Biotechnology Books

Book SynopsisThis book helps individuals make informed choices about in vitro fertilization, abortion, egg freezing, surrogacy, and other matters of reproduction. Scott Gilbert and Clara Pinto-Correia explain why some of the major forms of assisted reproductive technologies were invented, how they are used, and what they can and cannot accomplish.Trade ReviewScott Gilbert and Clara Pinto-Correia come to readers as whole persons in this unusual and much-needed book... Each part of this rich tapestry of stories is woven in an acute consciousness of complex social, personal, and technical histories. Each part requires-as well as nurtures-emotional, intellectual, and sociohistorical intelligence. -- from the foreword by Donna Haraway Impressive in its breadth, Fear, Wonder, and Science in the New Age of Reproductive Biotechnology contains case studies, historical narratives, and ethical conundrums showcasing the advances in our understanding of the basic science of human fertilization and development. Correcting misconceptions that have permeated the mainstream infertility literature, Gilbert and Pinto-Correia write the kind of lucid explanations of these complex technological feats that have probably never reached this readership but should have a long time ago. -- Katayoun Chamany, New School University Every book on science and its social uses should be like this one. But Fear, Wonder, and Science in the New Age of Reproductive Technology is probably an unrepeatable marvel. To bring it to pass, a scientist with philosophical inclinations and literary flair has joined up with a novelist with scientific training and a moving and culturally resonant personal story. They have created what may be the most accessible source to date for how humans are made, how the process can be manipulated technologically, and how benign impulses can go awry in the face of biological and social complexities. -- Stuart Newman, New York Medical College This pathbreaking book is a milestone, giving us a new way of understanding human fertility, reproduction and childbirth. Scott Gilbert and Clara Pinto-Correia's contrasting yet complementary perspectives will educate, enliven, delight and inform any reader. The insights presented here will enable us to question, break, and move beyond the reigning contemporary paradigms of disempowerment, and find the true empowerment that both men and women so sorely need. -- Steven Borish, California State University - East BayTable of ContentsForeword: Making Babies, Making Kin, by Donna HarawayPrefaceAcknowledgmentsPart I. The Importance of the Story1. Conceptual Detox: Returning to Hogwarts to Learn Human Embryology, by Scott Gilbert2. Stories of Infertility and Its Conquest: The Sisterhood of Bloody Mary, by Clara Pinto-CorreiaPart II. Fertilization and Its Discontents3. Fertilization: Two Cells At The Verge of Death Cooperate to Form a New Body That Lasts Decades, by Scott Gilbert4. Fertility Rites: Artificial Insemination and In Vitro Fertilization—Their Hopes and Their Fears, by Clara Pinto-CorreiaPart III. The Mother and Her Fetus 5. Normal Development and The Beginning of Human Life: Why Scientists Are Being Asked Theological Questions and Why Theologians Are Being Asked Scientific Questions, by Scott Gilbert6. Technological Motherhood, by Clara Pinto-CorreiaPart IV. Improving The Human Condition Through Biology: The Reality and the Fantasy7. Cloning Animals, Cells, and Genes: Where Did Cloning Come From, and Where Is It Going to Right Now?, by Scott Gilbert8. Glory Days: My Personal Account of Cloning, by Clara Pinto-CorreiaPart V. Epilogues9. Infertility Wars: How Life Feels After Everything Fails, and, By the Way, How Do We Survive It?, by Clara Pinto-Correia10. The Human Condition of Fear and Wonder: In Celebration of Bodies, by Scott GilbertAppendix: A Field Guide to Assisted Reproductive TechnologiesGlossaryNotesReferencesIndex

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Book SynopsisProgrammable Planet is a grand tour through the world of synthetic biology, telling the stories of the colorful visionaries whose ideas are shaping discoveries. Ted Anton explores the field from its beginning in fighting malaria in Africa to the COVID vaccines and beyond.Trade ReviewProgrammable Planet captures the passion and energy of those at the genesis of the construction of the genetically engineered world. -- Christopher Voigt, Daniel I.C. Wang Professor of Biological Engineering, Massachusetts Institute of TechnologyIf you’ve ever wondered about the promise—and the peril—of synthetic biology and its power to transform life, then Programmable Planet is the book for you. Ted Anton’s exploration of both the history and the future of the ways we engineer life is incisive, engaging, and downright fascinating. -- Deborah Blum, Pulitzer Prize–winning author of The Poison Squad: One Chemist’s Single-Minded Crusade for Food Safety in the Early Twentieth CenturyProgrammable Planet is a thoroughly engaging and enjoyable read. Anton is an expert storyteller who blends the human element with cutting-edge science like a synthetic biologist engineering a novel organism. Timely and at times provocative, the book provides a wonderful grounding for those interested in learning more about synthetic biology’s promise and threat. And we should all be interested in learning more. -- Aoife Brennan, president and chief executive officer, SynlogicIn this rollicking compendium, Anton documents a huge number of ways synthetic biology can be used in practice, embedding these examples in the experiences of the people involved. -- Drew Endy, Stanford UniversityTable of ContentsIntroductionPart I. Beginnings1. A Glass of Absinthe: A Malaria Medicine2. A Radical Philosophy3. Pandora’s Box: The Triumph and Temptation of Gene Editing4. The Silk Road: Directing Evolution5. Wild: Remaking LifePart II. Ripples in the Water6. Rush: Biology-Made Medicines7. New Nature: A Do-It-Yourself Environment8. Hearth and Home9. Fantastic Voyages: Mining and the Military10. The Killers: Viruses as HealersPart III. Bioindustrial Revolution11. Race to a Vaccine12. Global Production: Perils and Profits of a New Science13. The Moirai’s Gift14. To the Planets, and Beyond: Synthetic Biology in Space15. FuturamaAcknowledgmentsTimelineGlossaryFurther ReadingNotesIndex

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Book SynopsisFoundations of Confocal Scanned Imaging in Light Microscopy.- Fundamental Limits in Confocal Microscopy.- Special Optical Elements.- Points, Pixels, and Gray Levels: Digitizing Image Data.- Laser Sources for Confocal Microscopy.- Non-Laser Light Sources for Three-Dimensional Microscopy.- Objective Lenses for Confocal Microscopy.- The Contrast Formation in Optical Microscopy.- The Intermediate Optical System of Laser-Scanning Confocal Microscopes.- Disk-Scanning Confocal Microscopy.- Measuring the Real Point Spread Function of High Numerical Aperture Microscope Objective Lenses.- Photon Detectors for Confocal Microscopy.- Structured Illumination Methods.- Visualization Systems for Multi-Dimensional Microscopy Images.- Automated Three-Dimensional Image Analysis Methods for Confocal Microscopy.- Fluorophores for Confocal Microscopy: Photophysics and Photochemistry.- Practical Considerations in the Selection and Application of Fluorescent Probes.- Guiding Principles of Specimen PreservatioTable of ContentsFoundations of Confocal Scanned Imaging in Light Microscopy.- Fundamental Limits in Confocal Microscopy.- Special Optical Elements.- Points, Pixels, and Gray Levels: Digitizing Image Data.- Laser Sources for Confocal Microscopy.- Non-Laser Light Sources for Three-Dimensional Microscopy.- Objective Lenses for Confocal Microscopy.- The Contrast Formation in Optical Microscopy.- The Intermediate Optical System of Laser-Scanning Confocal Microscopes.- Disk-Scanning Confocal Microscopy.- Measuring the Real Point Spread Function of High Numerical Aperture Microscope Objective Lenses.- Photon Detectors for Confocal Microscopy.- Structured Illumination Methods.- Visualization Systems for Multi-Dimensional Microscopy Images.- Automated Three-Dimensional Image Analysis Methods for Confocal Microscopy.- Fluorophores for Confocal Microscopy: Photophysics and Photochemistry.- Practical Considerations in the Selection and Application of Fluorescent Probes.- Guiding Principles of Specimen Preservation for Confocal Fluorescence Microscopy.- Confocal Microscopy of Living Cells.- Aberrations in Confocal and Multi-Photon Fluorescence Microscopy Induced by Refractive Index Mismatch.- Interaction of Light with Botanical Specimens.- Signal-to-Noise Ratio in Confocal Microscopes.- Comparison of Widefield/Deconvolution and Confocal Microscopy for Three-Dimensional Imaging.- Blind Deconvolution.- Image Enhancement by Deconvolution.- Fiber-Optics in Scanning Optical Microscopy.- Fluorescence Lifetime Imaging in Scanning Microscopy.- Multi-Photon Molecular Excitation in Laser-Scanning Microscopy.- Multifocal Multi-Photon Microscopy.- 4Pi Microscopy.- Nanoscale Resolution with Focused Light: Stimulated Emission Depletion and Other Reversible Saturable Optical Fluorescence Transitions Microscopy Concepts.- Mass Storage, Display, and Hard Copy.- Coherent Anti-Stokes Raman Scattering Microscopy.- Related Methods for Three-Dimensional Imaging.- Tutorial on Practical Confocal Microscopy and Use of the Confocal Test Specimen.- Practical Confocal Microscopy.- Selective Plane Illumination Microscopy.- Cell Damage During Multi-Photon Microscopy.- Photobleaching.- Nonlinear (Harmonic Generation) Optical Microscopy.- Imaging Brain Slices.- Fluorescent Ion Measurement.- Confocal and Multi-Photon Imaging of Living Embryos.- Imaging Plant Cells.- Practical Fluorescence Resonance Energy Transfer or Molecular Nanobioscopy of Living Cells.- Automated Confocal Imaging and High-Content Screening for Cytomics.- Automated Interpretation of Subcellular Location Patterns from Three-Dimensional Confocal Microscopy.- Display and Presentation Software.- When Light Microscope Resolution Is Not Enough:Correlational Light Microscopy and Electron Microscopy.- Databases for Two- and Three-Dimensional Microscopical Images in Biology.- Confocal Microscopy of Biofilms — Spatiotemporal Approaches.- Bibliography of Confocal Microscopy.

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Book SynopsisPharmaceutical Biotechnology offers students taking Pharmacy and related Medical and Pharmaceutical courses a comprehensive introduction to the fast-moving area of biopharmaceuticals.Table of ContentsPreface. Acronyms. 1 Pharmaceuticals, biologics and biopharmaceuticals. 1.1 Introduction to pharmaceutical products. 1.2 Biopharmaceuticals and pharmaceutical biotechnology. 1.3 History of the pharmaceutical industry. 1.4 The age of biopharmaceuticals. 1.5 Biopharmaceuticals: current status and future prospects. 2 Protein structure. 2.1 Introduction. 2.2 Overview of protein structure. 2.3 Higher level structure. 2.4 Protein stability and folding. 2.5 Protein post-translational modifi cation. 3 Gene manipulation and recombinant DNA technology. 3.1 Introduction. 3.2 Nucleic acids: function and structure. 3.3 Recombinant production of therapeutic proteins. 3.4 Classical gene cloning and identifi cation. 4 The drug development process. 4.1 Introduction. 4.2 Discovery of biopharmaceuticals. 4.3 The impact of genomics and related technologies upon drug discovery. 4.4 Gene chips. 4.5 Proteomics. 4.6 Structural genomics. 4.7 Pharmacogenetics. 4.8 Initial product characterization. 4.9 Patenting. 4.10 Delivery of biopharmaceuticals. 4.10.3 Nasal, transmucosal and transdermal delivery systems. 4.11 Preclinical studies. 4.12 Pharmacokinetics and pharmacodynamics. 4.13 Toxicity studies. 4.14 The role and remit of regulatory authorities. 4.15 Conclusion. 5 Sources and upstream processing. 5.1 Introduction. 5.2 Sources of biopharmaceuticals. 5.3 Upstream processing. 6 Downstream processing. 6.1 Introduction. 6.2 Initial product recovery. 6.3 Cell disruption. 6.4 Removal of nucleic acid. 6.5 Initial product concentration. 6.6 Chromatographic purifi cation. 6.7 High-performance liquid chromatography of proteins. 6.8 Purifi cation of recombinant proteins. 6.9 Final product formulation. 7 Product analysis. 7.1 Introduction. 7.2 Protein-based contaminants. 7.3 Removal of altered forms of the protein of interest from the product stream. 7.4 Detection of protein-based product impurities. 7.5 Immunological approaches to detection of contaminants. 7.6 Endotoxin and other pyrogenic contaminants. 8 The cytokines: The interferon family. 8.1 Cytokines. 8.1.1 Cytokine receptors. 8.1.2 Cytokines as biopharmaceuticals. 8.2 The interferons. 8.3 Interferon biotechnology. 8.4 Conclusion. 9 Cytokines: Interleukins and tumour necrosis factor. 9.1 Introduction. 9.2 Interleukin-2. 9.3 Interleukin-1. 9.4 Interleukin-11. 9.5 Tumour necrosis factors. 10 Growth factors. 10.1 Introduction. 10.2 Haematopoietic growth factors. 10.3 Growth factors and wound healing. 11 Therapeutic hormones. 11.1 Introduction. 11.2 Insulin. 11.3 Glucagon. 11.4 Human growth hormone. 11.5 The gonadotrophins. 11.6 Medical and veterinary applications of gonadotrophins. 11.7 Additional recombinant hormones now approved. 11.8 Conclusion. 12 Recombinant blood products and therapeutic enzymes. 12.1 Introduction. 12.2 Haemostasis. 12.3 Anticoagulants. 12.4 Thrombolytic agents. 12.5 Enzymes of therapeutic value. 13 Antibodies, vaccines and adjuvants. 13.1 Introduction. 13.2 Traditional polyclonal antibody preparations. 13.3 Monoclonal antibodies. 13.4 Vaccine technology. 13.5 Adjuvant technology. 14 Nucleic-acid- and cell-based therapeutics. 14.1 Introduction. 14.2 Gene therapy. 14.3 Vectors used in gene therapy. 14.4 Gene therapy and genetic disease. 14.5 Gene therapy and cancer. 14.6 Gene therapy and AIDS. 14.7 Antisense technology. 14.8 Oligonucleotide pharmacokinetics and delivery. 14.9 Aptamers. 14.10 Cell- and tissue-based therapies. 14.11 Conclusion. Index.

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Book SynopsisThe biomaterials technology industry is already well established in the western world and is growing rapidly within Asian Pacific nations. It is often described as the 'next electronics industry', whilst the laser is described as a 'solution looking for a problem'.Table of ContentsAcknowledgements. Introduction. 1. Bioactivity and Biointegration of Orthopaedic and Dental Implants. 1.1. Introduction. 1.3. Biointegration of Orthopaedic and Dental Implants. 1.4. Controlling the Bone-Implant Interface. 2. Surface Modification of Biomaterials. 2.1. Introduction. 2.3. Metallic Implants. 2.4. Surface Modification of Biomaterials. 2.5. Laser Surface Modification of Biomaterials. 3. Wettability in Biomaterials Science and Modification Techniques. 3.1. Introduction. 3.2. Wettability, Adhesion and Bonding Theoretical Background. 3.3. Wettability in Biomaterial Science. 3.4. Current Methods of Wettability Modification. 3.5. Laser Wettability Characteristics Modification. 4. CO2 Laser Modification of the Wettability Characteristics of Magnesia Partially Stabilised Zirconia. 4.1. Introduction. 4.2. Experimental Procedures. 4.3. The Effects of CO2 Laser Radiation on Wettability Characteristics. 4.4. Surface Energy and its Component Parts. 4.5. Identification of the Predominant Mechanisms Active in Determining Wettability Characteristics. 4.6. The Role Played by Microstructures in Terms of Crystal Size and Phase in Effecting Surface Energy Changes. 4.7. Investigation of Wettability and Work Adhesion Using Physiological Liquids. 4.8. Summary. 5. In vitro Biocompatibility Evaluation of CO2 Laser Treated Magnesia Partially Stabilised Zirconia. 5.1. Introduction. 5.2. Sample Preparation. 5.3. Bone Like Apatite Formation. 5.4. Protein Adsorption. 5.5. Osteoblast Cell Response. 5.6. Predictions for Implantation in an in vivo Clinical Situation. 5.7. Summary. 6. The Effects of CO2 Laser Radiation on the Wettability Characteristics of a Titanium Alloy. 6.1. Introduction. 6.2. Experimental Procedures. 6.3. The Effects of CO2 Laser Radiation on Wettability Characteristics. 6.4. Surface Energy and its Component Analysis. 6.5. Identification of the Predominant Mechanisms Active in Determining Wettability Characteristics. 6.6. Investigation of Wettability and Work Adhesion Using Physiological Liquids. 6.7. Summary. 7. In vitro Biocompatibility Evaluation of CO2 Laser Treated Titanium Alloy. 7.1. Introduction. 7.2. Sample Preparation. 7.3. Bone Like Apatite Formation on Titanium Alloys. 7.4. Protein Adsorption. 7.5. Osteoblast Cell Adhesion. 7.6. Predictions for Implantation in an in vivo Clinical Situation. 7.7. Summary. 8. Enquiry into the Possible Generic Effects of the CO2 Laser Treatment on Bone Implant Biomaterials. 8.1. Introduction. 8.2. Ascertaining the Generic Effects of CO2 Laser Treatment on Bioinert Ceramics. 8.3. Ascertaining the Generic Effects of CO2 Laser Treatment on Metal Implants. 8.4. Summary. Conclusions. References. Index.

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Book SynopsisProviding an eclectic snapshot of the current state of the art and future implications of the field, Nanomaterials, Polymers, and Devices: Materials Functionalization and Device Fabrication presents topics grouped into three categorical focuses: The synthesis, mechanism and functionalization of nanomaterials, such as carbon nanotubes, graphene, silica, and quantum dots Various functional devices which properties and structures are tailored with emphasis on nanofabrication. Among discussed are light emitting diodes, nanophotonic, nano-optical, and photovoltaic devices Nanoelectronic devices, which include semiconductor, nanotube and nanowire-based electronics, single-walled carbon-nanotube based nanoelectronics, as well as thin-film transistors Table of ContentsCONTENTS Contributors vii Foreword xi 1 The Functionalization of Carbon Nanotubes and Nano-Onions 1Karthikeyan Gopalsamy, Zhen Xu, Chao Gao, and Eric S.-W. Kong 2 The Functionalization of Graphene and its Assembled Macrostructures 19Haiyan Sun, Zhen Xu, and Chao Gao 3 Devices Based on Graphene and Graphane 45Xiao-Dong Wen, Tao Yang, and Eric S.-W. Kong 4 Large-Area Graphene and Carbon Nanosheets for Organic Electronics: Synthesis and Growth Mechanism 81Han-Ik Joh, Sukang Bae, Sungho Lee, and Eric S.-W. Kong 5 Functionalization of Silica Nanoparticles for Corrosion Prevention of Underlying Metal 121Dylan J. Boday, Jason T. Wertz, and Joseph P. Kuczynski 6 New Nanoscale Material: Graphene Quantum Dots 141Dong-Ick Son and Won-Kook Choi 7 Recent Progress of Iridium(III) Red Phosphors for Phosphorescent Organic Light-Emitting Diodes 195Cheuk-Lam Ho and Wai-Yeung Wong 8 Four-Wave Mixing and Carrier Nonlinearities in Graphene–Silicon Photonic Crystal Cavities 215Tingyi Gu and Chee W. Wong 9 Polymer Photonic Devices 233Ziyang Zhang and Norbert Keil 10 Low Dielectric Contrast Photonic Crystals 273Jan H. Wülbern and Manfred Eich 11 Microring Resonator Arrays for Sensing Applications 291Daniel Pergande, Vanessa Zamora, Peter Lützow, and Helmut Heidrich 12 Polymers, Nanomaterials, and Organic Photovoltaic Devices 319Thomas Tromholt and Frederik C. Krebs 13 Next-Generation GaAs Photovoltaics 341Giacomo Mariani and Diana L. Huffaker 14 Nanocrystals, Layer-by-Layer Assembly, and Photovoltaic Devices 357Jacek J. Jasieniak, Brandon I. MacDonald, and Paul Mulvaney 15 Nanostructured Conductors for Flexible Electronics 395Jonghwa Park, Sehee Ahn, and Hyunhyub Ko 16 Graphene, Nanotube, and NW-Based Electronics 413Xi Liu, Xiaoling Shi, Lei Liao, Zhiyong Fan, and Johnny C. Ho 17 Nanoelectronics Based on Single-Walled Carbon Nanotubes 501Qing Cao and Shu-jen Han 18 Monolithic Graphene–Graphite Integrated Electronics 523Michael C. Wang, Jonghyun Choi, Jaehoon Bang, SungGyu Chun, Brandon Smith, and SungWoo Nam 19 Thin-Film Transistors Based on Transition Metal Dichalcogenides 539Woong Choi and Sunkook Kim Index 563

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Book SynopsisThis book gives an expert view of how the project management approach can be taken forward by the pharmaceutical industry over the next decade. The book integrates portfolio, program, and project management processes as fundamentals for effective and efficient drug product development.Table of ContentsPreface ix Acknowledgments xi About the Authors xiii Part One The Life Science Industry Context for Portfolio, Program, and Project Management 1. A Review of Project Management in Life Science Industry Sectors 3Thomas R. Dunson 2. The Impact of Organizational Size on Drug Project Management 21Eric Morfin 3. Drug Development in Biotechnology and How We Can Do It Better 33Susan Linna Part Two The Portfolio, Program, and Project Management Approaches and Processes 4. An Overview of the Organization and Processes of Portfolio, Program, and Project Management 53Pete Harpum 5. Portfolio Management in the Pharmaceutical Industry: Balancing Corporate Need with the Reality of Delivering Products to the Market 59John Bennett 6. Program Management in Drug Development 85Pauline Stewart-Long 7. Project Control 101Martin Powell 8. Managing Uncertainty in Drug Projects 135Pete Harpum and Thomas R. Dunson 9. Managing Drug Safety Risk 155Thomas R. Dunson and Eric Morfin 10. Developing Program Strategy 175Pete Harpum 11. Developing Products with “Added Value” 197Trevor J. Brown and Stephen Allport Part Three Integrating the Processes 12. Integrated Business Processes to Support Cross-Functional Drug Development 227Martin D. Hynes III 13. Integrated Drug Development: From Cradle to Grave and from Lab to Market 239Stephen Allport and Terry Cooke-Davies 14. The Development of P3M Capability in Drug Development Organizations 259John Arrowsmith, Patrick Grogan, and Bob Moore 15. Implementing Portfolio, Program, and Project Management Best Practices in Drug Development Organizations 287Pete Harpum, Ashley Jamieson, and Inge Fisher Bibliography 311 Index 313

