22.5.2 Scaffold Requirements......Page 3416
5.22.5.3 Extracellular Matrix Requirements......Page 3417
5.22.6 Interactive Role of Vasculature in Skeletal Regeneration......Page 3418
5.22.7 In vivo Models of Skeletal Regeneration......Page 3419
5.22.8 Clinical Translation......Page 3420
5.22.9 Summary......Page 3422
Relevant Website......Page 3423
Tendon Tissue Engineering: The Potential Application of Stem Cells, Biological Factors, and Repair Scaffolds to Improve Rotator Cuff Tendon Tears......Page 3424
6.15.2.1 Environmental Transport Processes of Nitroaromatic Explosives......Page 3425
5.23.6 What Are Stem Cells?......Page 3426
5.23.9 Application to Tendon......Page 3427
5.23.10.2.1 Acromioplasty......Page 3428
5.23.10.2.4 Bursa......Page 3429
5.23.12 Determining Ideal Conditions......Page 3430
5.23.15 Biological Agents......Page 3431
5.23.16.2 Scaffold Materials......Page 3434
5.23.16.3 Mechanical Properties......Page 3436
5.23.16.6 Immunogenicity......Page 3437
5.23.17 Conclusions and the Future......Page 3440
References......Page 3441
5.24.1 Introduction......Page 3444
5.24.2 Nutrients and Wastes......Page 3445
5.24.3 Cell Proliferation/Death......Page 3446
5.24.4 Matrix Deposition......Page 3447
5.24.5 Permeability/Diffusivity......Page 3449
5.24.7 Different Culture Systems......Page 3450
6.08.2.2 Petrochemical Industry – Polycyclic Aromatic Hydrocarbons......Page 3451
References......Page 3452
5.25.1 Introduction......Page 3453
5.25.2.1 Meniscus......Page 3454
5.25.2.2 The Intervertebral Disc......Page 3455
6.18.5 Treatment and Disposal of Biomass Containing Metals......Page 3456
5.25.4.1 Meniscus......Page 3457
5.25.5.2 Scaffold......Page 3458
5.25.5.3 Clinical Applications......Page 3459
References......Page 3461
5.26.1 Introduction......Page 3462
5.26.2.1 BM Stroma and Vasculature......Page 3463
5.26.2.2 Stem Cell Niches......Page 3464
5.26.3.3 Novel Technologies......Page 3466
5.26.4.2 Cancerous BM Niches......Page 3467
6.06.3.3.3(iii) Communities performing anaerobic degradation of halogenated hydrocarbons......Page 3469
References......Page 3470
Relevant Websites......Page 3471
5.27.1 Introduction......Page 3472
5.27.2.1 Scaffolds Based on Native Fibers......Page 3473
5.27.3.2 Muscles......Page 3474
5.27.4.1 History as a Suture......Page 3475
5.27.4.3 Toxicology......Page 3476
References......Page 3477
5.27.5 Summary......Page 3478
References......Page 3479
Relevant Websites......Page 3482
Tissue-Engineering Technology for Tissue Repair and Regeneration......Page 3483
5.28.1 Introduction......Page 3484
5.28.2.1.2 Stem cells......Page 3485
5.28.2.2 Scaffold materials......Page 3486
5.28.3 Tissue Generation with Tissue-Engineering Technology......Page 3489
5.28.4.1 Bone Tissue Engineering and Repair......Page 3491
5.28.4.2 Cartilage Tissue Engineering and Repair......Page 3494
6.12.8.1 NDO Enzymology......Page 3497
6.52.3.2 Cross-Linking Procedures......Page 3501
References......Page 3503
Induced Pluripotent Stem Cells and Their Application to’Personalized’Therapy......Page 3506
5.29.2 hiPSCs Are Similar to, but Not Identical to, hESCs......Page 3507
5.29.3.3 Operator Safety......Page 3508
5.29.3.4.4 Integrating vectors......Page 3509
5.29.3.5.1 Seeding density and splitting during reprogramming......Page 3510
5.29.3.5.4 Characterizing hiPSC lines......Page 3511
5.29.5 Generating Differentiated Cell Populations......Page 3512
5.29.7.1 Experience from Gene Therapy and Stem Cell Clinical Trials......Page 3514
5.29.7.3 Bypassing hiPSC Formation......Page 3515
References......Page 3516
5.30.1 Introduction......Page 3518
5.30.3 Requirement of Expansion Folds and Quality of HSPCs......Page 3519
5.30.5.1 Perfusion Bioreactor......Page 3520
5.30.5.3 Packed- and Fluidized-Bed Bioreactors......Page 3521
5.30.6.1 BM Environment or Niche......Page 3522
5.30.6.3 HSPCs Cultured in 3D Scaffolds......Page 3523
5.30.7 Brief Introduction of Clinical Application Tests with Expanded HSPCs......Page 3524
References......Page 3525
5.31.1 Introduction and Scope......Page 3526
5.31.2 Cord Blood Bank Models......Page 3527
5.31.3 Advantages and Disadvantages of Unrelated Cord Blood Hematopoietic Stem Cell Transplants......Page 3529
5.31.5.1 FACT-NetCord Standards......Page 3530
5.31.5.2 European Directives and Legislation......Page 3531
5.31.6 Improving the Quality of Cord Blood Units for Human Use......Page 3532
5.31.6.1 Optimizing Cell Dose and HLA Matching......Page 3533
5.31.6.3 Increasing Cell Dosages and Modulating the Route of Cell Delivery......Page 3534
References......Page 3535
5.32.1 Introduction – Cell-Based Therapy for Cardiac Disease......Page 3536
6.33.3 Methane as Electron Donor for Sulfate Reduction......Page 3537
5.32.5.2 Mesenchymal Stem Cells......Page 3538
5.32.5.3 Endothelial Progenitor Cells......Page 3540
5.32.5.5 ESCs and Derivatives......Page 3541
6.45.5 The Role of White-Rot Fungi and Their Enzymes on Second-Generation Bioethanol......Page 3542
5.32.7 Clinical Trials with Bone Marrow-Derived Stem Cells......Page 3543
5.32.8 Conclusions and Future Challenges......Page 3544
References......Page 3546
Expansion of hMSCs and Their Application......Page 3553
6.04.1 Introduction......Page 3554
5.33.2.4 Isolation of hMSCs from Adult Adipose Tissue......Page 3555
5.33.2.6.3 Dental pulp......Page 3556
5.33.3.2 Large Quantity Expansion of hMSCs......Page 3557
5.33.4.1 Risk Assessment......Page 3558
5.33.4.3.3 Osteogenic differentiation......Page 3559
5.33.5.2 MSCs for Improvement of HSC Transplantation......Page 3560
