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Book SynopsisUnderstanding games--whether computer games, card games, board games, or sports--by analyzing certain common traits.Characteristics of Games offers a new way to understand games: by focusing on certain traits--including number of players, rules, degrees of luck and skill needed, and reward/effort ratio--and using these characteristics as basic points of comparison and analysis. These issues are often discussed by game players and designers but seldom written about in any formal way. This book fills that gap. By emphasizing these player-centric basic concepts, the book provides a framework for game analysis from the viewpoint of a game designer. The book shows what all genres of games--board games, card games, computer games, and sports--have to teach each other. Today's game designers may find solutions to design problems when they look at classic games that have evolved over years of playing.

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Book SynopsisAn award-winning professor’s introduction to essential concepts of calculus and mathematical modeling for students in the biosciencesTrade Review“The choice of material is interesting and refreshing, and finds concrete applications for mathematical topics that might not be standard fare in the physics or chemistry curricula. The applications of the Poincaré-Bendixson theorem to locating limit cycles are a remarkable highlight.”—Chay Paterson, zbMATH Open"This is a wonderful book, wise and witty. It would have taught me most of the math I needed for my career in research – if I did all the problems."—Stephen Stearns, author of The Evolution of Life Histories and Evolutionary Medicine “This enlightening book covers not only the essential parts of calculus and dynamical system, but also how one can apply these tools in biological sciences. In addition, the last chapter of this book is a concise introduction to probability theory. Michael Frame motivates students with very well-selected examples.”—Hongyu He, Professor of Mathematics, Louisiana State University“This work is an important step toward a new curriculum model for the nascent field of mathematical biology: different content and authentic applications, geared toward a truly interdisciplinary audience.”—Rebecca Gasper, Assistant Professor of Mathematics, Creighton University

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Book SynopsisTable of Contents1. Insects and Their Ways. 2. The Anatomy, Physiology, and Development of Insects. 3. Systematics, Nomenclature, and Identification. 4. Behavior and Ecology. 5. Phylum Arthropoda. 6. Hexapoda. 7. The Entognathous Hexapods: Protura, Collembola, Diplura. 8. The Apterygote Insects: Microcoryphia and Thysanura. 9. Order Ephemeroptera: Mayflies. 10. Order Odonata: Dragonflies and Damselflies. 11. Order Orthoptera: Grasshoppers, Crickets, and Katydids. 12. Order Phasmatodea: Walkingsticks and Leaf Insects. 13. Order Grylloblattodea: Rockcrawlers. 14. Order Mantophasmatodea. 15. Order Dermaptera: Earwigs. 16. Order Plecoptera: Stoneflies. 17. Order Embiidina: Webspinners. 18. Order Zoraptera: Zorapterans, Angel Insects. 19. Order Isoptera: Termites. 20. Order Mantodea: Mantids. 21. Order Blattodea: Cockroaches. 22. Order Hemiptera: True Bugs, Cicadas, Hoppers, Psyllids, Whiteflies, Aphids, and Scale Insects. 23. Order Thysanoptera: Thrips. 24. Order Psocoptera: Psocids. 25. Order Phthiraptera: Lice. 26. Order Coleoptera: Beetles. 27. Order Neuroptera: Alderflies, Dobsonflies, Fishflies, Snakeflies, Lacewings, Antlions, and Owlflies. 28. Order Hymenoptera: Sawflies, Parasitic Wasps, Ants, Wasps, and Bees. 29. Order Trichoptera: Caddisflies. 30. Order Lepidoptera: Butterflies and Moths. 31. Order Siphonaptera: Fleas. 32. Order Mecoptera: Scorpionflies and Hangingflies. 33. Order Strepsiptera: Twisted-Winged Parasites. 34. Order Diptera: Flies. 35. Collecting, Preserving, and Studying Insects.

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Book SynopsisThe second edition of this textbook written for undergraduate students, graduate students and medical researchers, Genetics and Genomics in Medicine explains the science behind the uses of genetics and genomics in medicine today, and how it is being applied.Maintaining the features that made the first edition so popular, this second edition has been thoroughly updated in line with the latest developments in the field. DNA technologies are explained, with emphasis on the modern techniques that are revolutionizing the use of genetic information in medicine and indicating the role of genetics in common diseases. Epigenetics and non-coding RNA are covered in-depth as are genetic approaches to treatment and prevention, including pharmacogenomics, genetic testing, and personalized medicine. A dedicated chapter charts the latest insights into the molecular basis of cancers, cancer genomics and novel approaches to cancer detection. Coverage of genetic testing at the level of Trade ReviewThis excellent book is a must-have for any library, or anyone deeply interested in genetics and genomics in medicine. The writing is detailed yet easily understandable, and readers will come away much more knowledgeable on thesubject. This second edition is a much needed and exceptionally well-executed update to the original version.- Mark F. Sanders, PhD, UC Davis College of Biological SciencesTable of Contents1. Fundamentals of DNA, Chromosomes, and Cells 2. Fundamentals of Gene Structure, Gene Expression, and Human Genome Organization 3. Principles Underlying Core DNA Technologies 4. Principles of Genetic Variation 5. Single-gene Disorders: Inheritance Patterns, Phenotype Variability, and Allele Frequencies 6. Principles of Gene Regulation and Epigenetics 7. How Genetic Variation in DNA and Chromosomes Causes Disease8. Identifying Disease Genes and Genetic Susceptibility to Complex Disease9. Genetic Approaches to Treating Disease 10. Cancer Genetics and Genomics11. Genetic and Genomic Testing in Healthcare: Practical and Ethical Aspects

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Book SynopsisProvides tips for using servers and places to seek resources to find out about what's going on in the bioinformatics world. This book helps you: analyze all types of sequences; use all types of databases; work with DNA and protein sequences; conduct similarity searches; build a multiple sequence alignment; and edit and publish alignments.Table of ContentsIntroduction. Part I: Getting Started in Bioinformatics. Chapter 1: Finding Out What Bioinformatics Can Do for You. Chapter 2: How Most People Use Bioinformatics. Part II: A Survival Guide to Bioinformatics. Chapter 3: Using Nucleotide Sequence Databases. Chapter 4: Using Protein and Specialized Sequence Databases. Chapter 5: Working with a Single DNA Sequence. Chapter 6: Working with a Single Protein Sequence. Part III: Becoming a Pro in Sequence Analysis. Chapter 7: Similarity Searches on Sequence Databases. Chapter 8: Comparing Two Sequences. Chapter 9: Building a Multiple Sequence Alignment. Chapter 10: Editing and Publishing Alignments. Part IV: Becoming a Specialist: Advanced Bioinformatics Techniques. Chapter 11: Working with Protein 3-D Structures. Chapter 12: Working with RNA. Chapter 13: Building Phylogenetic Trees. Part V: The Part of Tens. Chapter 14: The Ten (Okay, Twelve) Commandments for Using Servers. Chapter 15: Some Useful Bioinformatics Resources. Index.

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Book SynopsisHANDBOOK OF ALCOHOLIC BEVERAGES A comprehensive two-volume set that describes the science and technology involved in the production and analysis of alcoholic beverages HANDBOOK OF ALCOHOLIC BEVERAGESTechnical, Analytical and Nutritional Aspects At the heart of all alcoholic beverages is the process of fermentation, particularly alcoholic fermentation, whereby sugars are converted to ethanol and many other minor products. The Handbook of Alcoholic Beverages tracks the major fermentation process, and the major chemical, physical and technical processes that accompany the production of the world's most familiar alcoholic drinks. Indigenous beverages and small-scale production are also covered to a significant extent. The overall approach is multidisciplinary, reflecting the true nature of the subject. Thus, aspects of biochemistry, biology (including microbiology), chemistry, health science, nutrition, physics and technology are allTable of ContentsList of Contributorsxv General Acknowledgments and Thanksxvii Volume 1 1 Introduction, Background and History 1 John A. Hudson and Alan J. Buglass 1.1 Alcoholic Beverages of the World: An Introduction to the Contents of This Book 3 1.2 History and Development of Alcoholic Beverages 12 1.2.1 The Beginnings (From the earliest Times to ca. 1100 AD) 12 1.2.2 Medieval Times and Beyond (ca. 1100–1750) 18 1.2.3 The Industrial Revolution and the Influences of Science and Technology (ca. 1750–1900) 24 1.2.4 Modern Times and Newer Processes (ca. 1900–Present Day) 28 1.2.5 The Development of Analytical Methods 35 References 40 1.3 Some Recent Trends and Developments 42 1.3.1 Overview 42 1.3.2 Big is Beautiful: Multinational Companies and the Globalization of Alcoholic Beverages 42 1.3.3 Small is Beautiful: The Growth in Microbreweries and Craft Breweries and the Localization of Products 44 1.3.4 Revival of Traditional Beer Styles 45 1.3.5 Changes in Beer Drinking Habits 47 1.3.6 Global Growth in Wine Drinking 48 1.3.7 Development of New Wine Industries 50 1.3.8 Revival of Cider and Perry: the Magic of Ice 52 1.3.9 The Rise of Flavored Alcoholic Beverages (‘Alcopops’) 52 1.3.10 Calorie-Counting and Health Perception of Alcoholic Drinks 53 1.3.11 Binge Drinking 54 1.3.12 Organic and Biodynamic Production of Alcoholic Beverages 56 1.3.13 Use of Genetically Modified (GM) Crops and Microorganisms 57 References 59 2 Fermented Beverages: Beers, Ciders, Wines and Related Drinks 63 Marianne McKay, Alan J. Buglass and Chang Gook Lee 2.1 Introduction: Overview of Fermentation and Microorganisms 65 2.1.1 Yeasts 67 2.1.2 Lactic Acid Bacteria 69 2.1.3 Molds and Spoilage Organisms 69 References 70 2.2 Alcoholic Fermentation 72 2.2.1 Introduction 72 2.2.2 Physiology and Morphology of Yeast 72 2.2.3 Nutritional Requirements of Yeast 73 2.2.4 The Use of Naturally Occurring (‘Wild’) Yeasts in Fermentations 75 2.2.5 The Killer Factor 76 2.2.6 The Use of Selected (Cultured) Yeast Strains 76 2.2.7 Fermentation Vessels 77 2.2.8 The Growth of a Yeast Population 77 2.2.9 An Overview of Alcoholic Fermentation 80 2.2.10 Flocculation 87 2.2.11 Aroma Compounds and Fermentation 88 References 93 2.3 Malolactic Fermentation 96 2.3.1 Introduction 96 2.3.2 Malolactic Bacteria: Morphology and Physiology 97 2.3.3 Identification of Malolactic Bacteria 98 2.3.4 Factors Affecting the Growth of Malolactic Bacteria 98 2.3.5 Interactions Between Bacteria and Other Organisms 100 2.3.6 Spontaneous Malolactic Fermentation 101 2.3.7 Inoculation with MLB Starter Culture 101 2.3.8 The Growth of Bacterial Populations 102 2.3.9 The Malolactic Fermentation Process 103 2.3.10 Production of Diacetyl 104 2.3.11 Microbial Stability 104 2.3.12 Monitoring Malolactic Fermentation 105 2.3.13 Finishing and/or Preventing Malolactic Fermentation 105 2.3.14 Production of Biogenic Amines by Malolactic Bacteria 106 2.3.15 Other Effects of MLF 106 2.3.16 Malolactic Fermentation and Aroma 107 2.3.17 Lactic Spoilage 111 References 112 2.4 Acetic and Other Fermentations 114 2.4.1 Introduction 114 2.4.2 Acetic Acid Bacteria 115 2.4.3 Lactic Acid Bacteria 117 2.4.4 The Activities of Yeasts other than Saccharomyces 117 2.4.5 Film Forming Yeasts 119 2.4.6 Molds 120 2.4.7 Prevention of Spoilage 120 References 121 2.5 Preservatives Used in the Production of Alcoholic Beverages 123 2.5.1 Introduction 123 2.5.2 Sulfur Dioxide (SO 2) 123 2.5.3 The Roles of SO 2 125 2.5.4 Sorbic Acid 128 2.5.5 DMDC (Velcorin) 129 2.5.6 Ascorbic Acid (Vitamin C) 129 2.5.7 Pimaricin (Natamycin) 130 2.5.8 Other Preservatives 130 References 131 2.6 Beer 132 2.6.1 The Basic Brewing Processes 132 2.6.2 Malting and Mashing 134 2.6.3 Boiling the Wort 148 2.6.4 Fermentation 157 2.6.5 Top Fermentation 163 2.6.6 Bottom Fermentation 167 2.6.7 Other Fermentations 169 2.6.8 Modern Methods of Fermentation 171 2.6.9 Beer Treatment: Fining, Filtration and Pasteurization 173 2.6.10 Packaging of Beer: Casking, Kegging, Bottling and Canning 182 2.6.11 Dispensing of Draught Beers 186 2.6.12 Oxidation and the Staling of Beer 192 2.6.13 Beer styles 196 References 207 2.7 Cereal-based and Other Fermented Drinks of Asia, Africa and Central/South America 211 2.7.1 The Rice ‘Wines’ of Asia 212 2.7.2 Native Fermented Drinks of Africa and South America 222 References 229 2.8 Cider and Perry 231 2.8.1 Introduction 231 2.8.2 The Basic Ingredients 233 2.8.3 Harvesting, Crushing and Pressing 238 2.8.4 Fermentation and Maturation 241 2.8.5 Traditional and Small-Scale Cider and Perry Production: Fermentation and Beyond 245 2.8.6 Large-Scale (Factory) Production of Cider and Perry: Fermentation and Beyond 251 2.8.7 Newer Techniques, Recent Developments and Innovations 254 2.8.8 Cider and Perry from Around the World 257 References 263 2.9 Wine 266 2.9.1 White Winemaking 267 2.9.2 Red Wine Production 300 2.9.3 Sparkling Wines 324 2.9.4 Fining, Filtration and Clarification 343 2.9.5 Wine Maturation and Ageing 354 2.9.6 Some Current Trends in Wine Production 371 References 377 2.10 Fortified Wines and Liqueur Wines 383 2.10.1 Overview and Scope 383 2.10.2 Sherry and Other Flor Wines 384 2.10.3 Flor and Oxidation in Sherry Wines 391 2.10.4 Other Flor Wines 394 2.10.5 Madeira 395 2.10.6 Estufagem and Cask Maturation of Madeira Wine 397 2.10.7 Port 399 2.10.8 Marsala and Málaga 408 2.10.9 Vins Doux Naturels, Liqueur Muscat and Similar Wines 409 2.10.10 Vins de Liqueurs and Similar Beverages 414 References 416 2.11 Fruit Wines and Other Nongrape Wines 419 2.11.1 Overview and Scope 419 2.11.2 Comparison of Fruit for Winemaking 420 2.11.3 Making Fruit Wines 423 2.11.4 Country Wine Styles 429 2.11.5 Mead 432 References 434 2.12 Aromatized Wines 436 2.12.1 Introduction and Brief History of Aromatization of Wine 436 2.12.2 Vermouth 437 2.12.3 Other Aromatized Wines and Apéritifs 444 References 445 2.13 Low Alcohol and Non-Alcoholic Beers, Ciders and Wines 447 2.13.1 Overview 447 2.13.2 Production of Low Alcohol Beverages by Limited or Checked Alcohol Methods 448 2.13.3 Dealcoholization Methods 450 References 453 3 Distilled Spirits 455 Alan J. Buglass, Marianne McKay and Chang Gook Lee 3.1 Introduction: Distillation Methods and Stills 457 3.1.1 A Brief History and Theory of Distillation 457 3.1.2 Batch Distillation 461 3.1.3 Continuous Column Distillation 466 References 468 3.2 Scotch Whisky 469 3.2.1 Introduction and Brief History 469 3.2.2 The Raw Materials 475 3.2.3 Malting, Mashing, Cooking and Fermentation 479 3.2.4 Distillation 487 3.2.5 Maturation, Blending and Other Postdistillation Processes 491 3.2.6 The Flavor and Styles of Scotch Malt Whiskies 498 References 512 3.3 Whiskeys 515 3.3.1 Scope 515 3.3.2 Irish Whiskey 516 3.3.3 The Whiskeys of America 519 3.3.4 Bourbon and Tennessee Whiskey 520 3.3.5 American Rye and Corn Whiskies 527 3.3.6 Whiskies from Other Countries 528 References 533 3.4 Other Cereal Based Spirits 535 3.4.1 Introduction and Scope 535 3.4.2 Gin and Similar Juniper Flavored Spirits 535 3.4.3 Akvavit (Aquavit) and Vodka 541 3.4.4 Asian Grain Spirits 543 References 553 3.5 Cane Spirits, Vegetable Based Spirits and Aniseed Flavored Spirits 555 3.5.1 Overview and Scope 555 3.5.2 History and Basic Description of Rum and Cachaça 556 3.5.3 Fermentation and Distillation Practices in the Production of Cachaça and Rum 560 3.5.4 Flavor Characteristics of Rum and Cachaça 564 3.5.5 Arrack, Mezcal and Tequila 566 3.5.6 Aniseed Flavored Spirits 570 References 572 3.6 Brandy 574 3.6.1 Introduction and Brief History 574 3.6.2 Cognac 585 3.6.3 Armagnac 588 3.6.4 Other Brandies 589 3.6.5 Quality Control in Brandy Production 591 3.6.6 Evaluating Brandy 591 References 593 3.7 Grape and Other Pomace Spirits 595 3.7.1 Introduction 595 3.7.2 Production of Pomace Spirits 596 3.7.3 Types of Pomace Spirits and Sensory Characteristics 598 References 600 3.8 Fruit Spirits 602 3.8.1 Introduction 602 3.8.2 Apple and Pear Spirits 603 3.8.3 Fruit Spirits of Central Europe 608 3.8.4 Plum Spirits of Eastern Europe 611 3.8.5 Other Fruit Spirits 612 References 613 3.9 Liqueurs and Their Flavorings 615 3.9.1 Introduction and Scope 615 3.9.2 Fruit and Fruit Flavored Liqueurs 617 3.9.3 Flower, Herb, Spice and Bitter Liqueurs 620 3.9.4 Cocoa, Coffee and Tea Liqueurs 624 3.9.5 Nut and Emulsion Liqueurs 624 3.9.6 Production and Use of Essences and Concentrates 625 References 626 Volume 2 4 Analytical Methods 629 Alan J. Buglass and Darren J. Caven-Quantrill 4.1 Introduction 631 4.1.1 Why Analyze Alcoholic Beverages? An Overview of the Need for Analysis 632 4.1.2 Process Monitoring 633 4.1.3 Identification of Origin, Determination of Authenticity and Detection of Fraud 636 4.1.4 Determination and Characterization of Beverage Components and Processes 639 4.1.5 Development of New Analytical Methods 642 References 645 4.2 Extraction and Focusing Methods in Sample Preparation 647 4.2.1 Overview 647 4.2.2 Liquid Extraction Techniques 648 4.2.3 Distillation Methods 659 4.2.4 Solid Phase Extraction and Related Methods (Sorption Techniques) 664 4.2.5 Headspace Methods 684 4.2.6 Combinations of Methods (With Particular Application to Enological Products) 688 4.2.7 Summary 690 References 690 4.3 Chromatographic Methods 705 4.3.1 Thin Layer Chromatography and Related Methods 706 4.3.2 Capillary Gas Chromatography 709 4.3.3 Liquid Chromatography 722 4.3.4 Counter Current Chromatographic Methods 752 References 755 4.4 Spectroscopic Methods 765 4.4.1 Nuclear Magnetic Resonance 767 4.4.2 Infrared Spectroscopy 784 4.4.3 Colorimetry, UV-Visible Spectroscopy and Fluorometry 793 4.4.4 Atomic Absorption and Emission Spectroscopy 814 4.4.5 Mass Spectrometry 825 References 843 4.5 Electrochemical Methods 855 4.5.1 Potentiometric Methods 856 4.5.2 Voltammetric Methods 863 4.5.3 Electrochemical Sensors 869 References 873 4.6 Other Methods 877 4.6.1 Electrophoretic Techniques 877 4.6.2 Flow Injection Techniques 889 4.6.3 Chemical and Physical Methods 896 References 907 4.7 Sensory Analysis 913 4.7.1 Introduction 913 4.7.2 Olfaction and Taste 914 4.7.3 Odor Theshold, Odor Activity and Low Impact Odorants 922 4.7.4 Sensory Tests 925 References 930 5 Nutritional and Health Aspects 933 Nigel J. Fuller, Suk Hean Lee and Alan J. Buglass 5.1 General Introduction 935 5.1.1 ‘Alcohol’ in Perspective 936 5.1.2 The Extent and General Implications of Alcoholic Beverage Consumption 938 5.1.3 Ingredients, Processing and the Nutrient Content of Alcoholic Beverages 941 5.1.4 Nutritional Considerations 943 5.1.5 Summary 946 References 946 5.2 Factors Influencing the Nutrient Content of Alcoholic Beverages 949 5.2.1 Wines 951 5.2.2 Beers 952 5.2.3 Cider and Perry 955 5.2.4 Distilled Beverages 955 5.2.5 Fortified wines 957 5.2.6 Alcopops 958 5.2.7 Cocktails 958 References 959 5.3 Macronutrient Content of Alcoholic Beverages 961 5.3.1 Water 963 5.3.2 Alcohol 966 5.3.3 Carbohydrates (Including Fiber) 967 5.3.4 Nitrogenous Compounds: Proteins, Peptides, Amino Acids, Amines and Nucleotides 970 5.3.5 Lipids 972 References 973 5.4 Micronutrient Content of Alcoholic Beverages 975 5.4.1 Vitamins 977 5.4.2 Electrolytes and Functional Elements (Minerals and Trace Elements) 981 5.4.3 Phytochemicals 986 References 990 5.5 Alcohol Ingestion, Absorption and Catabolism: Metabolic and Nutritional Consequences 993 5.5.1 Alcohol Catabolism 994 5.5.2 Methanol Catabolism 997 5.5.3 Effects of Alcohol on Intake of Foods and Energy 997 5.5.4 Consequences for Intermediary Metabolism of Alcohol Catabolism 998 5.5.5 Effects of Alcohol and its Metabolites on Absorption, Metabolism and Utilization of Key Nutrients 1000 References 1001 5.6 Health Consequences of Alcohol Intake 1003 5.6.1 Overview: Alcoholic Beverages and Society 1003 5.6.2 Harmful Effects of Excessive Alcohol Intake 1008 5.6.3 Possible Benefits of Low to Moderate Consumption of Alcoholic Beverages 1020 5.6.4 Conclusion 1022 References 1022 5.7 Carbohydrates in Alcoholic Beverages and Health 1030 5.7.1 Metabolizable Carbohydrate 1030 5.7.2 Low Carbohydrate Beers 1033 5.7.3 High Carbohydrate Beers 1034 5.7.4 Nonmetabolizable Carbohydrate 1035 References 1037 5.8 Antioxidant Value of Alcoholic Beverages 1038 5.8.1 Overview 1038 5.8.2 Summary of Aerobic Cell Metabolic Processes 1039 5.8.3 Short Review of Oxygen in Cell Metabolic Processes 1039 5.8.4 Incomplete Reduction of Oxygen, the Formation of Reactive Oxygen Species and Cell Damage 1041 5.8.5 Natural Antioxidants in Food 1043 5.8.6 Phenolic Substances in Alcoholic Beverages 1044 5.8.7 Some Chemical Characteristics of Phenolic Compounds 1045 5.8.8 Health Benefits and Antioxidant Potency of Alcoholic Beverages, their Phenolic Extracts and their Individual Phenolic Components 1050 5.8.9 Mechanisms of In Vivo Health Benefits of Dietary Phenols: Antioxidants or Otherwise? 1054 References 1061 5.9 Additives in Alcoholic Beverages 1065 5.9.1 Introduction 1065 5.9.2 Sulfur Dioxide and Other Preservatives 1065 5.9.3 Fining Agents and Adjuncts 1068 5.9.4 Other Additives 1069 5.9.5 Regulations and Legislation Relating to Additives 1071 References 1073 5.10 Residues in Alcoholic Beverages 1076 5.10.1 Introduction 1076 5.10.2 Pesticides 1076 5.10.3 Metal and Nonmetal Residues 1082 5.10.4 Industrial Contaminants 1086 References 1091 5.11 Other Trace Substances in Alcoholic Beverages 1093 5.11.1 Introduction 1093 5.11.2 Phytochemicals 1093 5.11.3 Nitrogenous Allergenic Substances 1098 5.11.4 Mycotoxins 1101 5.11.5 Other Trace Substances 1104 References 1107 Appendix 1 Units of Measurement and Interconversions 1111 Appendix 2 1113 Appendix 3 Pressure and Temperature Unit Conversions, and Numerical Values of Constants 1115 Glossary 1117 Index 1141