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Book SynopsisA step-by-step, integrated approach for successful, FDA-approved combination drug products Using a proven integrated approach to combination drug development, this book guides you step by step through all the preclinical, clinical, and manufacturing stages.Table of ContentsPreface xi Acknowledgments xiii Contributors xv 1 Overview of Combination Products Development and Regulatory Review 1 Evan B. Siegel 2 Detailed Regulatory Approaches to Development, Review, and Approval 5 James Barquest 2.1 Introduction 5 2.2 General Background 6 2.2.1 Definitions 6 2.2.2 FDA Organization and Jurisdiction 7 2.2.3 Clinical Investigation and Premarket Review Requirements for Drugs, Biological Products, and Medical Devices 11 2.2.4 FDA Information Resources 15 2.3 Combination Products: Regulatory Background 16 2.3.1 Definition 16 2.3.2 Intercenter Agreements 18 2.3.3 Office of Combination Products 19 2.3.4 Primary Mode of Action 20 2.3.5 Intended Use 30 2.3.6 Strategic Regulatory Considerations 31 2.3.7 The Request for Designation (RFD) Process 34 2.3.8 User Fees 44 2.3.9 FDA Meetings: Successful Regulatory Interactions 50 2.3.10 Current Good Manufacturing Practice for Combination Products 59 2.4 Postmarketing Considerations 67 2.4.1 Adverse Event Reporting 68 2.4.1.1 Device Malfunction Reporting (21 CFR 803.3(r)(2)(ii), 21 CFR 803.20) 68 2.4.1.2 Five-Day MDR Reporting (21 CFR 803.10(c)(2)(i)) 68 2.4.1.3 Drug and Biological Product “Alert” Reporting (21 CFR 314.80(c)(1) and 600.80(c)(1)) 73 2.4.1.4 Blood-Related Deaths (21 CFR 606.170) 73 2.4.2 Other Compliance Issues 73 References 74 3 Nonclinical Recommendations for Successful Characterization and Development of Combination Drug Products 77 Duane B. Lakings 3.1 Introduction 77 3.2 Pharmacology 79 3.2.1 Pharmacology and Safety Pharmacology Recommendations for CDPs with Multiple Marketed Drugs 80 3.2.2 Pharmacology and Safety Pharmacology Recommendations for CDPs with Marketed Drugs and a Single NME 83 3.2.3 Pharmacology and Safety Pharmacology Recommendations for CDPs with More Than One NME 83 3.3 Pharmacokinetics 84 3.3.1 Pharmacokinetic and Drug Metabolism Recommendations for CDPs with Multiple Marketed Drugs 89 3.3.2 Pharmacokinetic and Drug Metabolism Recommendations for CDPs with Marketed Drugs and a Single NME 91 3.3.3 Pharmacokinetic and Drug Metabolism Recommendations for CDPs with More Than One NME 91 3.4 Toxicology 92 3.4.1 Toxicology Recommendations for CDPs with Multiple Marketed Drugs 98 3.4.2 Toxicology Recommendations for CDPs with Marketed Drugs and a Single NME 102 3.4.3 Toxicology Recommendations for CDPs with More Than One NME 104 3.5 Conclusions 108 References 109 4 Clinical Pharmacology and Clinical Development of Combination Products 113 Chaline Brown 4.1 Introduction 113 4.2 Postapproval Clinical Safety Reporting 115 4.3 Clinical Development of Drug–Delivery System Combination Products 116 4.3.1 Advantages of a New Delivery Device Drug Product 117 4.3.1.1 Streamlined Regulatory Process Possible 117 4.3.1.2 Improvement in Efficacy over Previously Approved Delivery Routes 117 4.3.1.3 Noninjection Bioavailability for Peptides and Proteins 118 4.3.2 Considerations for a Combination Product with a Novel Delivery Route 119 4.3.2.1 Impact of Infusion Pumps on Pharmacodynamic Effects 119 4.3.2.2 Route-Dependent Pharmaceutical Metabolic Profile 119 4.3.2.3 Inherent Delivery Site Sensitivity 119 4.3.2.4 Addressing Concerns Regarding the Safety of Excipients in Novel Routes of Delivery 120 4.3.2.5 Addressing Concerns of Possible Immune System Reactions During Development 120 4.3.2.6 Addressing Effects Specific to Human Physiology During Development 120 4.3.2.7 Addressing Formulation Changes During Clinical Development 121 4.3.3 Case Study: Exubera® (Pfizer’s inhaled insulin, approved January 2006) 121 4.4 Clinical Development of Drug–Active Device Combination Products 127 4.4.1 Case Study: The Drug-Eluting Stent (DES) 128 4.4.2 Changing Scene for New DES Products 132 4.5 Clinical Development of Co-Packaged Combination Products 134 4.5.1 Co-Packaged Drug and Biologic Case Study: Interferon and Ribavirin for the Treatment of Hepatitis C 135 4.6 Clinical Development of Drug–In Vitro Diagnostic Combination Products 140 4.6.1 Retrospective Changes in Drug Labeling to Incorporate Genetic Tests 143 4.6.2 Prospective Co-Development of Drugs and In Vitro Diagnostics 144 4.6.3 Issues Surrounding Biomarker Development 146 4.6.4 Clinical Trial Design Issues in Drug–In Vitro Diagnostic Co-Development 147 4.6.5 FDA Guidance 149 4.6.6 Case Study: Herceptin® and HercepTest® 150 4.7 Clinical Development of Drug–Biologic Combination Products 153 4.7.1 Case Study 1: Mylotarg® (Monoclonal Antibody Linked to a Cytotoxic Drug) 154 4.7.2 Case Study 2: Bexxar® (Monoclonal Antibody Linked to a Radioisotope) 157 4.8 Clinical Development of Drug–Drug Combinations 160 4.8.1 General Considerations for FDC Efficacy Studies 162 4.8.2 Case Study: CombinatoRx, with Combination Therapy as a Business Model 163 4.9 Conclusion 165 References 165 5 Regulatory Strategy Considerations for Chemistry, Manufacturing, and Controls: An Integrated Approach 171 Patrick L. DeVillier 5.1 Introduction 171 5.2 Office of Combination Products (OCP) and Request for Designation (RFD) 172 5.3 Extent of Regulatory Oversight 173 5.4 Investigational Device Exemption and Investigational New Drug Exemption 174 5.5 Regulatory Compliant Product Development 175 5.6 Chemistry, Manufacturing, and Controls Review Requirements 177 5.7 Drug Component Requirements 178 5.8 Device Component Requirements 179 5.9 Sterilization Considerations 179 5.10 Stability Considerations 180 5.11 Bench Testing and Early Development Considerations 180 5.12 CDP Regulatory Cross-Mapping Guidance and Recommendations 181 5.13 Conclusions 200 References 200 List of Abbreviations 201 Index 205

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Book SynopsisProvides an introductory survey of nanotechnology. Based on the highly acclaimed 2003 Wiley title Introduction to Nanotechnology , This new textbook includes problem sets for each chapter, updated material from the earlier book, and rewritten sections to be more pedagogical in nature. .Trade Review"This book would be an excellent choice for a one- or two-semester course in a materials science, chemistry, or physics course. It would also be of interest to any of our readers interested in learning about nanotechnology. It is written to provide the reader with a sound foundation for understanding the key fundamentals of nanotechnology. This book will be popular." (IEEE Electrical Insulation Magazine, January/February 2009)Table of ContentsPreface xv 1. Physics of Bulk Solids 1 1.1 Structure 1 1.1.1 Size Dependence of Properties 1 1.1.2 Crystal Structures 2 1.1.3 Face-Centered Cubic Nanoparticles 7 1.1.4 Large Face-Centered Cubic Nanoparticles 9 1.1.5 Tetrahedrally Bonded Semiconductor Structures 10 1.1.6 Lattice Vibrations 14 1.2 Surfaces of Crystals 16 1.2.1 Surface Characteristics 16 1.2.2 Surface Energy 17 1.2.3 Face-Centered Cubic Surface Layers 18 1.2.4 Surfaces of Zinc Blende and Diamond Structures 21 1.2.5 Adsorption of Gases 23 1.2.6 Electronic Structure of a Surface 25 1.2.7 Surface Quantum Well 26 1.3 Energy Bands 26 1.3.1 Insulators, Semiconductors, and Conductors 26 1.3.2 Reciprocal Space 27 1.3.3 Energy Bands and Gaps of Semiconductors 28 1.3.4 Effective Mass 34 1.3.5 Fermi Surfaces 35 1.4 Localized Particles 36 1.4.1 Donors, Acceptors, and Deep Traps 36 1.4.2 Mobility 37 1.4.3 Excitons 38 Problems 40 References 41 2. Methods of Measuring Properties of Nanostructures 43 2.1 Introduction 43 2.2 Structure 44 2.2.1 Atomic Structures 44 2.2.2 Crystallography 45 2.2.3 Particle Size Determination 50 2.2.4 Surface Structure 54 2.3 Microscopy 54 2.3.1 Transmission Electron Microscopy 54 2.3.2 Field Ion Microscopy 59 2.3.3 Scanning Microscopy 59 2.4 Spectroscopy 66 2.4.1 Infrared and Raman Spectroscopy 66 2.4.2 Photoemission, X-Ray, and Auger Spectroscopy 72 2.4.3 Magnetic Resonance 78 2.5 Various Bulk Properties 81 2.5.1 Mechanical Properties 81 2.5.2 Electrical Properties 81 2.5.3 Magnetic Properties 82 2.5.4 Other Properties 82 Problems 82 References 83 3. Properties of Individual Nanoparticles 85 3.1 Introduction 85 3.2 Metal Nanoclusters 86 3.2.1 Magic Numbers 86 3.2.2 Theoretical Modeling of Nanoparticles 88 3.2.3 Geometric Structure 91 3.2.4 Electronic Structure 94 3.2.5 Reactivity 97 3.2.6 Fluctuations 100 3.2.7 Magnetic Clusters 100 3.2.8 Bulk-to-Nano Transition 103 3.3 Semiconducting Nanoparticles 104 3.3.1 Optical Properties 104 3.3.2 Photofragmentation 106 3.3.3 Coulomb Explosion 107 3.4 Rare-Gas and Molecular Clusters 107 3.4.1 Inert-Gas Clusters 107 3.4.2 Superfluid Clusters 108 3.4.3 Molecular Clusters 109 3.4.4 Nanosized Organic Crystals 111 3.5 Methods of Synthesis 111 3.5.1 RF Plasma 111 3.5.2 Chemical Methods 111 3.5.3 Thermolysis 112 3.5.4 Pulsed-Laser Methods 114 3.5.5 Synthesis of Nanosized Organic Crystals 114 3.6 Summary 118 Problems 118 4. The Chemistry of Nanostructures 121 4.1 Chemical Synthesis of Nanostructures 121 4.1.1 Solution Synthesis 121 4.1.2 Capped Nanoclusters 122 4.1.3 Solgel Processing 124 4.1.4 Electrochemical Synthesis of Nanostructures 125 4.2 Reactivity of Nanostructures 125 4.3 Catalysis 127 4.3.1 Nature of Catalysis 127 4.3.2 Surface Area of Nanoparticles 127 4.3.3 Porous Materials 131 4.4 Self-Assembly 135 4.4.1 The Self-Assembly Process 135 4.4.2 Semiconductor Islands 136 4.4.3 Monolayers 139 Problems 141 5. Polymer and Biological Nanostructures 143 5.1 Polymers 143 5.1.1 Polymer Structure 143 5.1.2 Sizes of Polymers 146 5.1.3 Nanocrystals of Polymers 148 5.1.4 Conductive Polymers 151 5.1.5 Block Copolymers 152 5.2 Biological Nanostructures 154 5.2.1 Sizes of Biological Nanostructures 154 5.2.2 Polypeptide Nanowire and Protein Nanoparticles 160 5.2.3 Nucleic Acids 162 5.2.3.1 DNA Double Nanowire 162 5.2.3.2 Genetic Code and Protein Synthesis 166 5.2.3.3 Proteins 167 5.2.3.4 Micelles and Vesicles 169 5.2.3.5 Multilayer Films 172 Problems 174 References 174 6. Cohesive Energy 177 6.1 Ionic Solids 177 6.2 Defects in Ionic Solids 183 6.3 Covalently Bonded Solids 185 6.4 Organic Crystals 186 6.5 Inert-Gas Solids 190 6.6 Metals 191 6.7 Conclusion 193 Problems 193 7. Vibrational Properties 195 7.1 The Finite One-Dimensional Monatomic Lattice 195 7.2 Ionic Solids 197 7.3 Experimental Observations 199 7.3.1 Optical and Acoustical Modes 199 7.3.2 Vibrational Spectroscopy of Surface Layers of Nanoparticles 201 7.3.2.1 Raman Spectroscopy of Surface Layers 201 7.3.2.2 Infrared Spectroscopy of Surface Layers 201 7.4 Phonon Confinement 207 7.5 Effect of Dimension on Lattice Vibrations 209 7.6 Effect of Dimension on Vibrational Density of States 211 7.7 Effect of Size on Debye Frequency 215 7.8 Melting Temperature 216 7.9 Specific Heat 218 7.10 Plasmons 220 7.11 Surface-Enhanced Raman Spectroscopy 222 7.12 Phase Transitions 223 Problems 226 References 227 8. Electronic Properties 229 8.1 Ionic Solids 229 8.2 Covalently Bonded Solids 232 8.3 Metals 234 8.3.1 Effect of Lattice Parameter on Electronic Structure 235 8.3.2 Free-Electron Model 235 8.3.3 The Tight-Binding Model 239 8.4 Measurements of Electronic Structure of Nanoparticles 242 8.4.1 Semiconducting Nanoparticles 242 8.4.2 Organic Solids 248 8.4.3 Metals 250 Problems 251 9. Quantum Wells, Wires, and Dots 253 9.1 Introduction 253 9.2 Fabricating Quantum Nanostructures 253 9.2.1 Solution Fabrication 254 9.2.2 Lithography 257 9.3 Size and Dimensionality Effects 261 9.3.1 Size Effects 261 9.3.2 Size Effects on Conduction Electrons 263 9.3.3 Conduction Electrons and Dimensionality 264 9.3.4 Fermi Gas and Density of States 265 9.3.5 Potential Wells 268 9.3.6 Partial Confinement 272 9.3.7 Properties Dependent on Density of States 273 9.4 Excitons 275 9.5 Single-Electron Tunneling 276 9.6 Applications 280 9.6.1 Infrared Detectors 280 9.6.2 Quantum Dot Lasers 280 Problems 285 References 285 10. Carbon Nanostructures 287 10.1 Introduction 287 10.2 Carbon Molecules 287 10.2.1 Nature of the Carbon Bond 287 10.2.2 New Carbon Structures 289 10.3 Carbon Clusters 289 10.3.1 Small Carbon Clusters 289 10.3.2 Buckyball 292 10.3.3 The Structure of Molecular C60 293 10.3.4 Crystalline C60 296 10.3.5 Larger and Smaller Buckyballs 300 10.3.6 Buckyballs of Other Atoms 300 10.4 Carbon Nanotubes 301 10.4.1 Fabrication 301 10.4.2 Structure 304 10.4.3 Electronic Properties 306 10.4.4 Vibrational Properties 312 10.4.5 Functionalization 314 10.4.6 Doped Carbon Nanotubes 322 10.4.7 Mechanical Properties 325 10.5 Nanotube Composites 327 10.5.1 Polymer–Carbon Nanotube Composites 327 10.5.2 Metal–Carbon Nanotube Composites 329 10.6 Graphene Nanostructures 330 Problems 335 11. Bulk Nanostructured Materials 337 11.1 Solid Methods for Preparation of Disordered Nanostructures 337 11.1.1 Methods of Synthesis 337 11.1.2 Metal Nanocluster Composite Glasses 340 11.1.3 Porous Silicon 343 11.2 Nanocomposites 347 11.2.1 Layered Nanocomposites 347 11.2.2 Nanowire Composites 349 11.2.3 Composites of Nanoparticles 350 11.3 Nanostructured Crystals 351 11.3.1 Natural Nanocrystals 351 11.3.2 Crystals of Metal Nanoparticles 352 11.3.3 Arrays of Nanoparticles in Zeolites 355 11.3.4 Nanoparticle Lattices in Colloidal Suspensions 357 11.3.5 Computational Prediction of Cluster Lattices 358 11.4 Electrical Conduction in Bulk Nanostructured Materials 359 11.4.1 Bulk Materials Consisting of Nanosized Grains 359 11.4.2 Nanometer-Thick Amorphous Films 364 11.5 Other Properties 364 Problems 365 12. Mechanical Properties of Nanostructured Materials 367 12.1 Stress–Strain Behavior of Materials 367 12.2 Failure Mechanisms of Conventional Grain-Sized Materials 370 12.3 Mechanical Properties of Consolidated Nano-Grained Materials 371 12.4 Nanostructured Multilayers 374 12.5 Mechanical and Dynamical Properties of Nanosized Devices 376 12.5.1 General Considerations 376 12.5.2 Nanopendulum 378 12.5.3 Vibrations of a Nanometer String 380 12.5.4 The Nanospring 381 12.5.5 The Clamped Beam 382 12.5.6 The Challenges and Possibilities of Nanomechanical Sensors 385 12.5.7 Methods of Fabrication of Nanosized Devices 387 Problems 390 13. Magnetism in Nanostructures 393 13.1 Basics of Ferromagnetism 393 13.2 Behavior of Powders of Ferromagnetic Nanoparticles 398 13.2.1 Properties of a Single Ferromagnetic Nanoparticle 398 13.2.2 Dynamics of Individual Magnetic Nanoparticles 400 13.2.3 Measurements of Superparamagnetism and the Blocking Temperature 402 13.2.4 Nanopore Containment of Magnetic Particles 405 13.3 Ferrofluids 406 13.4 Bulk Nanostructured Magnetic Materials 413 13.4.1 Effect of Nanosized Grain Structure on Magnetic Properties 413 13.4.2 Magnetoresistive Materials 416 13.4.3 Carbon Nanostructured Ferromagnets 424 13.5 Antiferromagnetic Nanoparticles 429 Problems 430 14. Nanoelectronics, Spintronics, Molecular Electronics, and Photonics 433 14.1 Nanoelectronics 433 14.1.1 N and P Doping and PN Junctions 433 14.1.2 MOSFET 435 14.1.3 Scaling of MOSFETs 436 14.2 Spintronics 440 14.2.1 Definition and Examples of Spintronic Devices 440 14.2.2 Magnetic Storage and Spin Valves 440 14.2.3 Dilute Magnetic Semiconductors 445 14.3 Molecular Switches and Electronics 449 14.3.1 Molecular Switches 449 14.3.2 Molecular Electronics 453 14.3.3 Mechanism of Conduction through a Molecule 458 14.4 Photonic Crystals 459 Problems 465 Reference 466 15. Superconductivity in Nanomaterials 467 15.1 Introduction 467 15.2 Zero Resistance 467 15.2.1 The Superconducting Gap 469 15.2.2 Cooper Pairs 470 15.3 The Meissner Effect 472 15.3.1 Magnetic Field Exclusion 472 15.3.2 Type I and Type II Superconductors 474 15.4 Properties of Flux 478 15.4.1 Quantization of Flux 478 15.4.2 Vortex Configurations 479 15.4.3 Flux Creep and Flux Flow 480 15.4.4 Vortex Pinning 484 15.5 Dependence of Superconducting Properties on Size Effects 484 15.6 Resistivity and Sheet Resistance 484 15.7 Proximity Effect 488 15.8 Superconductors as Nanomaterials 490 15.9 Tunneling and Josephson Junctions 491 15.9.1 Tunneling 491 15.9.2 Weak Links 491 15.9.3 Josephson Effect 493 15.9.4 Josephson Junctions 494 15.9.5 Ultrasmall Josephson Junctions 494 15.10 Superconducting Quantum Interference Device (Squid) 495 15.11 Buckministerfullerenes 496 15.11.1 The Structure of C60 and Its Crystal 496 15.11.2 Alkali-Doped C60 496 15.11.3 Superconductivity in C60 497 Problems 498 References 499 Appendix A Formulas for Dimensionality 501 A.1 Introduction 501 A.2 Delocalization 501 A.3 Square and Parabolic Wells 502 A.4 Partial Confinement 503 Appendix B Tabulations of Semiconducting Material Properties 507 Appendix C Face-Centered Cubic and Hexagonal Close-Packed Nanoparticles 515 C.1 Introduction 515 C.2 Face-Centered Cubic Nanoparticles 515 C.3 Hexagonal Close-Packed Nanoparticles 519 Index 521

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Book SynopsisThis book highlights the importance and recent success of computational intelligence methods over a diverse range of bioinformatics problems. It encourages others to use these methods and approaches in their research, while also serving as an introduction to computational intelligence methods and applications to the consumers of the research.Table of ContentsPreface. Contributors. Part One Gene Expression Analysis and Systems Biology. 1. Hybrid of Neural Classifi er and Swarm Intelligence in Multiclass Cancer Diagnosis with Gene Expression Signatures (Rui Xu, Georgios C. Anagnostopoulos, and Donald C. Wunsch II). 1.1 Introduction. 1.2 Methods and Systems. 1.3 Experimental Results. 1.4 Conclusions. 2. Classifying Gene Expression Profi les with Evolutionary Computation (Jin-Hyuk Hong and Sung-Bae Cho). 2.1 DNA Microarray Data Classifi cation. 2.2 Evolutionary Approach to the Problem. 2.3 Gene Selection with Speciated Genetic Algorithm. 2.4 Cancer Classifi ction Based on Ensemble Genetic Programming. 2.5 Conclusion. 3. Finding Clusters in Gene Expression Data Using EvoCluster (Patrick C. H. Ma, Keith C. C. Chan, and Xin Yao). 3.1 Introduction. 3.2 Related Work. 3.3 Evolutionary Clustering Algorithm. 3.4 Experimental Results. 3.5 Conclusions. 4. Gene Networks and Evolutionary Computation (Jennifer Hallinan). 4.1 Introduction. 4.2 Evolutionary Optimization. 4.3 Computational Network Modeling. 4.4 Extending Reach of Gene Networks. 4.5 Network Topology Analysis. 4.6 Summary. Part Two Sequence Analysis and Feature Detection. 5. Fuzzy-Granular Methods for Identifying Marker Genes from Microarray Expression Data (Yuanchen He, Yuchun Tang, Yan-Qing Zhang, and Rajshekhar Sunderraman). 5.1 Introduction. 5.2 Traditional Algorithms for Gene Selection. 5.3 New Fuzzy-Granular-Based Algorithm for Gene Selection. 5.4 Simulation. 5.5 Conclusions. 6. Evolutionary Feature Selection for Bioinformatics (Laetitia Jourdan, Clarisse Dhaenens, and El-Ghazali Talbi). 6.1 Introduction. 6.2 Evolutionary Algorithms for Feature Selection. 6.3 Feature Selection for Clustering in Bioinformatics. 6.4 Feature Selection for Classifi cation in Bioinformatics. 6.5 Frameworks and Data Sets. 6.6 Conclusion. 7. Fuzzy Approaches for the Analysis CpG Island Methylation Patterns (Ozy Sjahputera, Mihail Popescu, James M. Keller, and Charles W. Caldwell). 7.1 Introduction. 7.2 Methods. 7.3 Biological Signifi cance. 7.4 Conclusions. Part Three Molecular Structure and Phylogenetics. 8. Protein–Ligand Docking with Evolutionary Algorithms(René Thomsen). 8.1 Introduction. 8.2 Biochemical Background. 8.3 The Docking Problem. 8.4 Protein–Ligand Docking Algorithms. 8.5 Evolutionary Algorithms. 8.6 Effect of Variation Operators. 8.7 Differential Evolution. 8.8 Evaluating Docking Methods. 8.9 Comparison between Docking Methods. 8.10 Summary. 8.11 Future Research Topics. 9. RNA Secondary Structure Prediction Employing Evolutionary Algorithms (Kay C. Wiese, Alain A. Deschênes, and Andrew G. Hendriks). 9.1 Introduction. 9.2 Thermodynamic Models. 9.3 Methods. 9.4 Results. 9.5 Conclusion. 10. Machine Learning Approach for Prediction of Human Mitochondrial Proteins (Zhong Huang, Xuheng Xu, and Xiaohua Hu). 10.1 Introduction. 10.2 Methods and Systems. 10.3 Results and Discussion. 10.4 Conclusions. 11. Phylogenetic Inference Using Evolutionary Algorithms(Clare Bates Congdon). 11.1 Introduction. 11.2 Background in Phylogenetics. 11.3 Challenges and Opportunities for Evolutionary Computation. 11.4 One Contribution of Evolutionary Computation: Graphyl. 11.5 Some Other Contributions of Evolutionary computation. 11.6 Open Questions and Opportunities. Part Four Medicine. 12. Evolutionary Algorithms for Cancer Chemotherapy Optimization (John McCall, Andrei Petrovski, and Siddhartha Shakya). 12.1 Introduction. 12.2 Nature of Cancer. 12.3 Nature of Chemotherapy. 12.4 Models of Tumor Growth and Response. 12.5 Constraints on Chemotherapy. 12.6 Optimal Control Formulations of Cancer Chemotherapy. 12.7 Evolutionary Algorithms for Cancer Chemotherapy Optimization. 12.8 Encoding and Evaluation. 12.9 Applications of EAs to Chemotherapy Optimization Problems. 12.10 Related Work. 12.11 Oncology Workbench. 12.12 Conclusion. 13. Fuzzy Ontology-Based Text Mining System for Knowledge Acquisition, Ontology Enhancement, and Query Answering from Biomedical Texts (Lipika Dey and Muhammad Abulaish). 13.1 Introduction. 13.2 Brief Introduction to Ontologies. 13.3 Information Retrieval form Biological Text Documents: Related Work. 13.4 Ontology-Based IE and Knowledge Enhancement System. 13.5 Document Processor. 13.6 Biological Relation Extractor. 13.7 Relation-Based Query Answering. 13.8 Evaluation of the Biological Relation Extraction Process. 13.9 Biological Relation Characterizer. 13.10 Determining Strengths of Generic Biological Relations. 13.11 Enhancing GENIA to Fuzzy Relational Ontology. 13.12 Conclusions and Future Work. References. Appendix Feasible Biological Relations. Index.