5.33.5.4 Other Application of hMSCs......Page 3561
References......Page 3562
Relevant Websites......Page 3564
5.34.1 Introduction......Page 3565
6.54.3.1 Uranium(VI) Reduction......Page 3566
5.34.2.4 Induced Pluripotent Cells: iPS Cells......Page 3567
References......Page 3568
Stem Cell Therapy Facility Design......Page 3570
6.20.1 Introduction......Page 3571
5.35.2.1.2 Device configuration......Page 3572
6.30.2.1.1 Microbiology......Page 3574
5.35.2.5.2 Stem cells therapy center......Page 3575
5.35.3.1.1 Laboratory design requirements......Page 3576
5.35.3.2 P2 Laboratory Design......Page 3578
5.35.3.4 Cell Bank Design......Page 3579
5.35.3.6.3 Water system center......Page 3580
References......Page 3581
5.36.1 Introduction......Page 3582
5.36.2 Definition and Characteristics of MSCs......Page 3583
5.36.4 Application of Human MSCs in Regenerative Medicine......Page 3584
5.36.5 Aging and Replicative Senescence Affect the Use of MSCs in Regenerative Therapy......Page 3585
5.36.6.1 Osteogenesis......Page 3587
5.36.6.2 Angiogenesis......Page 3588
5.36.6.3 Interaction between Vascular and Bone Tissue......Page 3589
5.36.6.5 VEGF and Osteogenesis......Page 3590
5.36.6.6 Therapeutic Implications of Osteogenesis–Angiogenesis Interaction in Bone Regeneration......Page 3591
References......Page 3592
5.37.1 Introduction......Page 3594
5.37.2.1.1 Negative contrast agents......Page 3595
5.37.2.1.2 Positive contrast agents......Page 3597
6.34.3.3 Gaseous Electron Donors......Page 3598
5.37.3.2 Cancer......Page 3599
5.37.3.3 Liver Disease......Page 3600
5.37.3.6 Myocardial Infarction......Page 3601
5.37.4.1 Stem Cell Therapy for Neurological Disorders......Page 3602
5.37.4.2 Stem Cell Therapy for Myocardial Infarction......Page 3604
References......Page 3605
6.08.1 Introduction......Page 3607
6.17.6 Phytoremediation......Page 3608
5.38.4.1 Cryopreservation of hES Cells and iPS Cells......Page 3609
5.38.4.2.1 Cryopreservation of human HSCs......Page 3610
5.38.4.2.2 Cryopreservation of MSCs......Page 3611
References......Page 3612
5.39.1 Introduction......Page 3615
6.09.1.2 Bioavailability: A Target-Specific Biological Phenomenon......Page 3616
5.39.5 Selection of Biotherapeutic Protein Expression Systems......Page 3617
5.39.7 Development of Mammalian Expression Vectors......Page 3619
5.39.9 Downstream Processing of Biopharmaceuticals......Page 3621
5.39.12 Formulation and Drug Delivery Systems......Page 3623
References......Page 3624
Bioseparations: Membrane Processes......Page 3625
5.40.1 Introduction......Page 3626
6.43.5 Modification of Proteins......Page 3627
5.40.2.4.1 Medium exchange, perfusion, harvest, and centrifugation......Page 3628
5.40.3.1.1 Adsorption and entrapment......Page 3629
5.40.3.3.1 Modules and housings......Page 3630
5.40.4.1.1 Fouling models, pore blockage, cake filtration, and Vmax/Pmax......Page 3631
5.40.4.3.1 Cartridges, capsules, and housings......Page 3632
5.40.5.2.1 Tangential flow, normal flow, retro-/parvo-, and prefiltration......Page 3633
5.40.5.4.1 Retro- and parvo-virus filtration, industrial examples......Page 3634
5.40.6.2.1 Chemistry and pore structures......Page 3635
5.40.6.4.1 Bind/elute, flow-through, displacement, monoliths, and resins......Page 3636
5.40.7.1.2 Nonlinear film model and gel concentration......Page 3637
5.40.7.1.3 Diafiltration, Donnan effects, and equilibrium binding effects......Page 3638
5.40.7.3.2 System design......Page 3639
5.40.7.4.1 Industrial examples......Page 3640
5.40.8.2.1 Chemistry......Page 3643
5.40.8.4.1 MAb and Fab′2 processes......Page 3644
References......Page 3645
Relevant Websites......Page 3646
Pharmaceutical Proteins – Structure, Stability, and Formulation......Page 3647
5.41.1 Introduction......Page 3648
5.41.2 The Structure of Proteins......Page 3649
5.41.3.1 Physical Instability......Page 3652
5.41.3.2 Chemical Instability......Page 3654
5.41.3.2.3 β-Elimination, cleavage (proteolysis), and racemization......Page 3655
5.41.4.1.2 Sugar and polyols......Page 3656
5.41.4.1.3 Surfactants......Page 3657
6.31.3.3 Modeling......Page 3658
5.41.4.3 Stability Testing of Protein Formulations......Page 3661
5.41.5.2 The Stability of Proteins during Freeze-Drying......Page 3662
5.41.5.2.5 Drying......Page 3663
5.41.5.4 Mechanism of Cryo- and Lyoprotection......Page 3664
5.41.5.4.1 Instability of proteins in the solid state......Page 3665
References......Page 3666
5.42.1 Introduction......Page 3668
5.42.3 2D versus 3D Cancer Model......Page 3669
5.42.4 3D Models......Page 3670
5.42.4.3 Scaffold-Based 3D Culture......Page 3671
References......Page 3673
5.43.1 Introduction......Page 3675
5.43.2.2 Cell-Based 2D Model......Page 3676
5.43.2.3.1 Scaffold-free cellular spheroid models......Page 3677
5.43.2.3.3 3D microfluidic models......Page 3678
5.43.3.1 Liver Model......Page 3679
5.43.3.1.1 In vitro 2D hepatocyte models......Page 3680
5.43.3.2 Neural Models......Page 3681
5.43.3.2.6 Brain slices......Page 3682
5.43.3.3.4 Scaffold-based cancer models......Page 3683
5.43.5 Summary......Page 3684
References......Page 3686
5.44.1 Introduction......Page 3688
5.44.2.2 Primary Neuronal Cells......Page 3690
5.44.2.5 Induced Pluripotent Stem Cells......Page 3691
5.44.3.2 3-D Culture......Page 3692
5.44.4.2 Microscopic Imaging Assay......Page 3693
5.44.5 Discussion......Page 3694
References......Page 3695
5.45.1 Introduction......Page 3696
5.45.3.1 Context......Page 3698
5.45.3.2.1 NT2.D1-astrocytes and neurons......Page 3699