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Book Synopsis* A major new edition of this highly successful, authoritative, superbly illustrated text * Distinguished, internationally renowned Editors * Completely revised with over half of the chapters having a major rewrite * Includes two new chapters on signal transduction and responses to pathogens .Trade Review“Biochemistry and Molecular Biology of Plants, 2nd edi­tion is a beast, but it’s a user-friendly one that should be wel­comed into one’s life to provide much-appreciated com­pan­ion­ship to fur­ther one’s plant bio­logy studies.” (AoB Blog, 1 November 2015) Table of ContentsThe Editors xi List of Contributors xii Preface xv About the Companion Website xvi COMPARTMENTS 1 Membrane Structure and Membranous Organelles 2 Introduction 2 1.1 Common properties and inheritance of cell membranes 2 1.2 The fluid-mosaic membrane model 4 1.3 Plasma membrane 10 1.4 Endoplasmic reticulum 13 1.5 Golgi apparatus 18 1.6 Exocytosis and endocytosis 23 1.7 Vacuoles 27 1.8 The nucleus 28 1.9 Peroxisomes 31 1.10 Plastids 32 1.11 Mitochondria 39 Summary 44 2 The Cell Wall 45 Introduction 45 2.1 Sugars are building blocks of the cell wall 45 2.2 Macromolecules of the cell wall 51 2.3 Cell wall architecture 73 2.4 Cell wall biosynthesis and assembly 80 2.5 Growth and cell walls 90 2.6 Cell differentiation 99 2.7 Cell walls as sources of food, feed, fiber, and fuel, and their genetic improvement 108 Summary 110 3 Membrane Transport 111 Introduction 111 3.1 Overview of plant membrane transport systems 111 3.2 Pumps 120 3.3 Ion channels 128 3.4 Cotransporters 142 3.5 Water transport through aquaporins 146 Summary 148 4 Protein Sorting and Vesicle Traffic 151 Introduction 151 4.1 The cellular machinery of protein sorting 151 4.2 Targeting proteins to the plastids 153 4.3 Targeting proteins to mitochondria 157 4.4 Targeting proteins to peroxisomes 159 4.5 Transport in and out of the nucleus 160 4.6 ER is the secretory pathway port of entry and a protein nursery 161 4.7 Protein traffic and sorting in the secretory pathway: the ER 175 4.8 Protein traffic and sorting in the secretory pathway: the Golgi apparatus and beyond 182 4.9 Endocytosis and endosomal compartments 188 Summary 189 5 The Cytoskeleton 191 Introduction 191 5.1 Introduction to the cytoskeleton 191 5.2 Actin and tubulin gene families 194 5.3 Characteristics of actin filaments and microtubules 196 5.4 Cytoskeletal accessory proteins 202 5.5 Observing the cytoskeleton: Statics and dynamics 207 5.6 Role of actin filaments in directed intracellular movement 210 5.7 Cortical microtubules and expansion 216 5.8 The cytoskeleton and signal transduction 219 5.9 Mitosis and cytokinesis 222 Summary 238 CELL REPRODUCTION 6 Nucleic Acids 240 Introduction 240 6.1 Composition of nucleic acids and synthesis of nucleotides 240 6.2 Replication of nuclear DNA 245 6.3 DNA repair 250 6.4 DNA recombination 255 6.5 Organellar DNA 260 6.6 DNA transcription 268 6.7 Characteristics and functions of RNA 270 6.8 RNA processing 278 Summary 288 7 Amino Acids 289 Introduction 289 7.1 Amino acid biosynthesis in plants: research and prospects 289 7.2 Assimilation of inorganic nitrogen into N-transport amino acids 292 7.3 Aromatic amino acids 302 7.4 Aspartate-derived amino acids 318 7.5 Branched-chain amino acids 326 7.6 Glutamate-derived amino acids 330 7.7 Histidine 333 Summary 336 8 Lipids 336 Introduction 337 8.1 Structure and function of lipids 337 8.2 Fatty acid biosynthesis 344 8.3 Acetyl-CoA carboxylase 348 8.4 Fatty acid synthase 350 8.5 Desaturation and elongation of C16 and C18 fatty acids 352 8.6 Synthesis of unusual fatty acids 360 8.7 Synthesis of membrane lipids 365 8.8 Function of membrane lipids 373 8.9 Synthesis and function of extracellular lipids 382 8.10 Synthesis and catabolism of storage lipids 389 8.11 Genetic engineering of lipids 395 Summary 400 9 Genome Structure and Organization 401 Introduction 401 9.1 Genome structure: a 21st]century perspective 401 9.2 Genome organization 404 9.3 Transposable elements 416 9.4 Gene expression 422 9.5 Chromatin and the epigenetic regulation of gene expression 430 Summary 436 10 Protein Synthesis, Folding, and Degradation 438 Introduction 438 10.1 Organellar compartmentalization of protein synthesis 438 10.2 From RNA to protein 439 10.3 Mechanisms of plant viral translation 447 10.4 Protein synthesis in plastids 450 10.5 Post-translational modification of proteins 457 10.6 Protein degradation 463 Summary 475 11 Cell Division 476 Introduction 476 11.1 Animal and plant cell cycles 476 11.2 Historical perspective on cell cycle research 477 11.3 Mechanisms of cell cycle control 482 11.4 The cell cycle in action 488 11.5 Cell cycle control during development 497 Summary 506 ENERGY FLOW 12 Photosynthesis 508 Introduction 508 12.1 Overview of photosynthesis 508 12.2 Light absorption and energy conversion 511 12.3 Photosystem structure and function 519 12.4 Electron transport pathways in chloroplast membranes 529 12.5 ATP synthesis in chloroplasts 537 12.6 Organization and regulation of photosynthetic complexes 540 12.7 Carbon reactions: the Calvin-Benson cycle 542 12.8 Rubisco 548 12.9 Regulation of the Calvin-Benson cycle by light 551 12.10 Variations in mechanisms of CO 2 fixation 557 Summary 565 13 Carbohydrate Metabolism 567 Introduction 567 13.1 The concept of metabolite pools 570 13.2 The hexose phosphate pool: a major crossroads in plant metabolism 571 13.3 Sucrose biosynthesis 573 13.4 Sucrose metabolism 577 13.5 Starch biosynthesis 580 13.6 Partitioning of photoassimilates between sucrose and starch 587 13.7 Starch degradation 593 13.8 The pentose phosphate/triose phosphate pool 597 13.9 Energy and reducing power for biosynthesis 601 13.10 Sugar-regulated gene expression 606 Summary 608 14 Respiration and Photorespiration 610 Introduction 610 14.1 Overview of respiration 610 14.2 Citric acid cycle 613 14.3 Plant mitochondrial electron transport 620 14.4 Plant mitochondrial ATP synthesis 632 14.5 Regulation of the citric acid cycle and the cytochrome pathway 634 14.6 Integration of the cytochrome pathway and nonphosphorylating pathways 635 14.7 Interactions between mitochondria and other cellular compartments 639 14.8 Biochemical basis of photorespiration 646 14.9 The photorespiratory pathway 648 14.10 Role of photorespiration in plants 652 Summary 655 METABOLIC AND DEVELOPMENTAL INTEGRATION 15 Long]Distance Transport 658 Introduction 658 15.1 Selection pressures and long-distance transport systems 658 15.2 Cell biology of transport modules 664 15.3 Short-distance transport events between xylem and nonvascular cells 668 15.4 Short-]distance transport events between phloem and nonvascular cells 673 15.5 Whole-plant organization of xylem transport 691 15.6 Whole-plant organization of phloem transport 696 15.7 Communication and regulation controlling phloem transport events 705 Summary 710 16 Nitrogen and Sulfur 711 Introduction 711 16.1 Overview of nitrogen in the biosphere and in plants 711 16.2 Overview of biological nitrogen fixation 715 16.3 Enzymology of nitrogen fixation 715 16.4 Symbiotic nitrogen fixation 718 16.5 Ammonia uptake and transport 735 16.6 Nitrate uptake and transport 735 16.7 Nitrate reduction 739 16.8 Nitrite reduction 744 16.9 Nitrate signaling 745 16.10 Interaction between nitrate assimilation and carbon metabolism 745 16.11 Overview of sulfur in the biosphere and plants 746 16.12 Sulfur chemistry and function 747 16.13 Sulfate uptake and transport 750 16.14 The reductive sulfate assimilation pathway 752 16.15 Cysteine synthesis 755 16.16 Synthesis and function of glutathione and its derivatives 758 16.17 Sulfated compounds 763 16.18 Regulation of sulfate assimilation and interaction with nitrogen and carbon metabolism 764 Summary 767 17 Biosynthesis of Hormones 769 Introduction 769 17.1 Gibberellins 769 17.2 Abscisic acid 777 17.3 Cytokinins 785 17.4 Auxins 795 17.5 Ethylene 806 17.6 Brassinosteroids 810 17.7 Polyamines 818 17.8 Jasmonic acid 821 17.9 Salicylic acid 826 17.10 Strigolactones 830 Summary 833 18 Signal Transduction 834 Introduction 834 18.1 Characteristics of signal perception, transduction, and integration in plants 834 18.2 Overview of signal perception at the plasma membrane 838 18.3 Intracellular signal transduction, amplification, and integration via second messengers and MAPK cascades 843 18.4 Ethylene signal transduction 847 18.5 Cytokinin signal transduction 850 18.6 Integration of auxin signaling and transport 852 18.7 Signal transduction from phytochromes 857 18.8 Gibberellin signal transduction and its integration with phytochrome signaling during seedling development 861 18.9 Integration of light, ABA, and CO2 signals in the regulation of stomatal aperture 866 18.10 Prospects 870 Summary 870 19 Molecular Regulation of Reproductive Development 872 Introduction 872 19.1 The transition from vegetative to reproductive development 872 19.2 The molecular basis of flower development 881 19.3 The formation of male gametes 889 19.4 The formation of female gametes 897 19.5 Pollination and fertilization 902 19.6 The molecular basis of self]incompatibility 908 19.7 Seed development 913 Summary 923 20 Senescence and Cell Death 925 Introduction 925 20.1 Types of cell death 925 20.2 PCD during seed development and germination 930 20.3 Cell death during the development of secretory bodies, defensive structures and organ shapes 932 20.4 PCD during reproductive development 937 20.5 Senescence and PCD in the terminal development of leaves and other lateral organs 940 20.6 Pigment metabolism in senescence 948 20.7 Macromolecule breakdown and salvage of nutrients in senescence 951 20.8 Energy and oxidative metabolism during senescence 957 20.9 Environmental influences on senescence and cell death I: Abiotic interactions 961 20.10 Environmental influences on senescence and cell death II: PCD responses to pathogen attack 964 20.11 Plant hormones in senescence and defense-related PCD 974 Summary 982 PLANT ENVIRONMENT AND AGRICULTURE 21 Responses to Plant Pathogens 984 Introduction 984 21.1 Pathogens, pests, and disease 984 21.2 An overview of immunity and defense 985 21.3 How pathogens and pests cause disease 989 21.4 Preformed defenses 1009 21.5 Induced defense 1012 21.6 Effector-triggered immunity, a second level of induced defense 1022 21.7 Other sources of genetic variation for resistance 1032 21.8 Local and systemic defense signaling 1033 21.9 Plant gene silencing confers virus resistance, tolerance, and attenuation 1042 21.10 Control of plant pathogens by genetic engineering 1044 Summary 1050 22 Responses to Abiotic Stress 1051 Introduction 1051 22.1 Plant responses to abiotic stress 1051 22.2 Physiological and cellular responses to water deficit 1054 22.3 Gene expression and signal transduction in response to dehydration 1061 22.4 Freezing and chilling stress 1068 22.5 Flooding and oxygen deficit 1076 22.6 Oxidative stress 1085 22.7 Heat stress 1094 22.8 Crosstalk in stress responses 1097 Summary 1099 23 Mineral Nutrient Acquisition, Transport, and Utilization 1101 Introduction 1101 23.1 Overview of essential mineral elements 1102 23.2 Mechanisms and regulation of plant K+ transport 1103 23.3 Phosphorus nutrition and transport 1113 23.4 The molecular physiology of micronutrient acquisition 1118 23.5 Plant responses to mineral toxicity 1127 Summary 1131 24 Natural Products 1132 Introduction 1132 24.1 Terpenoids 1133 24.2 Biosynthesis of the basic five-carbon unit 1135 24.3 Repetitive additions of C5 units 1138 24.4 Formation of parent carbon skeletons 1141 24.5 Modification of terpenoid skeletons 1143 24.6 Metabolic engineering of terpenoid production 1145 24.7 Cyanogenic glycosides 1146 24.8 Cyanogenic glycoside biosynthesis 1152 24.9 Functions of cyanogenic glycosides 1157 24.10 Glucosinolates 1158 24.11 Alkaloids 1159 24.12 Alkaloid biosynthesis 1164 24.13 Biotechnological application of alkaloid biosynthesis research 1171 24.14 Phenolic compounds 1178 24.15 Phenolic biosynthesis 1185 24.16 The phenylpropanoid-acetate pathway 1188 24.17 The phenylpropanoid pathway 1195 24.18 Universal features of phenolic biosynthesis 1202 24.19 Evolution of secondary pathways 1205 Summary 1206 Further reading 1207 Index 1222