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Book SynopsisA real-world guide to the production and manufacturing of biopharmaceuticals While much has been written about the science of biopharmaceuticals, there is a need for practical, up-to-date information on key issues at all stages of developing and manufacturing commercially viable biopharmaceutical drug products. This book helps fill the gap in the field, examining all areas of biopharmaceuticals manufacturing, from development and formulation to production and packaging. Written by a group of experts from industry and academia, the book focuses on real-world methods for maintaining product integrity throughout the commercialization process, clearly explaining the fundamentals and essential pathways for all development stages. Coverage includes: Research and early development phase?appropriate approaches for ensuring product stability Development of commercially viable formulations for liquid and lyophilized dosage forms Trade Review"This book is intended as a comprehensive look at the growing area of producing and manufacturing biopharmaceuticals, right the way through from development to commercialisation. Each chapter is written by an expert in that area and authors hail from both industry and academia." (TCE- The Chemical Engineer, 1 December 2010)Table of ContentsIntroduction (John Carpenter). Part I Preformulation and Development of Stability Indicating Assays: Biophysical Characterization Techniques. 1. The Structure of Biological Therapeutics (Sherry Martin-Moe, Y. John Wang, Tim Osslund, Tahir Mahmood, Rohini Deshpande, and Susan Hershenson). 2. Chemical Instability in Peptide and Protein Pharmaceuticals (Elizabeth M. Topp, Lei Zhang, Hong Zhao, Robert W. Payne, Gabriel J. Evans and Mark Cornell Manning). 3. Physical Instability in Peptide and Protein Pharmaceuticals (Byeong Chang and Bernice Yang). 4. Immunogenicity of Therapeutic Proteins (Steven J Swanson). 5. Preformulation Research: Assessing Protein Solution Behavior Early During Therapeutic Development (Bernardo Perez-Ramirez, Nicholas Guziewicz and Robert Simler). 6. Formulation Development of Phase I/II Biopharmaceuticals: An Efficient and Timely Approach (Nicholas W. Warne). 7. Late Stage Formulation Development and Characterization of Biopharmaceuticals (Adeolla O Grillo). 8. An Empirical Phase Diagram/ High Throughput Screening Approach to the Characterization and Formulation of Biopharmaceuticals (Sangeeta B. Joshi; Akhilesh Bhambhani; Yuhong Zeng; and C. Russell Middaugh). 9. Fluorescence and Phosphorescence Methods to Probe Protein Structure and Stability in Ice: the Case of Azurin (Giovanni Strambini). 10. Applications of Sedimentation Velocity Analytical Ultracentrifugation (Tom Laue). 11. Field Flow Fractionation with Multi-angle Light Scattering for Measuring Particle Size of Virus-like Particles (Joyce A Sweeney and Christopher Hamm). 12. Light Scattering Techniques and their Application to Formulation and Aggregation Concerns (Philip Wyatt and Michael Larkin). Part 2 Development of a Formulation for Liquid Dosage Form. 13. Efficient Approaches to Formulation Development of Biopharmaceuticals (Rajiv Nayar and Mitra Mosharraf). 14. Prediction of Protein Aggregation Propensities from Primary Sequence Information (Mark Cornell Manning, Gabriel J. Evans, Cody M. Van Pelt and Robert W. Payne). 15. High Concentration Antibody Formulations (Steven J. Shire, Jun Liu, Wolfgang Friess, Susanne Matheus and Hanns-Christian Mahler). 16. Development of Formulations for Therapeutic Monoclonal Antibodies and Fc Fusion Proteins (Sampath kumar Krishnan, Monica M. Pallitto and Margaret S. Ricci). 17. Reversible Self-Association of Pharmaceutical Proteins: Characterization and Case Studies (Vikas K. Sharma, Harminder Bajaj and Devendra S. Kalonia). Part 3 Development of Formulation for Lyophilized Dosage Form. 18. Design of a Formulation for Freeze Drying (Feroz Jameel and Mike J. Pikal). 19. Protein Conformation and Reactivity in Amorphous Solids (Lei Zhang, Sandipan Sinha and Elizabeth M. Topp). 20. The Impact of Buffer on Solid-State Properties and Stability of Freeze-Dried Dosage Forms (Evgenyi Y. Shalaev and Larry A. Gatlin). 21. Stabilization of Lyophilized Pharmaceuticals by Control of Molecular Mobility: Impact of Thermal History (Suman Luthra and Micheal J. Pikal). 22. Structural Analysis of Proteins in Dried Matrices (Andrea Hawe, Sandipan Sinha, Wolfgang Friess and Wim Jiskoot). 23. The Impact of Formulation and Drying Processes on the Characteristics and Performance of Biopharmaceutical Powders (Vu L. Truong and Ahmad M. Abdul-Fattah). Part 4 Manufacturing Sciences. 24. Manufacturing Fundamentals for Biopharmaceuticals (Maninder Hora). 25. Protein Stability during Bioprocessing (Mark Cornell Manning, Gabriel J. Evans and Robert W. Payne). 26. Freezing and Thawing of Protein Solutions (Satish Singh and Sandeep Neema). 27. Strategies for Bulk Storage and Shipment of Proteins (Feroz Jameel, Chakradhar Padala and Theodore W. Randolph). 28. Drying Process Methods for Biopharmaceutical Products: An Overview (Ahmad M. Abdul-Fattah and Vu L. Truong). 29. Spray Drying of Biopharmaceuticals and Vaccines (Jim Searles and Govindan (Dan) Mohan). 30. Development and Optimization of Freeze Drying Process (Feroz Jameel and Jim Searles). 31. Considerations for Successful Lyophilization Process Scale-up, Technology Transfer and Routine Production (Samir Sane and Chung C. Hsu). 32. Process Robustness in Freeze-Drying of Biopharmaceuticals (D.Q. Wang, D. MacLean and X. Ma). 33. Filling Processes and Technologies for Liquid Biopharmaceuticals (Ananth Sethuraman, Xiaogang Pan, Bhavya Mehta and Vinay Radhakrishnan). 34. Leachables and Extractables (Jim Castner, Pedro Benites and Michael Bresnick). 35. Primary Container/Closure Selection for Biopharmaceuticals (Olivia Henderson). 36. Pre-filled Syringes for Biopharmaceuticals (Robert Swift and Robin Hwang). 37. Impact of Manufacturing Processes on the Drug Product Stability and Quality (Nitin Rathore, Rahul S. Rajan and Erwin Freund). Index.

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Book SynopsisBiointerfaces are central to biology and medicine and crucial in research relating to implants, biosensors, drug delivery, proteomics, and many other fields.Trade Review"Ohshima (pharmaceutical science, Tokyo U. of Science) sets out a set of tools for discussing various phenomena at biological interfaces - such as cell surfaces - in terms of biophysical chemistry." (SciTech Book News, December 2010) Table of ContentsPreface xiii List of Symbols xv Part I Potential and Charge at Interfaces 1 1 Potential and Charge of a Hard Particle 3 1.1 Introduction 3 1.2 The Poisson-Boltzmann Equation 3 1.3 Plate 6 1.3.1 Low Potential 8 1.3.2 Arbitrary Potential: Symmetrical Electrolyte 8 1.3.3 Arbitrary Potential: Asymmetrical Electrolyte 13 1.3.4 Arbitrary Potential: General Electrolyte 14 1.4 Sphere 16 1.4.1 Low Potential 17 1.4.2 Surface Charge Density-Surface Potential Relationship: Symmetrical Electrolyte 18 1.4.3 Surface Charge Density-Surface Potential Relationship: Asymmetrical Electrolyte 21 1.4.4 Surface Charge Density-Surface Potential Relationship: General Electrolyte 22 1.4.5 Potential Distribution Around a Sphere with Arbitrary Potential 25 1.5 Cylinder 31 1.5.1 Low Potential 32 1.5.2 Arbitrary Potential: Symmetrical Electrolyte 33 1.5.3 Arbitrary Potential: General Electrolytes 34 1.6 Asymptotic Behavior of Potential and Effective Surface Potential 37 1.6.1 Plate 38 1.6.2 Sphere 41 1.6.3 Cylinder 42 1.7 Nearly Spherical Particle 43 References 45 2 Potential Distribution Around a Nonuniformly Charged Surface and Discrete Charge Effects 47 2.1 Introduction 47 2.2 The Poisson-Boltzmann Equation for a Surface with an Arbitrary Fixed Surface Charge Distribution 47 2.3 Discrete Charge Effect 56 References 62 3 Modified Poisson-Boltzmann Equation 63 3.1 Introduction 63 3.2 Electrolyte Solution Containing Rod-like Divalent Cations 63 3.3 Electrolyte Solution Containing Rod-like Zwitterions 70 3.4 Self-atmosphere Potential of Ions 77 References 82 4 Potential and Charge of a Soft Particle 83 4.1 Introduction 83 4.2 Planar Soft Surface 83 4.2.1 Poisson–Boltzmann Equation 83 4.2.2 Potential Distribution Across a Surface Charge Layer 87 4.2.3 Thick Surface Charge Layer and Donnan Potential 90 4.2.4 Transition Between Donnan Potential and Surface Potential 91 4.2.5 Donnan Potential in a General Electrolyte 92 4.3 Spherical Soft Particle 93 4.3.1 Low Charge Density Case 93 4.3.2 Surface Potential–Donnan Potential Relationship 95 4.4 Cylindrical Soft Particle 100 4.4.1 Low Charge Density Case 100 4.4.2 Surface Potential–Donnan Potential Relationship 101 4.5 Asymptotic Behavior of Potential and Effective Surface Potential of a Soft Particle 102 4.5.1 Plate 102 4.5.2 Sphere 103 4.5.3 Cylinder 104 4.6 Nonuniformly Charged Surface Layer: Isoelectric Point 104 References 110 5 Free Energy of a Charged Surface 111 5.1 Introduction 111 5.2 Helmholtz Free Energy and Tension of a Hard Surface 111 5.2.1 Charged Surface with Ion Adsorption 111 5.2.2 Charged Surface with Dissociable Groups 116 5.3 Calculation of the Free Energy of the Electrical Double Layer 118 5.3.1 Plate 119 5.3.2 Sphere 120 5.3.3 Cylinder 121 5.4 Alternative Expression for Fel 122 5.5 Free Energy of a Soft Surface 123 5.5.1 General Expression 123 5.5.2 Expressions for the Double-Layer Free Energy for a Planar Soft Surface 127 5.5.3 Soft Surface with Dissociable Groups 128 References 130 6 Potential Distribution Around a Charged Particle in a Salt-Free Medium 132 6.1 Introduction 132 6.2 Spherical Particle 133 6.3 Cylindrical Particle 143 6.4 Effects of a Small Amount of Added Salts 146 6.5 Spherical Soft Particle 152 References 162 Part II Interaction Between Surfaces 163 7 Electrostatic Interaction of Point Charges in an Inhomogeneous Medium 165 7.1 Introduction 165 7.2 Planar Geometry 166 7.3 Cylindrical Geometry 180 References 185 8 Force and Potential Energy of the Double-Layer Interaction Between Two Charged Colloidal Particles 186 8.1 Introduction 186 8.2 Osmotic Pressure and Maxwell Stress 186 8.3 Direct Calculation of Interaction Force 188 8.4 Free Energy of Double-Layer Interaction 198 8.4.1 Interaction at Constant Surface Charge Density 199 8.4.2 Interaction at Constants Surface Potential 200 8.5 Alternative Expression for the Electric Part of the Free Energy of Double-Layer Interaction 201 8.6 Charge Regulation Model 201 References 202 9 Double-Layer Interaction Between Two Parallel Similar Plates 203 9.1 Introduction 203 9.2 Interaction Between Two Parallel Similar Plates 203 9.3 Low Potential Case 207 9.3.1 Interaction at Constant Surface Charge Density 208 9.3.2 Interaction at Constant Surface Potential 211 9.4 Arbitrary Potential Case 214 9.4.1 Interaction at Constant Surface Charge Density 214 9.4.2 Interaction at Constant Surface Potential 224 9.5 Comparison Between the Theory of Derjaguin and Landau and the Theory of Verwey and Overbeek 226 9.6 Approximate Analytic Expressions for Moderate Potentials 227 9.7 Alternative Method of Linearization of the Poisson–Boltzmann Equation 231 9.7.1 Interaction at Constant Surface Potential 231 9.7.2 Interaction at Constant Surface Charge Density 234 References 240 10 Electrostatic Interaction Between Two Parallel Dissimilar Plates 241 10.1 Introduction 241 10.2 Interaction Between Two Parallel Dissimilar Plates 241 10.3 Low Potential Case 244 10.3.1 Interaction at Constant Surface Charge Density 244 10.3.2 Interaction at Constant Surface Potential 251 10.3.3 Mixed Case 252 10.4 Arbitrary Potential: Interaction at Constant Surface Charge Density 252 10.4.1 Isodynamic Curves 252 10.4.2 Interaction Energy 258 10.5 Approximate Analytic Expressions for Moderate Potentials 262 References 263 11 Linear Superposition Approximation for the Double-Layer Interaction of Particles at Large Separations 265 11.1 Introduction 265 11.2 Two Parallel Plates 265 11.2.1 Similar Plates 265 11.2.2 Dissimilar Plates 270 11.2.3 Hypothetical Charge 276 11.3 Two Spheres 278 11.4 Two Cylinders 279 References 281 12 Derjaguin’s Approximation at Small Separations 283 12.1 Introduction 283 12.2 Two Spheres 283 12.2.1 Low Potentials 285 12.2.2 Moderate Potentials 286 12.2.3 Arbitrary Potentials: Derjaguin’s Approximation Combined with the Linear Superposition Approximation 288 12.2.4 Curvature Correction to Derjaguin’ Approximation 290 12.3 Two Parallel Cylinders 292 12.4 Two Crossed Cylinders 294 References 297 13 Donnan Potential-Regulated Interaction Between Porous Particles 298 13.1 Introduction 298 13.2 Two Parallel Semi-infinite Ion-penetrable Membranes (Porous Plates) 298 13.3 Two Porous Spheres 306 13.4 Two Parallel Porous Cylinders 310 13.5 Two Parallel Membranes with Arbitrary Potentials 311 13.5.1 Interaction Force and Isodynamic Curves 311 13.5.2 Interaction Energy 317 13.6 pH Dependence of Electrostatic Interaction Between Ion-penetrable Membranes 320 References 322 14 Series Expansion Representations for the Double-Layer Interaction Between Two Particles 323 14.1 Introduction 323 14.2 Schwartz’s Method 323 14.3 Two Spheres 327 14.4 Plate and Sphere 342 14.5 Two Parallel Cylinders 348 14.6 Plate and Cylinder 353 References 356 15 Electrostatic Interaction Between Soft Particles 357 15.1 Introduction 357 15.2 Interaction Between Two Parallel Dissimilar Soft Plates 357 15.3 Interaction Between Two Dissimilar Soft Spheres 363 15.4 Interaction Between Two Dissimilar Soft Cylinders 369 References 374 16 Electrostatic Interaction Between Nonuniformly Charged Membranes 375 16.1 Introduction 375 16.2 Basic Equations 375 16.3 Interaction Force 376 16.4 Isoelectric Points with Respect To Electrolyte Concentration 378 Reference 380 17 Electrostatic Repulsion Between Two Parallel Soft Plates After Their Contact 381 17.1 Introduction 381 17.2 Repulsion Between Intact Brushes 381 17.3 Repulsion Between Compressed Brushes 382 References 387 18 Electrostatic Interaction Between Ion-Penetrable Membranes In a Salt-free Medium 388 18.1 Introduction 388 18.2 Two Parallel Hard Plates 388 18.3 Two Parallel Ion-Penetrable Membranes 391 References 398 19 van der Waals Interaction Between Two Particles 399 19.1 Introduction 399 19.2 Two Molecules 399 19.3 A Molecule and a Plate 401 19.4 Two Parallel Plates 402 19.5 A Molecule and a Sphere 404 19.6 Two Spheres 405 19.7 A Molecule and a Rod 407 19.8 Two Parallel Rods 408 19.9 A Molecule and a Cylinder 408 19.10 Two Parallel Cylinders 410 19.11 Two Crossed Cylinders 412 19.12 Two Parallel Rings 412 19.13 Two Parallel Torus-Shaped Particles 413 19.14 Two Particles Immersed In a Medium 417 19.15 Two Parallel Plates Covered with Surface Layers 418 References 419 20 DLVO Theory of Colloid Stability 420 20.1 Introduction 420 20.2 Interaction Between Lipid Bilayers 420 20.3 Interaction Between Soft Spheres 425 References 429 Part III Electrokinetic Phenomena at Interfaces 431 21 Electrophoretic Mobility of Soft Particles 433 21.1 Introduction 433 21.2 Brief Summary of Electrophoresis of Hard Particles 433 21.3 General Theory of Electrophoretic Mobility of Soft Particles 435 21.4 Analytic Approximations for the Electrophoretic Mobility of Spherical Soft Particles 440 21.4.1 Large Spherical Soft Particles 440 21.4.2 Weakly Charged Spherical Soft Particles 444 21.4.3 Cylindrical Soft Particles 447 21.5 Electrokinetic Flow Between Two Parallel Soft Plates 449 21.6 Soft Particle Analysis of the Electrophoretic Mobility of Biological Cells and Their Model Particles 454 21.6.1 RAW117 Lymphosarcoma Cells and Their Variant Cells 454 21.6.2 Poly(N-isopropylacrylamide) Hydrogel-Coated Latex 455 21.7 Electrophoresis of Nonuniformly Charged Soft Particles 457 21.8 Other Topics of Electrophoresis of Soft Particles 463 References 464 22 Electrophoretic Mobility of Concentrated Soft Particles 468 22.1 Introduction 468 22.2 Electrophoretic Mobility of Concentrated Soft Particles 468 22.3 Electroosmotic Velocity in an Array of Soft Cylinders 475 References 479 23 Electrical Conductivity of a Suspension of Soft Particles 480 23.1 Introduction 480 23.2 Basic Equations 480 23.3 Electrical Conductivity 481 References 484 24 Sedimentation Potential and Velocity in a Suspension of Soft Particles 485 24.1 Introduction 485 24.2 Basic Equations 485 24.3 Sedimentation Velocity of a Soft Particle 490 24.4 Average Electric Current and Potential 490 24.5 Sedimentation Potential 491 24.6 Onsager’s Reciprocal Relation 494 24.7 Diffusion Coefficient of a Soft Particle 495 References 495 25 Dynamic Electrophoretic Mobility of a Soft Particle 497 25.1 Introduction 497 25.2 Basic Equations 497 25.3 Linearized Equations 499 25.4 Equation of Motion of a Soft Particle 501 25.5 General Mobility Expression 501 25.6 Approximate Mobility Formula 503 References 506 26 Colloid Vibration Potential in a Suspension of Soft Particles 508 26.1 Introduction 508 26.2 Colloid Vibration Potential and Ion Vibration Potential 508 References 513 27 Effective Viscosity of a Suspension of Soft Particles 515 27.1 Introduction 515 27.2 Basic Equations 516 27.3 Linearized Equations 518 27.4 Electroviscous Coefficient 520 27.5 Approximation for Low Fixed-Charge Densities 523 27.6 Effective Viscosity of a Concentrated Suspension of Uncharged Porous Spheres 527 Appendix 27a 530 References 531 Part IV other Topics 533 28 Membrane Potential and Donnan Potential 535 28.1 Introduction 535 28.2 Membrane Potential and Donnan Potential 535 References 541 Index 543

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Book SynopsisHighlighting the critical importance of enzymes in pharmaceutical and biotechnology research, Enzyme Technologies presents thorough discussions on chemical biology of enzymes, redesigning binding and catalytic specificities of enzymes, and applications of enzymes to biotechnology research in the post-genomic era.Trade Review“The book serves as a valuable desk reference volume and describes well the key concepts of the standard and emerging enzyme technologies that together constitute some of the fundamental principles and knowledge on which drug discovery research is based.” (ChemMedChem, 1 August 2015)Table of ContentsContributors vii Preface ix Part A _Enzymes – essential workhorses in pharmaceutical research 1 1 Assay Technologies for Proteases 3 Anuradha Roy, Gerald H. Lushington, James McGee, and Rathnam Chaguturu 2 Discovery and Development of Isozyme-Selective Inhibitors Involved in Lipid Metabolism 55 Taichi Ohshiro and Hiroshi Tomoda 3 Covalent Enzyme Inhibition in Drug Discovery and Development 81 Shujaath Mehdi 4 Preclinomics: Enzyme Assays and Rodent Models for Metabolic diseases 131 Wu-Kuang Yeh and Richard G. Peterson Part B _Enzymes – indispensable tools for improving druggability 163 5 Enzymes and Targeted Activation of Prodrugs 165 Yanhui Yang, Yu Chen, Herve Aloysius, Daigo Inoyama, and Longqin Hu 6 Evolution of an Orally Active Prodrug of Gemcitabine 237 James R. McCarthy 7 Enzymatically Activated Phosphate and Phosphonate Prodrugs 253 Ivan S. Krylov and Charles E. McKenna Part C E nzymes – powerful weapons for correcting Nature’s errors 301 8 Treatment Options for Mucopolysaccharidosis Type II (Hunter’s Syndrome) 303 Michael Beck 9 Enzyme Replacement Therapy for Fabry Disease 321 Ley Nadine Lacbawan, Wei Zheng, and Ozlem Goker-Alpan 10 Methods and Principles of Pancreatic Function Tests 335 Henrike von Schassen, Jutta Keller, and Peter Layer Index 341

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Book SynopsisThe application of immunoassays to genetically engineered plants and related areas is the focus of this book. Contributors are a group of international experts from government agencies, academics and industries.Table of Contents1. Introduction (Guomin Shan). 2. Principle of Immunoassays (Kerrm Yau and Claudia Sheedy). 3. Antibody Engineering in Agricultural Biotechnology (Patrick Doyle, Mehdi Arbabi-Ghahroudi, Claudia Sheedy, Kerrm Yau and J. Christopher Hall). 4. Microtiter Plate ELISA (Michael Brown). 5. Lateral Flow Devices (Murali Bandle, Rick Thompson and Guomin Shan). 6. Immunoassay Method Validation (Jean Schmidt and Clara Alarcon). 7. Reference Materials and Considerations (Tandace A. Scholdberg and G. Ronald Jenkins). 8. Automation of Immunoassays (Michele Yarnall). 9. Data Interpretation and Sources of Error (Rod Herman and Guomin Shan). 10. Immunoassay Applications in Trait Discovery, Product Development and Registration (Beryl Packer, Andre Silvanovich and David Grothaus). 11. Immunoassay Applications in Grain Products and Food Processing (Gina Clapper and Lulu Kurman). 12. Immunoassay Applications on Soil Monitoring (Guomin Shan). 13. Immunoassay Applications in Plant-based Biopharma (Thomas Patterson and Greg Gilles). 14. Immunoassays in Veterinary Plant-made Vaccines (Giorgio De Guzman, Robert P. Shepherd and Amanda M. Walmsley). 15. Immunoassay as a GE Detection Method In International Trade (Ray Shillito and Thomas Currier). 16. Future Perspectives and Challenges (Lucy Liu, Ai-Guo Gao, Leslie Harrison, Kerrm Yau, John Lawry and G. Shan).