5.45.4.2 Current Developmental Toxicity Tests......Page 3700
5.45.4.3 NT2.D1 Cells and Developmental Toxicity......Page 3701
5.45.5.2 Bioreactors and 3-D Culture......Page 3703
5.45.6.2 Nature of the BBB......Page 3704
5.45.7.2 NT2.D1s in Chronic In Vitro Neurotoxicity Assessment Protocols......Page 3705
5.45.7.4 NT2.D1 Testing – Advanced Protocols: Bioreactors and 3-D Culture......Page 3706
5.45.7.5 Long-Term Chronic Neurotoxicity Testing: 3-D and Microcirculation......Page 3707
References......Page 3708
5.46.1 Introduction......Page 3709
5.46.2.2.1 Pegylation......Page 3710
5.46.2.3.1 Liposomes, niosomes, and surfactant vehicles......Page 3711
5.46.2.3.2 Solid lipid nanoparticles......Page 3713
5.46.2.3.3 Polymeric nanoparticles......Page 3714
6.21.5 Use of Biosolids in Landfill Phytoremediation......Page 3715
5.46.3.1 Parenteral Delivery......Page 3717
5.46.3.2 Oral Delivery......Page 3718
5.46.3.3 Nasal Delivery......Page 3719
5.46.3.4 Pulmonary Delivery......Page 3721
5.46.3.5 Transdermal Delivery......Page 3722
References......Page 3724
5.47.1 Introduction......Page 3727
5.47.2.1 Overview......Page 3728
5.47.2.2 Polymer–Drug Conjugate with Peptide Linkers......Page 3729
5.47.2.3 Polymer–Drug Conjugate with Nonpeptide Linkers......Page 3731
5.47.3.1 Overview......Page 3732
5.47.3.3 Hydrogel with Enzyme Substrates as Cross-Linkers......Page 3733
5.47.3.4 Enzyme-Sensitive Self-Assembling Hydrogel......Page 3736
5.47.3.5 Technical Issues in Design and Characterization......Page 3739
5.47.4.2 Enzyme-Sensitive Liposomes......Page 3740
5.47.4.3 Enzyme-Sensitive Polymeric Particles......Page 3741
5.47.4.4 Enzyme-Sensitive Self-Assembling Peptide and Protein Particles......Page 3743
References......Page 3744
5.48.1 Introduction......Page 3747
5.48.2.1 Epidermis......Page 3748
5.48.4 Types of Microneedles......Page 3749
5.48.6 Microneedle Fabrication......Page 3750
5.48.7.1 Silicon Microneedles......Page 3751
5.48.7.2 Dissolving Polymer Microneedles......Page 3752
5.48.7.4 Glass Microneedles......Page 3753
5.48.8 Method of Coating Solid Microneedles......Page 3754
5.48.9.1 Transdermal Drug Delivery......Page 3755
5.48.9.3 Intravascular Drug Delivery......Page 3758
5.48.9.4 Ocular Drug Delivery......Page 3759
5.48.10.1 Advantages of Drug Delivery Using Microneedles......Page 3760
5.48.11 Mathematical Models of Transdermal Delivery by Microneedles......Page 3761
References......Page 3762
5.49.1.1 Background and Scope......Page 3765
5.49.2.1 CNT Solubility and Dispersion......Page 3766
5.49.2.2 Functionalization......Page 3768
5.49.3.2 Gene Therapy......Page 3769
5.49.3.3 Targeted Drug Delivery......Page 3771
5.49.4.1 CNT Toxicity and Regulatory Considerations......Page 3772
5.49.4.4 Skin Toxicity......Page 3773
References......Page 3776
5.50.1.1 The Blood–Brain Barrier......Page 3778
5.50.2.1 Transcellular Diffusion......Page 3780
5.50.2.3.2 Adsorptive-mediated transcytosis......Page 3781
5.50.3 CNS Delivery Strategies......Page 3783
5.50.3.3.1 Exploitation of small molecule transporters......Page 3784
5.50.3.3.4 Lipidic derivatives......Page 3785
5.50.3.4.2 Polymer nanoparticles......Page 3786
References......Page 3787
5.51.1 Overview......Page 3789
5.51.2.2 The Immune System and Recognition of Non-Self......Page 3790
5.51.2.5 Bone Marrow (BM) Transplantation and the Risk of Graft-versus-Host Disease......Page 3791
5.51.3.2 The Multiphasic Nature of AMR......Page 3792
5.51.3.3.3 Intravenous immunoglobulin (IV Ig)......Page 3793
5.51.5 Experimental Progress in Prevention of AMR Using Free Bone Grafting......Page 3794
5.51.6.2.1 Complement activation plays a key role in mediating AMR......Page 3795
5.51.6.3 Induction of transplant accommodation in presensitized recipients developing AMR......Page 3796
5.51.7 Summary and Conclusions......Page 3798
References......Page 3799
5.52.1 Introduction......Page 3804
5.52.2 Kidney Anatomy and Physiology......Page 3805
5.52.3 Principles of Modern Dialysis......Page 3806
5.52.3.2 Membrane Support Structure......Page 3807
5.52.4 Improved Dialysis Therapies......Page 3808
5.52.5 Emerging Technologies in Tissue Engineering and Regenerative Medicine......Page 3810
5.52.5.1 Kidney Organogenesis......Page 3811
5.52.5.2 Stem Cell Technologies......Page 3812
5.52.5.5 Nuclear Transplantation and Generation of Renal Tissue......Page 3813
5.52.5.7 Bioprinting......Page 3814
5.52.6 Conclusions and Future Prospects......Page 3816
Relevant Websites......Page 3817
5.53.1 Introduction......Page 3818
5.53.2 Artificial Pancreas......Page 3819
5.53.3 Cell- and Tissue-Based Therapies for IDD......Page 3820
5.53.3.1.3 Engineered non-β pancreatic cells......Page 3821
5.53.3.1.4 Differentiated stem or progenitor cells......Page 3822
5.53.3.2.1 Encapsulated cell systems......Page 3823
5.53.3.2.3 Manufacturing considerations......Page 3824
5.53.3.3.1 Encapsulated cell systems......Page 3825
5.53.3.3.3 In vivo monitoring......Page 3826
5.53.4 Concluding Remarks......Page 3827
References......Page 3828
5.54.1 Introduction......Page 3831
5.54.2 Brief History of Blood Substitute Research......Page 3832
5.54.3.1 Preparation of Native Hb......Page 3833
5.54.3.2.1 Intramolecularly cross-linked Hb......Page 3836
5.54.3.2.3 Polymer conjugated Hb......Page 3837
5.54.3.3 Encapsulation of Hb......Page 3838
5.54.3.4.3 Human Hb transgenic plants......Page 3839
5.54.4 The Application Prospect of Blood Substitutes......Page 3840
5.54.5.1 Oxygen-Carrying Capacity......Page 3841
5.54.5.4 Physical and Chemical Properties of HBOC Products......Page 3842