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Book SynopsisExploring themes that preoccupied Albert Camus--absurdity, silence, revolt, fidelity, and moderation--Robert Zaretsky portrays a moralist who refused to be fooled by the nobler names we assign to our actions, and who pushed himself, and those about him, to challenge the status quo. For Camus, rebellion against injustice is the human condition.Trade ReviewEnlightening… Zaretsky probes Camus’s multifaceted sensibility. -- John Taylor * Times Literary Supplement *A Life Worth Living departs from the chronological approach… Instead, Zaretsky tells [Camus’s] story according to the five themes that preoccupied his life and work: absurdity, silence, measure, fidelity, and revolt. The result is a much more human portrait of a man whose life is often reduced to a meditation on the bleakness of absurdism. By chronicling the ideas rather than the events of Camus’s life, Zaretsky shows that ‘Camus was all too human: an obvious point that our desperate need for heroes, especially now, often obscures.’ -- Linda Kinstler * New Republic *This is a wonderful introduction to Albert Camus and an overview for those who have already read him. Zaretsky effortlessly explores sometimes difficult concepts in an accessible, even conversational study that blends significant aspects of Camus’ life—his Algerian background, life in France, the importance of the war; the Resistance and the TB that afflicted him for much of his life—with his works, in such a way that it offers a strong sense of the writings and the writer… The result is a concise portrait of an intellectual deeply concerned with ethics, but with an abiding love of the sensual, and life’s beauty. -- Steven Carroll * Sydney Morning Herald *In the beautifully titled and beautifully written A Life Worth Living: Albert Camus and the Quest for Meaning, historian Robert Zaretsky considers Camus’s lifelong quest to shed light on the absurd condition, his ‘yearning for a meaning or a unity to our lives,’ and its timeless yet increasingly timely legacy… A remarkable read in its entirety. -- Maria Popova * Brain Pickings *Some writers are lucky enough to be remembered 50 years after they die, and a few are even beloved. What is vanishingly rare, however, is for a long-dead writer to remain controversial. Albert Camus is one of those exceptions, a writer who still has the power to ignite political passions, because he managed to incorporate the history of the 20th century so deeply into his writing… Readers new to Camus will find in Zaretsky a deeply informed and warmly admiring guide. -- Adam Kirsch * Daily Beast *It is extremely limiting to think of Albert Camus as an existentialist philosopher of the absurd. While Camus was never trained as a philosopher, Zaretsky demonstrates that many other themes marked Camus’s thought. Camus was a highly principled person, and a strong advocate for justice… Camus’s voice still has resonance. * Christian Century *More than a half-century after his untimely death in 1960 at age 46, Camus continues to engage us… Zaretsky provides thorough and rigorous examinations into the author’s life and work while also helping us understand the disquiet of a man who gave readers seeking sustenance in art some of the most lyrical and encouraging advice in 20th-century literature. -- Kevin Rabalais * The Australian *For a good short study of [Camus’s] life, work and philosophy, try Robert Zaretsky’s A Life Worth Living: Albert Camus and the Quest for Meaning. -- Stephen Romei * The Australian *The centenary [of Camus’s birth] has spurred books, papers and reconsideration of his contributions to literature and his times. Robert Zaretsky’s is one of the best. The Algerian-French Nobel Prize winner, known for novels such as The Stranger and The Plague and essays including ‘The Myth of Sisyphus’ and ‘Reflections on the Guillotine,’ wrote piercingly and urgently about facing injustice, the need for revolt, confronting absurdity and the search for meaning. Zaretsky underscores why the ideas of Camus, who died in a car accident in 1960, remain important today. -- Peter M. Gianotti * Newsday *Offer[s] concise, eloquent, and learned treatments of the life and work of the French-Algerian moralist… Camus contained multitudes and…Zaretsky returns to this truth again and again. -- Barry Lenser * PopMatters *What emerges is the paradoxical portrait of an exceptional everyman: imperfect, plagued by doubt, melancholic, flawed, but also sensitive, hopeful, passionate and heroic… A Life Worth Living reveals much about Camus, the times he lived in and wrote against… Those looking for a better understanding of the context in which Camus penned his books and essays on murder, torture, suicide, silence and rebellion will find much to ruminate on… Zaretsky is especially adept at seamlessly weaving Camus’ own words into the text, and the result is that the reader feels almost as though she is reading Camus as opposed to a biographer… Zaretsky’s book is good reading for dark times, a wonderfully written monograph about an absurd hero whose life serves as a reminder that, ‘while we have no reason to hope, we must also never despair.’ -- Jon Morris * PopMatters *Zaretsky identifies Camus as a moralist, not a moralizer, one who poses questions rather than imposes answers. Like such courageous moralists as Montaigne, Voltaire, Hugo and Zola, Camus extended his private quest for truth into the public sphere… In pithy prose worthy of his subject, Zaretsky reminds us that, in an age of suicide bombings and state-sanctioned murder, Camus is an author worth reading. -- Steven G. Kellman * Texas Observer *Zaretsky brings to light in this wonderfully readable intellectual biography of the iconoclastic pied noir the continued relevance of Camus in contemporary life… This volume offers a portrait of Camus not simply as an existentialist (as is typical) but rather as a ‘Mediterranean humanist’ disillusioned by the world’s failure to live up to its purest ideals. -- L. A. Wilkinson * Choice *Zaretsky delivers a lucid perspective on the intellectual provenance of the writer’s moral philosophy through an examination of Notebooks, The Myth of Sisyphus, The Rebel, The Plague, and The Stranger. His scrutiny converges on Camus’s sense of the fundamental absurdity of life and why suicide is not an option; his sensitivity to the positive and negative aspects of silence; his understanding of the human condition; and his conviction that rebellious response to injustice be measured, not extreme… An admirable, comprehensible introduction to Camus. -- Lonnie Weatherby * Library Journal *Zaretsky offers an invigorating blend of history, criticism, and biography in a stirring reassessment of the Nobel Prize–winning existentialist writer Albert Camus… Zaretsky demonstrates Camus’s commitment to justice and the joy of existence, evident in his rejection of Soviet communism, as well as his principled opposition to terrorism and capital punishment. Camus emerges as a compassionate thinker who always ruthlessly interrogated his own beliefs and assumptions. Zaretsky’s elegant prose and passion for the subject, meanwhile, will inspire both novices in existentialism as well as experts to revisit the contributions of this great French writer. * Publishers Weekly *A marvelously wise, concise, and adventurous exploration of Camus, his intellectual antecedents, the battles that raged around him, and his continuing power to unsettle and inspire us to this day. -- Sarah Bakewell, author of How to Live: A Life of Montaigne

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Book SynopsisThis workbook with digital access is the perfect companion for the coursebook. The resource reinforces learning, promotes application of theory and helps students practise the essential skills of handling data, evaluating information and problem solving. The workbook includes a range of formative exercises, mapped directly onto the coursebook. For each chapter, a range of exercises builds on the topics and concepts that have been introduced. It includes exam command terms throughout to help familiarise students with their appropriate use. Questions include a skills focus that require students to draw graphs or provide workings.

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Book SynopsisTo understand modern principles of sustainable management and the conservation of wildlife species requires intimate knowledge about demography, animal behavior, and ecosystem dynamics. This book weaves together these disparate elements for senior undergraduate and graduate students.Trade Review“I recommend the book unreservedly to wildlife managers, park rangers, biological resource managers, and those working in ecotourism.” (Tahrcountry, 10 August 2014)Table of ContentsPreface xi About the companion website xiii 1 Introduction: goals and decisions 1 1.1 How to use this book 1 1.2 What is wildlife conservation and management? 2 1.3 Goals of management 3 1.4 Hierarchies of decision 6 1.5 Policy goals 7 1.6 Feasible options 7 1.7 Summary 8 Part 1 Wildlife ecology 9 2 Food and nutrition 11 2.1 Introduction 11 2.2 Constituents of food 11 2.3 Variation in food supply 14 2.4 Measurement of food supply 17 2.5 Basal metabolic rate and food requirement 20 2.6 Morphology of herbivore digestion 23 2.7 Food passage rate and food requirement 26 2.8 Body size and diet selection 27 2.9 Indices of body condition 28 2.10 Summary 33 3 Home range and habitat use 35 3.1 Introduction 35 3.2 Estimating home range size and utilization frequency 36 3.3 Estimating habitat availability and use 38 3.4 Selective habitat use 40 3.5 Using resource selection functions to predict population response 42 3.6 Sources of variation in habitat use 42 3.7 Movement within the home range 45 3.8 Movement among home ranges 48 3.9 Summary 51 4 Dispersal, dispersion, and distribution 53 4.1 Introduction 53 4.2 Dispersal 53 4.3 Dispersion 55 4.4 Distribution 56 4.5 Distribution, abundance, and range collapse 61 4.6 Species reintroductions or invasions 62 4.7 Summary 67 5 Population growth and regulation 69 5.1 Introduction 69 5.2 Rate of increase 69 5.3 Geometric or exponential population growth 73 5.4 Stability of populations 73 5.5 The theory of population limitation and regulation 76 5.6 Evidence for regulation 81 5.7 Applications of regulation 85 5.8 Logistic model of population regulation 86 5.9 Stability, cycles, and chaos 88 5.10 Intraspecific competition 90 5.11 Interactions of food, predators, and disease 93 5.12 Summary 93 6 Competition and facilitation between species 95 6.1 Introduction 95 6.2 Theoretical aspects of interspecific competition 96 6.3 Experimental demonstrations of competition 98 6.4 The concept of the niche 103 6.5 The competitive exclusion principle 106 6.6 Resource partitioning and habitat selection 106 6.7 Competition in variable environments 113 6.8 Apparent competition 113 6.9 Facilitation 114 6.10 Applied aspects of competition 119 6.11 Summary 122 7 Predation 123 7.1 Introduction 123 7.2 Predation and management 123 7.3 Definitions 123 7.4 The effect of predators on prey density 124 7.5 The behavior of predators 125 7.6 Numerical response of predators to prey density 129 7.7 The total response 130 7.8 Behavior of the prey 136 7.9 Summary 138 8 Parasites and pathogens 139 8.1 Introduction and definitions 139 8.2 Effects of parasites 139 8.3 The basic parameters of epidemiology 140 8.4 Determinants of spread 143 8.5 Endemic pathogens 144 8.6 Endemic pathogens: synergistic interactions with food and predators 144 8.7 Epizootic diseases 146 8.8 Emerging infectious diseases of wildlife 147 8.9 Parasites and the regulation of host populations 150 8.10 Parasites and host communities 151 8.11 Parasites and conservation 152 8.12 Parasites and control of pests 155 8.13 Summary 156 9 Consumer–resource dynamics 157 9.1 Introduction 157 9.2 Quality and quantity of a resource 157 9.3 Kinds of resource 157 9.4 Consumer–resource dynamics: general theory 158 9.5 Kangaroos and their food plants in semi-arid Australian savannas 161 9.6 Wolf–moose–woody plant dynamics in the boreal forest 167 9.7 Other population cycles 172 9.8 Summary 175 10 The ecology of behavior 177 10.1 Introduction 177 10.2 Diet selection 177 10.3 Optimal patch or habitat use 183 10.4 Risk-sensitive habitat use 186 10.5 Social behavior and foraging 187 10.6 Summary 190 11 Climate change and wildlife 191 11.1 Introduction 191 11.2 Evidence for climate change 191 11.3 Wildlife responses to climate change 192 11.4 Mechanisms of response to climate change 196 11.5 Complex ecosystem responses to climate change 199 11.6 Summary 201 Part 2 Wildlife conservation and management 203 12 Counting animals 205 12.1 Introduction 205 12.2 Total counts 205 12.3 Sampled counts: the logic 207 12.4 Sampled counts: methods and arithmetic 212 12.5 Indirect estimates of population size 220 12.6 Indices 227 12.7 Harvest-based population estimates 228 12.8 Summary 231 13 Age and stage structure 233 13.1 Introduction 233 13.2 Demographic rates 233 13.3 Direct estimation of life table parameters 235 13.4 Indirect estimation of life table parameters 236 13.5 Relationships among parameters 238 13.6 Age-specific population models 239 13.7 Elasticity of matrix models 242 13.8 Stage-specific models 243 13.9 Elasticity of the loggerhead turtle model 245 13.10 Short-term changes in structured populations 246 13.11 Environmental stochasticity and age-structured populations 246 13.12 Summary 249 14 Experimental management 251 14.1 Introduction 251 14.2 Differentiating success from failure 251 14.3 Technical judgments can be tested 252 14.4 The nature of the evidence 255 14.5 Experimental and survey design 257 14.6 Some standard analyses 262 14.7 Summary 271 15 Model evaluation and adaptive management 273 15.1 Introduction 273 15.2 Fitting models to data and estimation of parameters 274 15.3 Measuring the likelihood of the observed data 276 15.4 Evaluating the likelihood of alternate models using AIC 278 15.5 Adaptive management 281 15.6 Summary 284 16 Population viability analysis 285 16.1 Introduction 285 16.2 Environmental stochasticity 285 16.3 PVA based on the exponential growth model 286 16.4 PVA based on the diffusion model 287 16.5 PVA based on logistic growth 290 16.6 Demographic stochasticity 291 16.7 Estimating both environmental and demographic stochasticity 294 16.8 PVA based on demographic and environmental stochasticity 296 16.9 Strengths and weaknesses of PVA 296 16.10 Extinction caused by environmental change 298 16.11 Extinction threat due to introduction of exotic predators or competitors 298 16.12 Extinction threat due to unsustainable harvesting 300 16.13 Extinction threat due to habitat loss 302 16.14 Summary 302 17 Conservation in practice 305 17.1 Introduction 305 17.2 How populations go extinct 305 17.3 How to prevent extinction 315 17.4 Rescue and recovery of near-extinctions 316 17.5 Conservation in National Parks and reserves 317 17.6 Community conservation outside National Parks and reserves 322 17.7 International conservation 323 17.8 Summary 324 18 Wildlife harvesting 325 18.1 Introduction 325 18.2 Fixed-quota harvesting strategy 325 18.3 Fixed-proportion harvesting strategy 329 18.4 Harvesting in practice: dynamic variation in quotas or effort 332 18.5 No-harvest reserves 334 18.6 Age- or sex-biased harvesting 335 18.7 Commercial harvesting 340 18.8 Bioeconomics 340 18.9 Game cropping and the discount rate 344 18.10 Summary 346 19 Wildlife control 347 19.1 Introduction 347 19.2 Definitions 347 19.3 Effects of control 348 19.4 Objectives of control 348 19.5 Determining whether control is appropriate 349 19.6 Methods of control 350 19.7 Summary 356 20 Evolution and conservation genetics 357 20.1 Introduction 357 20.2 Maintenance of genetic variation 358 20.3 Natural selection 359 20.4 Natural selection and life history tradeoffs 361 20.5 Natural selection due to hunting 363 20.6 Natural selection due to fishing 365 20.7 Selection due to environmental change 367 20.8 Ecological dynamics due to evolutionary changes 372 20.9 Heterozygosity 374 20.10 Genetic drift and mutation 375 20.11 Inbreeding depression 376 20.12 How much genetic variation is needed? 377 20.13 Effective population size 378 20.14 Effect of sex ratio 379 20.15 How small is too small? 380 20.16 Summary 380 21 Habitat loss and metapopulation dynamics 381 21.1 Introduction 381 21.2 Habitat loss and fragmentation 381 21.3 Ecological effects of habitat loss 384 21.4 Metapopulation dynamics 386 21.5 Territorial metapopulations 389 21.6 Mainland–island metapopulations 390 21.7 Source–sink metapopulations 391 21.8 Metacommunity dynamics of competitors 392 21.9 Metacommunity dynamics of predators and prey 393 21.10 Corridors 394 21.11 Summary 398 22 Ecosystem management and conservation 399 22.1 Introduction 399 22.2 Definitions 400 22.3 Gradients of communities 400 22.4 Niches 400 22.5 Food webs and intertrophic interactions 400 22.6 Community features and management consequences 402 22.7 Multiple states 404 22.8 Regulation of top-down and bottom-up processes 405 22.9 Ecosystem consequences of bottom-up processes 407 22.10 Ecosystem disturbance and heterogeneity 408 22.11 Ecosystem management at multiple scales 410 22.12 Biodiversity 411 22.13 Island biogeography and dynamic processes of diversity 413 22.14 Ecosystem function 415 22.15 Summary 417 Appendices 419 Glossary 423 References 435 Index 489

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Book SynopsisTable of ContentsList of Case Studies ix Preface x Acknowledgments xiii About the Companion Website xiv Part I Biodiversity and Its Importance 3 1 Conservation and Conservation Biology 4 What is Conservation? 4 A Brief History of Conservation 6 An Overview of Conservation Ethics 10 What is Conservation Biology? 13 A Brief History of Conservation Biology 15 Summary 19 2 What is Biodiversity? 21 Species, Genes, and Ecosystems 22 Structure and Function 23 Measuring Biodiversity 24 The Mismeasure of Biodiversity 26 Biodiversity and Spatial Scales 26 Biodiversity Verbs 30 The Related Concepts of “Integrity” and “Sustainability” 31 Summary 33 3 Species Diversity 35 What is a Species? 35 How Many Species Are There? 37 The Intrinsic Value of Species and Their Conservation Status 39 The Instrumental Values of Species 46 The Uniqueness Value of Species 62 Summary 65 4 Ecosystem Diversity 67 What is an Ecosystem? 67 The Values of Ecosystems 71 Ecosystem Diversity and Species Diversity 80 Ecosystems and Landscapes 85 Summary 88 5 Genetic Diversity 90 What is Genetic Diversity? 90 The Importance of Genetic Diversity 101 Processes That Diminish Genetic Diversity 110 Cultural Diversity 117 Summary 124 Part II Threats to Biodiversity 129 6 Mass Extinctions and Global Change 130 Extinction Episodes of the Past 131 Estimating the Current Rate of Extinction 135 The Recent History of Global Climate Change 139 How Did We Get to this Point? What is the Way Ahead? 150 Summary 152 7 Extinction Processes 154 Why Are Some Species More Vulnerable to Extinction than Others? 154 Populations 161 Population Viability Analysis 166 Summary 177 8 Ecosystem Degradation and Loss 179 Contamination 183 Roads, Dams, and Other Structures 189 Earth, Fire, Water 195 Deforestation 198 Desertification 204 Draining, Dredging, Damming, Etc. 206 Fragmentation 211 Summary 221 9 Overexploitation 223 The Long History of Overexploitation 223 Types of Exploitation 230 Consequences of Overexploitation 238 Some Final Perspectives on Exploitation 243 Summary 249 10 Invasive Exotics 251 How Do Species Move? 252 Impacts of Invasive Exotics 261 Success Rates 269 Irony 271 Summary 277 Part III Maintaining Biodiversity 279 11 Protecting Ecosystems 280 Reserve Selection 281 Reserve Design 290 Reserve Management 299 Summary 307 12 Sustaining Ecosystems 309 Forestry 310 Livestock Grazing 316 Fisheries 322 Ecological Management 325 Restoring Ecosystems 325 Summary 337 13 Managing Populations 338 Providing Resources 339 Controlling Threats 348 Direct Manipulations 364 Epilogue 376 Summary 378 14 Conservation near People 381 Cultivated Ecosystems 382 Built Ecosystems 391 Zoos and Gardens 396 The Ex Situ–In Situ Interface 405 Conservation of Domesticated Species 410 Summary 414 Part IV The Human Factors 419 15 Social Factors 420 Values Differ 420 Describing Values 431 Values Change 434 Summary 443 16 Economics 445 The Benefits 446 The Costs 456 The Distribution of Benefits and Costs 459 Problems and Solutions 461 Summary 481 17 Politics and Action 483 Setting Priorities for Action 483 Rights and Responsibilities 493 International Agencies 496 Governments 501 Nongovernmental Organizations 505 Corporations 508 Communities 510 Individuals 512 Summary 517 Epilogue 520 Glossary 522 Literature Cited 536 Species Index 631 Subject Index 643