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Book SynopsisThis book provides professionals in the pharmaceutical industries a basic understanding of the key elements of pharmaceutical and biotech manufacturing and design.Table of ContentsPreface xiii 1 US Regulations for the Pharmaceutical Industries 1 1.1 Introduction 1 1.2 The FDA: Formation of a Regulatory Agency 2 1.3 FDA’s Seven Program Centers and Their Responsibility 6 1.3.1 Center for Biologics Evaluation and Research 6 1.3.2 Center for Drug Evaluation and Research 6 1.3.3 Center for Devices and Radiological Health 6 1.3.4 Center for Food Safety and Applied Nutrition 6 1.3.5 Center for Veterinary Medicine 6 1.3.6 Office of Combinational Products 6 1.3.7 Office of Regulatory Affairs 7 1.4 New Drug Development 7 1.4.1 Discovery 7 1.4.2 Investigational New Drug Application 8 1.4.3 Preclinical Studies (Animal) 9 1.4.4 Clinical Studies 10 1.5 Commercializing the New Drug 16 1.5.1 New Drug Application 17 1.6 Harmonization 23 1.6.1 Common Technical Document 23 1.7 Review Process of US NDA 25 1.8 Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs 27 1.8.1 Organization and Personnel 27 1.8.2 Building and Facilities 28 1.8.3 Equipment 28 1.8.4 Control of Components and Drug Product Containers and Closures 29 1.8.5 Production and Process Controls 29 1.8.6 Packaging and Labeling Control 30 1.8.7 Holding and Distribution 31 1.8.8 Laboratory Controls 31 1.8.9 Records and Reports 32 1.8.10 Returned and Salvaged Drug Products 33 1.8.11 Other 33 1.9 Compliance 34 1.9.1 Quality System 35 1.9.2 Facilities and Equipment System 35 1.9.3 Materials System 36 1.9.4 Production System 36 1.9.5 Packaging and Labeling System 36 1.9.6 Laboratory Control System 36 1.10 Electronic Records and Electronic Signatures 37 1.10.1 Electronic Records 37 1.10.2 Electronic Signatures 38 1.11 Employee Safety 38 1.11.1 Process Safety Information 39 1.11.2 Process Hazard Analysis 40 1.11.3 Operating Procedures 41 1.11.4 Training 41 1.11.5 New Facility Startup 41 1.11.6 Mechanical Integrity 42 1.11.7 Hot Work Permit 42 1.11.8 Management of Change 42 1.11.9 Incident Investigation 43 1.11.10 Emergency Planning and Response 43 1.11.11 Compliance Audits 43 1.12 US EPA 43 1.12.1 Clean Air Act 44 1.12.2 Safe Drinking Water Act 45 1.12.3 Resource Conservation and Recovery Act 46 1.12.4 Emergency Planning and Community Right‐to‐Know Act 47 1.12.5 Clean Water Act 48 1.13 Process Analytical Technology 49 1.13.1 Process Understanding 49 1.13.2 Principles and Tools 50 1.13.3 Strategy for Implementation 51 1.14 Conclusion 51 References 51 Further Reading 52 2 Pharmaceutical Water Systems 53 2.1 Pharmaceutical Water Systems Basics 53 2.1.1 Fundamentals of Fluid Mechanics for Pharmaceutical Water Systems 58 2.2 Pharmaceutical Water Equipment 77 2.2.1 Centrifugal Pumps 77 2.2.2 Centrifugal Pump Installation Considerations 81 2.3 Thermodynamics Interlude 82 2.4 Heat Transfer for Pharmaceutical Water Production 90 2.5 Evaporation 109 2.6 Ion Exchange Systems 115 2.7 Reverse Osmosis 116 2.7.1 Principles of Reverse Osmosis 118 2.7.2 Reverse Osmosis Installation and Operational Costs 121 2.7.3 Reverse Osmosis Design Hint 122 2.8 cGMP Design and Facility Maintenance Considerations for Pharmaceutical Water Systems 122 References 128 Further Reading 129 3 Heating, Ventilating, and Air Conditioning 131 3.1 Fundamentals of HVAC Electrical Systems 132 3.1.1 Electric Motors 133 3.1.2 Motor Plate and Associated Data 134 3.2 Design Considerations 140 3.2.1 Weather Data 143 3.2.2 Temperature and Humidity 143 3.2.3 Ventilation 147 3.2.4 Air Filtration 149 3.2.5 Internal Loads 150 3.2.6 Air Distribution 150 3.2.7 Room Pressurization 151 3.2.8 Sound and Acoustic Criteria 152 3.2.9 Building Control Systems 158 3.3 Cleanrooms 158 3.3.1 Cleanroom Design Fundamentals 158 3.3.2 Cleanroom Monitoring, Maintenance, and Design Considerations for USP and USP Facilities 169 References 172 Further Reading 172 4 Pressure Vessels, Reactors, and Fermentors 175 4.1 Introduction 175 4.1.1 Pressure Vessels 175 4.1.2 Basics of Pressure Vessel Design and Specifications 178 4.1.3 Pharmaceutical Reactors 188 4.1.4 Kinetics and Reactor Fundamentals 188 4.1.5 Bioreactor Principles 197 4.1.6 Fermentor Principles 209 4.1.7 Heat Transfer Aspects of Fermentors 211 4.1.8 Bioreactor and Fermentor Design, Maintenance, Operating, and cGMP Considerations 214 4.2 Safety Relief Valves and Rupture Discs 219 4.2.1 Safety Relief Devices, Definition of Terms 219 4.2.2 Relief Valve Design and Specifications 223 4.2.3 Requirements and Capacity 223 References 237 Further Reading 238 5 Reliability, Availability, and Maintainability 239 5.1 Introduction to RAM 239 5.2 The Role of Reliability 240 5.3 The Role of Maintainability 247 5.4 The Preventive Maintenance Program 252 5.4.1 System Replacement Considerations 253 5.5 Human Factors 254 5.6 The Role of Availability 259 5.7 Basic Mathematics for Reliability, Availability, and Maintainability 259 5.8 Series and Parallel Configurations 271 5.9 Spares and Replacement Parts 271 References 276 Further Reading 277 6 Parenteral Operations 279 6.1 Introduction 279 6.2 Parenteral Definitions, Regulations, and Guidelines 280 6.2.1 Nomenclature and Definitions 280 6.3 Lyophilization 282 6.3.1 Background 282 6.3.2 Lyophilization Glossary 283 6.3.3 Lyophilizer Design and Operation 284 6.4 Lyophilizer Maintenance Issues 294 6.4.1 Maintenance Systems Analysis 294 References 296 Further Reading 296 7 Tableting Technology 299 7.1 Introduction 299 7.2 The Role of the FDA in the Manufacturing, Processing, Packing, and Holding of Drugs: The Relationship Between Regulations and Pharmaceutical Engineering 300 7.3 Tablet Blending Operations 304 7.3.1 Dry Granulation 305 7.3.2 Wet Granulation 320 7.4 Tableting Operations 322 7.4.1 Tablet Manufacturing 324 7.4.2 Tablet Press Maintenance 329 7.5 Coating 330 7.5.1 Tablet Coating 330 7.5.2 Tablet Coater Maintenance 331 7.6 Capsules 333 7.6.1 Capsule Fundamentals 334 7.6.2 Capsule Materials and Manufacturing 334 References 337 Further Reading 338 8 Corrosion and Passivation in Pharmaceutical Operations 339 8.1 Corrosion 339 8.2 Corrosion and Corrosion Protection in Pharmaceutical Operations 339 8.2.1 Definition of Corrosion 343 8.2.2 Corrosion Fundamentals 343 8.3 General Corrosion Protection in Pharmaceutical Operations 344 8.3.1 Electrochemical Action 344 8.3.2 Environmental Characteristics and Corrosion 349 8.3.3 Properties of Metals that Influence Corrosion 350 8.3.4 Effects of Fabrication and Assembly on Corrosion 350 8.3.5 Protective Films and Corrosion 352 8.3.6 Corrosion Activity in Solutions 352 8.3.7 Types of Corrosion 354 8.4 Corrosion‐ Resistant Metals and Alloys 365 8.4.1 Iron Alloys 366 8.4.2 Aluminum and Aluminum Alloys 367 8.5 Passivation and Rouging 368 8.5.1 Passivation 368 8.5.2 Rouging 369 8.6 General Corrosion Protective Measures 370 8.6.1 General Design Considerations for Corrosion Prevention 370 8.7 Pourbaix Diagrams 374 References 377 Further Reading 378 9 Pharmaceutical Materials of Construction 379 9.1 Introduction 379 9.2 Materials Selection and Performance Requirements 379 9.2.1 Introduction of Polymeric Materials for Single Use Systems 380 9.3 Advantages and Disadvantages of Stainless Steels and Polymers for cGMP and Non‐cGMP Pharmaceutical Applications 381 9.4 Disposal of Single Use Components 382 9.5 Performance Considerations for Pharmaceutical Materials of Construction 392 9.5.1 Stainless Steels 392 9.5.2 Copper and Copper Alloys 394 9.5.3 Carbon Steels and Alloy Steels 396 9.5.4 Polymeric Materials: Overview 399 9.5.5 Preventing Pharmaceutical Materials Component Materials Failures 402 9.6 Practical Piping Calculations 403 References 408 Further Reading 409 10 Commissioning and Validation 411 10.1 Introduction to Commissioning and Validation 411 10.1.1 Introduction to Construction Specifications 411 10.2 Commissioning 416 10.2.1 Description of Tasks 419 10.2.2 Commissioning Costs 425 10.3 Validation 425 10.4 Process Validation 459 10.5 Electronic Records and Electronic Signatures 484 10.5.1 Application of Risk Assessment Methods to Outsourcing 491 10.5.2 Validation Costs 492 10.6 Comparison Between Commissioning and Validation 493 References 493 Further Reading 493 11 Topics and Concepts Relating to Pharmaceutical Engineering 495 11.1 Preliminary Concepts 495 11.1.1 Basic Statistical Concepts and Computational Techniques 495 11.2 Introduction to Six Sigma 508 11.2.1 Six Sigma Organization and Background 508 11.2.2 DMAIC: The Basic Six Sigma Acronym 514 11.2.3 Define 514 11.2.4 Measure 516 11.2.5 Analyze 519 11.2.6 Improve 520 11.2.7 Control 523 11.2.8 Lean Six Sigma 524 11.3 Process Analytical Technology 530 11.4 Quality by Design 537 References 540 Further Reading 540 Index 543

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Book SynopsisThis book covers the area of advanced ceramic composites broadly, providing important introductory chapters to fundamentals, processing, and applications of advanced ceramic composites. Within each section, specific topics covered highlight the state of the art research within one of the above sections.Trade Review“For professionals or students I would recommend this book as a valuable source of reference and information.” (Materials World, 1 March 2013) "The book provides easy understanding by students as well as professionals interested in advanced ceramic composites." (Metall, 1 January 2012)Table of ContentsPreface xvii Foreword by Michel Barsoum xxiii About the Authors xxv Section One Fundamentals of Nature and Characteristics of Ceramics 1. Ceramics: Definition and Characteristics 3 1.1 Materials Classification 3 1.2 Historical Perspective; Definition and Classification of Ceramics 4 1.3 Properties of Structural Ceramics 8 1.4 Applications of Structural Ceramics 9 References 12 2. Bonding, Structure, and Physical Properties 14 2.1 Primary Bonding 15 2.1.1 Ionic Bonding 15 2.1.2 Covalent Bonding 18 2.1.3 Pauling’s Rules 19 2.1.4 Secondary Bonding 21 2.2 Structure 21 2.2.1 NaCl-type Rock-Salt Structure 22 2.2.2 ZnS-Type Wurtzite Structure 22 2.2.3 ZnS-Type Zinc Blende Structure 23 2.2.4 CsCl Cesium Chloride Structure 23 2.2.5 CaF2 Fluorite Structure 23 2.2.6 Antifl uorite Structure 24 2.2.7 Rutile Structure 24 2.2.8 Al2O3 Corundum Structure 24 2.2.9 Spinel Structure 25 2.2.10 Perovskite Structure 26 2.2.11 Ilmenite Structure 26 2.2.12 Silicate Structures 26 2.3 Oxide Ceramics 28 2.4 Non-Oxide Ceramics 30 References 33 3. Mechanical Behavior of Ceramics 34 3.1 Theory of Brittle Fracture 34 3.1.1 Theoretical Cohesive Strength 34 3.1.2 Inglis Theory 35 3.1.3 Griffi th’s Theory 37 3.1.4 Irwin’s Theory 39 3.1.5 Concept of Fracture Toughness 39 3.2 Cracking in Brittle Materials 40 3.3 Strength Variability of Ceramics 42 3.4 Physics of the Fracture of Brittle Solids 42 3.4.1 Weakest Link Fracture Statistics 44 3.5 Basic Mechanical Properties 48 3.5.1 Vickers Hardness 48 3.5.2 Instrumented Indentation Measurements 48 3.5.3 Compressive Strength 50 3.5.4 Flexural Strength 51 3.5.5 Elastic Modulus 52 3.5.6 Fracture Toughness 53 3.5.6.1 Long Crack Methods 54 3.5.6.2 Fracture Toughness Evaluation Using Indentation Cracking 55 3.6 Toughening Mechanisms 59 References 63 Section Two Processing of Ceramics 4. Synthesis of High-Purity Ceramic Powders 67 4.1 Synthesis of ZrO2 Powders 67 4.2 Synthesis of TiB2 Powders 68 4.3 Synthesis of Hydroxyapatite Powders 70 4.4 Synthesis of High-Purity Tungsten Carbide Powders 71 References 75 5. Sintering of Ceramics 76 5.1 Introduction 76 5.2 Classification 78 5.3 Thermodynamic Driving Force 79 5.4 Solid-State Sintering 82 5.5 Competition between Densifi cation and Grain Growth 84 5.6 Liquid-Phase Sintering 88 5.7 Important Factors Infl uencing the Sintering Process 90 5.8 Powder Metallurgical Processes 92 5.8.1 Ball Milling 92 5.8.2 Compaction 94 5.8.2.1 Cold Pressing 94 5.8.2.2 Cold Isostatic Pressing 96 5.8.3 Pressureless Sintering 97 5.8.4 Reactive Sintering 98 5.8.5 Microwave Sintering 99 References 103 6. Thermomechanical Sintering Methods 105 6.1 Hot Pressing 105 6.2 Extrusion 108 6.3 Hot Isostatic Pressing 110 6.4 Hot Rolling 112 6.5 Sinter Forging 114 6.6 Spark Plasma Sintering 116 References 118 Section Three Surface Coatings 7. Environment and Engineering of Ceramic Materials 123 7.1 Environmental Infl uence on Properties of Engineering Ceramics 124 7.1.1 Oxidation Resistance 125 7.1.2 Corrosion Resistance 126 7.1.3 Creep Resistance 126 7.1.4 Hard Bearing Surfaces 126 7.1.5 Thermal and Electrical Insulation 126 7.1.6 Abrasion-Resistant Ceramics 127 7.1.7 Fretting Wear Resistance, Surface Fatigue, Impact Resistance 127 7.1.8 Erosion and Cavitation Resistance 127 7.2 Classification and Engineering of Ceramic Materials 128 7.2.1 Non-Oxide Ceramics 128 7.2.2 Oxide Ceramics 132 References 135 8. Thermal Spraying of Ceramics 137 8.1 Mechanism of Thermal Spraying 137 8.1.1 Advantages of Thermal Spraying 140 8.1.2 Disadvantages of Thermal Spraying 141 8.2 Classification of Thermal Spraying 141 8.2.1 Combustion Thermal Spraying 142 8.2.1.1 Flame (Powder or Wire) Spraying 142 8.2.1.2 High-Velocity Oxy-Fuel Spraying 144 8.2.1.3 Detonation Spray Technique 145 8.2.2 Electric Arc Spraying 148 8.2.3 Cold Spraying 149 8.2.4 Plasma Spraying 150 8.2.4.1 Atmospheric Plasma Spraying 152 8.2.4.2 Vacuum Plasma Spraying 154 8.3 Splat Formation and Spread 154 8.4 Near Net Shape Forming 156 8.5 Overview 157 References 158 9. Coatings and Protection of Structural Ceramics 160 9.1 Coatings 160 9.2 Protective Coatings 162 9.2.1 Biological Applications 162 9.3 Rocket Nozzle Inserts 163 9.4 Thermal Barrier Coatings 165 9.5 Wear Resistance 166 9.6 Corrosion Protection by Ceramics 168 9.7 Optically Transparent Ceramics 169 9.8 Ceramic Pottery and Sculptures 169 References 170 Section Four Processing and Properties of Toughened Ceramics 10. Toughness Optimization in Zirconia-Based Ceramics 175 10.1 Introduction 175 10.2 Transformation Characteristics of Tetragonal Zirconia 176 10.3 Phase Equilibria and Microstructure 177 10.4 Transformation Toughening 178 10.4.1 Thermodynamics of Transformation 179 10.4.2 Micromechanical Modeling 180 10.5 Stabilization of Tetragonal Zirconia 182 10.6 Production and Properties of Y-TZP Ceramics 183 10.7 Different Factors Influencing Transformation Toughening 184 10.7.1 Grain Size 187 10.7.2 Grain Shape and Grain Boundary Phase 188 10.7.3 Yttria Content 192 10.7.4 Yttria Distribution 193 10.7.5 MS Temperature 197 10.7.6 Transformation Zone Size and Shape 197 10.7.7 Residual Stress 199 10.8 Additional Toughening Mechanisms 199 10.8.1 Stress-Induced Microcracking 200 10.8.2 Ferroelastic Toughening 201 10.9 Coupled Toughening Response 203 10.10 Toughness Optimization in Y-TZP-Based Composites 203 10.10.1 Influence of Thermal Residual Stresses 206 10.10.2 Influence of Zirconia Matrix Stabilization 207 10.11 Outlook 208 References 208 11. S-Phase SiAlON Ceramics: Microstructure and Properties 215 11.1 Introduction 215 11.2 Materials Processing and Property Measurements 216 11.3 Microstructural Development 217 11.4 Mechanical Properties 220 11.4.1 Load-Dependent Hardness Properties 226 11.4.2 R-Curve Behavior 228 11.5 Concluding Remarks 230 References 232 12. Toughness and Tribological Properties of MAX Phases 234 12.1 Emergence of MAX Phases 234 12.2 Classification of MAX Phases 235 12.3 Damage Tolerance of MAX Phases 238 12.4 Wear of Ti3SiC2 MAX Phase 244 12.5 Concluding Remarks 254 References 254 Section Five High-Temperature Ceramics 13. Overview: High-Temperature Ceramics 259 13.1 Introduction 259 13.2 Phase Diagram and Crystal Structure 260 13.3 Processing, Microstructure, and Properties of Bulk TiB2 261 13.3.1 Preparation of TiB2 Powder 261 13.3.2 Densification and Microstructure of Binderless TiB2 265 13.4 Use of Metallic Sinter-Additives on Densification and Properties 269 13.5 Influence of Nonmetallic Additives on Densification and Properties 271 13.6 Important Applications of Bulk TiB2-Based Materials 281 13.7 Concluding Remarks 281 References 283 14. Processing and Properties of TiB2 and ZrB2 with Sinter-Additives 286 14.1 Introduction 286 14.2 Materials Processing 287 14.3 TiB2–MoSi2 System 288 14.3.1 Densification, Microstructure, and Sintering Reactions 288 14.3.2 Mechanical Properties 288 14.3.3 Depth Sensing Instrumented Indentation Response 290 14.3.4 Residual Strain-Induced Property Degradation 293 14.3.5 Relationship between Indentation Work Done and Phase Assemblage 295 14.4 TiB2–TiSi2 System 296 14.4.1 Sintering Reactions and Densifi cation Mechanisms 296 14.4.2 Mechanical Properties 298 14.4.3 Residual Stress or Strain and Property Degradation 298 14.5 ZrB2–SiC–TiSi2 Composites 300 14.6 Concluding Remarks 301 References 302 15. High-Temperature Mechanical and Oxidation Properties 305 15.1 Introduction 305 15.2 High-Temperature Property Measurements 309 15.3 High-Temperature Mechanical Properties 310 15.3.1 High-Temperature Flexural Strength 310 15.3.2 Hot Hardness Property 311 15.4 Oxidation Behavior of TiB2–MoSi2 312 15.5 Oxidation Behavior of TiB2–TiSi2 315 15.5.1 Oxidation Kinetics 315 15.5.2 Morphological Characteristics of Oxidized Surfaces 317 15.6 Concluding Remarks 317 References 318 Section Six Nanoceramic Composites 16. Overview: Relevance, Characteristics, and Applications of Nanostructured Ceramics 323 16.1 Introduction 323 16.2 Problems Associated with Synthesis of Nanosized Powders 326 16.2.1 Methods of Synthesis of Nanoscaled Ceramic Powders 326 16.2.2 Challenges Posed by the Typical Properties of Nanoscaled Powders 327 16.3 Challenges Faced during Processing 328 16.3.1 Problems Arising due to Fine Powders 328 16.3.2 Challenges Faced due to Agglomerated Powders 329 16.4 Processing of Bulk Nanocrystalline Ceramics 330 16.4.1 Processes Used for Developing Bulk Nanocrystalline Ceramics 330 16.4.2 Mechanisms Leading to Enhanced Sintering Kinetics on Pressure Application 331 16.5 Mechanical Properties of Bulk Ceramic Nanomaterials 332 16.5.1 Mechanical Properties 332 16.5.1.1 Hardness and Yield Strength 332 16.5.1.2 Fracture Strength and Fracture Toughness 335 16.5.1.3 Superplasticity 338 16.6 Applications of Nanoceramics 339 16.7 Conclusion and Outlook 341 References 343 17. Oxide Nanoceramic Composites 347 17.1 Overview 347 17.2 Al2O3-Based Nanocomposites 349 17.3 ZrO2-Based Nanocomposites 355 17.4 Case Study 356 17.4.1 Yttria-Stabilized Tetragonal Zirconia Polycrystal Nanoceramics 356 17.4.2 ZrO2–ZrB2 Nanoceramic Composites 357 References 363 18. Microstructure Development and Properties of Non-Oxide Ceramic Nanocomposites 366 18.1 Nanocomposites Based on Si3N4 366 18.2 Other Advanced Nanocomposites 371 18.2.1 Mullite–SiC 371 18.2.2 Yttrium Aluminum Garnet–SiC 371 18.2.3 SiC–TiC 371 18.2.4 Hydroxyapatite–ZrO2 Nanobiocomposites 371 18.2.5 Stress-Sensing Nanocomposites 372 18.3 WC-Based Nanocomposites 372 18.3.1 Background 372 18.3.2 WC–ZrO2 Nanoceramic Composites 375 18.3.3 WC–ZrO2–Co Nanocomposites 380 18.3.4 Toughness of WC–ZrO2-Based Nanoceramic Composites 384 18.3.5 Comparison with Other Ceramic Nanocomposites 385 References 387 Section Seven Bioceramics and Biocomposites 19. Overview: Introduction to Biomaterials 393 19.1 Introduction 393 19.2 Hard Tissues 394 19.3 Some Useful Definitions and Their Implications 395 19.3.1 Biomaterial 395 19.3.2 Biocompatibility 397 19.3.3 Host Response 397 19.4 Cell–Material Interaction 398 19.5 Bacterial Infection and Biofilm Formation 400 19.6 Different Factors Influencing Bacterial Adhesion 402 19.6.1 Material Factors 404 19.6.2 Bacteria-Related Factors 405 19.6.3 External Factors 406 19.7 Experimental Evaluation of Biocompatibility 406 19.8 Overview of Properties of Some Biomaterials 413 19.8.1 Coating on Metals 413 19.8.2 Glass-Ceramics-Based Biomaterials 417 19.9 Outlook 418 References 419 20. Calcium Phosphate-Based Bioceramic Composites 422 20.1 Introduction 422 20.2 Bioinert Ceramics 424 20.3 Calcium Phosphate-Based Biomaterials 425 20.4 Calcium Phosphate–Mullite Composites 428 20.4.1 Mechanical Properties 430 20.4.2 Biocompatibility (In Vitro and In Vivo) 431 20.5 Hydroxyapatite–Ti System 434 20.6 Enhancement of Antimicrobial Properties of Hydroxyapatite 434 20.6.1 Hydroxyapatite–Ag System 437 20.6.2 Hydroxyapatite–ZnO System 439 References 443 21. Tribological Properties of Ceramic Biocomposites 448 21.1 Introduction 448 21.2 Tribology of Ceramic Biocomposites 449 21.3 Tribological Properties of Mullite-Reinforced Hydroxyapatite 450 21.3.1 Materials and Experiments 451 21.3.2 Effect of Lubrication on the Wear Resistance of Mullite-Reinforced Hydroxyapatite 451 21.3.3 Surface Topography of Mullite-Reinforced Hydroxyapatite after Fretting Wear 454 21.4 Tribological Properties of Plasma-Sprayed Hydroxyapatite Reinforced with Carbon Nanotubes 454 21.4.1 Bulk Wear Resistance of Hydroxyapatite Reinforced with Carbon Nanotubes 454 21.4.2 Nanomechanical Properties of Hydroxyapatite Reinforced with Carbon Nanotubes 457 21.4.3 Nanoscratching of Hydroxyapatite Reinforced with Carbon Nanotubes 461 21.5 Laser Surface Treatment of Calcium Phosphate Biocomposites 461 References 470 Index 472

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Book SynopsisThis book provides readers with new paradigms on the mutation discovery in the post-genome era. The completion of human and other genome sequencing, along with other new technologies, such as mutation analysis and microarray, has dramatically accelerated the progress in positional cloning of genes from mutated models.Table of ContentsPreface. Acknowledgments. Contributors. 1. Gene Discovery: From Positional Cloning to Genomic Cloning (Weikuan Gu and Daniel Goldowitz). 2. High-Throughput Gene Expression Analysis and the Identification of Expression QTLs (Rudi Alberts and Klaus Schughart). 3. DNA Methylation in the Pathogenesis of Autoimmunity (Xueqing Xu, Ping Yang, Zhang Shu, Yun Bai, and Cong-Yi Wang). 4. Cell-Based Analysis with Microfl uidic Chip (Wang Qi and Zhao Long). 5. Missing Dimension: Protein Turnover Rate Measurement in Gene Discovery (Gary Guishan Xiao). 6. Bioinformatics Tools for Gene Function Prediction (Yan Cui). 7. Determination of Genomic Locations of Target Genetic Loci (Bo Chang). 8. Mutation Discovery Using High-Throughput Mutation Screening Technology (Kai Li, Hanlin Gao, Hong-Guang Xie, Wanping Sun, and Jia Zhang). 9. Candidate Screening through Gene Expression Profile (Michal Korostynski). 10. Candidate Screening through High-Density SNP Array (Ching-Wan Lam and Kin-Chong Lau). 11. Gene Discovery by Direct Genome Sequencing (Kunal Ray, Arijit Mukhopadhyay, and Mainak Sengupta). 12. Candidate Screening through Bioinformatics Tools (Song Wu and Wei Zhao). 13. Using an Integrative Strategy to Identify Mutations (Yan Jiao and Weikuan Gu). 14. Determination of the Function of a Mutation (Bouchra Edderkaoui). 15. Confi rmation of a Mutation by Multiple Molecular Approaches (Hector Martinez-Valdez and Blanca Ortiz-Quintero). 16. Confi rmation of a Mutation by MicroRNA (Hongwei Zheng and Yongjun Wang). 17. Confi rmation of Gene Function Using Translational Approaches (Caroline J. Zeiss). 18. Confi rmation of Single Nucleotide Mutations (Jochen Graw). 19. Initial Identifi cation and Confi rmation of a QTL Gene (David C. Airey and Chun Li). 20. Gene Discovery of Crop Disease in the Postgenome Era (Yulin Jia). 21. Impact of Genomewide Structural Variation on Gene Discovery (Lisenka E.L.M. Vissers and Joris A. Veltman). 22. Impact of Whole Genome Protein Analysis on Gene Discovery of Disease Models (Sheng Zhang, Yong Yang, and Theodore W. Thannhauser). Index.

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Book SynopsisThis book consolidates various aspects of nanomaterials, highlighting their versatility as well as how the same materials can be used in seemingly diverse applications spanning across disciplines. It captures the multi-disciplinary and multi-functional aspects of nanomaterials in a holistic way. Chapters address the key attributes of nanoscale materials that make them special and desirable as novel materials; functionality that emerges based on these unique attributes; multiple uses of nanomaterials incuding combining properties and materials selection, and then separate chapters devoted to energy, biomedical materials, environmental applications, and chemical engineering applications.Trade Review"Leading nanomaterial specialists have contributed to the content of this book. Each chapter provides a comprehensive review of the latest literature. References provided in each chapter will be helpful for readers to study individual topics in detail." (Azonano.com, 3 February 2012)Table of ContentsPreface. Section I. Overview. 1. Key attributes of nano-scale materials and functionalities emerging from them (S. M. Mukhopadhyay). 2. Societal Impact and Future Trends in Nanomaterials (S. M. Mukhopadhyay). Section II. Processing and Analysis. 3. Fabrication Techniques for Growing Carbon Nanotubes (I. T. Barney). 4. Nanoparticles and Polymer Nanocomposites (G. A. Jimenez, B. J. Lee, and S. C. Jana). 5. Laser-Assisted Fabrication Techniques (T. Murray). 6. Experimental Characterization of Nanomaterials (A. Jackson). 7. Modeling and Simulation of Nanoscale Materials (S. Patnaik and M. Tsige). Section III. Applications. 8. Nanomaterials for Alternate Energy (H. Huang and B. Z. Jang). 9. Enhancement of Through-Thickness Thermal conductivity in Adhesively Bonded Joints Using Aligned Carbon Nanotubes (S. Sihn, S. Ganguli, A. K. Roy, L. Qu, and L. Dai). 10. Applications of Metal Nanoparticles in Environmental Cleanup (S. R. Kanel, C. Su, U. Patel, and A. Agrawal). 11. Application of Carbon Nanomaterials in Water Treatment: Removal of Common Chemical and Biological Contaminants by Adsorption (V. K. K. Updahyayula, J. R. Ruparelia, and A. Agrawal). 12. Peptide Nanotubes for Biomedical and Environmental Applications (B. W. Park and D. S. Kim). Index.