5.54.5.5 Quality Control......Page 3843
References......Page 3844
5.55.1 Introduction......Page 3846
5.55.2 Membrane Techniques......Page 3847
6.26.2.1 ASMs Application to MBRs......Page 3848
5.55.2.3.1 Improvement of hemocompatibility......Page 3849
6.25.6 A General Framework for Application of WWTP Models......Page 3850
5.55.3.2.1 Protein A-based adsorbents for antibodies removal......Page 3851
5.55.3.2.2 Adsorbents employing through PlasmaSelect state antibodies as ligands......Page 3852
5.55.3.3.1 Adsorbents for immunoglobulins removal......Page 3853
5.55.4.1 BioLogical DT/DTPF System......Page 3854
5.55.5 Perspectives......Page 3855
References......Page 3856
5.56.1 Introduction......Page 3857
6.33.2 Electron Donors for Biological Sulfate Reduction of Wastewaters from Power Plants and Metallurgical’Industries......Page 3858
5.56.1.3 Current Water Treatment Processes to Produce Endotoxin-Free Dialysis Water......Page 3860
5.56.1.4 Current Water Treatment Processes to Produce Endotoxin-Free Dialysate......Page 3862
5.56.2.1 Preparation Techniques......Page 3863
5.56.2.2 Properties of Commercial Ceramic Membranes......Page 3865
5.56.3.2 Ceramic Membrane Performance for Endotoxin Removal......Page 3866
References......Page 3867
Vol6......Page 3869
Introduction......Page 3870
Biodegradation: Principles, Scope, and Technologies......Page 3872
6.03.2 Back to the Environment......Page 3883
6.03.5 Categories of Environmental Metabolites......Page 3885
6.03.6 Pan-Enzymes......Page 3886
6.03.8 The Environmental Fate of Chemical Pollutants......Page 3887
6.03.9 Chemical Logic versus Microbiological Sense......Page 3888
6.03.11 Metabolic Engineering of Biodegradation: From Systems to Synthetic Biology......Page 3889
6.03.12 Conclusion......Page 3890
References......Page 3891
Molecular Approaches for the Analysis of Natural Attenuation and’Bioremediation......Page 3893
6.04.3.1 Denaturing Gradient Gel Electrophoresis/Temperature Gradient Gel Electrophoresis......Page 3897
6.04.3.2 Terminal-Restriction Fragment Length Polymorphism......Page 3898
6.04.3.5 DNA Microarrays......Page 3899
6.04.4 Metagenomics......Page 3900
6.04.5 Conclusions......Page 3901
References......Page 3902
6.05.1 Introduction......Page 3905
6.05.2.1 Whole-Genome Open Reading Frame Arrays......Page 3906
6.05.2.3 Community Genome Arrays......Page 3907
6.05.2.4 Metagenomic Arrays......Page 3908
6.05.2.5.3 GeoChip 3.0 studies......Page 3909
6.05.2.6 Other Arrays......Page 3910
References......Page 3911
6.06.1 Introduction: Molecular Tools Used to Study Environmental Communities......Page 3914
6.06.2 Potential of Metagenomics for Bioremediation......Page 3915
6.06.3 Application of Metagenomics to Contaminated Environments......Page 3916
6.06.3.2 Functional Screening of Clone Libraries from Contaminated Environments......Page 3917
6.06.3.3.1 Gene-based methods......Page 3918
6.06.3.3.2 From gene-based methods to ‘brute force’ sequencing......Page 3919
6.06.3.3.3(ii) Communities performing anaerobic degradation of nonhalogenated hydrocarbons......Page 3920
6.06.4 Conclusions – Advancing the Field......Page 3921
Relevant Websites......Page 3924
6.07.1 Introduction......Page 3925
6.07.2 Unsaturated Zone Treatment Methods......Page 3926
6.07.2.2 Enhanced Natural Attenuation......Page 3927
6.07.3.1 Natural Attenuation......Page 3928
6.07.3.3 Enhanced Anaerobic Natural Attenuation......Page 3930
6.07.6 Conclusions and Future Prospects......Page 3931
6.08.1.1 Pollution Problem......Page 3934
6.08.1.2.1 Types of bioaugmentation......Page 3935
6.08.1.2.2 Making the decision to bioaugment......Page 3936
6.08.2.1 Gasoline Stations – BTEX and MTBE......Page 3937
6.08.2.3 Dry-Cleaners (and Other Degreasing Facilities) – Chlorinated Ethenes......Page 3938
6.08.2.6 Industrial Plants – Chlorobenzenes, Polychlorinated Dibenzo-p-Dioxins, and Polychlorinated Dibenzofurans......Page 3940
6.08.2.7 Manufacturing Plants for Electrical Equipment – PCBs......Page 3941
6.08.2.8 Smelters, Mines, and Coal-Burning Power Plants – Heavy Metals......Page 3942
6.08.3 Pros and Cons of Bioaugmentation......Page 3943
6.08.4.2 Harnessing Genetically Engineered Microorganisms and Mobile Genetic Elements......Page 3944
6.08.5 Conclusions......Page 3945
Bioavailability and Bioaccessibility as Key Factors in Bioremediation......Page 3947
6.09.1.3 Defining Bioavailability and Bioaccessibility......Page 3948
6.09.2.1 Contaminant Uptake by Microorganisms – Importance of Water Solubility......Page 3949
6.09.2.5 Mobile Sorbents......Page 3950
6.09.2.9 Bioavailability and Microbial Community Dynamics......Page 3951
6.09.2.10 Forming Biomass from Poorly Accessible Contaminant – The Carrying Capacity of Contaminated Soil......Page 3952
6.09.3.4 Ecological Adaptations......Page 3953
6.10.1 Introduction and Scope......Page 3959
6.10.3 Overview of Microbial Biodegradation Principles and Their Application to Aromatic Hydrocarbons......Page 3962
6.10.3.2 Aerobic Metabolism of Aromatic Hydrocarbons......Page 3963
6.10.4 Interactions between Habitat Characteristics, Microbes, and Aromatic Compounds Determine Their Biodegradability......Page 3965
6.10.5 Summary......Page 3966
6.11.1 Introduction......Page 3968
6.11.2 Traditional Approaches to the Study of Aromatic Hydrocarbon Metabolic Pathways......Page 3969
6.11.5 Proteomic Analysis of Samples from HMW PAH Degradation......Page 3972
Acknowledgments......Page 3975
Relevant Websites......Page 3977
6.12.1 Introduction......Page 3978