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Book SynopsisTable of ContentsContributors Foreword Preface Part 1 Introduction 1 What is Clinical Genetics and Genomic medicine? 2 Inheritance 3 Cytogenetic & Molecular genetic techniques 4 How to read a genetic test report 5 Genetic Counselling Part 2 Cardiology 6 Structure and Congenital Heart Disease 7 Ischamic Heart Disease 8 Cardiomyopthies 9 Arrhythmias and Sudden Cardiac Death Part 3 Dermatology 10 Tuberous Sclerosis 11 Gorlin syndrome 12 Dariers Disease 13 Lamellar Icthyosis 14 Mal De Meleda 15 Cutaneous Porphyria 16 Epidermolysis Bullosa 17 Cowden syndrome and Cowden-like syndrome 18 Muir-Torre Syndrome 18 X-linked Icthyosis 20 Birt-Hogg-Dube Part 4 Endocrinology 21 Disorders of sexual development and differentiation 22 Congenital adrenal hyperplasia 23 Androgen Insensitivity Syndrome 24 Klinefelters syndrome 25 Turners Syndrome 26 Diabetes Mellitus 27 Diabetes Insipidus 28 Fabry-Anderson Part 5 Metabolic 29 Introduction to the genetics of metabolic disorders 30 Overview of disorders of amino acid metabolism 31 Overview of disorders of carbohydrate metabolism 32 Overview of disorders of lipid metabolism 33 Overview of peroxisomal disorders 34 Disorders of purine and pyrimidine metabolism Part 6 Gastroenterology 35 IBD 36 Wilsons 37 Heamochromatosis 38 Coeliac Disease 39 Pancreatic cancer Part 7 Haematology 40 Malignant Haematology 41 Non malignanat Haematology Part 8 Immunology 42 Severe combined immunodeficiency 43 DNA repair defects 44 Congenital abnormalities affecting the development of the thymus 45 Common variable immunodeficiency 46 X-linked (and autosomal recessive) agammaglobulinaemia 47 Wiskott-Aldrich syndrome 48 Hyperimmunoglobulin M syndromes 49 Hyperimmunoglobulin E syndrome 50 Chronic mucocutaneous candidiasis 51 Genetic disorders associated with immune dysregulation and/or autoimmunity 52 Genetic disorders associated with familial haemophagocytic lymphohistiocytosis 53 Mendelian susceptibility to mycobacterial disease 54 Chronic granulomatous disease 55 Defects in leukocyte migration 56 Defects of Toll like receptors and their signalling pathways 57 Complement deficiencies 58 Autoinflammatory diseases and periodic fever syndromes Part 9 Neurology 59 SMA 60 MND/ALS 61 Fragile X 62 HD 63 Dementia 64 Parkinsons 65 Myotonic dystrophy Part 10 Paediatrics and Obstetrics 66 Fetal anomaly screening 67 Prenatal diagnostic testing and Preimplantation Genetic Diagnosis 68 Edwards ' Syndrome 69 Patau syndrome 70 Williams syndrome 71 Di George syndrome Part 11 Oncology 72 Introduction to Cancer 73 Neurofibromatosis 74 Urological Cancers 75 Peutz-Jegher Syndrome 76 Von Hippel-Lindau 77 Inherited Bowel (Lower GI) Cancers 78 Inherited upper GI cancers 79 Inherited Breast Cancer 80 Retinoblastoma 81 Multiple Endocrine Neoplasia Part 12 Opthalmology 82 Congential and Childhood Cataracts 83 Colour blindness and Achromatopsia 84 Retinitis Pigmentosa 85 Primary Congential Glaucoma 86 Bardet-Biedl Syndrome Part 13 Renal 87 PCKD 88 Nephronophthisis 89 Medullary cystic kidney disease 90 Tuberous sclerosis 91 von Hippel-Lindau 92 Alport syndrome 93 Cystinosis 94 Cystinuria Part 14 MSK 95 Marfans 96 EDS 97 Congenital Limb Deficiencies 98 DMD 99 Charcot–Marie–Tooth (CMT) 100 Ankylosing Spondylitis 101 Skeletal dysplasias Glossary Index

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Book SynopsisBiology and Ecology of Fishes Immerse yourself in the world of fish ecology with the newest edition of this essential introduction The study of fish ecology has traditionally proceeded along two tracks: the first is more basic, concerned with the anatomy, physiology and theoretical ecology of fish, and the second is more practical, concerning itself with fish populations, management, and habitats. Many fish researchers have come to view this distinction as artificial, and to develop a new study of fish that combines both tracks in a single holistic approach. It has never been more critical for introductory textbooks to represent this combined study in order to prepare the next generation of fish biologists and fishery scientists. Biology and Ecology of Fishes meets this need with a textbook that incorporates both biology and population management. Beginning with a general introduction to aquatic life and ecosystems, this book covers anatomical, environmental, and ethological topics to give a thoroughly rounded view of its subject, promising to serve as the fundamental introduction to multidisciplinary fish studies. Readers of the third edition of Biology and Ecology of Fishes will also find: Detailed coverage of subjects including growth and bioenergetics, feeding and predation, mortality and recruitment and moreIncreased attention to stressors of fish populations and communitiesNew and revised chapters that introduce quantitative methods and present emerging issues facing fish populations and communities Biology and Ecology of Fishes is a useful overview for advanced undergraduate and graduate students studying fish ecology or fishery biology, as well as a reference for researchers and professionals in fish ecology, fish population management, and related fields.Table of ContentsPreface vii Acknowledgments ix Part 1 Introduction 1 1 Introduction to Aquatic Ecosystems 3 2 Fish Diversity 14 3 Morphology and Evolution of Fishes 21 Part 2 Bioenergetics and Growth 33 4 Balanced Energy Equation 35 5 Metabolism and Other Energy Uses 42 6 Patterns of Growth and Reproduction 66 7 Estimating Growth and Condition of Fish 86 8 Bioenergetics Models 99 Part 3 Population Processes 115 9 Abundance and Size Structure of Fish Stocks 117 10 Mortality 131 11 Density- Dependence and Independence 142 12 Recruitment 153 13 Social Behavior 169 14 Competition 186 15 Positive Interactions 201 16 Movement and Habitat Use 210 Part 4 Feeding and Predation 229 17 Predation and Foraging Behavior 231 18 Optimal Foraging and Patch Use 246 19 Diet Composition and Ration in Nature 263 20 Predation Risk and Refuges 276 Part 5 Reproduction and Life Histories 295 21 Reproductive Traits 297 22 Reproductive Behavior and Spawning Migrations 306 23 Life- History Patterns and Reproductive Strategies 318 24 Ontogeny and Early Life of Fishes 332 Part 6 Fish Communities in Aquatic Ecosystems 349 25 Description and Measurement of Fish Communities 351 26 Aquatic Food Webs 364 27 Temperature and Fish Distributions 379 28 Fish Communities in Temperate Streams 391 29 Tropical Rivers 407 30 Fish Communities in Lakes 422 31 Marine Ecosystems 439 Part 7 Human Influences on Fish and Fisheries 453 32 Fisheries Harvest 455 33 Invasive Species 476 34 Aquaculture 489 35 Climate Change and Consequences for Fish 503 36 Conservation of Freshwater Fishes 519 Index 533

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Book SynopsisTable of ContentsPart I The Microbes 1 The Microbial World 1 14 Biogeochemical Cycles 521 15 Microbial Biotechnology 553 2 Bacteria and Archaea 35 3 Eukaryotic Microorganisms 97 4 Virology 133 5 Microbial Metabolism 171 Part II Microbial Genetics 6 Cultivating Microorganisms 231 7 DNA Replication and Gene Expression 269 8 Viral Replication Strategies 309 9 Bacterial Genetic Analysis and Manipulation 339 10 Microbial Genomics 377 11 Regulation of Gene Expression 407 Part III Microbial Physiology and Ecology 12 Microbial Ecosystems 441 13 Symbiotic Microbiome 481 Part IV Microbes and Disease 16 Introduction to Infectious Diseases 597 17 Clinical Microbiology and Immunology 635 18 Adaptive Immunity 671 19 Bacterial Pathogenesis 711 20 Viral Pathogenesis 761 21 Eukaryotic Pathogenesis 795 22 Control of Infectious Disease 827 23 The Microbiology of Food and Water 881 Appendix A Scientific Articles A- 1 Appendix B Microscopy A- 11 Appendix C Taxonomy and Nomenclature of Microbes A- 17 Appendix D Origin of Blood Cells A- 19 Glossary G- 1 Index I- 1

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Book SynopsisWriting Scientific Research Articles The new edition of the popular guide for novice and professional scientists alike, providing effective strategies and step-by-step advice for writing scientific papers for publicationFor scientists writing a research article for submission to an international peer-reviewed journal, knowing how to write can be as important as knowing what to write. Writing Scientific Research Articles: Strategy and Steps provides systematic guidance on writing effective scientific papers with the greatest chance for publication. Using clear language, this highly practical guide shows scientists how to apply their analysis and synthesis skills to produce a compelling research article and increase their competence in written communication of science. The third edition is fully revised to reflect changes in the review process and science journal publication. Incorporating current developments in technology and pedagogical practice, brand-new sections cover mapping and planning manuscripts, choosing results, systematic reviews, structured abstracts, and more. Updated material on referee criteria offers valuable insights on what journal editors and referees want to publish and why. Offering a hands-on approach to developing the academic writing skills of scientists in all disciplines and from all language backgrounds, Writing Scientific Research Articlesprovides a genre-based pedagogy and clear processes for writing each section of a manuscript across the full range of research article formats and funding applicationspresents tested strategies for responding to referee comments and developing discipline-specific language skills for manuscript writing and polishingpairs each learning step with updated practical exercises to develop writing and data presentation skills based on expert analysis of well-written papers, including provided example articlesincludes chapters on the difference between review papers and research papers, and on skill development using journal clubs and writing groupsfeatures a wealth of new information on topics including Open Access publishing, online reviews, and predatory conferences and journalsDesigned for use by individuals as a self-study guide or by groups working with an instructor, Writing Scientific Research Articles: Strategy and Steps is a must-have guide for early-career researchers with limited writing experience, scientists for whom English is an additional language, upper-level undergraduates and graduate students writing for publication, and STEM and English language professionals involved in teaching manuscript writing and publication skills and mentoring students andcolleagues.Table of ContentsPreface to the third edition ix Preface to the second edition xi Preface to the first edition xiii Section 1: A framework for success 1 1 How to use this book 3 1.1 Getting started with writing for international publication 3 1.2 Publishing in the international literature 4 1.3 Aims of the book 8 1.4 How the book is structured 9 1.5 How to use this book if you are. . . 10 2 Research article structures 13 2.1 Conventional article structures: AIMRaD and its variations 13 3 Reviewers’ criteria for evaluating manuscripts 19 3.1 Titles as content signposts 20 Section 2: When and how to write each article section 23 4 Results as a “story”: the key driver of an article 25 5 Results: turning data into knowledge 27 5.1 Designing figures 28 5.2 Designing tables 30 5.3 Figure legends and table titles 31 5.4 Supplementary material 33 5.5 Archiving data 34 6 Writing about results 35 6.1 Structure of Results sections 35 6.2 Functions of Results sentences 36 6.3 Verb tense in Results sections 36 7 The Methods section 39 7.1 Purpose of the Methods section 39 7.2 Organising Methods sections 40 7.3 Methods in supplementary material 41 7.4 Publishing methods papers 41 7.5 Use of passive and active verbs 41 8 The Introduction 47 8.1 Argument stages towards a compelling Introduction 47 8.2 Stage 1: Locating your project within an existing field of scientific research 50 8.3 Using references in Stages 2 and 3 51 8.4 Avoiding plagiarism when using others’ work 54 8.5 Stage 3: Indicating the gap or research niche 55 8.6 Stage 4: The statement of purpose or main activity 56 8.7 Stages 5 and 6: Highlighting benefit and mapping the article 57 8.8 Suggested process for drafting an Introduction 57 8.9 Editing for logical flow 58 9 The Discussion section 63 9.1 Important structural issues 63 9.2 Information elements to highlight the key messages 64 9.3 Negotiating the strength of claims 66 10 The title and keywords 69 10.1 Strategy 1: Provide as much relevant information as possible, but be concise 69 10.2 Strategy 2: Use carefully chosen keywords prominently 69 10.3 Strategy 3: Choose strategically – noun phrase, statement, or question? 70 10.4 Strategy 4: Avoid ambiguity in noun phrases 71 11 The Abstract and highlights 73 11.1 Why Abstracts are so important 73 11.2 Selecting additional keywords 73 11.3 Abstracts: typical information elements 73 11.4 Visual abstracts 75 11.5 “Highlights” and other significance or summary sections 75 12 Writing review articles 77 12.1 What editors want to publish 79 12.2 The “take‐home message” of a review 79 12.3 The structure of review articles 87 12.4 Visual elements in review articles: tables, figures, and boxes 89 12.5 Checklist for review article manuscripts 91 12.6 Systematic review articles 91 12.7 Submission and revision of review articles 93 Section 3: Getting your manuscript published 95 13 Submitting a manuscript 97 13.1 Five practices of successful authors 97 13.2 Understanding the peer‐review process 98 13.3 Understanding the editor’s role 99 13.4 The contributor’s covering letter 99 13.5 Understanding the reviewer’s role 101 13.6 Understanding the editor’s role (continued) 103 14 How to respond to peer reviews 105 14.1 Rules of thumb for responding to reviews 105 14.2 How to deal with manuscript rejection 106 14.3 How to deal with “conditional acceptance” or “revise and resubmit” 106 15 A process for preparing a manuscript 115 15.1 Manuscript mapping 116 15.2 Editing procedures 117 15.3 A pre‐review checklist 120 Section 4: Developing your writing and publication skills further 121 16 Skill‐development strategies for groups and individuals 123 16.1 Journal clubs 123 16.2 Writing groups 124 16.3 Selecting feedback strategies for different purposes 124 16.4 Becoming a reviewer 126 16.5 Training for responding to reviewers 127 17 Developing discipline‐specific English skills 129 17.1 Editor expectations of language use 129 17.2 Strategic (and acceptable!) language re‐use: sentence templates 130 17.3 More about noun phrases 133 17.4 Concordancing: a tool for developing your discipline‐specific English 134 17.5 Using the English articles (a/an, the) appropriately in science writing 138 17.6 Using “which” and “that” 141 18 Writing funding proposals 143 18.1 A process for preparing and submitting a funding proposal 144 18.2 Easy mistakes to make 147 Section 5: Provided example articles 149 19 PEA1: Kaiser et al. (2003) 151 20 PEA2: Britton-Simmons & Abbott (2008) 165 21 PEA3: Ganci et al. (2012) 177 Answer pages 191 Appendix: Measures of journal impact and quality 221 A.1 Journal impact 221 A.2 Using indices of journal quality 222 References 225 Index 229

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Book SynopsisEleanor Lawrence is a freelance science writer and editor, and co-author of Longman Dictionary of Environmental Science.Table of Contents Preface to the Sixteenth Edition Abbreviations Units and Conversions SI Prefixes Greek Alphabet Common Latin and Greek Noun Endings THE DICTIONARY Appendices 1. An Outline of the Plant Kingdom (Domain Eukarya) 2. An Outline of the Kingdom Fungi (Domain Eukarya) 3. An Outline of the Animal Kingdom (Domain Eukarya) 4. An Outline of the Protists (Domain Eukarya) 5. An Outline of the Domain Bacteria 6. An Outline of the Domain Archaea 7. Virus Families 8. Geological Timescale 9. Etymological Origins of Some Common Word Elements in Biology

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Book SynopsisAllan Jones, Chancellor's Award Fellow in Ecology, Environmental Science and Zoology at the University of Dundee, UK.  Rob Reed, Emeritus Professor (Education and Science) at Central Queensland University, Australia.  Jonathan Weyers, Honorary Senior Lecturer at the University of Dundee, U

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Book SynopsisMartha R. Taylor has been teaching biology for more than 35 years. She earned her B.A. in biology from Gettysburg Collegeand her M.S. and Ph.D. in science education from Cornell University. At Cornell, Dr. Taylor has served as assistant director of the Office ofInstructional Support and has taught introductory biology for both majors andnonmajors. Most recently, she was a lecturer in the Learning Strategies Center, teaching supplemental biology courses. Her experience working with students inclassrooms, in laboratories, and with tutorials has increased her commitment tohelping students create their own knowledge of and appreciation for biology. She was the author of the Student Study Guide for ten editions of Campbell Biology. Eric J. Simon is a professor in the Department of Biology and Health Science at New England College in Henniker,New Hampshire. He teaches introductory biology to science majors and non rsity, and a Ph.D. in biochemistryTable of ContentsUNIT I: THE LIFE OF THE CELL 1. Biology: The Scientific Study of Life 2. The Chemical Basis of Life 3. The Molecules of Cells 4. A Tour of the Cell 5. The Working Cell 6. How Cells Harvest Chemical Energy 7. Photosynthesis: Using Light to Make Food UNIT II. CELLULAR REPRODUCTION AND GENETICS 8. The Cellular Basis of Reproduction and Inheritance 9. Patterns of Inheritance 10. Molecular Biology of the Gene 11. How Genes Are Controlled 12. DNA Technology and Genomics UNIT III. CONCEPTS OF EVOLUTION 13. How Populations Evolve 14. The Origin of Species 15. Tracing Evolutionary History UNIT IV. THE EVOLUTION OF BIOLOGICAL DIVERSITY 16. Microbial Life: Prokaryotes and Protists 17. The Evolution of Plant and Fungal Diversity 18. The Evolution of Invertebrate Diversity 19. The Evolution of Vertebrate Diversity UNIT V. ANIMALS: FORM AND FUNCTION 20. Unifying Concepts of Animal Structure and Function 21. Nutrition and Digestion 22. Gas Exchange 23. Circulation 24. The Immune System 25. Control of Body Temperature and Water Balance 26. Hormones and the Endocrine System 27. Reproduction and Embryonic Development 28. Nervous Systems 29. The Senses 30. How Animals Move VI. PLANTS: FORM AND FUNCTION 31. Plant Structure, Growth, and Reproduction 32. Plant Nutrition and Transport 33. Control Systems in Plants UNIT VII. ECOLOGY 34. The Biosphere: An Introduction to Earth'sDiverse Environments 35. Behavorial Adaptations to the Environment 36. Population Ecology 37. Communities and Ecosystems 38. Conservation Biology Appendix 1. Metric Conversion Table Appendix 2. The Periodic Table Appendix 3. The Amino Acids of Proteins Appendix 4. Chapter Review Answers Appendix 5. Credits

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Book SynopsisGet ready to laugh nonstop with hundreds of classic knock-knock jokes, silly one-liners, and hilarious puns sure to tickle your funny bone.From silly wordplay to treacherous tongue twisters, this humongous book has something for every kind of jokester. Never get tired of the same old jokes again. Jam packed with thousands of the funniest jokes, these goofy gags will have kids rolling on the floor with laughter.Including: Where did Sir Lancelot go to pay his parking tickets? Knight court. What does the Abominable Snowman get if he stays out in the sun too long? Freezer burn. Why did the pirate join a health club? He wanted to be in ship shape. What’s a Scarecrow''s favorite fruit? Strawberries! Kid-friendly content makes this a must-have for your family''s bookshelf. So, what are you waiting for? Start laughing with The Most Ginormous Joke Book Ever!