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Book SynopsisSix years after its first edition, Computed Tomography: Principles, Design, Artifacts, and Recent Advances, Second Edition provides and updated overview of the evolution of CT, the mathematical and physical aspects of the technology, and the fundamentals of image reconstruction algorithms.Table of ContentsPreface. Nomenclature and Abbreviations. 1. Introduction. 1.1 Conventional X-ray Tomography. 1.2 History of Computed Tomography. 1.3 Different Generations of CT Scanners. 1.4 Problems. References. 2. Preliminaries. 2.1 Mathematics Fundamentals. 2.2 Fundamentals of X-ray Physics. 2.3 Measurement of Line Integrals and Data Conditioning. 2.4 Sampling Geometry and Sinogram. 2.5 Problems. References. 3. Image Reconstruction. 3.1 Introduction. 3.2 Several Approaches to Image Reconstruction. 3.3 The Fourier Slice Theorem. 3.4 The Filtered Backprojection Algorithm. 3.5 Fan-Beam Reconstruction. 3.6 Iterative Reconstruction. 3.7 Problems. References. 4. Image Presentation. 4.1 CT Image Display. 4.2 Volume Visualization. 4.3 Impact of Visualization Tools. 4.4 Problems. References. 5. Key Performance Parameters of the CT Scanner. 5.1 High-Contrast Spatial Resolution. 5.2 Low-Contrast Resolution. 5.3 Temporal Resolution. 5.4 CT Number Accuracy and Noise. 5.5 Performance of the Scanogram. 5.6 Problems. References. 6. Major Components of the CT Scanner. 6.1 System Overview. 6.2 The X-ray Tube and High-Voltage Generator. 6.3 The X-ray Detector and Data-Acquisition Electronics. 6.4 The Gantry and Slip Ring. 6.5 Collimation and Filtration. 6.6 The Reconstruction Engine. 6.7 Problems. References. 7. Image Artifacts: Appearances, Causes, and Corrections. 7.1 What Is an Image Artifact? 7.2 Different Appearances of Image Artifacts. 7.3 Artifacts Related to System Design. 7.4 Artifacts Related to X-ray Tubes. 7.5 Detector-induced Artifacts. 7.6 Patient-induced Artifacts. 7.7 Operator-induced Artifacts. 7.8 Problems. References. 8. Computer Simulation Analysis. 8.1 What Is Computer Simulation? 8.2 Simulation Overview. 8.3 Simulation of Optics. 8.4 Computer Simulation of Physics-related Performance. 8.5 Problems. References. 9. Helical or Spiral CT. 9.1 Introduction. 9.2 Terminology and Reconstruction. 9.3 Slice Sensitivity Profile and Noise. 9.4 Helically Related Image Artifacts. 9.5 Problems. References. 10. Miltislice CT. 10.1 The Need for Multislice CT. 10.2 Detector Configurations of Multislice CT. 10.3 Nonhelical Mode of Reconstruction. 10.4 Multislice Helical Reconstruction. 10.5 Multislice Artifacts. 10.6 Problems. References. 11. X-ray Radiation and Dose-Reduction Techniques. 11.1 Biological Effects of X-ray Radiation. 11.2 Measurement of X-ray dose. 11.3 Methodologies for Dose Reduction. 11.4 Problems. References. 12. Advanced CT Applications. 12.1 Introduction. 12.2 Cardiac Imaging. 12.3 CT Fluoroscopy. 12.4 CT Perfusion. 12.5 Screening and Quantitative CT. 12.6 Dual-Energy CT. 12.7 Problems. References. Glossary. Index.

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Book SynopsisWritten by esteemed experts in the field, Models and Algorithms for Biomolecules and Molecular Networks provides readers with a global perspectives on the relevant biological phenomena, modeling frameworks, technical challenges, and algorithms.Table of ContentsList of Figures xiii List of Tables xix Foreword xxi Acknowledgments xxiii 1 Geometric Models of Protein Structure and Function Prediction 1 1.1 Introduction 1 1.2 Theory and Model 2 1.2.1 Idealized Ball Model 2 1.2.2 Surface Models of Proteins 3 1.2.3 Geometric Constructs 4 1.2.4 Topological Structures 6 1.2.5 Metric Measurements 9 1.3 Algorithm and Computation 13 1.4 Applications 15 1.4.1 Protein Packing 15 1.4.2 Predicting Protein Functions from Structures 17 1.5 Discussion and Summary 20 References 22 Exercises 25 2 Scoring Functions for Predicting Structure and Binding of Proteins 29 2.1 Introduction 29 2.2 General Framework of Scoring Function and Potential Function 31 2.2.1 Protein Representation and Descriptors 31 2.2.2 Functional Form 32 2.2.3 Deriving Parameters of Potential Functions 32 2.3 Statistical Method 32 2.3.1 Background 32 2.3.2 Theoretical Model 33 2.3.3 Miyazawa--Jernigan Contact Potential 34 2.3.4 Distance-Dependent Potential Function 41 2.3.5 Geometric Potential Functions 45 2.4 Optimization Method 49 2.4.1 Geometric Nature of Discrimination 50 2.4.2 Optimal Linear Potential Function 52 2.4.3 Optimal Nonlinear Potential Function 53 2.4.4 Deriving Optimal Nonlinear Scoring Function 55 2.4.5 Optimization Techniques 55 2.5 Applications 55 2.5.1 Protein Structure Prediction 56 2.5.2 Protein--Protein Docking Prediction 56 2.5.3 Protein Design 58 2.5.4 Protein Stability and Binding Affinity 59 2.6 Discussion and Summary 60 2.6.1 Knowledge-Based Statistical Potential Functions 60 2.6.2 Relationship of Knowledge-Based Energy Functions and Further Development 64 2.6.3 Optimized Potential Function 65 2.6.4 Data Dependency of Knowledge-Based Potentials 66 References 67 Exercises 75 3 Sampling Techniques: Estimating Evolutionary Rates and Generating Molecular Structures 79 3.1 Introduction 79 3.2 Principles of Monte Carlo Sampling 81 3.2.1 Estimation Through Sampling from Target Distribution 81 3.2.2 Rejection Sampling 82 3.3 Markov Chains and Metropolis Monte Carlo Sampling 83 3.3.1 Properties of Markov Chains 83 3.3.2 Markov Chain Monte Carlo Sampling 85 3.4 Sequential Monte Carlo Sampling 87 3.4.1 Importance Sampling 87 3.4.2 Sequential Importance Sampling 87 3.4.3 Resampling 91 3.5 Applications 92 3.5.1 Markov Chain Monte Carlo for Evolutionary Rate Estimation 92 3.5.2 Sequentail Chain Growth Monte Carlo for Estimating Conformational Entropy of RNA Loops 95 3.6 Discussion and Summary 96 References 97 Exercises 99 4 Stochastic Molecular Networks 103 4.1 Introduction 103 4.2 Reaction System and Discrete Chemical Master Equation 104 4.3 Direct Solution of Chemical Master Equation 106 4.3.1 State Enumeration with Finite Buffer 106 4.3.2 Generalization and Multi-Buffer dCME Method 108 4.3.3 Calculation of Steady-State Probability Landscape 108 4.3.4 Calculation of Dynamically Evolving Probability Landscape 108 4.3.5 Methods for State Space Truncation for Simplification 109 4.4 Quantifying and Controlling Errors from State Space Truncation 111 4.5 Approximating Discrete Chemical Master Equation 114 4.5.1 Continuous Chemical Master Equation 114 4.5.2 Stochastic Differential Equation: Fokker—Planck Approach 114 4.5.3 Stochastic Differential Equation: Langevin Approach 116 4.5.4 Other Approximations 117 4.6 Stochastic Simulation 118 4.6.1 Reaction Probability 118 4.6.2 Reaction Trajectory 118 4.6.3 Probability of Reaction Trajectory 119 4.6.4 Stochastic Simulation Algorithm 119 4.7 Applications 121 4.7.1 Probability Landscape of a Stochastic Toggle Switch 121 4.7.2 Epigenetic Decision Network of Cellular Fate in Phage Lambda 123 4.8 Discussions and Summary 127 References 128 Exercises 131 5 Cellular Interaction Networks 135 5.1 Basic Definitions and Graph-Theoretic Notions 136 5.1.1 Topological Representation 136 5.1.2 Dynamical Representation 138 5.1.3 Topological Representation of Dynamical Models 139 5.2 Boolean Interaction Networks 139 5.3 Signal Transduction Networks 141 5.3.1 Synthesizing Signal Transduction Networks 142 5.3.2 Collecting Data for Network Synthesis 146 5.3.3 Transitive Reduction and Pseudo-node Collapse 147 5.3.4 Redundancy and Degeneracy of Networks 153 5.3.5 Random Interaction Networks and Statistical Evaluations 157 5.4 Reverse Engineering of Biological Networks 159 5.4.1 Modular Response Analysis Approach 160 5.4.2 Parsimonious Combinatorial Approaches 166 5.4.3 Evaluation of Quality of the Reconstructed Network 171 References 173 Exercises 178 6 Dynamical Systems and Interaction Networks 183 6.1 Some Basic Control-Theoretic Concepts 185 6.2 Discrete-Time Boolean Network Models 186 6.3 Artificial Neural Network Models 188 6.3.1 Computational Powers of ANNs 189 6.3.2 Reverse Engineering of ANNs 190 6.3.3 Applications of ANN Models in Studying Biological Networks 192 6.4 Piecewise Linear Models 192 6.4.1 Dynamics of PL Models 194 6.4.2 Biological Application of PL Models 195 6.5 Monotone Systems 200 6.5.1 Definition of Monotonicity 201 6.5.2 Combinatorial Characterizations and Measure of Monotonicity 203 6.5.3 Algorithmic Issues in Computing the Degree of Monotonicity 𝖬 207 References 209 Exercises 214 7 Case Study of Biological Models 217 7.1 Segment Polarity Network Models 217 7.1.1 Boolean Network Model 218 7.1.2 Signal Transduction Network Model 218 7.2 ABA-Induced Stomatal Closure Network 219 7.3 Epidermal Growth Factor Receptor Signaling Network 220 7.4 C. elegans Metabolic Network 223 7.5 Network for T-Cell Survival and Death in Large Granular Lymphocyte Leukemia 223 References 224 Exercises 225 Glossary 227 Index 229

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Book SynopsisDesigned to provide busy clinicians with a comprehensive guide to the investigation, diagnosis, and treatment of Acute Coronary Syndrome (ACS), this book encompasses the latest technologies, including the use of biomarkers and non-invasive imaging procedures.Table of ContentsList of contributors xiii Foreword xv Eugene Braunwald Chapter 1 Pathophysiology of acute coronary syndromes 1 Alisa B. Rosen and Eli V. Gelfand Introduction 1 Formation of atherosclerotic plaque 2 Plaque instability and the development of ACS 5 Myocardial ischemia 7 Thrombus formation 7 Platelets 7 Secondary hemostasis 9 Dynamic obstruction 10 Progressive mechanical obstruction 10 Inflammation 11 Secondary unstable angina 11 References 11 Chapter 2 Diagnosis of acute coronary syndrome 13 Eli V. Gelfand and Alisa B. Rosen Introduction 13 Definition of myocardial infarction 13 History 14 Risk factors 17 Physical examination 17 Electrocardiography 19 The pathophysiologic basis of ST segment changes during ischemia 19 Electrocardiography in ST-elevation MI and identification of the infarct-related artery 20 Electrocardiography in unstable angina and NSTEMI 26 Cardiac biomarkers 26 Noninvasive imaging 29 Echocardiography 29 Myocardial perfusion imaging 30 Coronary computed tomography 30 Cardiovascular magnetic resonance imaging 31 Stress testing for diagnosis of ACS 32 Overall diagnostic pathway for ACS 32 References 34 Chapter 3 Unstable angina and non-ST-elevation myocardial infarction 37 Eli V. Gelfand and Christopher P. Cannon Introduction 37 Causes of UA/NSTEMI 37 Presentation of UA/NSTEMI 38 General strategies in management of UA/NSTEMI 39 Risk stratification of patients with UA/NSTEMI 40 Initial management of UA/NSTEMI in the emergency department 42 Pharmacologic treatment of ischemia in UA/NSTEMI 43 Beta-blockers 44 Nitrates 44 Calcium channel blockers 45 Angiotensin-converting enzyme inhibitors 45 Morphine 46 Oxygen 46 Invasive versus conservative strategy 46 Antiplatelet therapy in UA/NSTEMI 49 Aspirin 54 Clopidogrel 55 Prasugrel 57 Glycoprotein IIb/IIIa inhibitors 58 Anticoagulant therapy in UA/NSTEMI 61 Unfractionated heparin 61 Enoxaparin 62 Direct thrombin inhibitors 65 Fondaparinux 66 Oral anticoagulation in UA/NSTEMI 67 Fibrinolysis in UA/NSTEMI 68 Early lipid-lowering therapy in patients with UA/NSTEMI 68 Predischarge noninvasive risk stratification after UA/NSTEMI 69 Overall management of UA/NSTEMI 71 References 71 Chapter 4 ST-segment-elevation myocardial infarction 79 Eli V. Gelfand and Christopher P. Cannon Introduction 79 Global treatment goals in STEMI 79 Prehospital management and triage 80 Transport decisions 82 Management prior to reperfusion 82 Primary reperfusion therapy for STEMI 83 Fibrinolysis 83 Combination fibrinolysis 86 Markers of fibrinolysis effectiveness 86 Complications of fibrinolysis 88 Primary percutaneous coronary intervention 88 Comparison of PCI with fibrinolysis 90 Timing of primary PCI 91 PCI following fibrinolytic therapy 94 Rescue PCI 94 Facilitated PCI 94 Routine PCI after successful fibrinolysis 96 Overall reperfusion strategy 97 Coronary artery bypass grafting for treatment of STEMI 98 Adjunctive pharmacologic treatment of STEMI 98 Antiplatelet agents 98 Anticoagulation therapy 101 Other adjunctive therapy 105 Hospital care following successful reperfusion 110 References 114 Chapter 5 Special considerations in acute coronary syndromes 123 Jason Ryan and Eli V. Gelfand Secondary unstable angina 123 Acute coronary syndrome in patients with diabetes mellitus 123 General considerations 123 Primary ACS therapy in diabetics 124 Glycemic control in diabetics with ACS 125 Coronary revascularization in diabetics 126 Metabolic syndrome and ACS 127 Chronic kidney disease in ACS 127 Young patients with ACS 130 ACS in the setting of cocaine use 130 ACS in patients with normal coronary arteries or mild CAD 132 Myocarditis 132 Acute transient apical ballooning syndrome 133 Postoperative ACS 134 ACS in a pregnant woman 135 Hyperthyroidism and ACS 136 ACS in patients exposed to radiation 137 Trauma and ACS 137 References 137 Chapter 6 Complications of acute coronary syndrome 141 Jan M. Pattanayak and Eli V. Gelfand Introduction 141 Pump failure 141 General principle 141 Clinical presentation 142 Prognosis 144 Treatment 144 Right ventricular infarction 148 Introduction 148 Clinical presentation 148 Diagnosis 149 Management 150 Prognosis 152 Mechanical complications of ACS 152 Introduction 152 Left ventricular free wall rupture 152 Ventricular septal rupture 153 Acute mitral regurgitation 154 Left ventricular aneurysm 155 Left ventricular pseudoaneurysm 157 Pericardial complications 157 Arrhythmic complications of ACS 159 Bradyarrhythmias 159 Atrial fibrillation 163 Ventricular tachycardia and fibrillation 163 Complications involving bleeding 164 Complications of percutaneous coronary intervention 165 References 170 Chapter 7 Post-hospitalization care of patients with acute coronary syndrome 173 Jersey Chen and Eli V. Gelfand Introduction 173 Pharmacologic measures 173 Aspirin 173 Clopidogrel 174 Beta adrenergic blockade 177 Renin–angiotensin–aldosterone inhibitors 179 Lipid-lowering therapy 185 Warfarin 189 Influenza vaccination 192 Medications of limited benefit to patients following ACS 192 Vitamins/antioxidants 192 Estrogen replacement therapy 192 Nonsteroidal anti-inflammatory agents and related compounds 194 Nonpharmacologic measures 195 Antiarrhythmic devices 195 Therapy of comorbidities following ACS 198 Diabetes mellitus 198 Hypertension 199 Depression 199 Lifestyle recommendations following ACS 200 General physical activity and structured cardiac rehabilitation 200 Sexual activity after ACS 201 Smoking cessation 201 Diet/nutrition and weight loss 202 References 204 Appendix 209 Index 217

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Book SynopsisThis book provides a broad survey of models and efficient algorithms for Nonnegative Matrix Factorization (NMF). This includes NMF's various extensions and modifications, especially Nonnegative Tensor Factorizations (NTF) and Nonnegative Tucker Decompositions (NTD).Trade Review"[A] focus on the algorithms that are most useful in practice and aim to derive and implement, in MATLAB, efficient and simple iterative algorithms that work with real-world data." (Book News, December 2009)Table of ContentsPreface. Acknowledgments. Glossary of Symbols and Abbreviations. 1 Introduction – Problem Statements and Models. 1.1 Blind Source Separation and Linear Generalized Component Analysis. 1.2 Matrix Factorization Models with Nonnegativity and Sparsity Constraints. 1.2.1 Why Nonnegativity and Sparsity Constraints? 1.2.2 Basic NMF Model. 1.2.3 Symmetric NMF. 1.2.4 Semi-Orthogonal NMF. 1.2.5 Semi-NMF and Nonnegative Factorization of Arbitrary Matrix. 1.2.6 Three-factor NMF. 1.2.7 NMF with Offset (Affine NMF). 1.2.8 Multi-layer NMF. 1.2.9 Simultaneous NMF. 1.2.10 Projective and Convex NMF. 1.2.11 Kernel NMF. 1.2.12 Convolutive NMF. 1.2.13 Overlapping NMF. 1.3 Basic Approaches to Estimate Parameters of Standard NMF. 1.3.1 Large-scale NMF. 1.3.2 Non-uniqueness of NMF and Techniques to Alleviate the Ambiguity Problem. 1.3.3 Initialization of NMF. 1.3.4 Stopping Criteria. 1.4 Tensor Properties and Basis of Tensor Algebra. 1.4.1 Tensors (Multi-way Arrays) – Preliminaries. 1.4.2 Subarrays, Tubes and Slices. 1.4.3 Unfolding – Matricization. 1.4.4 Vectorization. 1.4.5 Outer, Kronecker, Khatri-Rao and Hadamard Products. 1.4.6 Mode-n Multiplication of Tensor by Matrix and Tensor by Vector, Contracted Tensor Product. 1.4.7 Special Forms of Tensors. 1.5 Tensor Decompositions and Factorizations. 1.5.1 Why Multi-way Array Decompositions and Factorizations? 1.5.2 PARAFAC and Nonnegative Tensor Factorization. 1.5.3 NTF1 Model. 1.5.4 NTF2 Model. 1.5.5 Individual Differences in Scaling (INDSCAL) and Implicit Slice Canonical Decomposition Model (IMCAND). 1.5.6 Shifted PARAFAC and Convolutive NTF. 1.5.7 Nonnegative Tucker Decompositions. 1.5.8 Block Component Decompositions. 1.5.9 Block-Oriented Decompositions. 1.5.10 PARATUCK2 and DEDICOM Models. 1.5.11 Hierarchical Tensor Decomposition. 1.6 Discussion and Conclusions. 2 Similarity Measures and Generalized Divergences. 2.1 Error-induced Distance and Robust Regression Techniques. 2.2 Robust Estimation. 2.3 Csiszár Divergences. 2.4 Bregman Divergence. 2.4.1 Bregman Matrix Divergences. 2.5 Alpha-Divergences. 2.5.1 Asymmetric Alpha-Divergences. 2.5.2 Symmetric Alpha-Divergences. 2.6 Beta-Divergences. 2.7 Gamma-Divergences. 2.8 Divergences Derived from Tsallis and Rényi Entropy. 2.8.1 Concluding Remarks. 3 Multiplicative Iterative Algorithms for NMF with Sparsity Constraints. 3.1 Extended ISRA and EMML Algorithms: Regularization and Sparsity. 3.1.1 Multiplicative NMF Algorithms Based on the Squared Euclidean Distance. 3.1.2 Multiplicative NMF Algorithms Based on Kullback-Leibler I-Divergence. 3.2 Multiplicative Algorithms Based on Alpha-Divergence. 3.2.1 Multiplicative Alpha NMF Algorithm. 3.2.2 Generalized Multiplicative Alpha NMF Algorithms. 3.3 Alternating SMART: Simultaneous Multiplicative Algebraic Reconstruction Technique. 3.3.1 Alpha SMART Algorithm. 3.3.2 Generalized SMART Algorithms. 3.4 Multiplicative NMF Algorithms Based on Beta-Divergence. 3.4.1 Multiplicative Beta NMF Algorithm. 3.4.2 Multiplicative Algorithm Based on the Itakura-Saito Distance. 3.4.3 Generalized Multiplicative Beta Algorithm for NMF. 3.5 Algorithms for Semi-orthogonal NMF and Orthogonal Three-Factor NMF. 3.6 Multiplicative Algorithms for Affine NMF. 3.7 Multiplicative Algorithms for Convolutive NMF. 3.7.1 Multiplicative Algorithm for Convolutive NMF Based on Alpha-Divergence. 3.7.2 Multiplicative Algorithm for Convolutive NMF Based on Beta-Divergence. 3.7.3 Efficient Implementation of CNMF Algorithm. 3.8 Simulation Examples for Standard NMF. 3.9 Examples for Affine NMF. 3.10 Music Analysis and Decomposition Using Convolutive NMF. 3.11 Discussion and Conclusions. 4 Alternating Least Squares and Related Algorithms for NMF and SCA Problems. 4.1 Standard ALS Algorithm. 4.1.1 Multiple Linear Regression – Vectorized Version of ALS Update Formulas. 4.1.2 Weighted ALS. 4.2 Methods for Improving Performance and Convergence Speed of ALS Algorithms. 4.2.1 ALS Algorithm for Very Large-scale NMF. 4.2.2 ALS Algorithm with Line-Search. 4.2.3 Acceleration of ALS Algorithm via Simple Regularization. 4.3 ALS Algorithm with Flexible and Generalized Regularization Terms. 4.3.1 ALS with Tikhonov Type Regularization Terms. 4.3.2 ALS Algorithms with Sparsity Control and Decorrelation. 4.4 Combined Generalized Regularized ALS Algorithms. 4.5 Wang-Hancewicz Modified ALS Algorithm. 4.6 Implementation of Regularized ALS Algorithms for NMF. 4.7 HALS Algorithm and its Extensions. 4.7.1 Projected Gradient Local Hierarchical Alternating Least Squares (HALS) Algorithm. 4.7.2 Extensions and Implementations of the HALS Algorithm. 4.7.3 Fast HALS NMF Algorithm for Large-scale Problems. 4.7.4 HALS NMF Algorithm with Sparsity, Smoothness and Uncorrelatedness Constraints. 4.7.5 HALS Algorithm for Sparse Component Analysis and Flexible Component Analysis. 4.7.6 Simplified HALS Algorithm for Distributed and Multi-task Compressed Sensing. 4.7.7 Generalized HALS-CS Algorithm. 4.7.8 Generalized HALS Algorithms Using Alpha-Divergence. 4.7.9 Generalized HALS Algorithms Using Beta-Divergence. 4.8 Simulation Results. 4.8.1 Underdetermined Blind Source Separation Examples. 4.8.2 NMF with Sparseness, Orthogonality and Smoothness Constraints. 4.8.3 Simulations for Large-scale NMF. 4.8.4 Illustrative Examples for Compressed Sensing. 4.9 Discussion and Conclusions. 5 Projected Gradient Algorithms. 5.1 Oblique Projected Landweber (OPL) Method. 5.2 Lin’s Projected Gradient (LPG) Algorithm with Armijo Rule. 5.3 Barzilai-Borwein Gradient Projection for Sparse Reconstruction (GPSR-BB). 5.4 Projected Sequential Subspace Optimization (PSESOP). 5.5 Interior Point Gradient (IPG) Algorithm. 5.6 Interior Point Newton (IPN) Algorithm. 5.7 Regularized Minimal Residual Norm Steepest Descent Algorithm (RMRNSD). 5.8 Sequential Coordinate-Wise Algorithm (SCWA). 5.9 Simulations. 5.10 Discussions. 6 Quasi-Newton Algorithms for Nonnegative Matrix Factorization. 6.1 Projected Quasi-Newton Optimization. 6.1.1 Projected Quasi-Newton for Frobenius Norm. 6.1.2 Projected Quasi-Newton for Alpha-Divergence. 6.1.3 Projected Quasi-Newton for Beta-Divergence. 6.1.4 Practical Implementation. 6.2 Gradient Projection Conjugate Gradient. 6.3 FNMA algorithm. 6.4 NMF with Quadratic Programming. 6.4.1 Nonlinear Programming. 6.4.2 Quadratic Programming. 6.4.3 Trust-region Subproblem. 6.4.4 Updates for A. 6.5 Hybrid Updates. 6.6 Numerical Results. 6.7 Discussions. 7 Multi-Way Array (Tensor) Factorizations and Decompositions. 7.1 Learning Rules for the Extended Three-way NTF1 Problem. 7.1.1 Basic Approaches for the Extended NTF1 Model. 7.1.2 ALS Algorithms for NTF1. 7.1.3 Multiplicative Alpha and Beta Algorithms for the NTF1 Model. 7.1.4 Multi-layer NTF1 Strategy. 7.2 Algorithms for Three-way Standard and Super Symmetric Nonnegative Tensor Factorization. 7.2.1 Multiplicative NTF Algorithms Based on Alpha- and Beta-Divergences. 7.2.2 Simple Alternative Approaches for NTF and SSNTF. 7.3 Nonnegative Tensor Factorizations for Higher-Order Arrays. 7.3.1 Alpha NTF Algorithm. 7.3.2 Beta NTF Algorithm. 7.3.3 Fast HALS NTF Algorithm Using Squared Euclidean Distance. 7.3.4 Generalized HALS NTF Algorithms Using Alpha- and Beta-Divergences. 7.3.5 Tensor Factorization with Additional Constraints. 7.4 Algorithms for Nonnegative and Semi-Nonnegative Tucker Decompositions. 7.4.1 Higher Order SVD (HOSVD) and Higher Order Orthogonal Iteration (HOOI) Algorithms. 7.4.2 ALS Algorithm for Nonnegative Tucker Decomposition. 7.4.3 HOSVD, HOOI and ALS Algorithms as Initialization Tools for Nonnegative Tensor Decomposition. 7.4.4 Multiplicative Alpha Algorithms for Nonnegative Tucker Decomposition. 7.4.5 Beta NTD Algorithm. 7.4.6 Local ALS Algorithms for Nonnegative TUCKER Decompositions. 7.4.7 Semi-Nonnegative Tucker Decomposition. 7.5 Nonnegative Block-Oriented Decomposition. 7.5.1 Multiplicative Algorithms for NBOD. 7.6 Multi-level Nonnegative Tensor Decomposition - High Accuracy Compression and Approximation. 7.7 Simulations and Illustrative Examples. 7.7.1 Experiments for Nonnegative Tensor Factorizations. 7.7.2 Experiments for Nonnegative Tucker Decomposition. 7.7.3 Experiments for Nonnegative Block-Oriented Decomposition. 7.7.4 Multi-Way Analysis of High Density Array EEG – Classification of Event Related Potentials. 7.7.5 Application of Tensor Decompositions in Brain Computer Interface – Classification of Motor Imagery Tasks. 7.7.6 Image and Video Applications. 7.8 Discussion and Conclusions. 8 Selected Applications. 8.1 Clustering. 8.1.1 Semi-Binary NMF. 8.1.2 NMF vs. Spectral Clustering. 8.1.3 Clustering with Convex NMF. 8.1.4 Application of NMF to Text Mining. 8.1.5 Email Surveillance. 8.2 Classification. 8.2.1 Musical Instrument Classification. 8.2.2 Image Classification. 8.3 Spectroscopy. 8.3.1 Raman Spectroscopy. 8.3.2 Fluorescence Spectroscopy. 8.3.3 Hyperspectral Imaging. 8.3.4 Chemical Shift Imaging. 8.4 Application of NMF for Analyzing Microarray Data. 8.4.1 Gene Expression Classification. 8.4.2 Analysis of Time Course Microarray Data. References. Index.