6.12.2 Degradation of Toluene, Benzene, and Ethylbenzene......Page 3979
6.12.2.1 TDO Enzymology......Page 3980
6.12.2.2 TDO Substrate Specificity......Page 3982
6.12.3 Degradation of Isopropylbenzene (Cumene)......Page 3983
6.12.4 Degradation of Other Alkylbenzenes with Side Chains of Three or More Carbon Atoms......Page 3984
6.12.5 Degradation of Xylenes......Page 3985
6.12.9 Degradation of PAHs......Page 3989
6.12.10 Concluding Remarks......Page 3991
References......Page 3992
Relevant Website......Page 3997
Dehalogenation of Polychlorinated Dibenzo-p-Dioxins and’Dibenzofurans, Polychlorinated Biphenyls, and Brominated Flame Retardants, and Potential as a Bioremediation Strategy......Page 3998
6.13.3 Biodehalogenation and Dehalorespiration of Organohalides......Page 4000
6.13.3.1 Polychlorinated Biphenyls......Page 4001
6.13.3.1.4 Biostimulation and bioaugmentation to enhance PCB dechlorination......Page 4002
6.13.3.2.2 Evidence for dehalogenation of PBDEs......Page 4003
6.13.3.3.1 Environmental significance of PCDD/Fs......Page 4004
6.13.3.3.4 Identification of PCDD/F dehalogenators......Page 4005
6.13.3.3.5 Dechlorination/detoxification pathways for PCDD/Fs......Page 4006
6.13.4.1 Management of Contaminated Sediments......Page 4007
6.13.4.2 Advances Needed for Applying Biostimulation and Bioaugmentation to Sediment Remediation......Page 4008
6.13.4.3 Outlook for the Future......Page 4009
References......Page 4010
Relevant Websites......Page 4011
Microbial Degradation of Polychlorinated Biphenyls......Page 4013
6.14.1 Introduction......Page 4014
6.14.2.1 History and Sources of PCBs......Page 4015
6.14.2.4 Toxicity of PCBs......Page 4016
6.14.3 Biodegradation of PCBs by Higher Organisms......Page 4017
6.14.3.3 Biotransformation of PCBs by Fungi......Page 4018
6.14.4.2 Mineralization versus Co-Metabolism......Page 4019
6.14.4.4 Anaerobic Reductive Dechlorination of PCBs......Page 4020
6.14.4.7 Enantioselective Biodegradation of PCBs......Page 4023
6.14.6 Genetically Modified Bacteria for PCB Biodegradation......Page 4024
Acknowledgments......Page 4026
References......Page 4027
Relevant Websites......Page 4028
Biodegradation and Bioremediation of TNT and Other Nitro Explosives......Page 4029
6.15.2 Nitroaromatic Explosives......Page 4031
6.15.2.2 (Bio)degradation Pathways of Nitroaromatic Explosives......Page 4033
6.15.3.1 Environmental Transport Processes of Nitramine Explosives......Page 4035
6.15.4.1 Environmental Transport Processes of Nitroester and Nitroalkane Explosives......Page 4037
6.15.5 Bioremediation of Environments Contaminated by Nitro Explosives......Page 4038
References......Page 4040
6.16.1 Introduction......Page 4044
6.16.2 Fungi......Page 4045
6.16.3.2 Aromatic Peroxygenases......Page 4046
6.16.3.4 Laccase......Page 4048
6.16.4.1 Natural Compounds as Mediators......Page 4049
6.16.5.2 Bioremediation of Soil......Page 4051
6.16.5.2.2 Immobilization of contaminants to soil humic substances with the aid of oxidative enzymes......Page 4053
6.16.6 Concluding Remarks......Page 4055
References......Page 4056
6.17.3 Soil Microorganisms – Structure and Analysis Tools......Page 4058
6.17.4 Microorganisms and the Contamination by Heavy Metals......Page 4059
6.17.5 Biological Methods of Remediation – Bioremediation......Page 4060
6.17.7 Metallophyte Plants......Page 4062
6.17.8 Interaction between Microorganisms and Plants......Page 4063
References......Page 4064
6.18.1 Introduction......Page 4068
6.18.4 Factors Affecting Metal Uptake by Plants......Page 4070
References......Page 4073
Relevant Websites......Page 4074
6.19.1 Introduction......Page 4075
6.19.2.2 Production of Protein and PUFA-Enriched Cyanobacteria and Microalgae Using Wastewater......Page 4076
6.19.2.3 Use of Strains Isolated from Special Environments......Page 4078
6.19.4 Biodegradation of Toxic and Persistent Organic Pollutants......Page 4079
6.19.5 Use of Immobilized Microalgae and Cyanobacteria for Nutrient and Heavy Metal Removal......Page 4080
References......Page 4082
Transgenic Plants and Associated Bacteria for Phytoremediation of’Organic Pollutants......Page 4083
6.20.2 Phytoremediation: Cleaning Up Pollution with Plants and Associated Bacteria......Page 4085
6.20.2.1.4 Phytovolatilization: Volatilization through the leaves......Page 4086
6.20.2.2 The Green Liver Model......Page 4087
6.20.2.4 Advantages and Disadvantages of Phytoremediation......Page 4088
6.20.2.5.1 Phytoremediation of chlorinated compounds......Page 4089
6.20.2.5.2 Phytoremediation of explosives......Page 4091
6.20.3.1.1 Transgenic plants expressing phase I enzymes of the green liver model......Page 4092
6.20.3.1.3 Transgenic plants expressing secretory enzymes......Page 4094
6.20.3.2.1 Transgenic rhizospheric bacteria for phytoremediation......Page 4095
6.20.4 Conclusions......Page 4096
Relevant Websites......Page 4097
6.21.1 Introduction......Page 4098
6.21.2.1 Gas Emission......Page 4099
6.21.2.3 Heavy Metals in Soil and Groundwater......Page 4100
6.21.4 Phytoremediation of Landfills......Page 4101
6.21.5.1 Nutrients in Biosolids......Page 4102
6.21.5.3 Contaminants from Biosolids......Page 4103
References......Page 4104
Methanotrophs: Multifunctional Bacteria with Promising Applications in Environmental Bioengineering......Page 4107
6.22.2.1 Biodiversity of Methanotrophs......Page 4108
6.22.3 Cultivation of Methanotrophs......Page 4111
6.22.4.1.1 Methane emissions from landfill gas......Page 4113
6.22.4.2 Biodegradation of Hazardous Organic Compounds......Page 4114