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Book SynopsisThis book is the first to set out a coherent set of principles that underpin geobiology, and will act as a foundational text that will speed the intellectual dissemination of those principles.Trade Review“In summary, Fundamentals of Geobiology would be a welcome addition to any geoscientist’s bookshelf, especially those interested in sedimentary geology, palaeobiology or Earth history.” (The Geological Journal, 1 January 2013) “It would be this reviewer’s “stranded on a desert island” selection. Summing Up: Highly recommended. Upper-division undergraduates through professionals.” (Choice, 1 January 2013) PROSE Awards 2012: Honorable Mention in the Earth Sciences Category. Table of ContentsContributors, xi 1. What is Geobiology?, 1 Andrew H. Knoll, Donald E. Canfield, and Kurt O. Konhauser 1.1 Introduction, 1 1.2 Life interacting with the Earth, 2 1.3 Pattern and process in geobiology, 2 1.4 New horizons in geobiology, 3 2. The Global Carbon Cycle: Biological Processes, 5 Paul G. Falkowski 2.1 Introduction, 5 2.2 A brief primer on redox reactions, 5 2.3 Carbon as a substrate for biological reactions, 5 2.4 The evolution of photosynthesis, 8 2.5 The evolution of oxygenic phototrophs, 11 2.6 Net primary production, 13 2.7 What limits NPP on land and in the ocean?, 15 2.8 Is NPP in balance with respiration?, 16 2.9 Conclusions and extensions, 17 3. The Global Carbon Cycle: Geological Processes, 20 Klaus Wallmann and Giovanni Aloisi 3.1 Introduction, 20 3.2 Organic carbon cycling, 20 3.3 Carbonate cycling, 22 3.4 Mantle degassing, 23 3.5 Metamorphism, 24 3.6 Silicate weathering, 24 3.7 Feedbacks, 25 3.8 Balancing the geological carbon cycle, 26 3.9 Evolution of the geological carbon cycle through Earth's history: proxies and models, 27 3.10 The geological C cycle through time, 30 3.11 Limitations and perspectives, 32 4. The Global Nitrogen Cycle, 36 Bess Ward 4.1 Introduction, 36 4.2 Geological nitrogen cycle, 36 4.3 Components of the global nitrogen cycle, 38 4.4 Nitrogen redox chemistry, 40 4.5 Biological reactions of the nitrogen cycle, 40 4.6 Atmospheric nitrogen chemistry, 45 4.7 Summary and areas for future research, 46 5. The Global Sulfur Cycle, 49 Donald E. Canfield and James Farquhar 5.1 Introduction, 49 5.2 The global sulfur cycle from two perspectives, 49 5.3 The evolution of S metabolisms, 53 5.4 The interaction of S with other biogeochemical cycles, 55 5.5 The evolution of the S cycle, 59 5.6 Closing remarks, 61 6. The Global Iron Cycle, 65 Brian Kendall, Ariel D. Anbar, Andreas Kappler and Kurt O. Konhauser 6.1 Overview, 65 6.2 The inorganic geochemistry of iron: redox and reservoirs, 65 6.3 Iron in modern biology and biogeochemical cycles, 69 6.4 Iron through time, 73 6.5 Summary, 83 7. The Global Oxygen Cycle, 93 James F. Kasting and Donald E. Canfield 7.1 Introduction, 93 7.2 The chemistry and biochemistry of oxygen, 93 7.3 The concept of redox balance, 94 7.4 The modern O2 cycle, 94 7.5 Cycling of O2 and H2 on the early Earth, 98 7.6 Synthesis: speculations about the timing and cause of the rise of atmospheric O2, 102 8. Bacterial Biomineralization, 105 Kurt Konhauser and Robert Riding 8.1 Introduction, 105 8.2 Mineral nucleation and growth, 105 8.3 How bacteria facilitate biomineralization, 106 8.4 Iron oxyhydroxides, 111 8.5 Calcium carbonates, 116 9. Mineral–Organic–Microbe Interfacial Chemistry, 131 David J. Vaughan and Jonathan R. Lloyd 9.1 Introduction, 131 9.2 The mineral surface (and mineral–bio interface) and techniques for its study, 131 9.3 Mineral-organic-microbe interfacial processes: some key examples, 140 10. Eukaryotic Skeletal Formation, 150 Adam F. Wallace, Dongbo Wang, Laura M. Hamm, Andrew H. Knoll and Patricia M. Dove 10.1 Introduction, 150 10.2 Mineralization by unicellular organisms, 151 10.3 Mineralization by multicellular organisms, 164 10.4 A brief history of skeletons, 173 10.5 Summary, 175 11. Plants and Animals as Geobiological Agents, 188 David J. Beerling and Nicholas J. Butterfield 11.1 Introduction, 188 11.2 Land plants as geobiological agents, 188 11.3 Animals as geobiological agents, 195 11.4 Conclusions, 200 12. A Geobiological View of Weathering and Erosion, 205 Susan L. Brantley, Marina Lebedeva and Elisabeth M. Hausrath 12.1 Introduction, 205 12.2 Effects of biota on weathering, 207 12.3 Effects of organic molecules on weathering, 209 12.4 Organomarkers in weathering solutions, 211 12.5 Elemental profiles in regolith, 213 12.6 Time evolution of profile development, 217 12.7 Investigating chemical, physical, and biological weathering with simple models, 218 12.8 Conclusions, 222 13. Molecular Biology’s Contributions to Geobiology, 228 Dianne K. Newman, Victoria J. Orphan and Anna-Louise Reysenbach 13.1 Introduction, 228 13.2 Molecular approaches used in geobiology, 229 13.3 Case study: anaerobic oxidation of methane, 238 13.4 Challenges and opportunities for the next generation, 242 14. Stable Isotope Geobiology, 250 D.T. Johnston and W.W. Fischer 14.1 Introduction, 250 14.2 Isotopic notation and the biogeochemical elements, 253 14.3 Tracking fractionation in a system, 255 14.4 Applications, 258 14.5 Using isotopes to ask a geobiological question in deep time, 261 14.6 Conclusions, 265 15. Biomarkers: Informative Molecules for Studies in Geobiology, 269 Roger E. Summons and Sara A. Lincoln 15.1 Introduction, 269 15.2 Origins of biomarkers, 269 15.3 Diagenesis, 269 15.4 Isotopic compositions, 270 15.5 Stereochemical considerations, 272 15.6 Lipid biosynthetic pathways, 273 15.7 Classification of lipids, 273 15.8 Lipids diagnostic of Archaea, 277 15.9 Lipids diagnostic of Bacteria, 280 15.10 Lipids of Eukarya, 283 15.11 Preservable cores, 283 15.12 Outlook, 287 16. The Fossil Record of Microbial Life, 297 Andrew H. Knoll 16.1 Introduction, 297 16.2 The nature of Earth’s early microbial record, 297 16.3 Paleobiological inferences from microfossil morphology, 299 16.4 Inferences from microfossil chemistry and ultrastructure (new technologies), 302 16.5 Inferences from microbialites, 306 16.6 A brief history, with questions, 308 16.7 Conclusions, 311 17. Geochemical Origins of Life, 315 Robert M. Hazen 17.1 Introduction, 315 17.2 Emergence as a unifying concept in origins research, 315 17.3 The emergence of biomolecules, 317 17.4 The emergence of macromolecules, 320 17.5 The emergence of self-replicating systems, 323 17.6 The emergence of natural selection, 326 17.7 Three scenarios for the origins of life, 327 18. Mineralogical Co-evolution of the Geosphere and Biosphere, 333 Robert M. Hazen and Dominic Papineau 18.1 Introduction, 333 18.2 Prebiotic mineral evolution I – evidence from meteorites, 334 18.3 Prebiotic mineral evolution II – crust and mantle reworking, 335 18.4 The anoxic Archean biosphere, 336 18.5 The Great Oxidation Event, 340 18.6 A billion years of stasis, 341 18.7 The snowball Earth, 341 18.8 The rise of skeletal mineralization, 342 18.9 Summary, 343 19. Geobiology of the Archean Eon, 351 Roger Buick 19.1 Introduction, 351 19.2 Carbon cycle, 351 19.3 Sulfur cycle, 354 19.4 Iron cycle, 355 19.5 Oxygen cycle, 357 19.6 Nitrogen cycle, 359 19.7 Phosphorus cycle, 360 19.8 Bioaccretion of sediment, 360 19.9 Bioalteration, 365 19.10 Conclusions, 366 20. Geobiology of the Proterozoic Eon, 371 Timothy W. Lyons, Christopher T. Reinhard, Gordon D. Love and Shuhai Xiao 20.1 Introduction, 371 20.2 The Great Oxidation Event, 371 20.3 The early Proterozoic: Era geobiology in the wake of the GOE, 372 20.4 The mid-Proterozoic: a last gasp of iron formations, deep ocean anoxia, the 'boring' billion, and a mid-life crisis, 375 20.5 The history of Proterozoic life: biomarker records, 381 20.6 The history of Proterozoic life: mid-Proterozoic fossil record, 383 20.7 The late Proterozoic: a supercontinent, oxygen, ice, and the emergence of animals, 384 20.8 Summary, 392 21. Geobiology of the Phanerozoic, 403 Steven M. Stanley 21.1 The beginning of the Phanerozoic Eon, 403 21.2 Cambrian mass extinctions, 405 21.3 The terminal Ordovician mass extinction, 405 21.4 The impact of early land plants, 406 21.5 Silurian biotic crises, 406 21.6 Devonian mass extinctions, 406 21.7 Major changes of the global ecosystem in Carboniferous time, 406 21.8 Low-elevation glaciation near the equator, 407 21.9 Drying of climates, 408 21.10 A double mass extinction in the Permian, 408 21.11 The absence of recovery in the early Triassic, 409 21.12 The terminal Triassic crisis, 409 21.13 The rise of atmospheric oxygen since early in Triassic time, 410 21.14 The Toarcian anoxic event, 410 21.15 Phytoplankton, planktonic foraminifera, and the carbon cycle, 411 21.16 Diatoms and the silica cycle, 411 21.17 Cretaceous climates, 411 21.18 The sudden Paleocene–Eocene climatic shift, 414 21.19 The cause of the Eocene–Oligocene climatic shift, 415 21.20 The re-expansion of reefs during Oligocene time, 416 21.21 Drier climates and cascading evolutionary radiations on the land, 416 22. Geobiology of the Anthropocene, 425 Daniel P. Schrag 22.1 Introduction, 425 22.2 The Anthropocene, 425 22.3 When did the Anthropocene begin?, 426 22.4 Geobiology and human population, 427 22.5 Human appropriation of the Earth, 428 22.6 The carbon cycle and climate of the Anthropocene, 430 22.7 The future of geobiology, 433 Acknowledgements, 434 References, 435 Index, 437 Colour plate pages fall between pp. 228 and 229

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Book SynopsisGet submerged in the amazing world of sharks! Your expert host, award-winning marine biologist Dr. David Shiffman, will show you howand whywe should protect these mysterious, misunderstood guardians of the ocean. Sharks are some of the most fascinating, most ecologically important, most threatened, and most misunderstood animals on Earth. More often feared than revered, their role as predators of the deep have earned them a reputation as a major threat to humans. But the truth is that sharks are not a danger to usthey're in danger from us. In Why Sharks Matter, marine conservation biologist Dr. David Shiffman explains why it's crucial that we overcome our misconceptions and rise above cinematic jump scares to embrace sharks as the imperiled and elegant ocean guardians they really are. Sharing his own fascinating experiences working with sharks, Shiffman tells us why healthy shark populations are a must for supporting ocean ecosystemsand the coastal economies that depend on them whTrade ReviewShiffman says he wants 'to teach you why sharks are remarkable and awe-inspiring animals, why we're better off with sharks than we are without them, and what you can do to help protect the alarming and increasing number of sharks of conservation concern.' He succeeds on all counts.—San Francisco ChronicleThe argument of Shiffman's book is that we should do a better job of protecting sharks, and his method is to dip analysis and policy recommendations in a sugar coating of cool facts. For Shiffman, our inability to conceptualize relative risk is both an ecological and aesthetic tragedy, undermining conservation efforts while preventing us from exulting in the glory of sharks—with their dermal denticles, their total lack of bones and their ability to hear an injured fish from a mile away.—Molly Young, New York TimesWhether this book makes you pause and reflect on your perception of sharks, or teaches you some new facts about these predators, Shiffman hopes he has shed light on human side of shark conservation through this work.—Forbes[Shiffman] delivers the book he was born to write.—The RevelatorJoin award-winning marine biologist Dr. David Shiffman in an approachable, humorous and adventure-packed narrative about sharks—the mysterious guardians of the ocean. You'll learn why we should overcome our misconceptions regarding these creatures, delve deep into Shiffman's own experiences with sharks, and explore decades of scientific research and policymaking related to shark conservation.—Scuba DivingA fun, engaging and informative read.—Biological ConservationWritten by a US shark-conservation expert with a solid academic background...[Shiffman] question[s] the easy assumptions we divers sometimes make for emotional reasons about protecting sharks, rather than being guided by the science.—DivernetShiffman is quick to celebrate those who advance the interests of sharks, profiling a diverse group of dedicated scientists (itself laudable in a field dominated by white men). His bluntness and specificity is refreshing in the face of so much advocacy that just sets its sights at 'raising awareness.'—New ScientistShiffman is an entertaining writer, not afraid to nerd out over sharks and share plenty of interesting stories. But what I really appreciate is that every piece of information is grounded in science. Think of it as the anti-Shark Week: the book is entertaining and informative without being sensational or lurid.—Cool Green Science (The Nature Conservancy)Those that want to learn more about sharks and their conservation will find [Why Sharks Matter] a valuable resource. Shiffman is aiming to educate this generation and inspire them to help make the difference that will see shark populations rebuild....As such, this is a book as much about people as it is about sharks.—Colin A. Simpfendorfer, Current BiologyA humorous and pleasant read, packed with lots of facts and stories.—The Marine BiologistTable of ContentsIntroductionChapter 1. Shark Basics, and Fun Facts to Keep You ReadingChapter 2. Sharks Are Not a Threat to HumansChapter 3. The Ecological Significance of Sharks Chapter 4. What Are the Threats to Sharks and How Threatened Are They? Chapter 5. How Can We Protect Sharks? Chapter 6. Sustainable Fisheries for Shark Conservation: Target-Based PoliciesChapter 7. Fishing and Trade Bans for Shark Conservation: Limit-Based PoliciesChapter 8. How Are Scientists Helping Sharks?Chapter. How Are Environmentalists Helping Sharks?Chapter 10. How Can You Help Sharks? (Dos and Please Just Don'ts)AfterwordAcknowledgmentsBibliographyIndexColor plates follow page ___

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Book SynopsisHighly praised for its broad, practical coverage, the second edition of this popular text incorporated the major statistical models and issues relevant to epidemiological studies. Epidemiology: Study Design and Data Analysis, Third Edition continues to focus on the quantitative aspects of epidemiological research. Updated and expanded, this edition shows students how statistical principles and techniques can help solve epidemiological problems.New to the Third Edition New chapter on risk scores and clinical decision rules New chapter on computer-intensive methods, including the bootstrap, permutation tests, and missing value imputation New sections on binomial regression models, competing risk, information criteria, propensity scoring, and splines Many more exercises and examples using both Stata and SAS More than 60 new figures After introducing study design and reviewTrade Review"This text, like its predecessors, hits the mark. … The author writes extremely well and the text is resplendent with exercises. It would be a crime if Epidemiology: Study Design and Data Analysis were never used as a text! … I wish a text like this had been available for my coursework. Enhancing its value as a text, it will be extremely useful as a reference book for its intended audience—researchers and applied statisticians. … the only excuse for an epidemiologist or applied statistician not to have it on his or her bookshelf is that he or she has not seen or heard of it. Make this book your next purchase!"—Gregory E. Gilbert, The American Statistician, November 2014Praise for Previous Editions:"As a text in quantitative epidemiology, this book also works nicely as a text in biostatistics…The presentation style is relaxed, the examples are helpful, and the level of technical difficulty makes the material approachable without oversimplification…It is sufficiently broad and deep in coverage to compete with standard texts in the field and has the added bonus of emphasizing study design. Methods and issues related to designs commonly used in a wide variety of health sciences are included…"-Ken Hess, Department of Biomathematics and Biostatistics, Anderson Cancer Center"The second edition of this epidemiology text is strengthened to cater to the two audiences the author has in mind: applied statisticians wishing to learn how their statistical expertise can be used in the epidemiology field and statistic-curious researchers who want to understand how statistical techniques can be used to solve epidemiological problems. …The result is a book that will invariably appeal to the intended audience, one with practical applications of techniques and interpretations of results in an epidemiological context. …The book is most certainly an ambitious attempt at covering a broad array of the most important epidemiologic study designs and analytical methods. This is further enforced by the addition of the meta-analysis chapter. …This book will be valuable to statisticians in applying their discipline to epidemiology. Mark Woodward's excellent second edition will effectively serve post-graduate or advanced undergraduate students studying epidemiology, as well as statisticians or researchers who are regularly confronted with epidemiological questions."-Journal of the American Statistical Association"This book provides very good coverage of major issues in the design of epidemiological studies, and a decent, but very quick, tour of commonly used statistical models for such studies."-Short Book Reviews Publication of the International Statistical Institute, K.S. Brown, University of Waterloo, Canada"Amazingly, Woodward manages to describe quite sophisticated models and analysis with nothing more complicated than summation signs. …I highly recommend it."-Statistics in Medicine, 2006"The second edition of this concisely written book covers all statistical methods being of relevance for the planning and analysis of epidemiological studies where the author avoids unnecessary mathematical details for the sake of comprehensibility. The presented statistical principles are always carefully discussed in the context of epidemiological concepts, for instance depending on the different study designs. Detailed practical examples coming from real studies as far as possible illustrate their application. …The book can be highly recommended to researchers in epidemiology who want to understand better the statistical principles being typically applied in this field and to statisticians who want to understand more about statistics in epidemiology, but also to graduate students in epidemiology, public health, medical research and statistics."-Biometrics, Sept. 2005"I think anyone with an interest in both biostatistics and epidemiology will want a copy this book on their bookshelf … it is a first-rate reference book." "I find Professor Woodward's text the most complete and practical introduction to the design and analysis of epidemiological studies I've encountered… an excellent text for either a course introducing epidemiologists to statistical thought and methods or a course introducing statisticians to epidemiological thought and methods… students appreciate having a readable textbook replete with understandable examples and worked exercises…offers a complete introduction to statistical and epidemiological methods in the study of disease in human populations. All of the standard topics are included, and the second edition even has a chapter on meta-analysis. …This book can be used as a text to introduce epidemiological methods to graduate students in statistics who have no background in epidemiology, or vice versa…Professor Woodward is to be congratulated on a job well done."-Dan McGee, Dept of Statistics, Florida State UniversityTable of ContentsFundamental Issues. Basic Analytical Procedures. Assessing Risk Factors. Confounding and Interaction. Cohort Studies. Case-Control Studies. Intervention Studies. Sample Size Determination. Modeling Quantitative Outcome Data. Modeling Binary Outcome Data. Modeling Follow-Up Data. Meta-Analysis. Risk Scores and Clinical Decision Rules. Computer-Intensive Methods. Appendices. Index.