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Book SynopsisThere is an increasing need throughout the biomedical sciences for a greater understanding of knowledge-based systems and their application to genomic and proteomic research. This book discusses knowledge-based and statistical approaches, along with applications in bioinformatics and systems biology. The text emphasizes the integration of different methods for analysing and interpreting biomedical data. This, in turn, can lead to breakthrough biomolecular discoveries, with applications in personalized medicine. Key Features: Explores the fundamentals and applications of knowledge-based and statistical approaches in bioinformatics and systems biology. Helps readers to interpret genomic, proteomic, and metabolomic data in understanding complex biological molecules and their interactions. Provides useful guidance on dealing with large datasets in knowledge bases, a common issue in bioinformatics. Written by leading international experts in this Table of ContentsPreface. List of Contributors. PART I FUNDAMENTALS. Section 1 Knowledge-Driven Approaches. 1 Knowledge-based bioinformatics (Eric Karl Neumann). 1.1 Introduction. 1.2 Formal reasoning for bioinformatics. 1.3 Knowledge representations. 1.4 Collecting explicit knowledge. 1.5 Representing common knowledge. 1.6 Capturing novel knowledge. 1.7 Knowledge discovery applications. 1.8 Semantic harmonization: the power and limitation of ontologies. 1.9 Text mining and extraction. 1.10 Gene expression. 1.11 Pathways and mechanistic knowledge. 1.12 Genotypes and phenotypes. 1.13 The Web's role in knowledge mining. 1.14 New frontiers. 1.15 References. 2 Knowledge-driven approaches to genome-scale analysis (Hannah Tipney and Lawrence Hunter). 2.1 Fundamentals. 2.2 Challenges in knowledge-driven approaches. 2.3 Current knowledge-based bioinformatics tools. 2.4 3R systems: reading, reasoning and reporting the way towards biomedical discovery. 2.5 The Hanalyzer: a proof of 3R concept. 2.6 Acknowledgements. 2.7 References. 3 Technologies and best practices for building bio-ontologies (Mikel Egaña Aranguren, Robert Stevens, Erick Antezana, Jesualdo Tomás Fernández-Breis, Martin Kuiper, and Vladimir Mironov). 3.1 Introduction. 3.2 Knowledge representation languages and tools for building bio-ontologies. 3.3 Best practices for building bio-ontologies. 3.4 Conclusion. 3.5 Acknowledgements. 3.6 References. 4 Design, implementation and updating of knowledge bases (Sarah Hunter, Rolf Apweiler, and Maria Jesus Martin). 4.1 Introduction. 4.2 Sources of data in bioinformatics knowledge bases. 4.3 Design of knowledge bases. 4.4 Implementation of knowledge bases. 4.5 Updating of knowledge bases. 4.6 Conclusions. 4.7 References. Section 2 Data-Analysis Approaches. 5 Classical statistical learning in bioinformatics (Mark Reimers). 5.1 Introduction. 5.2 Significance testing. 5.3 Exploratory analysis. 5.4 Classification and prediction. 5.5 References. 6 Bayesian methods in genomics and proteomics studies (Ning Sun and Hongyu Zhao). 6.1 Introduction. 6.2 Bayes theorem and some simple applications. 6.3 Inference of population structure from genetic marker data. 6.4 Inference of protein binding motifs from sequence data. 6.5 Inference of transcriptional regulatory networks from joint analysis of protein–DNA binding data and gene expression data. 6.6 Inference of protein and domain interactions from yeast two-hybrid data. 6.7 Conclusions. 6.8 Acknowledgements. 6.9 References. 7 Automatic text analysis for bioinformatics knowledge discovery (Dietrich Rebholz-Schuhmann and Jung-jae Kim). 7.1 Introduction. 7.2 Information needs for biomedical text mining. 7.3 Principles of text mining. 7.4 Development issues. 7.5 Success stories. 7.6 Conclusion. 7.7 References. PART II APPLICATIONS. Section 3 Gene and Protein Information. 8 Fundamentals of gene ontology functional annotation (Varsha K. Khodiyar, Emily C. Dimmer, Rachael P. Huntley, and Ruth C. Lovering). 8.1 Introduction. 8.2 Gene Ontology (GO). 8.3 Comparative genomics and electronic protein annotation. 8.4 Community annotation. 8.5 Limitations. 8.6 Accessing GO annotations. 8.7 Conclusions. 8.8 References. 9 Methods for improving genome annotation (Jonathan Mudge and Jennifer Harrow). 9.1 The basis of gene annotation. 9.2 The impact of next generation sequencing on genome annotation. 9.3 References. 10 Sequences from prokaryotic, eukaryotic, and viral genomes available clustered according to phylotype on a Self-Organizing Map (Takashi Abe, Shigehiko Kanaya, and Toshimichi Ikemura). 10.1 Introduction. 10.2 Batch-learning SOM (BLSOM) adapted for genome informatics. 10.3 Genome sequence analyses using BLSOM. 10.4 Conclusions and discussion. 10.5 References. Section 4 Biomolecular Relationships and Meta-Relationships. 11 Molecular network analysis and applications (Minlu Zhang, Jingyuan Deng, Chunsheng V. Fang, Xiao Zhang, and Long Jason Lu). 11.1 Introduction. 11.2 Topology analysis and applications. 11.3 Network motif analysis. 11.4 Network modular analysis and applications. 11.5 Network comparison. 11.6 Network analysis software and tools. 11.7 Summary. 11.8 Acknowledgement. 11.9 References. 12 Biological pathway analysis: an overview of Reactome and other integrative pathway knowledge bases (Robin A. Haw, Marc E. Gillespie, and Michael A. Caudy). 12.1 Biological pathway analysis and pathway knowledge bases. 12.2 Overview of high-throughput data capture technologies and data repositories. 12.3 Brief review of selected pathway knowledge bases. 12.4 How does information get into pathway knowledge bases? 12.5 Introduction to data exchange languages. 12.6 Visualization tools. 12.7 Use case: pathway analysis in Reactome using statistical analysis of high-throughput data sets. 12.8 Discussion: challenges and future directions of pathway knowledge bases. 12.9 References. 13 Methods and challenges of identifying biomolecular relationships and networks associated with complex diseases/phenotypes, and their application to drug treatments (Mie Rizig). 13.1 Complex traits: clinical phenomenology and molecular background. 13.2 Why it is challenging to infer relationships between genes and phenotypes in complex traits? 317 13.3 Bottom-up or top-down: which approach is more useful in delineating complex traits key drivers? 13.4 High-throughput technologies and their applications in complex traits genetics. 13.5 Integrative systems biology: a comprehensive approach to mining high-throughput data. 13.6 Methods applying systems biology approach in the identification of functional relationships from gene expression data. 13.7 Advantages of networks exploration in molecular biology and drug discovery. 13.8 Practical examples of applying systems biology approaches and network exploration in the identification of functional modules and disease-causing genes in complex phenotypes/diseases. 13.9 Challenges and future directions. 13.10 References. Trends and conclusion. Index.

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Book SynopsisStable radicals - molecules with odd electrons which are sufficiently long lived to be studied or isolated using conventional techniques - have enjoyed a long history and are of current interest for a broad array of fundamental and applied reasons, for example to study and drive novel chemical reactions, in the development of rechargeable batteries or the study of free radical reactions in the body. In Stable Radicals: Fundamentals and Applied Aspects of Odd-Electron Compounds a team of international experts provide a broad-based overview of stable radicals, from the fundamental aspects of specific classes of stable neutral radicals to their wide range of applications including synthesis, materials science and chemical biology. Topics covered include: triphenylmethyl and related radicals polychlorinated triphenylmethyl radicals: towards multifunctional molecular materials phenalenyls, cyclopentadienyls, and other carbon-centered radicals<Trade Review"This is a worthwhile and insightful anthology and leaves the reader with the impression that novel prospects and discoveries could surface at any moment from junctions on the stable radical chemical topology." (Angewandte Chemie, 2011) Table of ContentsPreface xv List of Contributors xvii 1. Triarylmethyl and Related Radicals 1 Thomas T. Tidwell 1.1 Introduction 1 1.1.1 Discovery of the triphenylmethyl radical 1 1.1.2 Bis(triphenylmethyl) peroxide 3 1.2 Free radical rearrangements 4 1.3 Other routes to triphenylmethyl radicals 5 1.4 The persistent radical effect 7 1.5 Properties of triphenylmethyl radicals 8 1.6 Steric effects and persistent radicals 9 1.7 Substituted triphenylmethyl radicals and dimers 9 1.8 Tris(heteroaryl)methyl and related triarylmethyl radicals 12 1.9 Delocalized persistent radicals: analogues of triarylmethyl radicals 14 1.10 Tetrathiatriarylmethyl (TAM) and related triarylmethyl radicals 16 1.11 Perchlorinated triarylmethyl radicals 20 1.12 Other triarylmethyl radicals 23 1.13 Diradicals and polyradicals related to triphenylmethyl 24 1.14 Outlook 28 Acknowledgements 28 References 28 2. Polychlorotriphenylmethyl Radicals: Towards Multifunctional Molecular Materials 33 Jaume Veciana and Imma Ratera 2.1 Introduction 33 2.2 Functional molecular materials based on PTM radicals 35 2.2.1 Materials with magnetic properties 37 2.2.2 Materials with electronic properties 53 2.2.3 Materials with optical properties 65 2.3 Multifunctional switchable molecular materials based on PTM radicals 69 2.3.1 Photo switchable molecular systems 69 2.3.2 Redox switchable molecular systems 70 2.4 Conclusions 75 References 76 3. Phenalenyls, Cyclopentadienyls, and Other Carbon-Centered Radicals 81 Yasushi Morita and Shinsuke Nishida 3.1 Introduction 81 3.2 Open shell graphene 82 3.3 Phenalenyl 84 3.4 2,5,8-Tri-tert-butylphenalenyl radical 86 3.5 Perchlorophenalenyl radical 92 3.6 Dithiophenalenyl radicals 94 3.7 Nitrogen-containing phenalenyl systems 97 3.7.1 Molecular design and topological isomers 97 3.7.2 2,5,8-Tri-tert-butyl-1,3-diazaphenalenyl 97 3.7.3 Hexaazaphenalenyl derivatives 102 3.7.4 β-Azaphenalenyl derivatives 103 3.8 Oxophenalenoxyl systems 106 3.8.1 Molecular design and topological isomers 106 3.8.2 3-Oxophenalenoxyl (3OPO) system 108 3.8.3 4- and 6-Oxophenalenoxyl (4OPO, 6OPO) systems 110 3.8.4 Redox-based spin diversity 114 3.8.5 Molecular crystalline secondary battery 115 3.8.6 Spin-center transfer and solvato-/thermochromism 117 3.9 Phenalenyl-based zwitterionic radicals 119 3.10 π-Extended phenalenyl systems 122 3.10.1 Triangulenes 122 3.10.2 Trioxytriangulene with redox-based spin diversity nature 125 3.10.3 Bis- and tris-phenalenyl system and singlet biradical characters 125 3.11 Curve-structured phenalenyl system 130 3.12 Non-alternant stable radicals 131 3.12.1 Cyclopentadienyl radicals 131 3.12.2 Cyclopentadienyl radicals within a larger π-electronic framework 135 3.13 Stable triplet carbenes 136 3.14 Conclusions 139 Acknowledgements 139 References 140 4. The Nitrogen Oxides: Persistent Radicals and van der Waals Complex Dimers 147 D. Scott Bohle 4.1 Introduction 147 4.2 Synthetic access 149 4.3 Physical properties 149 4.4 Structural chemistry of the monomers and dimers 150 4.4.1 Nitric oxide and dinitrogen dioxide 150 4.4.2 Nitrogen dioxide and dinitrogen tetroxide 152 4.5 Electronic structure of nitrogen oxides 153 4.6 Reactivity of nitric oxide and nitrogen dioxide and their van der Waals complexes 155 4.7 The kinetics of nitric oxide’s termolecular reactions 156 4.8 Biochemical and organic reactions of nitric oxide 158 4.9 General reactivity patterns 160 4.9.1 Oxidation 160 4.9.2 Reduction 161 4.9.3 Coordination 162 4.9.4 Addition of nucleophiles 162 4.9.5 General organic reactions 165 4.9.6 Reactions with other nucleophiles 165 4.10 The colored species problem in nitric oxide chemistry 166 4.11 Conclusions 166 References 166 5. Nitroxide Radicals: Properties, Synthesis and Applications 173 Hakim Karoui, François Le Moigne, Olivier Ouari and Paul Tordo 5.1 Introduction 173 5.2 Nitroxide structure 174 5.2.1 Characteristics of the aminoxyl group 174 5.2.2 X-ray structures of nitroxides 175 5.2.3 Quantum mechanical (QM), molecular dynamics (MD) and molecular mechanics (MM) calculations 177 5.2.4 Influence of solvent polarity on the EPR parameters of nitroxides 180 5.3 Nitroxide multiradicals 181 5.3.1 Electron spin–spin exchange coupling 182 5.3.2 Miscellaneous aspects of di- and polynitroxides 184 5.4 Nitronyl nitroxides (NNOs) 185 5.4.1 Synthesis of nitronyl nitroxides 186 5.4.2 Nitronyl nitroxide as a nitric oxide trap 186 5.4.3 Nitronyl nitroxides as building blocks for magnetic materials 188 5.5 Synthesis of nitroxides 191 5.5.1 Oxidation of amines 191 5.5.2 Oxidation of hydroxylamines 191 5.5.3 Chiral nitroxides 191 5.5.4 Nitroxide design for nitroxide mediated polymerization (NMP) 193 5.6 Chemical properties of nitroxides 196 5.6.1 The Persistent Radical Effect 197 5.6.2 Redox reactions 197 5.6.3 Approaches to improve the resistance of nitroxides toward bioreduction 198 5.6.4 Hydrogen abstraction reactions 199 5.6.5 Cross-coupling reactions 200 5.6.6 Nitroxides in synthetic sequences 200 5.7 Nitroxides in supramolecular entities 206 5.7.1 Interaction of nitroxides with cyclodextrins 207 5.7.2 Interaction of nitroxides with calix[4]arenes 209 5.7.3 Interaction of nitroxides with curcubiturils 210 5.7.4 Interaction of nitroxides with micelles 211 5.7.5 Fullerene-linked nitroxides 212 5.8 Nitroxides for dynamic nuclear polarization (DNP) enhanced NMR 213 5.8.1 DNP for biological NMR and real-time metabolic imaging 213 5.8.2 Nitroxides as polarizing agents for DNP 214 5.9 Nitroxides as pH-sensitive spin probes 216 5.10 Nitroxides as prefluorescent probes 217 5.11 EPR-spin trapping technique 217 5.11.1 Immuno spin trapping 219 5.11.2 Conclusion 219 5.12 Conclusions 220 References 220 6. The Only Stable Organic Sigma Radicals: Di-tert-Alkyliminoxyls 231 Keith U. Ingold 6.1 Introduction 231 6.2 The discovery of stable iminoxyls 232 6.2.1 Synthesis of di-tert-butyl ketoxime 233 6.2.2 Synthesis of di-tert-butyliminoxyl 234 6.2.3 Stability of di-tert-butyliminoxyl 235 6.3 Hydrogen atom abstraction by di-tert-butyliminoxyl 236 6.3.1 The O−H bond dissociation enthalpy (BDE) in (Me 3 C) 2 C=NOH 236 6.3.2 Oxidation of hydrocarbons with di-tert-butyliminoxyl 237 6.3.3 Oxidation of phenols with di-tert-butyliminoxyl 238 6.3.4 Oxidation of amines with di-tert-butyliminoxyl 239 6.3.5 Oxidation of di-tert-butylketoxime with di-tert-butyliminoxyl 239 6.4 Other reactions and non-reactions of di-tert-butyliminoxyl 241 6.5 Di-tert-alkyliminoxyls more sterically crowded than di-tert-butyliminoxyl 241 6.6 Di-(1-Adamantyl)iminoxyl: a truly stable σ radical 242 References 243 7. Verdazyls and Related Radicals Containing the Hydrazyl [R 2 N−NR] Group 245 Robin G. Hicks 7.1 Introduction 245 7.2 Verdazyl radicals 246 7.2.1 Synthesis of verdazyls 246 7.2.2 Stability, physical properties and electronic structure of verdazyls 250 7.2.3 Verdazyl radical reactivity 256 7.2.4 Inorganic verdazyl analogues 264 7.3 Tetraazapentenyl radicals 265 7.4 Tetrazolinyl radicals 266 7.5 1,2,4-Triazolinyl radicals 268 7.6 1,2,4,5-Tetrazinyl radicals 269 7.7 Benzo-1,2,4-triazinyl radicals 270 7.8 Summary 273 References 273 8. Metal Coordinated Phenoxyl Radicals 281 Fabrice Thomas 8.1 Introduction 281 8.2 General properties of phenoxyl radicals 282 8.2.1 Electronic structure and stabilization 282 8.2.2 Electrochemistry of phenoxyl radicals 283 8.2.3 Structure of non-coordinated phenoxyl radicals 284 8.2.4 UV-Vis spectroscopy 284 8.2.5 EPR spectroscopy 284 8.3 Occurrence of tyrosyl radicals in proteins 285 8.4 Complexes with coordinated phenoxyl radicals 287 8.4.1 General ligand structures 287 8.4.2 Vanadium complexes 290 8.4.3 Chromium complexes 291 8.4.4 Manganese complexes 292 8.4.5 Iron complexes 294 8.4.6 Cobalt complexes 297 8.4.7 Nickel complexes 299 8.4.8 Copper complexes 303 8.4.9 Zinc complexes 310 8.5 Conclusions 313 8.6 Abbreviations 313 References 313 9. The Synthesis and Characterization of Stable Radicals Containing the Thiazyl (SN) Fragment and Their Use as Building Blocks for Advanced Functional Materials 317 Robin G. Hicks 9.1 Introduction 317 9.2 Radicals based exclusively on sulfur and nitrogen 319 9.2.1 NS• and SNS• 319 9.2.2 S3 N3• 320 9.2.3 S3 N2•+ and related radical cations 320 9.2.4 Poly(thiazyl), (SN)X 322 9.3 “Organothiazyl” radicals 323 9.3.1 Thioaminyl radicals 323 9.3.2 1,2,3,5-Dithiadiazolyl radicals 329 9.3.3 1,3,2,4-Dithiadiazolyl radicals 336 9.3.4 1,3,2-Dithiazolyl radicals 339 9.3.5 1,2,3-Dithiazolyl radicals 342 9.3.6 Bis(1,2,3-dithiazole) and related radicals 345 9.3.7 1,2,4-Thiadiazinyl radicals 348 9.3.8 1,2,4,6-Thiatriazinyl and -selenatriazinyl radicals 349 9.3.9 Larger cyclic thiazyl radicals 355 9.4 Thiazyl radicals as “advanced materials” 355 9.4.1 Charge transport properties of thiazyl radicals 356 9.4.2 Thiazyl radical-based charge transfer salts 360 9.4.3 Magnetic properties of thiazyl radicals 364 9.5 Conclusions 373 References 373 10. Stable Radicals of the Heavy p-Block Elements 381 Jari Konu and Tristram Chivers 10.1 Introduction 381 10.2 Group 13 element radicals 382 10.2.1 Boron 382 10.2.2 Aluminum, gallium, and indium 384 10.3 Group 14 element radicals 388 10.3.1 Cyclic group 14 radicals 389 10.3.2 Acyclic group 14 radicals 391 10.4 Group 15 element radicals 395 10.4.1 Phosphorus 395 10.4.2 Arsenic, antimony, and bismuth 400 10.5 Group 16 element radicals 400 10.5.1 Sulfur 400 10.5.2 Selenium and tellurium 401 10.6 Group 17 element radicals 402 10.7 Summary and future prospects 403 References 404 11. Application of Stable Radicals as Mediators in Living-Radical Polymerization 407 Andrea R. Szkurhan, Julie Lukkarila and Michael K. Georges 11.1 Introduction 407 11.2 Living polymerizations 408 11.2.1 Living-radical polymerization background 408 11.3 Stable free radical polymerization 409 11.3.1 Background of the work performed at the Xerox Research Centre of Canada 409 11.3.2 General considerations and mechanism 410 11.3.3 Unimolecular initiators 411 11.3.4 Persistent radical effect 413 11.3.5 Requirements of stable radicals as mediating agents 413 11.3.6 Nitroxides as mediating agents 414 11.3.7 Nitroxides and their ability to moderate polymerizations 414 11.3.8 Rate enhancement of stable free radical polymerization through the use of additives 416 11.4 Non-nitroxide-based radicals as mediating agents 416 11.4.1 Triazolinyl radicals 416 11.4.2 Verdazyl radicals 417 11.4.3 Other radicals as mediators 418 11.5 Aqueous stable free radical polymerization processes 420 11.5.1 Living-radical miniemulsion polymerization 421 11.5.2 Emulsion polymerization 422 11.5.3 Other aqueous polymerization processes 423 11.6 The application of stable free radical polymerization to new materials 423 11.6.1 Statistical copolymers 423 11.6.2 Block copolymers 424 11.7 Conclusions 425 List of abbreviations 425 References 425 12. Nitroxide-Catalyzed Alcohol Oxidations in Organic Synthesis 433 Christian Brückner 12.1 Introduction 433 12.2 Mechanism of TEMPO-catalyzed alcohol oxidations 434 12.3 Nitroxides used as catalysts 435 12.3.1 Monomeric nitroxides 435 12.3.2 Ionic liquid nitroxides 436 12.3.3 Supported nitroxides 436 12.4 Chemoselectivity: oxidation of primary vs secondary alcohols 437 12.5 Chemoselectivity: oxidation of primary vs benzylic alcohols 438 12.6 Oxidation of secondary alcohols to ketones 439 12.7 Oxidations of alcohols to carboxylic acids 439 12.7.1 Oxidations leading to linear carboxylic acids 439 12.7.2 (Diol) oxidations leading to lactones 443 12.8 Stereoselective nitroxide-catalyzed oxidations 444 12.9 Secondary oxidants used in nitroxide-catalyzed reactions 446 12.9.1 Elemental halogens 446 12.9.2 Sodium hypochlorite (bleach) 446 12.9.3 Bis(acetoxy)iodobenzene (BAIB) 447 12.9.4 Oxygen (air) 448 12.9.5 Peroxides 449 12.9.6 Other organic secondary oxidants 450 12.9.7 Anodic, electrochemical oxidation 451 12.10 Use of nitroxide-catalyzed oxidations in tandem reactions 451 12.11 Predictable side reactions 453 12.11.1 Oxidations of sulfur 453 12.11.2 Oxidations of nitrogen 453 12.11.3 Oxidations of carbon 454 12.12 Comparison with other oxidation methods 454 12.13 Nitroxide-catalyzed oxidations and green chemistry 455 Acknowledgements 456 References 456 13. Metal–Nitroxide Complexes: Synthesis and Magnetostructural Correlations 461 Victor Ovcharenko 13.1 Introduction 461 13.2 Two types of nitroxide for direct coordination of the metal to the nitroxyl group 462 13.2.1 Complexes containing only >N−•O as a coordinating group 462 13.2.2 Complexes containing >N−•O and other functional groups as donor fragments 464 13.3 Ferro- and ferrimagnets based on metal–nitroxide complexes 465 13.3.1 Molecular magnets based on 1-D systems 470 13.3.2 Molecular magnets based on 2-D systems 474 13.3.3 Molecular magnets based on 3-D systems 480 13.4 Heterospin systems based on polynuclear compounds of metals with nitroxides 483 13.4.1 Reactions whose products retain both the multinuclear fragment and nitroxide 484 13.4.2 Transformation of polynuclear fragments in reactions with nitroxides 487 13.4.3 Transformation of both the polynuclear fragment and the starting nitroxide 489 13.5 Breathing crystals 490 13.6 Other studies of metal–nitroxides 494 13.6.1 Analytical applications 494 13.6.2 NMR spectroscopy 494 13.6.3 Stabilization of nitroxides with β-hydrogen atoms 496 13.6.4 Increased reactivity 496 13.6.5 Hidden exchange interactions 497 13.6.6 Contrast agents 499 13.7 Conclusions 500 References 500 14. Rechargeable Batteries Using Robust but Redox Active Organic Radicals 507 Takeo Suga and Hiroyuki Nishide 14.1 Introduction 507 14.2 Redox reaction of organic radicals 508 14.3 Mechanism and performance of an organic radical battery 509 14.4 Molecular design and synthesis of redox active radical polymers 512 14.4.1 Poly(methacrylate)s and poly(acrylate)s 512 14.4.2 Poly(vinyl ether)s and poly(allene)s 514 14.4.3 Poly(cyclic ether)s 514 14.4.4 Poly(norbornene)s 514 14.4.5 Poly(acetylene)s 514 14.4.6 Poly(styrene)s 515 14.4.7 Combination of radicals with biopolymers and ionic liquids 515 14.5 A totally organic-based radical battery 515 14.6 Conclusions 517 References 518 15. Spin Labeling: A Modern Perspective 521 Lawrence J. Berliner 15.1 Introduction 521 15.2 The early years 522 15.3 Advantages of nitroxides 523 15.4 Applications of spin labeling to biochemical and biological systems 524 15.4.1 Stoichiometry and specificity: proteins and enzymes 524 15.4.2 The reporter group approach: who makes the news? 525 15.5 Distance measurements 526 15.5.1 Metal–spin label distance measurements 526 15.5.2 Spin label–spin label distance measurements 526 15.5.3 Example of strong dipolar interactions 527 15.5.4 Multiple-quantum EPR and distance measurements 528 15.6 Site directed spin labeling (SDSL): how is it done? 529 15.6.1 The SDSL paradigm 530 15.6.2 SDSL parameters 530 15.7 Other spin labeling applications 531 15.7.1 pH sensitive spin labels 532 15.7.2 Spin labeled DNA – structure, dynamics and sequence analysis 532 15.8 Conclusions 534 References 534 16. Functional in vivo EPR Spectroscopy and Imaging Using Nitroxide and Trityl Radicals 537 Valery V. Khramtsov and Jay L. Zweier 16.1 Introduction 537 16.2 Nitroxyl radicals 538 16.3 Triarylmethyl (trityl) radicals 539 16.4 In vivo EPR oximetry using nitroxyl and trityl probes 539 16.4.1 Magnetic resonance approaches for in vivo oximetry 540 16.4.2 Nitroxide probes for EPR oximetry 540 16.4.3 TAM oximetric probes 545 16.5 EPR spectroscopy and imaging of pH using nitroxyl and trityl probes 547 16.5.1 pH-sensitive nitroxyl radicals 547 16.5.2 Dual function pH- and oxygen-sensitive trityl radicals 553 16.6 Redox- and thiol-sensitive nitroxide probes 556 16.6.1 Nitroxides as redox-sensitive EPR probes 556 16.6.2 Disulfide nitroxide biradicals as GSH-sensitive EPR probes 558 16.7 Conclusions 562 Acknowledgements 563 References 563 17. Biologically Relevant Chemistry of Nitroxides 567 Sara Goldstein and Amram Samuni 17.1 Introduction 567 17.2 Mechanisms of nitroxide reactions with biologically relevant small radicals 569 17.3 Nitroxides as SOD mimics 571 17.4 Nitroxides as catalytic antioxidants in biological systems 573 17.5 Conclusions 576 Acknowledgements 576 References 576 Index 579