6.22.5 Engineering Challenges in the Use of Methanotrophs in Environmental Biotechnology......Page 4115
References......Page 4116
6.23.1 Introduction......Page 4121
6.23.3 Biostimulation......Page 4122
6.23.3.2 Slow-Release Fertilizers......Page 4123
6.23.3.3 Oleophilic Biostimulants......Page 4124
6.23.4.1 Laboratory Studies on Bioremediation of Oil......Page 4125
6.23.4.3 Field Studies......Page 4127
6.23.5 Bioaugmentation or Biostimulation?......Page 4129
References......Page 4130
Biological Wastewater Treatment Systems......Page 4133
6.24.2.1 The Cell......Page 4134
6.24.3.2 Precipitation and cellular uptake of phosphorus......Page 4137
6.24.4.1 Mineralization and immobilization......Page 4138
6.24.4.5 Coupling between Microbiology and Water Circulation......Page 4139
6.24.5 Reaction Kinetics in Biological Treatment Systems......Page 4140
6.24.6.1 Treatment Wetlands......Page 4142
6.24.6.3 Functionality of SSF Wetlands......Page 4143
6.24.7.3 The Biological Process......Page 4144
6.24.7.4 Nutrient Removal Capacity......Page 4145
6.24.7.7 Strengths and Weaknesses of WWTP......Page 4146
References......Page 4147
Relevant Websites......Page 4148
6.25.2 Wastewater Treatment Model Terminology......Page 4149
6.25.3.1 Activated Sludge Models (Suspended Growth Systems)......Page 4150
6.25.3.5 Biofilm Models (Attached Growth Systems)......Page 4153
6.25.5 Guidelines for Application of WWTP Models......Page 4154
6.25.6.1 Objective......Page 4155
6.25.6.4 Calibration......Page 4158
6.25.7 Major Limitations of Activated Sludge Models......Page 4159
References......Page 4161
Activated Sludge Model-Based Modeling of Membrane Bioreactor Processes: A Critical Review with Special Regard to MBR Specificities......Page 4162
6.26.1 Introduction......Page 4163
6.26.2 Application of Unmodified ASMs to MBR Processes......Page 4165
6.26.2.2 Influent Fractionation for Unmodified ASMs......Page 4166
6.26.2.3 Process Kinetics and Stoichiometry......Page 4167
6.26.2.3.1 Parameter sensitivity in MBR vs. CAS......Page 4168
6.26.2.3.2 Nitrification kinetics......Page 4169
6.26.2.3.4 Phosphorus removal kinetics......Page 4171
6.26.2.3.7 Sludge production......Page 4172
6.26.3.1.1 EPS and SMP definition......Page 4173
6.26.3.2 Influent Fractionation for Modified ASMs......Page 4174
6.26.3.3.2 Stand-alone SMP models......Page 4175
6.26.3.4 Overview of ASM -Extensions Incorporating EPS/SMP Concepts......Page 4177
6.26.3.5 Model Identification – UAP/BAP Kinetics......Page 4179
6.26.4 Outlook and Future Perspectives......Page 4180
6.26.5 Conclusions......Page 4181
References......Page 4182
Relevant Websites......Page 4184
Biological Nitrogen Removal from Domestic Wastewater......Page 4185
6.27.1 Introduction......Page 4186
6.27.2.1 Conventional Nitrification/Denitrification......Page 4187
6.27.2.2 Simultaneous Nitrification/Denitrification......Page 4189
6.27.2.4 Bioaugmentation of Nitrifying Bacteria......Page 4190
6.27.3.1 The Anammox Process......Page 4191
6.27.3.2.2 Two-step anammox processes......Page 4192
6.27.3.2.3 Autotrophic denitrification of sludge digestion returns......Page 4193
6.27.4.2 Greenhouse Gas Emissions......Page 4195
Relevant Websites......Page 4196
6.28.2 Biological–Chemical Phosphorus Removal......Page 4197
6.28.3 Historical Background......Page 4198
6.28.4 Biochemical and Microbiological Aspects......Page 4199
6.28.5 Denitrifying Phosphorus Removal......Page 4200
6.28.5.2 Conditions that Stimulate the Growth of DPAOs......Page 4201
6.28.5.4 Two-Sludge Systems – the Dephanox Process......Page 4202
6.28.6 Future Perspectives......Page 4203
References......Page 4204
6.31.1 Introduction......Page 4208
6.31.2.1.2 Acidogenesis......Page 4209
6.31.2.2 Stoichiometry and Mass Balance......Page 4210
6.31.3.2.1 Hydrolysis......Page 4212
6.31.3.2.2 Fermentation and anaerobic oxidation of hydrolysis products......Page 4213
6.31.3.3.1 The rate-limiting step approach......Page 4215
6.31.3.3.2 Structured models......Page 4216
6.31.4.1 Anaerobic Biotransformation Considerations......Page 4217
Attached Growth Biological Systems in the Treatment of Potable Water and Wastewater......Page 4221
6.30.1.1 Attached Growth Systems......Page 4222
6.30.1.1.3 Beneficial aspects of biofilms......Page 4223
6.30.1.2.1 Trickling filters......Page 4224
6.30.2 Water Treatment......Page 3878
6.30.2.1.4 A case study......Page 4226
6.30.2.2 Potable Water Denitrification......Page 4227
6.30.2.2.3 Fluidized bed reactors......Page 4228
6.30.3.1.1 Microbiology......Page 4229
6.30.3.1.5 Continuous operation with recirculation......Page 4230
6.30.3.2.1 A case study......Page 4231
References......Page 4232
Relevant Websites......Page 4233
6.31.1 Introduction......Page 4234
6.31.2.1.2 Acidogenesis......Page 4235
6.31.2.2 Stoichiometry and Mass Balance......Page 4236
6.31.3.2.1 Hydrolysis......Page 4238
6.31.3.2.3 Methanogenesis......Page 4240
6.31.3.3.1 The rate-limiting step approach......Page 4241
6.31.4.2 Kinetics and Modeling......Page 4243
References......Page 4245
Constructed Wetlands for Water Treatment......Page 4247
6.29.2.1 Types of Constructed Wetlands......Page 4248
6.29.2.2 Hydrology......Page 4249
6.29.2.4 Second Approach to the Design of Constructed Wetlands – Kadlec and Knight Method......Page 4251
6.29.3 Constructed Wetland Bioprocesses......Page 4252
6.29.3.1 Removal of Organic Matter (or Biogenic Pollutants)......Page 4254
6.29.3.2 Removal of Phosphorus and Nitrogen......Page 4258
6.29.3.5 Removal of Organic Pollutants......Page 4259