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Book SynopsisTechniques of Crime Scene Investigation is a staple for any forensic science library and is routinely referenced by professional organizations as a study guide for certifications. It is professionally written and provides updated theoretical and practical applications using real casework. This text is a must-have for any CSI Unit or course teaching Crime Scene Investigation. â Kevin Parmelee, PhD, Detective (ret.), Somerset County, NJ Prosecutorâs OfficeSince the first English-language edition of Techniques of Crime Scene Investigation was published in 1964, the book has continued to be a seminal work in the field of forensic science, serving as a foundational textbook and reference title for professionals.This Ninth Edition includes several new chapters and has been fully updated and organized to present the effective use of science and technology in support of justice. New coverage to this edition addresses the debunking of a few forensTable of ContentsI: The Crime Scene 1. Introduction 2. First on Scene and Crime Scene Personnel 3. Documenting the Crime Scene 4. Physical Evidence Collection 5. Crime Scene Reconstruction II. Physical Evidence 6. Fingerprint Evidence 7. Blood, Forensic Biology, and DNA 8. Forensic Traces 9. Impression Evidence 10. Firearms Examination 11. Arson and Explosives 12. Illicit Drugs and Toxicology 13. Document Evidence III: The Investigation and Special Considerations 14. Ethics in Crime Scene Investigation 15. Sexual Assault Investigation 16. Burglary Investigation 17. Motor Vehicle Investigation 18. Death Investigation 19. Digital Evidence and the Electronic Crime Scene 20. Report Writing, Testimony and The Future App A. Equipment for Crime Scene Investigation App B. Forensic Science Related Websites

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Book Synopsis'A wise, intimate tale that is by turns joyful, sorrowful and explicit' Observer 'The author delves deep into Lottie’s psyche, shying away from nothing, to create a rounded and gripping portrait of a woman on the edge of change’ Daily Mail Lottie Kristin is independent from the start. Born in the middle of the century to a middle-class family in the very middle of America, Lottie is set apart by her smarts and sensuality. A girl who'd rather carry out dissections on a snowy back porch than join her family for Christmas dinner is a strange and exotic artifact in the town of Sleeping Bay. But by her early twenties, Lottie finds herself trapped in a marriage gone stale, with a daughter she adores but whose existence jeopardizes her place in the lab and her dream of becoming a scientist. How can a young woman make her way in a world determined to contain her brilliance, her will, and her longing to live? Bravely and wisely written, Artifact is an intimate and propulsive portrait of a whole woman, a celebration of her refusal to be defined by others’ imaginations, and a meditation on the glorious chaos of biological life.Trade ReviewA wise, intimate tale that is by turns joyful, sorrowful and explicit * Observer *Lottie … encapsulates the dichotomy of her life. She’s a smartly realised character – bright yet naïve, determined and single-minded ... Heyman handles her subject lightly, lacing it with humour * A Life in Books *The author delves deep into Lottie’s psyche, shying away from nothing, to create a rounded and gripping portrait of a woman on the edge of change * Daily Mail *A heroine for our times * Publishers Weekly *Praise for Scary Old Sex: Lusty, tough and life-affirming -- Elaine Showalter * Guardian *Hits the reader in the psyche, the gut and the groin with the force of a precision-aimed slingshot … Shocking, mesmerising and truthful -- Rowan Pelling * Sunday Telegraph *Both funny and eye-wateringly explicit -- Joan Bakewell * Independent *Rueful and funny and observant ... Heyman is an enlightened observer across many aspects of life ... These men and women are busily and blissfully humanizing themselves, the kind of bliss that lifts right off the page * New York Times *A terrific story collection ... Heyman is frank in her descriptions, but never cruel or unfeeling ... a tender, perceptive work * Wall Street Journal *So stylish, earthy and funny -- Deborah Moggach[An] impressive collection ... Heyman takes on the brutal intimacy of death and aging and provides new ways of seeing and experiencing these stages of life * San Francisco Chronicle *Heyman’s frank tales ... feel paradoxically taboo on the page, all the more so for their fierce candour * New Yorker *Sensual and sometimes shocking … Heyman writes with such intimacy and precision that she frequently makes you feel like a trespasser -- Imogen Lycett-Green * Daily Mail *Bold, hilarious and intelligent ... Heyman is upfront and her characters are richly internal * Irish Times *Delivers a shock of taboo desire that is lusciously sensual -- Michèle Roberts * Independent *Though her characters’ flaws, fears and phobias feel all too real, Heyman’s treatment of them is honest, human and kind * Daily Telegraph *

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Book Synopsis"An engrossing chronicle for readers ages 12 and older" The Wall Street JournalHow did our scientific quest to understand life begin? From the earliest questioning about the origins of life to the first use of the word virus, this compelling and informative non-fiction book for readers 12 plus unfolds the history of biology itself.For most of human history, we haven’t known the secrets of life itself. In this fascinating book, the renowned author of A History of US, Joy Hakim, takes us back through time to biology’s beginnings…Observe the inquisitive scholars of Ancient Greece and the Islamic Golden Age as they began to ask questions about how the human body works; journey to the Renaissance where Leonardo da Vinci was dissecting cadavers to uncover human anatomy; and stop in the late 1800s, where a baffled Dutch biologist found a tiny infectious particle destroying tobacco crops, which he named virus.Discovering Life’s Story: Biology’s Beginnings is the first in an all-new multivolume work that follows the course of human discovery as we have worked to unlock the biological secrets of our own existence.“Eye-catching photographs and illustrations supplement Hakim’s simple but engagingly fact-rich prose, making this an ideal introductory text for any budding naturalist, scientist or doctor.” Washington Post“A work of nonfiction for adolescent readers that has the brio of an adventure story ... Abundant illustrations—maps, portraits, engravings—help keep the pace excitingly brisk.” The Wall Street Journal, Best Books for Children of 2023Trade Review“Nonfiction books for children about the natural sciences tend (naturally, we might say) to deal with particulars: the life cycle of the honeybee, say. In ‘Biology’s Beginnings,’ Joy Hakim takes a fresh approach. . . . Ms. Hakim, author of the series ‘A History of Us,’ ranges with brio and assurance across time and across the globe as she describes the push-and-pull of armies and microbes, of popes and stargazers, of philosophers and doctors and explorers in the long and erratic acquisition of knowledge. . . . Great quantities of illustration—maps and portraits and engravings—establish a swift visual pace for this engrossing chronicle for readers ages 12 and older.” * The Wall Street Journal *Eye-catching photographs and illustrations supplement Hakim’s simple but engagingly fact-rich prose, making this an ideal introductory text for any budding naturalist, scientist or doctor. * Washington Post *A work of nonfiction for adolescent readers that has the brio of an adventure story. . . In prose that is textured, humane and spirited, Ms. Hakim describes the movements of armies and microbes, the discoveries of anatomists and astronomers, the insights of philosophers and doctors and explorers. Abundant illustrations—maps, portraits, engravings—help keep the pace excitingly brisk. * The Wall Street Journal, Best Books for Children 2023 *

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Book SynopsisClinical trials have become essential research tools for evaluating the benefits and risks of new interventions for the treatment and prevention of diseases, from cardiovascular disease to cancer to AIDS. Based on the authors’ collective experiences in this field, Introduction to Statistical Methods for Clinical Trials presents various statistical topics relevant to the design, monitoring, and analysis of a clinical trial.After reviewing the history, ethics, protocol, and regulatory issues of clinical trials, the book provides guidelines for formulating primary and secondary questions and translating clinical questions into statistical ones. It examines designs used in clinical trials, presents methods for determining sample size, and introduces constrained randomization procedures. The authors also discuss how various types of data must be collected to answer key questions in a trial. In addition, they explore common analysis methods, describe statistical methods that determine what an emerging trend represents, and present issues that arise in the analysis of data. The book concludes with suggestions for reporting trial results that are consistent with universal guidelines recommended by medical journals. Developed from a course taught at the University of Wisconsin for the past 25 years, this textbook provides a solid understanding of the statistical approaches used in the design, conduct, and analysis of clinical trials.Trade Review… There is much good material in this book. The individual chapters are well written and cover the technical aspects as well. A major strength is the ordering of topics to follow the thought process used in the development and implementation of a protocol from defining the question to reporting results. There are careful discussions on fundamental principles and the pivotal role played by statistics is well brought out. … there is much that practicing pharmaceutical statisticians will find useful in this book. They will find the coverage of fundamental principles useful and the technical content of the book a good reference source. …—Pharmaceutical Statistics, 2010… fits the need for a contemporary text and handbook that is oriented toward the clinical trial statistician. I highly recommend it and look forward to using it as both a primary and supplemental text in our curriculum, as well as a research resource.—James J. Dignam, University of Chicago, JASA, March 2009The (technical) statistical content is the main focus of the book and this is what helps it to stand apart from most others on clinical trials (even the more obviously statistically orientated ones). It takes the reader to quite a technical background that would serve him or her well if moving on to research problems in the various areas covered, yet does not lose sight of practical issues. … For those of us with the interest (and need) to grapple with these more statistical issues, I wholeheartedly recommend it.—Biometrics, December 2008…The book is very well written and clear. … the authors generally strike the right balance for the intended audience. The inclusion of many historically important as well as contemporary examples to illustrate various points throughout the text is a major strength, as is the inclusion of several modern topics not seen in other texts. As a basis for a course in clinical trials for graduate students in biostatistics, this book is outstanding. In addition, statisticians in the pharmaceutical industry, government, or academia … will find this text extremely informative and useful.” —Michael P. McDermott, University of Rochester Medical Center, Journal of Biopharmaceutical Statistics, 2008Table of ContentsPreface. Introduction to Clinical Trials. Defining the Question. Study Design. Sample Size. Randomization. Data Collection and Quality Control. Survival Analysis. Longitudinal Data. Quality of Life. Data Monitoring and Interim Analysis. Selected Issues in the Analysis. Closeout and Reporting. Special Topics. Appendix. References. Index.

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Book SynopsisPublished by Sinauer Associates, an imprint of Oxford University Press. Biogeography, first published in 1983, is one of the most comprehensive text and general reference books in the natural sciences. The fifth edition builds on the strengths of previous editions to provide an insightful and integrative explanation of how geographic variation across terrestrial and marine environments has influenced the fundamental processes of immigration, extinction, and evolution to shape species distributions and nearly all patterns of biological diversity. It is an empirically and conceptually rich text that illustrates general patterns and processes using examples from a broad diversity of life forms, time periods and aquatic and terrestrial ecosystems. Biogeography, Fifth Edition, is written as a primary text for undergraduate and graduate courses, and is also an invaluable reference for biogeographers, ecologists, evolutionary biologists, and conservation biologists. Its fundamental assertion is that patterns in biological diversity make little sense unless viewed within an explicit geographic context. Starting from principal patterns and fundamental principles, and assuming only a rudimentary knowledge of biology, geography, and Earth history, the text explains the relationships between geographic variation in biological diversity and the geological, ecological, and evolutionary processes that have produced them. The use of color illustrations, evaluated and optimized for colorblind readers, has transformed our abilities to illustrate key concepts and empirical patterns in the geography of nature. By providing a description of the historical development of biogeography, evolution and ecology, along with a comprehensive account of the principal patterns, fundamental principles and recent advances in each of these fields of science, our ultimate vision is for Biogeography to serve as the centerpiece of a one- or two-semester core course in biological diversity.Table of ContentsUNIT ONE. INTRODUCTION TO THE DISCIPLINE.- 1. The Science of Biogeography 2. The History and Reticulating Phylogeny of Biogeography UNIT TWO. THE GEOGRAPHIC AND ECOLOGICAL FOUNDATIONS OF BIOGEOGRAPHY.- 3. The Geographic Template: Visualization and Analysis of Biogeographic Patterns 4. Distributions of Species: Ecological Foundations 5. The Distribution and Dynamics of Communities, Biomes, and Ecosystems UNIT THREE. FUNDAMENTAL BIOGEOGRAPHIC PROCESSES AND EARTH HISTORY.- 6. Dispersal and Immigration 7. Speciation and Extinction 8. The Changing Earth 9. Glaciation and Biogeographic Dynamics of the Pleistocene UNIT FOUR. EVOLUTIONARY HISTORY OF LINEAGES AND BIOTAS.- 10. The Geography of Diversification and Regionalization 11. Reconstructing the Evolutionary History of Lineages 12. Reconstructing the History of Biotas UNIT FIVE. ECOLOGICAL BIOGEOGRAPHY.- 13. Island Biogeography 14. Areography, Ecogeography and Macroecology of Continental and Oceanic Biotas UNIT SIX. CONSERVATION AND THE FRONTIERS OF BIOGEOGRAPHY.- 15. Biogeography of Humanity, Biological Diversity and Conservation Biogeograph 16. From the Foundations to the Frontiers of Biogeography.

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Book SynopsisStart Small, Think Big is a series that sets young readers on a journey of discovery, beginning from the small and familiar to new areas of knowledge where they really have to think big! Little Brown Nut starts small, with a large, weighty fruit falling from the tallest tree in the Amazon rainforest. Inside is a little brown Brazil nut, surrounded by 19 others. It sits and waits for an agouti, a rodent with teeth so strong that it can free the nut from its hard casing. The story of the Brazil nut tree and the agouti is told clearly and carefully, with facts about germination, photosynthesis, seed dispersal. The narrative progresses in a way that builds understanding and the gorgeous illustrations bring the story and the science to life. Thinking BIG, the book shows why the rainforest is important to local people and the wider world. A big fold-out has a world map, an at-a-glance lifecycle, and a Rainforest I-Spy of the animals to take children back into the book.Trade ReviewI really enjoyed that the story follows a nut, a familiar object, all the way through its various journeys and cycle of life. I haven't seen a non-fiction book like this before and I think [the titles in the Start Small, Think Big series] are really special and a great addition to the bookshelf. I honestly can't wait to share these books with my class and use these across a series of different lessons, from Science and Understanding the World through to English lessons and looking at different text types. I am looking forward to seeing more of these. -- Lauren Maidman, Teacher * ReadingZone *By thinking big, and through science-based words and pictures full of information and wonder, the book shows why the rainforest is important to local people and the wider world. * Lancashire Post *November 2023 Book of the Month It’s a fascinating story, told in a way that will catch young reader’s attention and fire their interest in the rainforest. * LoveReading4Kids.co.uk *With captivating illustrations it’s an immersive journey into the rainforest complimented by insightful captions and perfect for young readers exploring science topics like tree life cycles and rainforest habitats. -- Scott Evans * The Reader Teacher *Table of ContentsTextured cover with a die-cut egg, 28 pages including a fold-out map of South America, an I-Spy game, a lifecycle illustration of a Brazil nut tree, and fascinating facts.

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Book SynopsisTHE NEW YORK TIMES BESTSELLERRichard Dawkins - author of The Selfish Gene, The Blind Watchmaker, and The God Delusion - is one of science's greatest communicators. This anthology of more than forty pieces is a kaleidoscopic argument for the power and the glory of science. Breathtaking, brilliant and passionate, these essays, journalism, lectures and letters make an unanswerable case for the wonder of scientific discovery and its power to stir the imagination; for the practical necessity of scientific endeavour to society; and for the importance of the scientific way of thinking – particularly in today’s ‘post-truth’ world.With an introduction and new commentary by the author, subjects range from evolution and Darwinian natural selection to the role of scientist as prophet, whether science is itself a religion, the probability of alien life in other worlds, and the beauties, cruelties and oddities of earthly life in this one. Alongside the explications, the celebrations and the controversies are wonderfully funny ventures into satire and parody, and moving personal reflections in memory and honour of others.Science in the Soul is a sparkling showcase for Professor Dawkins' rapier wit, the clarity, precision and vigour he brings to an argument, the beauty of his prose, the depth of his feeling and his capacity for joy.Trade Review[Dawkins] is a thunderously gifted science writer -- Oliver Moody * The Times *One of the best non-fiction writers alive today * Steven Pinker *The illumination of Dawkins’ incisive thinking on the intellectual world extends far beyond biology. What a treat to see so clearly how matter and meaning fit together, from fiction to philosophy to molecular biology, all in one unified vision!’ Daniel C. Dennett * Daniel C. Dennett *In this golden age of enlightened science writing it is stunning that no scientist has ever won the Nobel Prize for Literature. Pulitzer Prizes, yes, but it is time literature's highest award be granted to a scientist whose writings have changed not just science but society. No living scientist is more deserving of such recognition than Richard Dawkins, whose every book reflects his literary genius and scientific substance. Science in the Soul is the perfect embodiment of Nobel quality literature." -- Michael Shermer, Publisher Skeptic magazine, columnist Scientific American, author The Moral Arc and Heavens on EarthI thank Thor and Zeus that in their infinite wisdom they chose to make the great wordsmith of our age a great rationalist and vice versa. -- Matt Ridley, author of The Rational Optimist and The Evolution of EverythingA writer of tremendous clarity and force...in full polemical flight, Dawkins is a marvel. -- Kevin Powers * Sunday Business Post *This Dawkins is a dangerous guy. Like Marx. Or Darwin. * W. Daniel Hillis *The most influential man of reason…intellectually rigorous to a fault. -- Oliver Thring * Sunday Times News Review *With his latest book, ‘Science in the Soul’, Richard Dawkins continues the legacy of Carl Sagan, though of course, in a more combative mode...Richard Dawkins is one of the best science popularisers of our times. He is also an eminent evolutionary biologist...All the articles in this compilation are ultimately soul-elevating in the sense that they emphasise the importance of reason and spirit of science in approaching many of the problems which we may think as being outside the realm of science or domains where inducing a hostility to a scientific approach is possible....Dawkins is an extraordinarily talented author and persuader ...Dawkins also comes across in this collection of essays as a warm rational scientist who is interestingly so open to the innocent human fascination for the grandeur of nature. -- Aravindan Neelakandan * Swarajya Magazine *Dawkins at his most delicious. These are some of the finest treasures of non-fiction you'll find anywhere * Derren Brown *Now, more than ever, public intellectual scientists like Dawkins are needed to counter the forces of faith, fiction, and farce dominating our so-called “post-fact” society.The Oxford University professor is the embodiment of the concept of the public intellectual -- Iain Ellis * www.popmatters.com *