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Book SynopsisBioelectrochemistry: Fundamentals, Experimental Techniques and Application, covers the fundamental aspects of the chemistry, physics and biology which underlie this subject area. It describes some of the different experimental techniques that can be used to study bioelectrochemical problems and it describes various applications of biolelectrochemisty including amperometric biosensors, immunoassays, electrochemistry of DNA, biofuel cells, whole cell biosensors, in vivo applications and bioelectrosynthesis. By bringing together these different aspects, this work provides a unique source of information in this area,approaching the subject from a cross-disciplinary viewpoint.Trade Review"All chapters are readable and packed with information, all are well referenced and up-to-date. The bookis highly recommended to those with interests in bioelectrochemistry and its applications." (Chromatographia, September 2010)Table of ContentsList of Contributors. Preface. 1 Bioenergetics and Biological Electron Transport (Philip N. Bartlett). 1.1 Introduction. 1.2 Biological Cells. 1.3 Chemiosmosis. 1.3.1 The Proton Motive Force. 1.3.2 The Synthesis of ATP. 1.4 Electron Transport Chains. 1.4.1 The Mitochondrion. 1.4.2 The NADH–CoQ Reductase Complex. 1.4.3 The Succinate–CoQ Reductase Complex. 1.4.4 The CoQH2–Cyt c Reductase Complex. 1.4.5 The Cyt c Oxidase Complex. 1.4.6 Electron Transport Chains in Bacteria. 1.4.7 Electron Transfer in Photosynthesis. 1.4.8 Photosystem II. 1.4.9 Cytochrome bf Complex. 1.4.10 Photosystem I. 1.4.11 Bacterial Photosynthesis. 1.5 Redox Components. 1.5.1 Quinones. 1.5.2 Flavins. 1.5.3 NAD(P)H. 1.5.4 Hemes. 1.5.5 Iron–Sulfur Clusters. 1.5.6 Copper Centres. 1.6 Governing Principles. 1.6.1 Spatial Separation. 1.6.2 Energetics: Redox Potentials. 1.6.3 Kinetics: Electron Transfer Rate Constants. 1.6.4 Size of Proteins. 1.6.5 One-Electron and Two-Electron Couples. 1.7 ATP Synthase. 1.8 Conclusion. References. 2 Electrochemistry of Redox Enzymes (James F. Rusling, Bingquan Wang and Sei-eok Yun). 2.1 Introduction. 2.1.1 Historical Perspective. 2.1.2 Examples of Soluble Mediators. 2.1.3 Development of Protein-Film Voltammetry and Direct Enzyme Electrochemistry. 2.2 Mediated Enzyme Electrochemistry. 2.2.1 Electron Mediation. 2.2.2 Wiring with Redox Metallopolymer Hydrogels. 2.2.3 Wiring with Conducting Polymers. 2.2.4 NAD(P)þ/NAD(P)H Dependent Enzymes. 2.2.5 Regeneration of NAD(P)H from NAD(P)þ. 2.2.6 Regeneration of NAD(P)þ from NAD(P)H. 2.3 Direct Electron Transfer between Electrodes and Enzymes. 2.3.1 Enzymes in Solution. 2.3.2 Enzyme-Film Voltammetry: Basic Theory. 2.3.3 Adsorbed and Coadsorbed Enzyme Monolayers. 2.3.4 Self-Assembled Monolayers and Covalently Attached Enzymes. 2.3.5 Enzymes on Carbon Nanotube Electrodes. 2.3.6 Enzymes in Lipid Bilayer Films. 2.3.7 Polyion Films and Layer-by-Layer Methods. 2.4 Outlook for the Future. Acknowledgements. References. 3 Biological Membranes and Membrane Mimics (Tibor Hianik). 3.1 Introduction. 3.2 Membrane Structure and Composition. 3.2.1 Membrane Structure. 3.2.2 Membrane Lipids. 3.2.3 Membrane Proteins. 3.3 Models of Membrane Structure. 3.3.1 Lipid Monolayers. 3.3.2 Bilayer Lipid Membranes (BLM). 3.3.3 Supported Bilayer Lipid Membranes. 3.3.4 Liposomes. 3.4 Ordering, Conformation and Molecular Dynamics of Lipid Bilayers. 3.4.1 Structural Parameters of Lipid Bilayers Measured by X-ray Diffraction. 3.4.2 Interactions between Bilayers. 3.4.3 Dynamics and Order Parameters of Bilayers Determined by EPR and NMR Spectroscopy and by Optical Spectroscopy Methods. 3.5 Phase Transitions of Lipid Bilayers. 3.5.1 Lyotropic and Thermotropic Transitions. 3.5.2 Thermodynamics of Phase Transitions. 3.5.3 Trans–Gauche Isomerization. 3.5.4 Order Parameter. 3.5.5 Cooperativity of Transition. 3.5.6 Theory of Phase Transitions. 3.6 Mechanical Properties of Lipid Bilayers. 3.6.1 Anisotropy of Mechanical Properties of Lipid Bilayers. 3.6.2 The Model of an Elastic Bilayer. 3.6.3 Mechanical Properties of Lipid Bilayers and Protein–Lipid Interactions. 3.7 Membrane Potentials. 3.7.1 Diffusion Potential. 3.7.2 Electrostatic Potentials. 3.7.3 Methods of Surface Potential Measurement. 3.8 Dielectric Relaxation. 3.8.1 The Basic Principles of the Measurement of Dielectric Relaxation. 3.8.2 Application of the Method of Dielectric Relaxation to BLMs and sBLMs. 3.9 Transport Through Membranes. 3.9.1 Passive Diffusion. 3.9.2 Facilitated Diffusion of Charged Species Across Membranes. 3.9.3 Mechanisms of Ionic Transport. 3.9.4 Active Transport Systems. 3.10 Membrane Receptors and Cell Signaling. 3.10.1 Physical Reception. 3.10.2 Principles of Hormonal Reception. 3.10.3 Taste and Smell Reception. 3.11 Lipid-Film Coated Electrodes. 3.11.1 Modification of Lipid-Film Coated Electrodes by Functional Macromolecules. 3.11.2 Bioelectrochemical and Analytical Applications of Lipid Coated Electrodes. Acknowledgements. References. 4 NAD(P)-Based Biosensors (L. Gorton and P. N. Bartlett). 4.1 Introduction. 4.2 Electrochemistry of NAD(P)þ/NAD(P)H. 4.3 Direct Electrochemical Oxidation of NAD(P)H. 4.3.1 General Observations. 4.3.2 Effect of Adsorption. 4.3.3 Mechanism and Kinetics. 4.4 Soluble Cofactors. 4.4.1 Implications of the Low Eo0 Value for Practical Applications. 4.4.2 Special Prerequisites for Biosensors Based on NAD(P)-Dependent Dehydrogenases. 4.5 Mediators for Electrocatalytic NAD(P)H Oxidation. 4.5.1 Other Mediating Functionalities and Metal Coated Electrodes. 4.5.2 Electropolymerisation. 4.5.3 Carbon Paste. 4.5.4 Gold Nanoparticles. 4.6 Construction of Biosensors from NAD(P)H-Dependent Dehydrogenases. 4.6.1 Entrapment Behind a Membrane. 4.6.2 Covalent Attachment to a Nylon Net or Membrane. 4.6.3 Cross-Linking. 4.6.4 Entrapment in a Polymer Film. 4.6.5 Carbon Paste. 4.6.6 Self-Assembled Monolayers. 4.7 Conclusions. Acknowledgements. References. 5 Glucose Biosensors (Josep M. Montornes, Mark S. Vreeke and Ioanis Katakis). 5.1 Introduction to Glucose Sensors. 5.2 Biosensors. 5.2.1 Types of Sensors. 5.2.2 Transduction Mode. 5.3 Application Areas. 5.3.1 Clinical. 5.3.2 Food and Fermentation. 5.4 Design Requirements. 5.4.1 Disposable Glucose Sensor. 5.4.2 Continuous Glucose Sensor. 5.4.3 Implantable Glucose Sensor. 5.5 Biosensor Construction. 5.5.1 Artificial Mediators. 5.5.2 Immobilization of GOx. 5.5.3 Inner and Outer Membrane Function. 5.6 From Product Design Requirements to Performance. 5.6.1 Design Exercise for the Disposable Glucose Sensor. 5.7 Conclusions. Acknowledgement. References. 6 Phenolic Biosensors (Ulla Wollenberger, Fred Lisdat, Andreas Rose and Katrin Streffer). 6.1 Introduction. 6.2 Enzymes Used for Phenol Biosensors. 6.2.1 Phenol Oxidation by Water-Producing Oxidases and Oxygenases. 6.2.2 Reducing Enzymes. 6.3 Design of Phenol Biosensors. 6.3.1 Oxygen Consumption. 6.3.2 Bioelectrocatalysis Based on Phenol-Oxidizing Enzymes. 6.3.3 Electrocatalytic Sensors Based on Quinone-Reducing Enzymes. 6.4 Applications. 6.4.1 Waste Water Treatment. 6.4.2 Sensitive Label Detectors. 6.4.3 Catecholamines. 6.5 Summary and Conclusions. Acknowledgements. References. 7 Whole-Cell Biosensors (H. Shiku, K. Nagamine, T. Kaya, T. Yasukawa and T. Matsue). 7.1 Introduction. 7.2 Whole-Cell Biosensors Probing Cellular Functions. 7.2.1 Redox Reactions in Whole Cells. 7.2.2 Responses on a Microbial Chip with Collagen Gel. 7.3 Whole-Cell Microdevices Fabricated Using Bio-MEMS Technologies. 7.3.1 Potentiometric Devices: LAPS and ISFET. 7.3.2 Other Electrochemical Devices: Amperometric and Impedance Sensors. 7.3.3 Improvement of Cell Culture within Microenvironments. 7.4 Genetically Engineered Whole-Cell Microdevices. 7.4.1 Sensors with Gene-Modified Bacteria. 7.4.2 Transcriptional Responses on a Microbial Chip with Collagen Gel. 7.4.3 Cellular Devices for High-Throughput Screening. 7.4.4 Microdevice for On-Chip Transfection and On-Chip Transformation. 7.5 Conclusions. References. 8 Modelling Biosensor Responses (P. N. Bartlett, C. S. Toh, E. J. Calvo and V. Flexer). 8.1 Introduction. 8.2 Enzyme Kinetics. 8.2.1 Equilibrium and Steady-State. 8.2.2 Analysis of Enzyme Kinetic Data. 8.2.3 The Significance of KMS for Biosensor Applications. 8.3 Modelling Enzyme Electrodes. 8.3.1 The Flux Diagram for the Membrane|Enzyme|Electrode. 8.3.2 Solving the Coupled Diffusion/Reaction Problem for the Membrane Enzyme|Electrode. 8.3.3 Deriving a Complete Kinetic Model. 8.3.4 Experimental Verification of Approximate Analytical Kinetic Models. 8.4 Numerical Simulation Methods. 8.4.1 Explicit Numerical Methods. 8.4.2 The Crank–Nicholson Method. 8.4.3 Other Simulation Methods. 8.5 Modelling Redox Mediated Enzyme Electrodes. 8.5.1 Steady-State Kinetics. 8.5.2 Homogeneous Mediated Enzyme Electrode. 8.6 Modelling Homogeneous Enzyme with Attached Redox Mediator. 8.7 Non-Steady-State Techniques for Homogeneous Enzyme Systems. 8.7.1 Extraction of Kinetic Parameters. 8.8 The Heterogeneous Mediated Mechanism. 8.8.1 Enzyme Monolayers with Soluble Redox Mediator. 8.8.2 Enzyme Multilayers. 8.9 Conclusions. Acknowledgements. References. 9 Bioelectrosynthesis–Electrolysis and Electrodialysis (Derek Pletcher). 9.1 Introduction. 9.2 Setting the Scene. 9.2.1 Electrolytic Production of Organic Compounds. 9.2.2 Technological Factors. 9.2.3 Enzymes in Organic Synthesis. 9.2.4 Combining Enzyme Chemistry and Electrosynthesis. 9.3 Mechanisms of and Approaches to Bioelectrosynthesis. 9.3.1 Homogeneous Systems. 9.3.2 Electrode Coatings. 9.4 Examples of Syntheses. 9.4.1 The Oxidation of Alcohols and Diols. 9.4.2 The Oxidation of 4-Alkylphenols. 9.4.3 The Synthesis of Dihydroxyacetone Phosphate. 9.4.4 The Site Specific Oxidation of Sugars. 9.4.5 Hydroxylation of Unactivated C–H Bonds. 9.4.6 Reduction of Carbonyl Compounds. 9.4.7 Hydrogenation. 9.4.8 Conclusions. 9.5 Electrodialysis. 9.6 Conclusions. References. 10 Biofuel Cells (G. Tayhas R. Palmore). 10.1 Introduction. 10.2 Fundamentals of Fuel Cells. 10.2.1 How Fuel Cells Work. 10.2.2 Equations that Govern the Performance of a Fuel Cell. 10.3 Economics of Conventional Fuel Cells and Biofuel Cells. 10.4 Biofuel Cells that use Micro-Organisms as the Catalytic Element. 10.5 Biofuel Cells that use Oxidoreductases as the Catalytic Element. 10.6 Future Directions in Biofuel Cell Research. Acknowledgements. References. 11 Electrochemical Immunoassays (Julia Yakovleva and Jenny Emneus). 11.1 Introduction. 11.2 Basic Concepts in Immunoassay. 11.2.1 Antibodies: Structure, Properties and Production. 11.2.2 Classification of Immunoassays. 11.3 Electrochemical Immunoassays (ECIA). 11.3.1 Labels in ECIAs. 11.3.2 Electrochemical Detection Principles. 11.4 Different Assay Formats and Applications. 11.4.1 Heterogeneous ECIA. 11.4.2 Homogeneous ECIAs. 11.4.3 Electrochemical Immunosensors. 11.5 Future Perspectives and Recent Trends. References. 12 Electrochemical DNA Assays (Ana Maria Oliveira-Brett). 12.1 Introduction. 12.2 Electrochemistry of DNA. 12.2.1 Reduction. 12.2.2 Oxidation. 12.3 Adsorption of DNA at Electrode Surfaces. 12.3.1 Guanine Adsorbates. 12.3.2 Adsorbed dsDNA and ssDNA. 12.4 Electrochemistry for Sensing/Probing DNA Interactions. 12.4.1 Biomarkers for DNA Damage. 12.4.2 DNA–Metal Interactions. 12.4.3 DNA–Drug Interactions. 12.5 DNA Electrochemical Biosensors. 12.5.1 In Situ DNA Oxidative Damage. 12.5.2 DNA Hybridisation. 12.5.3 DNA Microarrays. 12.6 Conclusions. Acknowledgements. References. 13 In Vivo Applications: Glucose Monitoring, Fuel Cells (P. Vadgama and M. Schoenleber). 13.1 Introduction. 13.2 Biocompatibility. 13.2.1 General Concepts. 13.2.2 Protein Constituents. 13.2.3 Blood. 13.2.4 Tissue. 13.3 Materials Interfacing Strategy. 13.4 Implanted Glucose Biosensors. 13.4.1 Electrode Designs for Tissue Monitoring. 13.4.2 Electrode Designs for Blood Monitoring. 13.4.3 Early Phase Tissue Response. 13.4.4 Open Microflow. 13.4.5 Bioelectrochemical Fuel Cells. 13.5 Conclusions. References. Index.