6.29.4 Limitations of Wetland Bioprocesses......Page 4260
6.29.6 Conclusions......Page 4261
References......Page 4262
6.33.1 Sulfate-Containing Wastewaters and Biological Sulfate Reduction......Page 4264
6.33.3.1 AnMOS in the Environment......Page 4268
6.33.3.3 Microorganisms Involved in AnMO, Electron Transfer, and Metabolic Pathway......Page 4269
6.33.3.4 Methods to Study AnMO......Page 4271
6.33.3.6 Bioreactor Systems for AnMOS......Page 4273
6.33.3.7 Biotechnological Implications......Page 4275
References......Page 4277
Sulfate Reduction for Inorganic Waste and Process Water Treatment......Page 4280
6.34.2 Waste and Process Streams with Sulfate......Page 4281
6.34.3.1 Organic Waste Streams......Page 4282
6.34.3.2 Bulk Chemicals as Electron Donor......Page 4283
6.34.4 Effect of Process Conditions on Sulfate Reduction......Page 4284
6.34.4.4 Effect of Solid Retention Time......Page 4285
6.34.5.3 Expanded Granular Sludge Bed Reactor......Page 4286
6.34.6 Sulfate-Reducing Applications and Metal Recovery......Page 4287
6.34.6.3 Flow Schemes for Selective Metal Precipitation......Page 4288
References......Page 4289
6.35.1 Introduction......Page 4292
6.35.3.1 Microbial Processes......Page 4295
6.35.3.3 Control Parameters......Page 4296
6.35.3.4 Inhibition......Page 4300
6.35.4.1 Mesophilic and Thermophilic Digestion......Page 4301
6.35.5 Process Benefits......Page 4302
6.35.6.1 Disposal Methods......Page 4304
6.35.6.2.4 Recommendations and perspectives......Page 4305
References......Page 4306
Anaerobic Digestion of the Organic Fraction of Municipal Solid Waste for Methane Production: Research and Industrial Application......Page 4307
6.36.2 Waste Characteristics and Collection Strategies......Page 4308
6.36.3 The Importance for AD Design of Having Appropriate Values for B0 and G0......Page 4309
6.36.5 Sorting/Preparation Technologies......Page 4311
6.36.6 AD Technologies and Performances......Page 4312
6.36.7 Carbon Footprint and Global Warming Potential of AD of Biowaste......Page 4313
References......Page 4315
Occurrence, Toxicity, and Biodegradation of Selected Emerging Priority Pollutants in Municipal Sewage Sludge......Page 4317
6.37.2.1 Di-(2-Ethyl-Hexyl)Phthalate......Page 4319
6.37.3 Polycyclic Aromatic Hydrocarbons (PAHs)......Page 4321
6.37.4.1 Linear Alkylbenzene Sulfonates (LAS)......Page 4324
6.37.4.2 Alkyl phenol ethoxylates (APEs)......Page 4326
References......Page 4327
Relevant Websites......Page 4328
6.38.1 Introduction......Page 4329
6.38.2.2 Ecotoxicological Effects on Aquatic Life......Page 4330
6.38.2.3 Whole Effluent Toxicity......Page 4331
6.38.3.2 Occurrence and Biodegradation......Page 4332
6.38.4.2 Influence of Sludge Age......Page 4334
6.38.5.1 Compounds Susceptible to Co-Metabolism during Nitrification......Page 4335
6.38.5.5 Technological Opportunities......Page 4336
References......Page 4337
6.39.1 Introduction......Page 4339
6.39.2.1 Nitrification Control Biosensors......Page 4340
6.39.2.2 Oxygen Demand (o.d.) Monitoring Biosensors......Page 4342
6.39.4 Denitrification Control Biosensors......Page 4346
6.39.5 Other Types of Biosensors......Page 4347
References......Page 4348
Efficiency and Sustainability of Urban Wastewater Treatment with’Maximum Separation of the Solid and Liquid Fraction......Page 4350
References......Page 4357
Biotreatment of Drinking Water......Page 4359
6.41.2 Biofilms and Oligotrophic Growth......Page 4360
6.41.3.2.2 Microbial colonization and biofilm development......Page 4362
6.41.3.3.1 Design, operation, and placement......Page 4363
6.41.3.3.2 Microbial colonization and biofilm development......Page 4364
6.41.3.4.1 Design, operation, and placement......Page 4365
6.41.3.4.2.1 Schmutzdecke......Page 4366
6.41.3.4.3 Filter function and performance......Page 4367
6.41.4.2.1 Total and dissolved organic carbon......Page 4368
6.41.4.3 Suspended Biomass in the Water Matrix......Page 4369
6.41.4.4.3 Direct measurement on the filter material......Page 4370
References......Page 4371
6.42.1 Introduction......Page 4373
6.42.3.1 Energy and Biofuel Production......Page 4375
6.42.3.4 Bio-Adsorbent......Page 4380
6.42.3.6 Feed for Animals......Page 4381
6.42.4.3 Starch Industry Wastewater......Page 4383
6.42.5 Byproducts of the Olive-Oil Extraction Industry: An Emblematic Case......Page 4384
References......Page 4386
Relevant Website......Page 4387
6.43.1 Introduction......Page 4388
6.43.2 Extraction and Extraction Techniques......Page 4389
6.43.3 Modification of Carbohydrates......Page 4390
6.43.4 Modification of Lipids (Oils and Fats) and Glycerol......Page 4392
6.43.7 Production of d-Glucurono-γ-Lactone from Corn Wastes – A Case Study......Page 4395
References......Page 4396
6.45.1 Introduction......Page 4398
6.45.2 Fungal Transformation of Hazardous Organic Compounds in the Bioremediation of Polluted Soils’and’Industrial Wastewaters......Page 4399
6.45.2.2 Laccases as Green Agents in the Transformation of Pollutants......Page 4400
6.45.3.2 Other Potential Uses of Laccases......Page 4401
6.45.4 Revalorization of byproducts from Agriculture......Page 4402
6.45.4.1 Bioconversion of Olive-Oil Solid Wastes......Page 4403
6.45.5.2 Enzymatic Detoxification of Steam-Exploded Lignocellulose......Page 4404
Acknowledgments......Page 4405
Relevant Websites......Page 4406
6.45.1 Introduction......Page 4407
6.45.2 Fungal Transformation of Hazardous Organic Compounds in the Bioremediation of Polluted Soils’and’Industrial Wastewaters......Page 4408