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Book SynopsisWe are marching towards a future in which three-quarters of humans live in cities, more than half of the landmass of the planet is urbanized, and the rest is covered by farms,pasture, and plantations. Increasingly, as we become ever more city-centric, species and ecosystems crafted by millions of years of evolution teeter on the brink of extinction - or have already disappeared.A growing band of 'urban ecologists' is beginning to realize that natural selection is not so easily stopped. They are finding that more and more plants and animals are adopting new ways of living in the seemingly hostile environments of asphalt and steel that we humans have created. Carrion crows in the Japanese city of Sendai, for example, have learned to use passing traffic to crack nuts for them; otters and bobcats, no longer persecuted by humans, are waiting at the New York City gates; superb fairy-wrens in Australia have evolved different mating structures for nesting in strips of vegetation along roads; while distinct populations of London underground mosquitoes have been fashioned by the varied tube line environments.Menno Schilthuizen shows us that evolution can happen far more rapidly than Darwin had dared dream.Trade ReviewInvigorating and beautifully written. - BBC WildlifeMy eyes and ears have been opened to the emerging science of urban ecology by Menno Schilthuizen - Financial TimesDelightful and charmingly written - Daily TelegraphSpellbinding and important - Sunday Times

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Book SynopsisA Scientific American Top Ten Book of 2023If forests are the lungs of the planet, then animals migrating across oceans, streams, and mountains-eating, pooping, and dying along the way-are its heart and arteries, pumping nitrogen and phosphorus from deep-sea gorges up to mountain peaks, from the Arctic to the Caribbean. Without this conveyor belt of crucial, life-sustaining nutrients, the world would look very different. The dynamics that shape our physical world-atmospheric chemistry, geothermal forces, plate tectonics, and erosion through wind and rain-have been explored for decades. But the effects on local ecosystems of less glamorous forces-rotting carcasses and deposited feces-as well as their impact on the global climate cycle, have been largely overlooked. The simple truth is that pooping and peeing are daily rituals for almost all animals, the ellipses of ecology that flow through life. We eat, we poop, and we die. From the volcanoes of Iceland to the tropical waters of Hawaii,

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Book Synopsis Catch up Biology 2e covers the basic principles and concepts in biology that you will need if you are studying medicine or a related subject, or one of the biomedical sciences. The book focuses on human biology and covers: the basic molecules of life, such as proteins, carbohydrates, nucleic acids cells, tissues and processes, including energy metabolism, cell division, epithelial and connective tissues the key mammalian systems, for example, homeostasis, the endocrine, respiratory and digestive systems. Throughout the book the authors highlight clinical examples so that you can see the relevance of basic biology to your course. The book also contains questions (and answers) so that you can test your understanding of the subject as you work through the book. This new edition features two new chapters on microorganisms and on genetic disease. Catch up Biology is the ideal book to refresh your understanding of the basic concepts of biology.Table of ContentsThe molecules of life Water and life; Proteins; Carbohydrates; Lipids; Nucleic acids and genes Cells and tissues The cell; Microorganisms; Energy metabolism; Membrane transport; Cell division and mitosis; Reproduction; Inheritance; Genetic disease; Epithelial tissues; Connective tissues; Excitable tissues Systems Homeostasis; The endocrine system; The nervous system; The cardiovascular system; The respiratory system; The digestive system; The reproductive system; The urinary system; The immune system; The musculoskeletal system

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Book SynopsisA new translation of a leading architect’s magnum opus. Housing Copenhagen is primarily the translation of leading Danish modern architect Kay Fisker’s Kobenhavske Bolygtyper, maintaining the original layout along with drawings and diagrams. The text illustrates the main features of Fisker’s architecture and describes the cultural context within which the exploration of housing types was conducted. The systematic approach, the richness of selected examples, as well as the analytic content, make this book valuable beyond its historic and geographic limits. Due to a renewed interest in the field of housing, the translation will provide students and professionals with a clear and useful instrument for housing design from an architectural and urban perspective. Table of ContentsLuca Ortelli, Kay Fisker's architectureChiara Monterumisi, IntroductionKay Fisker, The evolution of Copenhagen Housing Types

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Book SynopsisIn this expert handbook both the topics and contributors are selected so as to provide an authoritative view of possible applications for this new technology. The result is an up-to-date survey of current challenges and opportunities in the design and operation of bioreactors for high-value products in the biomedical and chemical industries. Combining theory and practice, the authors explain such leading-edge technologies as single-use bioreactors, bioreactor simulators, and soft sensor monitoring, and discuss novel applications, such as stem cell production, process development, and multi-product reactors, using case studies from academia as well as from industry. A final section addresses the latest trends, including culture media design and systems biotechnology, which are expected to have an increasing impact on bioreactor design. With its focus on cutting-edge technologies and discussions of future developments, this handbook will remain an invaluable reference for many years to come.Table of ContentsPreface xv List of Contributors xvii 1 Challenges for Bioreactor Design and Operation 1 Carl-Fredrik Mandenius 1.1 Introduction 1 1.2 Biotechnology Milestones with Implications on Bioreactor Design 2 1.3 General Features of Bioreactor Design 8 1.4 Recent Trends in Designing and Operating Bioreactors 12 1.5 The Systems Biology Approach 17 1.6 Using Conceptual Design Methodology 20 1.7 An Outlook on Challenges for Bioreactor Design and Operation 29 References 32 2 Design and Operation of Microbioreactor Systems for Screening and Process Development 35 Clemens Lattermann and Jochen Büchs 2.1 Introduction 35 2.2 Key Engineering Parameters and Properties in Microbioreactor Design and Operation 36 2.2.1 Specific Power Input 37 2.2.2 Out-of-Phase Phenomena 40 2.2.3 Mixing in Microbioreactors 42 2.2.4 Gas–Liquid Mass Transfer 44 2.2.4.1 Influence of the Reactor Material 47 2.2.4.2 Influence of the Viscosity 49 2.2.5 Influence of Shear Rates 50 2.2.6 Ventilation in Shaken Microbioreactors 51 2.2.7 Hydromechanical Stress 52 2.3 Design of Novel Stirred and Bubble Aerated Microbioreactors 53 2.4 Robotics for Microbioreactors 54 2.5 Fed-Batch and Continuous Operation of Microbioreactors 56 2.5.1 Diffusion-Controlled Feeding of the Microbioreactor 56 2.5.2 Enzyme Controlled Feeding of the Microbioreactor 58 2.5.3 Feeding of Continuous Microbioreactors by Pumps 59 2.6 Monitoring and Control of Microbioreactors 60 2.6.1 DOT and pH Measurement 62 2.6.2 Respiratory Activity 63 2.7 Conclusion 66 Terms 67 Greek Letters 68 Dimensionless Numbers 69 List of Abbreviations 69 References 69 3 Bioreactors on a Chip 77 Danny van Noort 3.1 Introduction 77 3.2 Advantages of Microsystems 79 3.2.1 Concentration Gradients 81 3.3 Scaling Down the Bioreactor to the Microfluidic Format 82 3.4 Microfabrication Methods for Bioreactors-On-A-Chip 82 3.4.1 Etching of Silicon/Glass 83 3.4.2 Soft Lithography 83 3.4.3 Hot Embossing 84 3.4.4 Mechanical Fabrication Technique (Or Poor Man’s Microfluidics) 84 3.4.5 Laser Machining 85 3.4.6 Thin Metal Layers 86 3.5 Fabrication Materials 86 3.5.1 Inorganic Materials 86 3.5.2 Elastomers and Plastics 87 3.5.2.1 Elastomers 87 3.5.2.2 Thermosets 87 3.5.2.3 Thermoplastics 87 3.5.3 Hydrogels 88 3.5.4 Paper 88 3.6 Integrated Sensors for Key Bioreactor Parameters 89 3.6.1 Temperature 89 3.6.2 pH 90 3.6.3 O2 90 3.6.4 Co2 90 3.6.5 Cell Concentration (OD) 90 3.6.6 Humidity and Environment Stability 91 3.6.7 Oxygenation 91 3.7 Model Organisms Applied to BRoCs 91 3.8 Applications of Microfluidic Bioreactor Chip 92 3.8.1 A Chemostat BRoC 92 3.8.2 Using a BRoC as a Single-Cell Chemostat 95 3.8.3 Mammalian Cells in the Bioreactor on a Chip 96 3.8.4 Body-on-a-Chip Bioreactors 98 3.8.5 Organ-on-a-Chip Bioreactor-Like Applications 99 3.9 Scale Up 100 3.10 Conclusion 101 Abbreviations 102 References 103 4 Scalable Manufacture for Cell Therapy Needs 113 Qasim A. Rafiq, Thomas R.J. Heathman, Karen Coopman, Alvin W. Nienow, and Christopher J. Hewitt 4.1 Introduction 113 4.2 Requirements for Cell Therapy 115 4.2.1 Quality 115 4.2.2 Number of Cells Required 117 4.2.3 Anchorage-Dependent Cells 118 4.3 Stem Cell Types and Products 119 4.4 Paradigms in Cell Therapy Manufacture 120 4.4.1 Haplobank 121 4.4.2 Autologous Products 121 4.4.3 Allogeneic Products 123 4.5 Cell Therapy Manufacturing Platforms 124 4.5.1 Scale-Out Technology 125 4.5.2 Scale-Up Technology 127 4.6 Microcarriers and Stirred-Tank Bioreactors 128 4.6.1 Overview of Studies Using a Stirred-Tank Bioreactor and Microcarrier System 130 4.7 Future Trends for Microcarrier Culture 136 4.8 Preservation of Cell Therapy Products 138 4.9 Conclusions 139 References 140 5 Artificial Liver Bioreactor Design 147 Katrin Zeilinger and Jörg C. Gerlach 5.1 Need for Innovative Liver Therapies 147 5.2 Requirements to Liver Support Systems 147 5.3 Bioreactor Technologies Used in Clinical Trials 148 5.3.1 Artificial Liver Support Systems 148 5.3.2 Bioartificial Liver Support Systems 149 5.4 Optimization of Bioartificial Liver Bioreactor Designs 152 5.5 Improvement of Cell Biology in Bioartificial Livers 155 5.6 Bioreactors Enabling Cell Production for Transplantation 157 5.7 Cell Sources for Bioartificial Liver Bioreactors 158 5.7.1 Primary Liver Cells 158 5.7.2 Hepatic Cell Lines 161 5.7.3 Stem Cells 161 5.8 Outlook 163 References 164 6 Bioreactors for Expansion of Pluripotent Stem Cells and Their Differentiation to Cardiac Cells 175 Robert Zweigerdt, Birgit Andree, Christina Kropp, and Henning Kempf 6.1 Introduction 175 6.1.1 Requirement for Advanced Cell Therapies for Heart Repair 175 6.1.2 Pluripotent Stem Cell–Based Strategies for Heart Repair 176 6.2 Culture Technologies for Pluripotent Stem Cell Expansion 179 6.2.1 Matrix-Dependent Cultivation in 2D 179 6.2.2 Outscaling hPSC Production in 2D 179 6.2.3 Hydrogel-Supported Transition to 3D 182 6.3 3D Suspension Culture 182 6.3.1 Advantages of Using Instrumented Stirred Tank Bioreactors 182 6.3.2 Process Inoculation and Passaging Strategies: Cell Clumps Versus Single Cells 186 6.3.3 Microcarriers or Matrix-Free Suspension Culture: Pro and Contra 187 6.3.4 Optimization and Current Limitations of hPSC Processing in Stirred Bioreactors 188 6.4 Autologous Versus Allogeneic Cell Therapies: Practical and Economic Considerations for hPSC Processing 189 6.5 Upscaling hPSC Cardiomyogenic Differentiation in Bioreactors 190 6.6 Conclusion 192 List of Abbreviations 193 References 193 7 Culturing Entrapped Stem Cells in Continuous Bioreactors 201 Rui Tostoes and Paula M. Alves 7.1 Introduction 201 7.2 Materials Used in Stem Cell Entrapment 202 7.3 Synthetic Materials 203 7.3.1 Polymers 203 7.3.2 Peptides 207 7.3.3 Ceramic 208 7.4 Natural Materials 208 7.4.1 Proteins 208 7.4.2 Polysaccharides 209 7.4.3 Complex 211 7.5 Manufacturing and Regulatory Constraints 212 7.6 Mass Transfer in the Entrapment Material 214 7.7 Continuous Bioreactors for Entrapped Stem Cell Culture 216 7.8 Future Perspectives 220 References 221 8 Coping with Physiological Stress During Recombinant Protein Production by Bioreactor Design and Operation 227 Pau Ferrer and Francisco Valero 8.1 Major Physiological Stress Factors in Recombinant Protein Production Processes 227 8.1.1 Physiological Constraints Imposed by High-Cell-Density Cultivation Conditions 227 8.1.2 Metabolic and Physiologic Constraints Imposed by High-Level Expression of Recombinant Proteins 229 8.1.3 Physiological Constraints in Large-Scale Cultures 230 8.2 Monitoring Physiological Stress and Metabolic Load as a Tool for Bioprocess Design and Optimization 230 8.2.1 Monitoring of Physiological Responses to Recombinant Gene Expression Using Flow Cytometry 231 8.2.2 Monitoring of Reporter Metabolites 233 8.2.3 Omics Analytical Tools to Assess the Impact of Recombinant Protein Production on Cell Physiology 233 8.3 Design and Operation Strategies to Minimize/Overcome Problems Associated with Physiological Stress and Metabolic Load 241 8.3.1 Overcoming Overflow Metabolism and Substrate Toxicity 241 8.3.2 Improving the Energy and Building Block Supply 244 8.3.3 Expression Strategies and Recombinant Gene Transcriptional Tuning for Stress Minimization 245 8.4 Bioreactor Design Considerations to Minimize Shear Stress 246 Acknowledgments 247 References 248 9 Design, Applications, and Development of Single-Use Bioreactors 261 Nico M.G. Oosterhuis and Stefan Junne 9.1 Introduction 261 9.2 Design Challenges of Single-Use Bioreactors 263 9.2.1 Material Choice and Testing 263 9.2.2 Sterilization 267 9.2.3 Sensors and Sampling 267 9.2.4 Challenges for Scale-Up and Scale-Down of Single-Use Bioreactors 268 9.2.4.1 Scalability of Stirred Single-Use Bioreactors 270 9.2.4.2 Scalability of Orbital-Shaken Single-Use Bioreactors 273 9.2.4.3 Scalability of Wave-Mixed Single-Use Bioreactors 275 9.2.4.4 Recent Advances in the Description of the Mass Transfer in SUBs 276 9.3 Cell Culture Application 277 9.3.1 Wave-Mixed Bioreactors 277 9.3.2 Stirred Single-Use Bioreactors 278 9.3.3 Orbital-Shaken Single-Use Bioreactors 280 9.3.4 Mass Transfer Requirements for Cell Culture 280 9.3.5 Perfusion Processes in Single-Use Equipment 282 9.3.6 Plant, Phototrophic Algae and Hairy Root Cell Cultivation in Single-Use Bioreactors 284 9.4 Microbial Application of Single-Use Bioreactors 285 9.5 Outlook 288 List of Abbreviations 289 References 290 10 Computational Fluid Dynamics for Bioreactor Design 295 Anurag S. Rathore, Lalita Kanwar Shekhawat, and Varun Loomba 10.1 Introduction 295 10.2 Multiphase Flows 298 10.2.1 Eulerian–Lagrangian Approach 298 10.2.2 Euler–Euler Approach 303 10.2.3 Volume of Fluid Approach (VOF) 304 10.3 Turbulent Flow 305 10.3.1 Reynolds Stress Model 305 10.3.2 k–ε Model 306 10.3.3 Population Balance Model 306 10.4 CFD Simulations 308 10.4.1 Creation of Bioreactor Geometry 308 10.4.2 Meshing of Solution Domain 308 10.4.3 Solver 310 10.5 Case Studies for Application of CFD in Modeling of Bioreactors 310 10.5.1 CaseStudy1:UseofCFDasaToolforEstablishingProcessDesign Space for Mixing in a Bioreactor 311 10.5.2 Case Study 2: Prediction of Two-Phase Mass Transfer Coefficient in Stirred Vessel 313 10.5.3 Case Study 3: Numerical Modeling of Gas–Liquid Flow in Stirred Tanks 315 Summary 318 References 319 11 Scale-Up and Scale-Down Methodologies for Bioreactors 323 Peter Neubauer and Stefan Junne 11.1 Introduction 323 11.2 Bioprocess Scale-Down Approaches 324 11.2.1 A Historical View on the Development of Scale-Down Systems 324 11.2.1.1 Phase 1: Initial Studies of Mixing Behavior and Spatial Distribution Phenomena 325 11.2.1.2 Phase 2: Evolvement of Scale-Down Systems Based on Computational Fluid Dynamics 327 11.2.1.3 Phase 3: Recent Approaches Considering Hybrid Models 328 11.2.2 Scale-Up of Bioreactors 330 11.2.2.1 Dissolved Oxygen Concentration 331 11.2.2.2 Consideration of Similarities and Dimensionless Numbers 332 11.2.2.3 Shear Rate 333 11.2.2.4 Cell Physiology 333 11.2.3 Most Severe Challenges During Scale-Up 333 11.3 Characterization of the Large Scale 334 11.4 Computational Methods to Describe the Large Scale 337 11.5 Scale-Down Experiments and Physiological Responses 340 11.5.1 Scale-Down Experiments with Escherichia coli Cultures 340 11.5.2 Scale-Down Experiments with Corynebacterium glutamicum Cultures 343 11.5.3 Scale-Down Experiments with Bacillus subtilis Cultures 344 11.5.4 Scale-Down Experiments with Yeast Cultures 345 11.5.5 Scale-Down Experiments with Cell Line Cultures 346 11.6 Outlook 346 Nomenclature 347 References 347 12 Integration of Bioreactors with Downstream Steps 355 Ajoy Velayudhan and Nigel Titchener-Hooker 12.1 Introduction 355 12.2 Improvements in Cell-Culture 358 12.3 Interactions with Centrifugation Steps 359 12.4 Interactions with Filtration Steps 360 12.5 Interactions with Chromatographic Steps 361 12.6 Integrated Processes 364 12.7 Integrated Models 366 12.8 Conclusions 367 References 368 13 Multivariate Modeling for Bioreactor Monitoring and Control 369 Jarka Glassey 13.1 Introduction 369 13.2 Analytical Measurement Methods for Bioreactor Monitoring 370 13.2.1 Traditional Measurement Methods 371 13.2.2 Advanced Measurement Methods 372 13.2.2.1 Spectral Methods 372 13.2.2.2 Other Fingerprinting Methods 374 13.2.3 Data Characteristics and Challenges for Modeling 374 13.3 Multivariate Modeling Approaches 376 13.3.1 Feature Extraction and Classification 376 13.3.2 Regression Models 378 13.4 Case Studies 379 13.4.1 Feature Extraction Using PCA 379 13.4.2 Prediction of CQAs 383 13.5 Conclusions 386 Acknowledgments 387 References 387 14 Soft Sensor Design for Bioreactor Monitoring and Control 391 Carl-Fredrik Mandenius and Robert Gustavsson 14.1 Introduction 391 14.2 The Process Analytical Technology Perspective on Soft Sensors 392 14.3 Conceptual Design of Soft Sensors for Bioreactors 394 14.4 "Hardware Sensor" Alternatives 395 14.5 The Modeling Part of Soft Sensors 400 14.6 Strategy for Using Soft Sensors 402 14.7 Applications of Soft Sensors in Bioreactors 403 14.7.1 Online Fluorescence Spectrometry for Estimating Media Components in a Bioreactor 404 14.7.2 Temperature Sensors for Growth Rate Estimation of a Fed-Batch Bioreactor 405 14.7.3 Base Titration for Estimating the Growth Rate in a Batch Bioreactor 407 14.7.4 Online HPLC for the Estimation of Mixed-Acid Fermentation By-Products 409 14.7.5 Electronic Nose and NIR Spectroscopy for Controlling Cholera Toxin Production 411 14.8 Concluding Remarks and Outlook 413 References 414 15 Design-of-Experiments for Development and Optimization of Bioreactor Media 421 Carl-Fredrik Mandenius 15.1 Introduction 421 15.2 Fundamentals of Design-of-Experiments Methodology 422 15.2.1 Screening of Factors 423 15.2.2 Evaluation of the Experimental Design 425 15.2.3 Specific Design-of-Experiments Methods 429 15.3 Optimization of Culture Media by Design-of-Experiments 431 15.3.1 Media for Production of Metabolites and Proteins in Microbial Cultures 432 15.3.2 Media for the Production of Monoclonal Antibodies and Other Proteins in Mammalian Cell Cultures 438 15.3.3 Media for Differentiation and Production of Cells 441 15.3.4 Other Applications to Media Design 443 15.4 Conclusions and Outlook 447 References 448 16 Operator Training Simulators for Bioreactors 453 Volker C. Hass 16.1 Introduction 453 16.2 Simulators in the Process Industry 455 16.3 Training Simulators 456 16.3.1 Training Simulator Types 457 16.3.1.1 Simulators for "Standard" Processes 457 16.3.1.2 Company-Specific Simulators (Taylor-Made Simulators) 457 16.3.1.3 Process Automation and Control 458 16.3.1.4 Training Simulators in Academic Education 458 16.3.2 Training Simulator Purposes 459 16.3.2.1 Training of Process Handling 459 16.3.2.2 Training Simulators Supporting Engineering Tasks 461 16.4 Requirements on Training Simulators 461 16.4.1 Precise Simulation of the Chemical, Biological and Physical Events 462 16.4.2 Realistic Simulation of Automation and Control Actions 462 16.4.3 Real-Time and Accelerated Simulation 463 16.4.4 Realistic User Interfaces 463 16.4.5 Multipurpose Usage 463 16.4.6 Maintainability for User-Friendly Model Updates 464 16.4.7 Adaptability to Modified or Different Processes 464 16.5 Architecture of Training Simulators 464 16.6 Tools and Development Strategies 466 16.7 Process Models and Simulation Technology 468 16.7.1 Process Models 468 16.7.2 Modeling Strategy 471 16.7.3 Software Systems for Model Development 473 16.7.4 Multiple Use of Models 473 16.8 Training Simulator Examples 474 16.8.1 Bioreactor Training Simulator 474 16.8.2 Anaerobic Digestion Training Simulator 477 16.8.3 Bioethanol Plant Simulator 479 16.9 Concluding Remarks 482 References 484 Index 487