6.45.2.1 White-Rot Fungi as Potential Tools in Bioaugmentation Strategies......Page 4409
6.45.3.2 Other Potential Uses of Laccases......Page 4410
6.45.4 Revalorization of byproducts from Agriculture......Page 4411
6.45.4.2 Production of Laccases by Fungi on Agriculture Residues......Page 4412
6.45.5.2 Enzymatic Detoxification of Steam-Exploded Lignocellulose......Page 4413
Acknowledgments......Page 4414
Relevant Websites......Page 4415
6.46.1 Introduction......Page 4416
6.46.2.1.2 Thermoanaerobacter sp.......Page 4421
6.46.2.2.3 Zymomonas mobilis......Page 4422
6.46.2.3.3 Other yeasts......Page 4423
References......Page 4424
6.47.1 Introduction......Page 4426
6.47.2 Which Process Steps Can Be Considered Most Important?......Page 4428
6.47.2.1 Pretreatment......Page 4429
6.47.2.3 Separate Hydrolysis and Fermentation......Page 4432
6.47.2.5 Separation of Solids and Liquids......Page 4433
6.47.3 Process Modeling......Page 4434
6.47.3.1 Effect of Various Parameters on the Energy Demand and Production Cost......Page 4435
6.47.3.2 Co-Location with Other Plants......Page 4436
6.47.3.4 Integration with 1G Ethanol......Page 4437
References......Page 4438
Biohydrogen Production from Agricultural Agrofood-Based Resources......Page 4440
6.48.2.1 Biophotolysis-Based Hydrogen Production......Page 4442
6.48.2.2 Biological Water–Gas Shift Reaction......Page 4443
6.48.2.4 Biohydrogen Production by Hybrid Systems......Page 4444
6.48.3.2.1 Biohydrogen production from low-value starch residues......Page 4445
6.48.3.2.2 Biohydrogen production from lignocellulosic biomass......Page 4446
6.48.3.2.2.2 Biohydrogen from direct cellulose fermentation......Page 4447
6.48.4.1 Bioprocess Engineering of Single-Phase Fermentation Reactions......Page 4448
6.48.4.3 Metabolic Engineering......Page 4449
6.48.4.5.2 Dark fermentation followed by electrohydrogenesis......Page 4450
References......Page 4451
6.50.1 Introduction......Page 4453
6.50.2 Bioconversion of Ferulic Acid into Vanillin......Page 4455
6.50.4 Rice-Based Processes......Page 4456
6.50.5 Wheat-Based Processes......Page 4457
References......Page 4458
Relevant Websites......Page 4459
Microbial Fuel Cells and Bioelectrochemical Systems: Industrial and’Environmental Biotechnologies Based on Extracellular Electron Transfer......Page 4460
6.49.2 Fundamentals of Microbial Extracellular Electron-Transfer Processes......Page 4462
6.49.2.2 Direct Extracellular Electron Transfer......Page 4463
6.49.2.3.2 MET based on secondary microbial metabolites......Page 4464
6.49.2.3.3.2 Fermentation......Page 4467
6.49.3.1 Integration of MFCs in Wastewater-Treatment Plants – Exploiting the Double Benefit......Page 4468
6.49.3.3 MFCs for Robotics......Page 4469
6.49.4 Microbial BES for the Production of Chemicals: Microbial Electrolysis Cells......Page 4471
6.49.6.1 Bioelectrochemical Remediation Methods......Page 4472
6.49.6.2 Chlorinated Hydrocarbons......Page 4473
6.49.6.3 Nitrate......Page 4474
Reference......Page 4475
Relevant Websites......Page 4476
Mixed Culture Processes for Polyhydroxyalkanoate Production from’Agro-Industrial Surplus/Wastes as Feedstocks......Page 4477
6.51.1.2 PHA Structure and Properties......Page 4478
6.51.2.2 Bacterial PHA Synthesis......Page 4479
6.51.2.3.1 Feast and famine process: Fully aerobic or anaerobic/aerobic......Page 4480
6.51.3 Governing the Selective Pressure for PHA-Storing Organisms in FF Processes......Page 4482
6.51.3.2.1 SRT/specific growth rate......Page 4483
6.51.3.2.2 F/F ratio......Page 4484
6.51.3.2.4 Influent substrate concentration......Page 4485
6.51.3.3 Microbial Characterization of Mixed PHA-Accumulating Cultures......Page 4486
6.51.4.2 The Acidogenic Fermentation Stage......Page 4487
6.51.4.5 The Extraction Step......Page 4489
References......Page 4490
Biosorption for Industrial Applications......Page 4492
6.52.2.3 Characterization and Pretreatment of Biosorbent Particles (Based on Sargassum Biomass)......Page 4494
6.52.3.1 Biomass Reinforcement......Page 4496
6.52.3.1.1 Entrapment......Page 4497
6.52.3.2.1 FA and UFA cross-linking......Page 4498
6.52.3.3 Granulation Techniques......Page 4499
6.52.3.3.3 Spray drying......Page 4500
6.52.3.4 Conclusions to Biosorbent Formulation......Page 4501
6.52.4.3 Fluidized-Bed Column Sorption System......Page 4502
6.52.5.1 Specifications......Page 4503
6.52.5.2.1 Metal laden effluent......Page 4504
6.52.5.3.1 Column sizing......Page 4505
6.53.1 Introduction......Page 4508
6.53.2 Oxic and Anoxic Methane Oxidation......Page 4509
6.53.3 Methane-Oxidizing Consortia and Biofilms......Page 4510
6.53.4 Membrane-Attached Bioreactors......Page 4511
6.53.5 Technical-Scale Methanotrophic Membrane Biofilm Reactors......Page 4512
References......Page 4513
6.54.1 Introduction......Page 4515
6.54.3 Enzymatic Aspects of Microbial Dissimilatory Reduction of Radionuclides......Page 4516
6.54.3.4 Neptunium(V) Reduction......Page 4518
6.54.4.2 Shewanella Species......Page 4519
6.54.4.4 Desulfovibrio Species......Page 4520
6.54.6 Conclusions......Page 4521
Relevant Website......Page 4524
6.55.1 Introduction......Page 4525
6.55.2.1 Case History 1: Bioremediation of Uranium Mine–Water and Nanofilter Fabrication for Nuclear Waste Remediation......Page 4526
6.55.2.3 Case History 3: Bioconversion of Au-Containing Jewellery Waste into Nano-Au Catalyst for Glycerol Oxidation......Page 4528
6.55.2.4 Case History 4: Bioconversion of Selenium Oxyanions into Optically Active Chalcogenide Materials......Page 4529
References......Page 4530
Relevant Websites......Page 4531