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Book SynopsisA one-stop reference that reviews protein design strategies to applications in industrial and medical biotechnology Protein Engineering: Tools and Applications is a comprehensive resource that offers a systematic and comprehensive review of the most recent advances in the field, and contains detailed information on the methodologies and strategies behind these approaches. The authors—noted experts on the topic—explore the distinctive advantages and disadvantages of the presented methodologies and strategies in a targeted and focused manner that allows for the adaptation and implementation of the strategies for new applications. The book contains information on the directed evolution, rational design, and semi-rational design of proteins and offers a review of the most recent applications in industrial and medical biotechnology. This important book: Covers technologies and methodologies used in protein engineering Includes the strategies behind the approaches, designed to help with the adaptation and implementation of these strategies for new applications Offers a comprehensive and thorough treatment of protein engineering from primary strategies to applications in industrial and medical biotechnology Presents cutting edge advances in the continuously evolving field of protein engineering Written for students and professionals of bioengineering, biotechnology, biochemistry, Protein Engineering: Tools and Applications offers an essential resource to the design strategies in protein engineering and reviews recent applications.Table of ContentsPart I Directed Evolution 1 1 Continuous Evolution of Proteins In Vivo 3Alon Wellner, Arjun Ravikumar, and Chang C. Liu 1.1 Introduction 3 1.2 Challenges in Achieving In Vivo Continuous Evolution 5 1.3 Phage-Assisted Continuous Evolution (PACE) 10 1.4 Systems That Allow In Vivo Continuous Directed Evolution 13 1.4.1 Targeted Mutagenesis in E. coli with Error-Prone DNA Polymerase I 13 1.4.2 Yeast Systems That Do Not Use Engineered DNA Polymerases for Mutagenesis 16 1.4.3 Somatic Hypermutation as a Means for Targeted Mutagenesis of GOIs 18 1.4.4 Orthogonal DNA Replication (OrthoRep) 20 1.5 Conclusion 22 References 22 2 In Vivo Biosensors for Directed Protein Evolution 29Song Buck Tay and Ee Lui Ang 2.1 Introduction 29 2.2 Nucleic Acid-Based In Vivo Biosensors for Directed Protein Evolution 32 2.2.1 RNA-Type Biosensors 32 2.2.2 DNA-Type Biosensors 35 2.3 Protein-Based In Vivo Biosensors for Directed Protein Evolution 37 2.3.1 Transcription Factor-Type Biosensors 37 2.3.2 Enzyme-Type Biosensors 41 2.4 Characteristics of Biosensors for In Vivo Directed Protein Evolution 44 2.5 Conclusions and Future Perspectives 45 Acknowledgments 46 References 46 3 High-Throughput Mass Spectrometry Complements Protein Engineering 57Tong Si, Pu Xue, Kisurb Choe, Huimin Zhao, and Jonathan V. Sweedler 3.1 Introduction 57 3.2 Procedures and Instrumentation for MS-Based Protein Assays 59 3.3 Technology Advances Focusing on Throughput Improvement 62 3.4 Applications of MS-Based Protein Assays: Summary 63 3.4.1 Applications of MS-Based Assays: Protein Analysis 64 3.4.2 Applications of MS-Based Assays: Protein Engineering 66 3.5 Conclusions and Perspectives 68 Acknowledgments 68 References 69 4 Recent Advances in Cell Surface Display Technologies for Directed Protein Evolution 81Maryam Raeeszadeh-Sarmazdeh and Wilfred Chen 4.1 Cell Display Methods 81 4.1.1 Phage Display 81 4.1.2 Bacterial Display Systems 83 4.1.3 Yeast Surface Display 84 4.1.4 Mammalian Display 85 4.2 Selection Methods and Strategies 86 4.2.1 High-Throughput Cell Screening 86 4.2.1.1 Panning 86 4.2.1.2 FACS 86 4.2.1.3 MACS 87 4.2.2 Selection Strategies 88 4.2.2.1 Competitive Selection (Counter Selection) 88 4.2.2.2 Negative/Positive Selection 89 4.3 Modifications of Cell Surface Display Systems 89 4.3.1 Modification of YSD for Enzyme Engineering 89 4.3.2 Yeast Co-display System 91 4.3.3 Surface Display of Multiple Proteins 91 4.4 Recent Advances to Expand Cell-Display Directed Evolution Techniques 93 4.4.1 μSCALE (Microcapillary Single-Cell Analysis and Laser Extraction) 93 4.4.2 Combining Cell Surface Display and Next-Generation Sequencing 94 4.4.3 PACE (Phage-Assisted Continuous Evolution) 94 4.5 Conclusion and Outlook 96 References 97 5 Iterative Saturation Mutagenesis for Semi-rational Enzyme Design 105Ge Qu, Zhoutong Sun, and Manfred T. Reetz 5.1 Introduction 105 5.2 Recent Methodology Developments in ISM-Based Directed Evolution 108 5.2.1 Choosing Reduced Amino Acid Alphabets Properly 109 5.2.1.1 Limonene Epoxide Hydrolase as the Catalyst in Hydrolytic Desymmetrization 109 5.2.1.2 Alcohol Dehydrogenase TbSADH as the Catalyst in Asymmetric Transformation of Difficult-to-Reduce Ketones 110 5.2.1.3 P450-BM3 as the Chemo- and Stereoselective Catalyst in a Whole-Cell Cascade Sequence 112 5.2.1.4 Multi-parameter Evolution Aided by Mutability Landscaping 115 5.2.2 Further Methodology Developments of CAST/ISM 117 5.2.2.1 Advances Based on Novel Molecular Biological Techniques and Computational Methods 117 5.2.2.2 Advances Based on Solid-Phase Chemical Synthesis of SM Libraries 118 5.3 B-FIT as an ISM Method for Enhancing Protein Thermostability 120 5.4 Learning from CAST/ISM-Based Directed Evolution 121 5.5 Conclusions and Perspectives 121 Acknowledgment 124 References 124 Part II Rational and Semi-Rational Design 133 6 Data-driven Protein Engineering 135Jonathan Greenhalgh, Apoorv Saraogee, and Philip A. Romero 6.1 Introduction 135 6.2 The Data Revolution in Biology 136 6.3 Statistical Representations of Protein Sequence, Structure, and Function 138 6.3.1 Representing Protein Sequences 138 6.3.2 Representing Protein Structures 140 6.4 Learning the Sequence-Function Mapping from Data 141 6.4.1 Supervised Learning (Regression/Classification) 141 6.4.2 Unsupervised/Semisupervised Learning 144 6.5 Applying Statistical Models to Engineer Proteins 145 6.6 Conclusions and Future Outlook 147 References 148 7 Protein Engineering by Efficient Sequence Space Exploration Through Combination of Directed Evolution and Computational Design Methodologies 153Subrata Pramanik, Francisca Contreras, Mehdi D. Davari, and Ulrich Schwaneberg 7.1 Introduction 153 7.2 Protein Engineering Strategies 154 7.2.1 Computer-Aided Rational Design 155 7.2.1.1 FRESCO 155 7.2.1.2 FoldX 157 7.2.1.3 CNA 158 7.2.1.4 PROSS 159 7.2.1.5 ProSAR 160 7.2.2 Knowledge Based Directed Evolution 161 7.2.2.1 Iterative Saturation Mutagenesis (ISM) 161 7.2.2.2 Mutagenic Organized Recombination Process by Homologous In Vivo Grouping (MORPHING) 161 7.2.2.3 Knowledge Gaining Directed Evolution (KnowVolution) 162 7.3 Conclusions and Future Perspectives 171 Acknowledgments 171 References 171 8 Engineering Artificial Metalloenzymes 177Kevin A. Harnden, Yajie Wang, Lam Vo, Huimin Zhao, and Yi Lu 8.1 Introduction 177 8.2 Rational Design 177 8.2.1 Rational Design of Metalloenzymes Using De Novo Designed Scaffolds 177 8.2.2 Rational Design of Metalloenzymes Using Native Scaffolds 179 8.2.2.1 Redesign of Native Proteins 179 8.2.2.2 Cofactor Replacement in Native Proteins 181 8.2.2.3 Covalent Anchoring in Native Protein 184 8.2.2.4 Supramolecular Anchoring in Native Protein 187 8.3 Engineering Artificial Metalloenzyme by Directed Evolution in Combination with Rational Design 188 8.3.1 Directed Evolution of Metalloenzymes Using De Novo Designed Scaffolds 188 8.3.2 Directed Evolution of Metalloenzymes Using Native Scaffolds 189 8.3.2.1 Cofactor Replacement in Native Proteins 189 8.3.2.2 Covalent Anchoring in Native Protein 192 8.3.2.3 Non-covalent Anchoring in Native Proteins 194 8.4 Summary and Outlook 200 Acknowledgment 201 References 201 9 Engineered Cytochromes P450 for Biocatalysis 207Hanan Alwaseem and Rudi Fasan 9.1 Cytochrome P450 Monooxygenases 207 9.2 Engineered Bacterial P450s for Biocatalytic Applications 210 9.2.1 Oxyfunctionalization of Small Organic Substrates 211 9.2.2 Late-Stage Functionalization of Natural Products 220 9.2.3 Synthesis of Drug Metabolites 224 9.3 High-throughput Methods for Screening Engineered P450s 227 9.4 Engineering of Hybrid P450 Systems 229 9.5 Engineered P450s with Improved Thermostability and Solubility 230 9.6 Conclusions 231 Acknowledgments 232 References 232 Part III Applications in Industrial Biotechnology 243 10 Protein Engineering Using Unnatural Amino Acids 245Yang Yu, Xiaohong Liu, and Jiangyun Wang 10.1 Introduction 245 10.2 Methods for Unnatural Amino Acid Incorporation 246 10.3 Applications of Unnatural Amino Acids in Protein Engineering 247 10.3.1 Enhancing Stability 248 10.3.2 Mechanistic Study Using Spectroscopic Methods 248 10.3.3 Tuning Catalytic Activity 250 10.3.4 Tuning Selectivity 252 10.3.5 Enzyme Design 252 10.3.6 Protein Engineering Toward a Synthetic Life 255 10.4 Outlook 256 10.5 Conclusions 258 References 258 11 Application of Engineered Biocatalysts for the Synthesis of Active Pharmaceutical Ingredients (APIs) 265Juan Mangas-Sanchez, Sebastian C. Cosgrove, and Nicholas J. Turner 11.1 Introduction 265 11.1.1 Transferases 266 11.1.1.1 Transaminases 266 11.1.2 Oxidoreductases 267 11.1.2.1 Ketoreductases 267 11.1.2.2 Amino Acid Dehydrogenases 271 11.1.2.3 Cytochrome P450 Monoxygenases 272 11.1.2.4 Baeyer–Villiger Monoxygenases 273 11.1.2.5 Amine Oxidases 274 11.1.2.6 Hydroxylases 276 11.1.2.7 Imine Reductases 276 11.1.3 Lyases 278 11.1.3.1 Ammonia Lyases 278 11.1.4 Isomerases 278 11.1.5 Hydrolases 279 11.1.5.1 Esterases 279 11.1.5.2 Haloalkane Dehalogenase 279 11.1.6 Multi-enzyme Cascade 281 11.2 Conclusions 282 References 287 12 Directing Evolution of the Fungal Ligninolytic Secretome 295Javier Viña-Gonzalez and Miguel Alcalde 12.1 The Fungal Ligninolytic Secretome 295 12.2 Functional Expression in Yeast 297 12.2.1 The Evolution of Signal Peptides 297 12.2.2 Secretion Mutations in Mature Protein 300 12.2.3 The Importance of Codon Usage 301 12.3 Yeast as a Tool-Box in the Generation of DNA Diversity 302 12.4 Bringing Together Evolutionary Strategies and Computational Tools 305 12.5 High-Throughput Screening (HTS) Assays for Ligninase Evolution 306 12.6 Conclusions and Outlook 309 Acknowledgments 309 References 310 13 Engineering Antibody-Based Therapeutics: Progress and Opportunities 317Annalee W. Nguyen and Jennifer A. Maynard 13.1 Introduction 317 13.2 Antibody Formats 318 13.2.1 Human IgG1 Structure 318 13.2.2 Antibody-Drug Conjugates 319 13.2.3 Bispecific Antibodies 320 13.2.4 Single Domain Antibodies 321 13.2.5 Chimeric Antigen Receptors 321 13.3 Antibody Discovery 322 13.3.1 Antibody Target Identification 322 13.3.1.1 Cancer and Autoimmune Disease Targets 323 13.3.1.2 Infectious Disease Targets 323 13.3.2 Screening for Target-Binding Antibodies 324 13.3.2.1 Synthetic Library Derived Antibodies 324 13.3.2.2 Host-Derived Antibodies 325 13.3.2.3 Immunization 325 13.3.2.4 Pairing the Light and Heavy Variable Regions 326 13.3.2.5 Humanization 327 13.3.2.6 Hybrid Approaches to Antibody Discovery 328 13.4 Therapeutic Optimization of Antibodies 328 13.4.1 Serum Half-Life 328 13.4.1.1 Antibody Half-Life Extension 329 13.4.1.2 Antibody Half-Life Reduction 331 13.4.1.3 Effect of Half-Life Modification on Effector Functions 331 13.4.2 Effector Functions 331 13.4.2.1 Effector Function Considerations for Cancer Therapeutics 332 13.4.2.2 Effector Function Considerations for Infectious Disease Prophylaxis and Therapy 333 13.4.2.3 Effector Function Considerations for Treating Autoimmune Disease 334 13.4.2.4 Approaches to Engineering the Effector Functions of the IgG1 Fc 334 13.4.3 Tissue Localization 335 13.4.4 Immunogenicity 335 13.4.4.1 Reducing T-Cell Recognition 336 13.4.4.2 Reducing Aggregation 336 13.5 Manufacturability of Antibodies 336 13.5.1 Increasing Antibody Yield 337 13.5.1.1 Codon Usage 337 13.5.1.2 Signal Peptide Optimization 337 13.5.1.3 Expression Optimization 338 13.5.2 Alternative Production Methods 338 13.6 Conclusions 339 Acknowledgments 339 References 339 14 Programming Novel Cancer Therapeutics: Design Principles for Chimeric Antigen Receptors 353Andrew J. Hou and Yvonne Y. Chen 14.1 Introduction 353 14.2 Metrics to Evaluate CAR-T Cell Function 354 14.3 Antigen-Recognition Domain 356 14.3.1 Tuning the Antigen-Recognition Domain to Manage Toxicity 356 14.3.2 Incorporation of Multiple Antigen-Recognition Domains to Engineer “Smarter” CARs 356 14.3.3 Novel Antigen-Recognition Domains to Enhance CAR Modularity 359 14.3.4 Engineering CARs that Target Soluble Factors 360 14.4 Extracellular Spacer 360 14.5 Transmembrane Domain 362 14.6 Signaling Domain 362 14.6.1 First- and Second-Generation CARs 362 14.6.2 Combinatorial Co-stimulation 363 14.6.3 Other Co-stimulatory Domains: ICOS, OX40, TLR2 364 14.6.4 Additional Considerations for CAR Signaling Domains 364 14.7 High-Throughput CAR Engineering 366 14.8 Novel Receptor Modalities 367 References 369 Part IV Applications in Medical Biotechnology 377 15 Development of Novel Cellular Imaging Tools Using Protein Engineering 379Praopim Limsakul, Chi-Wei Man, Qin Peng, Shaoying Lu, and Yingxiao Wang 15.1 Introduction 379 15.2 Cellular Imaging Tools Developed by Protein Engineering 380 15.2.1 Fluorescent Proteins 380 15.2.1.1 The FP Color Palette 380 15.2.1.2 Photocontrollable Fluorescent Proteins 381 15.2.1.3 Other Engineered Fluorescent Proteins 383 15.2.2 Antibodies and Protein Scaffolds 383 15.2.2.1 Antibodies 383 15.2.2.2 Antibody-Like Protein Scaffolds 384 15.2.2.3 Directed Evolution 384 15.2.3 Genetically Encoded Non-fluorescent Protein Tags 385 15.3 Application in Cellular Imaging 386 15.3.1 Cell Biology Applications 386 15.3.1.1 Localization 386 15.3.1.2 Cell Signaling 387 15.3.2 Application in Diagnostics and Medicine 390 15.3.2.1 Detection 390 15.3.2.2 Screening for Drugs 392 15.4 Conclusion and Perspectives 393 References 394 Index 403

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Book SynopsisContent has been revised to include updated information on plasma sterilisation, CSSD, and the care bundle approach.

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Book Synopsis

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