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Book SynopsisThis book presents ways to analyze complex bioprocesses and drug delivery systems using control theory. Filled with detailed examples, case studies, computer projects, and step-by-step solutions to numerical problems using computational software, it addresses issues and solves problems that dominate both fields.Trade Review"This text — featuring examples from the biological sciences, including novel drug-delivery systems — will help students and pharmaceutical researchers to develop a better understanding of process dynamics and control theory, so that they can analyze and solve a variety of problems in bioprocess and drug-delivery systems." (Chemical Engineering Progress, 21 May 2013)Table of ContentsPreface xi Acknowledgments xv 1 Introduction 1 1.1 The Role of Process Dynamics and Control in Branches of Biology 1 1.2 The Role of Process Dynamics and Control in Drug-Delivery Systems 10 1.3 Instrumentation 12 1.4 Summary 18 Problems 18 References 19 2 Mathematical Models 21 2.1 Background 22 2.2 Dynamics of Bioreactors 27 2.3 One- and Two-Compartment Models 34 2.4 Enzyme Kinetics 37 2.5 Summary 39 Problems 39 References 41 3 Linearization and Deviation Variables 43 3.1 Computer Simulations 43 3.2 Linearization of Systems 44 3.3 Glycolytic Oscillation 55 3.4 Hodgkin–Huxley Model 57 3.5 Summary 60 Problems 61 References 63 4 Stability Considerations 65 4.1 Definition of Stability 65 4.2 Steady-State Conditions and Equilibrium Points 79 4.3 Phase-Plane Diagrams 80 4.4 Population Kinetics 80 4.5 Dynamics of Bioreactors 83 4.6 Glycolytic Oscillation 85 4.7 Hodgkin–Huxley Model 87 4.8 Summary 88 Problems 88 References 91 5 Laplace Transforms 93 5.1 Definition of Laplace Transforms 93 5.2 Properties of Laplace Transforms 95 5.3 Laplace Transforms of Functions, Derivatives, and Integrals 96 5.4 Laplace Transforms of Linear Ordinary Differential Equation (ODE) and Partial Differential Equation (PDE) 104 5.5 Continuous Fermentation 108 5.6 Two-Compartment Models 110 5.7 Gene Regulation 111 5.8 Summary 113 Problems 113 Reference 115 6 Inverse Laplace Transforms 117 6.1 Heaviside Expansions 117 6.2 Residue Theorem 126 6.3 Continuous Fermentation 134 6.4 Degradation of Plasmid DNA 136 6.5 Constant-Rate Intravenous Infusion 138 6.6 Transdermal Drug-Delivery Systems 139 6.7 Summary 146 Problems 146 References 148 7 Transfer Functions 149 7.1 Input–Output Models 149 7.2 Derivation of Transfer Functions 150 7.3 One- and Two-Compartment Models: Michaelis–Menten Kinetics 154 7.4 Controlled-Release Systems 157 7.5 Summary 158 Problems 158 8 Dynamic Behaviors of Typical Plants 163 8.1 First-, Second- and Higher-Order Systems 163 8.2 Reduced-Order Models 167 8.3 Transcendental Transfer Functions 169 8.4 Time Responses of Systems with Rational Transfer Functions 171 8.5 Time Responses of Systems with Transcendental Transfer Functions 190 8.6 Bone Regeneration 192 8.7 Nitric Oxide Transport to Pulmonary Arterioles 193 8.8 Transdermal Drug Delivery 194 8.9 Summary 194 Problems 195 References 197 9 Closed-loop Responses with P, Pi, and Pid Controllers 199 9.1 Block Diagram of Closed-Loop Systems 200 9.2 Proportional Control 203 9.3 PI Control 204 9.4 PID Control 206 9.5 Total Sugar Concentration in a Glutamic Acid Production 207 9.6 Temperature Control of Fermentations 209 9.7 DO Concentration 213 9.8 Summary 214 Problems 215 References 217 10 Frequency Response Analysis 219 10.1 Frequency Response for Linear Systems 219 10.2 Bode Diagrams 227 10.3 Nyquist Plots 229 10.4 Transdermal Drug Delivery 232 10.5 Compartmental Models 236 10.6 Summary 239 Problems 239 References 240 11 Stability Analysis of Feedback Systems 243 11.1 Routh–Hurwitz Stability Criterion 243 11.2 Root Locus Analysis 248 11.3 Bode Stability Criterion 249 11.4 Nyquist Stability Criterion 254 11.5 Cheyne–Stokes Respiration 257 11.6 Regulation of Biological Pathways 262 11.7 Pupillary Light Reflex 264 11.8 Summary 265 Problems 265 References 267 12 Design of Feedback Controllers 269 12.1 Tuning Methods for Feedback Controllers 269 12.2 Regulation of Glycemia 279 12.3 Dissolved Oxygen Concentration 282 12.4 Control of Biomass in a Chemostat 284 12.5 Controlled Infusion of Vasoactive Drugs 285 12.6 Bone Regeneration 286 12.7 Fed-Batch Biochemical Processes 288 12.8 Summary 289 Problems 289 References 291 13 Feedback Control of Dead-time Systems 293 13.1 Smith Predictor-Based Methods 294 13.2 Control of Biomass 300 13.3 Zymomonas mobilis Fermentation for Ethanol Production 302 13.4 Fed-Batch Cultivation of Acinetobacter calcoaceticus Rag-1 304 13.5 Regulation of Glycemia 304 13.6 Summary 306 Problems 306 References 309 14 Cascade and Feedforward Control Strategies 311 14.1 Cascade Control 311 14.2 Feedforward Control 317 14.3 Insulin Infusion 321 14.4 A Gaze Control System 323 14.5 Control of pH 326 14.6 Summary 330 Problems 331 References 333 15 Effective Time Constant 335 15.1 Linear Second-Order ODEs 335 15.2 Sturm–Liouville (SL) Eigenvalue Problems 337 15.3 Relaxation Time Constant 340 15.4 Implementation in Mathematica ® 342 15.5 Controlled-Release Devices 342 15.6 Summary 343 Problems 344 References 345 16 Optimum Control and Design 347 16.1 Orthogonal Collocation Techniques 348 16.2 Dynamic Programming 350 16.3 Optimal Control of Drug-Delivery Rates 350 16.4 Optimal Design of Controlled-Release Devices 351 16.5 Implementation in Mathematica ® 352 16.6 Summary 358 Problems 359 References 360 Index 361 Preface xi Acknowledgments xv 1 Introduction 1 1.1 The Role of Process Dynamics and Control in Branches of Biology 1 1.2 The Role of Process Dynamics and Control in Drug-Delivery Systems 10 1.3 Instrumentation 12 1.4 Summary 18 Problems 18 References 19 2 Mathematical Models 21 2.1 Background 22 2.2 Dynamics of Bioreactors 27 2.3 One- and Two-Compartment Models 34 2.4 Enzyme Kinetics 37 2.5 Summary 39 Problems 39 References 41 3 Linearization and Deviation Variables 43 3.1 Computer Simulations 43 3.2 Linearization of Systems 44 3.3 Glycolytic Oscillation 55 3.4 Hodgkin–Huxley Model 57 3.5 Summary 60 Problems 61 References 63 4 Stability Considerations 65 4.1 Definition of Stability 65 4.2 Steady-State Conditions and Equilibrium Points 79 4.3 Phase-Plane Diagrams 80 4.4 Population Kinetics 80 4.5 Dynamics of Bioreactors 83 4.6 Glycolytic Oscillation 85 4.7 Hodgkin–Huxley Model 87 4.8 Summary 88 Problems 88 References 91 5 Laplace Transforms 93 5.1 Definition of Laplace Transforms 93 5.2 Properties of Laplace Transforms 95 5.3 Laplace Transforms of Functions, Derivatives, and Integrals 96 5.4 Laplace Transforms of Linear Ordinary Differential Equation (ODE) and Partial Differential Equation (PDE) 104 5.5 Continuous Fermentation 108 5.6 Two-Compartment Models 110 5.7 Gene Regulation 111 5.8 Summary 113 Problems 113 Reference 115 6 Inverse Laplace Transforms 117 6.1 Heaviside Expansions 117 6.2 Residue Theorem 126 6.3 Continuous Fermentation 134 6.4 Degradation of Plasmid DNA 136 6.5 Constant-Rate Intravenous Infusion 138 6.6 Transdermal Drug-Delivery Systems 139 6.7 Summary 146 Problems 146 References 148 7 Transfer Functions 149 7.1 Input–Output Models 149 7.2 Derivation of Transfer Functions 150 7.3 One- and Two-Compartment Models: Michaelis–Menten Kinetics 154 7.4 Controlled-Release Systems 157 7.5 Summary 158 Problems 158 8 Dynamic Behaviors of Typical Plants 163 8.1 First-, Second- and Higher-Order Systems 163 8.2 Reduced-Order Models 167 8.3 Transcendental Transfer Functions 169 8.4 Time Responses of Systems with Rational Transfer Functions 171 8.5 Time Responses of Systems with Transcendental Transfer Functions 190 8.6 Bone Regeneration 192 8.7 Nitric Oxide Transport to Pulmonary Arterioles 193 8.8 Transdermal Drug Delivery 194 8.9 Summary 194 Problems 195 References 197 9 Closed-loop Responses with P, Pi, and Pid Controllers 199 9.1 Block Diagram of Closed-Loop Systems 200 9.2 Proportional Control 203 9.3 PI Control 204 9.4 PID Control 206 9.5 Total Sugar Concentration in a Glutamic Acid Production 207 9.6 Temperature Control of Fermentations 209 9.7 DO Concentration 213 9.8 Summary 214 Problems 215 References 217 10 Frequency Response Analysis 219 10.1 Frequency Response for Linear Systems 219 10.2 Bode Diagrams 227 10.3 Nyquist Plots 229 10.4 Transdermal Drug Delivery 232 10.5 Compartmental Models 236 10.6 Summary 239 Problems 239 References 240 11 Stability Analysis of Feedback Systems 243 11.1 Routh–Hurwitz Stability Criterion 243 11.2 Root Locus Analysis 248 11.3 Bode Stability Criterion 249 11.4 Nyquist Stability Criterion 254 11.5 Cheyne–Stokes Respiration 257 11.6 Regulation of Biological Pathways 262 11.7 Pupillary Light Reflex 264 11.8 Summary 265 Problems 265 References 267 12 Design of Feedback Controllers 269 12.1 Tuning Methods for Feedback Controllers 269 12.2 Regulation of Glycemia 279 12.3 Dissolved Oxygen Concentration 282 12.4 Control of Biomass in a Chemostat 284 12.5 Controlled Infusion of Vasoactive Drugs 285 12.6 Bone Regeneration 286 12.7 Fed-Batch Biochemical Processes 288 12.8 Summary 289 Problems 289 References 291 13 Feedback Control of Dead-time Systems 293 13.1 Smith Predictor-Based Methods 294 13.2 Control of Biomass 300 13.3 Zymomonas mobilis Fermentation for Ethanol Production 302 13.4 Fed-Batch Cultivation of Acinetobacter calcoaceticus Rag-1 304 13.5 Regulation of Glycemia 304 13.6 Summary 306 Problems 306 References 309 14 Cascade and Feedforward Control Strategies 311 14.1 Cascade Control 311 14.2 Feedforward Control 317 14.3 Insulin Infusion 321 14.4 A Gaze Control System 323 14.5 Control of pH 326 14.6 Summary 330 Problems 331 References 333 15 Effective Time Constant 335 15.1 Linear Second-Order ODEs 335 15.2 Sturm–Liouville (SL) Eigenvalue Problems 337 15.3 Relaxation Time Constant 340 15.4 Implementation in Mathematica ® 342 15.5 Controlled-Release Devices 342 15.6 Summary 343 Problems 344 References 345 16 Optimum Control and Design 347 16.1 Orthogonal Collocation Techniques 348 16.2 Dynamic Programming 350 16.3 Optimal Control of Drug-Delivery Rates 350 16.4 Optimal Design of Controlled-Release Devices 351 16.5 Implementation in Mathematica ® 352 16.6 Summary 358 Problems 359 References 360 Index 361

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Book SynopsisThis book grew out of an online interactive offered through statcourse. com, and it soon became apparent to the author that the course was too limited in terms of time and length in light of the broad backgrounds of the enrolled students.Table of ContentsPreface. 1. Very Large Arrays. 2. Permutation Tests. 3. Applying the Permutation Test. 4. Gathering and Preparing Data for Analysis. 5. Multiple Tests. 6. Bootstrap. 7. Classification Methods. 8. Applying Decision Trees. Glossary: Biological Terms. Glossary: Statistical Terms. Appendix: An R Primer. Bibliography. Author Index Subject Index.

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Book SynopsisComputational Fluid-Structure Interaction: Methods and Applications takes the reader from the fundamentals of computational fluid and solid mechanics to the state-of-the-art in computational FSI methods, special FSI techniques, and solution of real-world problems. Leading experts in the field present the material using a unique approach that combines advanced methods, special techniques, and challenging applications. This book begins with the differential equations governing the fluid and solid mechanics, coupling conditions at the fluidsolid interface, and the basics of the finite element method. It continues with the ALE and spacetime FSI methods, spatial discretization and time integration strategies for the coupled FSI equations, solution techniques for the fully-discretized coupled equations, and advanced FSI and spacetime methods. It ends with special FSI techniques targeting cardiovascular FSI, parachute FSI, and wind-turbine aerodynamics and FSI. Key feaTrade Review“Computational Fluid-Structure Interaction: Methods and Applications is a comprehensive reference for researchers and practicing engineers who would like to advance their existing knowledge on these subjects. It is also an ideal text for graduate and senior-level undergraduate courses in computational fluid mechanics and computational FSI.” (Expofairs, 18 October 2013)Table of ContentsSeries Preface xi Preface xiii Acknowledgements xix 1 Governing Equations of Fluid and Structural Mechanics 1 1.1 Governing Equations of Fluid Mechanics 1 1.1.1 Strong Form of the Navier–Stokes Equations of Incompressible Flows 1 1.1.2 Model Differential Equations 5 1.1.3 Nondimensional Equations and Numbers 6 1.1.4 Some Specific Boundary Conditions 7 1.1.5 Weak Form of the Navier–Stokes Equations 10 1.2 Governing Equations of Structural Mechanics 12 1.2.1 Kinematics 12 1.2.2 Principle of Virtual Work and Variational Formulation of Structural Mechanics 14 1.2.3 Conservation of Mass 15 1.2.4 Structural Mechanics Formulation in the Current Configuration 15 1.2.5 Structural Mechanics Formulation in the Reference Configuration 17 1.2.6 Additional Boundary Conditions of Practical Interest 18 1.2.7 Some Constitutive Models 19 1.2.8 Linearization of the Structural Mechanics Equations: Tangent Stiffness and Equations of Linear Elasticity 22 1.2.9 Thin Structures: Shell, Membrane, and Cable Models 25 1.3 Governing Equations of Fluid Mechanics in Moving Domains 31 1.3.1 Kinematics of ALE and Space–Time Descriptions 31 1.3.2 ALE Formulation of Fluid Mechanics 33 2 Basics of the Finite Element Method for Nonmoving-Domain Problems 37 2.1 An Abstract Variational Formulation for Steady Problems 37 2.2 FEM Applied to Steady Problems 38 2.3 Construction of Finite Element Basis Functions 42 2.3.1 Construction of Element Shape Functions 43 2.3.2 Finite Elements Based on Lagrange Interpolation Functions 46 2.3.3 Construction of Global Basis Functions 49 2.3.4 Element Matrices and Vectors and their Assembly into the Global Equation System 51 2.4 Finite Element Interpolation and Numerical Integration 53 2.4.1 Interpolation by Finite Elements 53 2.4.2 Numerical Integration 55 2.5 Examples of Finite Element Formulations 58 2.5.1 Galerkin Formulation of the Advection–Diffusion Equation 58 2.5.2 Stabilized Formulation of the Advection–Diffusion Equation 59 2.5.3 Galerkin Formulation of Linear Elastodynamics 62 2.6 Finite Element Formulation of the Navier–Stokes Equations 65 2.6.1 Standard Essential Boundary Conditions 65 2.6.2 Weakly Enforced Essential Boundary Conditions 70 3 Basics of the Isogeometric Analysis 73 3.1 B-Splines in 1D 74 3.2 NURBS Basis Functions, Curves, Surfaces, and Solids 75 3.3 h-, p-, and k-Refinement of NURBS Meshes 77 3.4 NURBS Analysis Framework 78 4 ALE and Space–Time Methods for Moving Boundaries and Interfaces 83 4.1 Interface-Tracking (Moving-Mesh) and Interface-Capturing (Nonmoving-Mesh) Techniques 83 4.2 Mixed Interface-Tracking/Interface-Capturing Technique (MITICT) 84 4.3 ALE Methods 84 4.4 Space–Time Methods 86 4.5 Advection–Diffusion Equation 89 4.5.1 ALE Formulation 89 4.5.2 Space–Time Formulation 91 4.6 Navier–Stokes Equations 92 4.6.1 ALE Formulation 92 4.6.2 Generalized-α Time Integration of the ALE Equations 95 4.6.3 Space–Time Formulation 98 4.7 Mesh Moving Methods 106 5 ALE and Space–Time Methods for FSI 111 5.1 FSI Formulation at the Continuous Level 111 5.2 ALE Formulation of FSI 114 5.2.1 Spatially-Discretized ALE FSI Formulation with Matching Fluid and Structure Discretizations 114 5.2.2 Generalized-α Time Integration of the ALE FSI Equations 118 5.2.3 Predictor–Multicorrector Algorithm and Linearization of the ALE FSI Equations 120 5.3 Space–Time Formulation of FSI 123 5.3.1 Core Formulation 123 5.3.2 Interface Projection Techniques for Nonmatching Fluid and Structure Interface Discretizations 127 5.4 Advanced Mesh Update Techniques 129 5.4.1 Solid-Extension Mesh Moving Technique (SEMMT) 129 5.4.2 Move-Reconnect-Renode Mesh Update Method (MRRMUM) 132 5.4.3 Pressure Clipping 134 5.5 FSI Geometric Smoothing Technique (FSI-GST) 136 6 Advanced FSI and Space–Time Techniques 139 6.1 Solution of the Fully-Discretized Coupled FSI Equations 139 6.1.1 Block-Iterative Coupling 140 6.1.2 Quasi-Direct Coupling 141 6.1.3 Direct Coupling 142 6.2 Segregated Equation Solvers and Preconditioners 144 6.2.1 Segregated Equation Solver for Nonlinear Systems (SESNS) 144 6.2.2 Segregated Equation Solver for Linear Systems (SESLS) 145 6.2.3 Segregated Equation Solver for Fluid–Structure Interactions (SESFSI) 146 6.3 New-Generation Space–Time Formulations 149 6.3.1 Mesh Representation 150 6.3.2 Momentum Equation 150 6.3.3 Incompressibility Constraint 151 6.4 Time Representation 151 6.4.1 Time Marching Problem 151 6.4.2 Design of Temporal NURBS Basis Functions 153 6.4.3 Approximation in Time 154 6.4.4 An Example: Circular-Arc Motion 154 6.5 Simple-Shape Deformation Model (SSDM) 157 6.6 Mesh Update Techniques in the Space–Time Framework 158 6.6.1 Mesh Computation and Representation 158 6.6.2 Remeshing Technique 158 6.7 Fluid Mechanics Computation with Temporal NURBS Mesh 159 6.7.1 No-Slip Condition on a Prescribed Boundary 159 6.7.2 Starting Condition 160 6.8 The Surface-Edge-Node Contact Tracking (SENCT-FC) Technique 163 6.8.1 Contact Detection and Node Sets 164 6.8.2 Contact Force and Reaction Force 165 6.8.3 Solving for the Contact Force 167 7 General Applications and Examples of FSI Modeling 171 7.1 2D Flow Past an Elastic Beam Attached to a Fixed, Rigid Block 171 7.2 2D Flow Past an Airfoil Attached to a Torsion Spring 174 7.3 Inflation of a Balloon 175 7.4 Flow Through and Around a Windsock 177 7.5 Aerodynamics of Flapping Wings 181 7.5.1 Surface and Volume Meshes 181 7.5.2 Flapping-Motion Representation 185 7.5.3 Mesh Motion 186 7.5.4 Fluid Mechanics Computation 187 8 Cardiovascular FSI 191 8.1 Special Techniques 194 8.1.1 Mapping Technique for Inflow Boundaries 194 8.1.2 Preconditioning Technique 195 8.1.3 Calculation of Wall Shear Stress 195 8.1.4 Calculation of Oscillatory Shear Index 196 8.1.5 Boundary Condition Techniques for Inclined Inflow and Outflow Planes 197 8.2 Blood Vessel Geometry, Variable Wall Thickness, Mesh Generation, and Estimated Zero-Pressure (EZP) Geometry 198 8.2.1 Arterial-Surface Extraction from Medical Images 198 8.2.2 Mesh Generation and EZP Arterial Geometry 199 8.2.3 Blood Vessel Wall Thickness Reconstruction 201 8.3 Blood Vessel Tissue Prestress 203 8.3.1 Tissue Prestress Formulation 203 8.3.2 Linearized Elasticity Operator 204 8.4 Fluid and Structure Properties and Boundary Conditions 205 8.4.1 Fluid and Structure Properties 205 8.4.2 Boundary Conditions 205 8.5 Simulation Sequence 209 8.6 Sequentially-Coupled Arterial FSI (SCAFSI) Technique 210 8.7 Multiscale Versions of the SCAFSI Technique 213 8.8 Computations with the SSTFSI Technique 215 8.8.1 Performance Tests for Structural Mechanics Meshes 215 8.8.2 Multiscale SCAFSI Computations 218 8.8.3 WSS Calculations with Refined Meshes 222 8.8.4 Computations with New Surface Extraction, Mesh Generation, and Boundary Condition Techniques 225 8.8.5 Computations with the New Techniques for the EZP Geometry, Wall Thickness, and Boundary-Layer Element Thickness 230 8.9 Computations with the ALE FSI Technique 233 8.9.1 Cerebral Aneurysms: Tissue Prestress 236 8.9.2 Total Cavopulmonary Connection 240 8.9.3 Left Ventricular Assist Device 250 9 Parachute FSI 259 9.1 Parachute Specific FSI-DGST 261 9.2 Homogenized Modeling of Geometric Porosity (HMGP) 262 9.2.1 HMGP in its Original Form 265 9.2.2 HMGP-FG 266 9.2.3 Periodic n-Gore Model 267 9.3 Line Drag 269 9.4 Starting Point for the FSI Computation 271 9.5 “Symmetric FSI” Technique 274 9.6 Multiscale SCFSI M2C Computations 275 9.6.1 Structural Mechanics Solution for the Reefed Stage 275 9.6.2 Fabric Stress Computations 278 9.7 Single-Parachute Computations 280 9.7.1 Various Canopy Configurations 280 9.7.2 Various Suspension Line Length Ratios 288 9.8 Cluster Computations 293 9.8.1 Starting Conditions 294 9.8.2 Computational Conditions 295 9.8.3 Results 297 9.9 Techniques for Dynamical Analysis and Model-Parameter Extraction 299 9.9.1 Contributors to Parachute Descent Speed 299 9.9.2 Added Mass 311 10 Wind-Turbine Aerodynamics and FSI 315 10.1 Aerodynamics Simulations of a 5MW Wind-Turbine Rotor 317 10.1.1 5MW Wind-Turbine Rotor Geometry Definition 317 10.1.2 ALE-VMS Simulations Using NURBS-based IGA 322 10.1.3 Computations with the DSD/SST Formulation Using Finite Elements 325 10.2 NREL Phase VI Wind-Turbine Rotor: Validation and the Role of Weakly-Enforced Essential Boundary Conditions 328 10.3 Structural Mechanics of Wind-Turbine Blades 334 10.3.1 The Bending-Strip Method 334 10.3.2 Time Integration of the Structural Mechanics Equations 340 10.4 FSI Coupling and Aerodynamics Mesh Update 342 10.5 FSI Simulations of a 5MW Wind-Turbine Rotor 343 10.6 Pre-Bending of the Wind-Turbine Blades 344 10.6.1 Problem Statement and the Pre-Bending Algorithm 346 10.6.2 Pre-Bending Results for the NREL 5MW Wind-Turbine Blade 349 References 353 Index 373

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Book SynopsisBACTERIAL ADHESION Molecular and Ecological Diversity Edited byMadilyn Fletcher Over the last twenty years, research has revealed the enormouscomplexity underlying the phenomenon of bacterial adhesion. Theinitial research goal was to understand the mechanism of attachmentand its effects on the bacteria as well as the host. As researchprogressed, however, it became evident that many differentattachment mechanisms exist. These diverse forms of adhesion arethe results of numerous evolutionary pressures, and each may bepart of a larger behavioral strategy. This comprehensive overview details how diversity in habitat andecological requirements has led to enormous variety in adhesivecell components, underlying genetic determinants, and behavioralstrategies. It presents the latest research on adhesion mechanismsand strategies found in diverse environments and microorganisms,including the new environment of biomaterials. Bacterial Adhesion: Molecular and Ecological DTable of ContentsBacterial Attachment in Aquatic Environments: A Diversity ofSurfaces and Adhesion Strategies (M. Fletcher). Bacterial Interactions with Surfaces in Soils (A. Mills & D.Powelson). Adhesion as a Strategy for Access to Nutrients (K. Marshall). Adhesion to Biomaterials (M. Mittelman). Adhesion in the Rhizosphere (A. Matthysse). The Cellulosome: A Cell Surface Organelle for the Adhesion to andDegradation of Cellulose (E. Bayer, et al.). Pseudomonas Aeruginosa: Versatile Attachment Mechanisms (A.Prince). Conceptual Advances in Research on the Adhesion of Bacteria to OralSurfaces (R. Ellen & R. Burne). Coaggregation: Enhancing Colonization in a Fluctuating Environment(J. London & P. Kolenbrander). Sensing, Response, and Adaptation to Surfaces: Swarmer CellDifferentiation and Behavior (R. Belas). Myxococcus Coadhesion and Role in the Life Cycle (L.Shimkets). Index.

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Book SynopsisThis book provides concepts and pragmatic illustrations from the industry to help the reader understand complex and difficult issues that are crucial in biomedical research and development. It is intended to bridge the gap between R&D scientists and corporate executives in the biomedical industry and to ensure a strong link between corporate and R&D strategies.Table of ContentsAbout This Book. About Strategy. About Environment. About Technology. Determining Competitive Position. Consistency and Competitiveness. Changing Competitive Position. Assessing the Fit of External Knowledge Sources. Competitive Technology Strategy: Some Implications for Teams. Index.

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Book SynopsisThis book is about how a knowledge and understanding of biological products and processes can lead to new insights in the synthesis, design and processing of inorganic-based materials. This approach is called 'biomimetics'. The book attempts to survey the new frontiers of biomimetic materials chemistry.Table of ContentsFrom the Contents: Biomineralization and Biomimetic Chemistry/ Biomimetic Strategies and Materials Processing/ Biogenic Cadmium Sulfide Semiconductors/ Biomimetic Synthesis of Nanoscale Particles in Organized Protein Cages/ Biomimetic Approaches to Nanoscale Fabrication/ Template-directed Nucleation and Growth of Inorganic Materials/ Construction of Organized Particulate Films by the Langmuir-Blodgett Technique/ Organization of Semiconductor Nanocrystals for Electrical Spectroscopies/ Polyamino Acids as Antiscalants, Dispersants, Antifreezes and Absorbent Gelling Materials/ Bacterial Fibers and their Mineralized Products: Bionites/ Biomimetic Inorganic-organic Composites/ Organoceramic Nanocomposites/ Ceramics Processing with Biogenic Additives.

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Book SynopsisBioseparations engineering is the "multidisciplinary application of fundamental engineering and biological principles to the design of adsorbents, systems, and processes for the separation of biological molecules.Trade Review"a comprehensive text that has brought together the theory and practice of bioseperations in an intelligent and well-presented fashion." (Bioseperations Engineering (Food & Bioproducts Processing, December 2001) "...Ladish reviews the techniques that have been developed over the past couple decades...in the hope that the explanations will apply to bioproducts not yet invented and biological molecules not yet produced...as well as to those currently being used." (SciTech Book News, Vol. 25, No. 4, December 2001)Table of ContentsPreface. Acknowledgements. Bioseparations. Sedimentation, Centrifugation, and Filtration. Membrane Separations. Precipitation, Crystallization, and Extraction. Principles of Liquid Chromatography. Liquid Chromatography Scale-Up. Principles of Gradient Elution Chromatography. Principles of Bioseparations for Biopharmaceuticals and Recombinant Protein Products. Affinity Chromatography: Bridge Between Molecular Biology, Combinatorial Methods, and Separations Science. Author Index. Subject Index.

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Book SynopsisWhile many books on medical instrumentation only cover hospital instrumentation, this comprehensive book also encompasses measurements in the growing fields of molecular biology and biotechnology, including applications such as cell engineering, tissue engineering, and biomaterials.Table of ContentsPreface. 1. Measurement Systems (Kevin Hugo). 2. Basic Concepts of Electronics (Hong Cao). 3. Analysis of Molecules in Clinical Medicine (Mat Klein). 4. Surface Characterization in Biomaterials and Tissue Engineering (Jorge E. Monzon). 5. Hematology (Susanne Clark Cazzanti). 6. Cellular Measurements in Biomaterials and Tissue Engineering (Jeffrey S. Schowalter). 7. Nervous Systems (Jang-Zern Tsai). 8. Heart and Circulation (Supan Tungjitkusolmun). 9. Lung, Kidney, Bone, and Skin (Shilpa Sawale). 10. Body Temperature, Heat, Fat, and Movement (Chao-Min Wu). Index.

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Book SynopsisA complete examination of the uses of the atomic force microscope in biology and medicine This cutting-edge text, written by a team of leading experts, is the first detailed examination of the latest, most powerful scanning probe microscope, the atomic force microscope (AFM).Table of ContentsPreface. Contributors. Chapter 1. Porosome: The Universal Secretory Machinery in Cells (Bhanu P. Jena). Chapter 2. Molecular Mechanism of SNARE-Induced Membrane Fusion (Bhanu P. Jena). Chapter 3. Molecular Mechanism of Secretory Vesicle Content Expulsion During Cell Secretion (Bhanu P. Jena). Chapter 4. Fusion Pores in Growth-Hormone-Secreting Cells of the Pituitary Gland: An AFM Study (Lloyd L. Anderson and Bhanu P. Jena). Chapter 5. Properties of Microbial Cell Surfaces Examined by Atomic Force Microscopy (Yves F. Dufre&ncirc;e). Chapter 6. Scanning Probe Microscopy of Plant Cell Wall and Its Constituents (Ksenija Radoti&cacute;, Miodrag Mi&cacute;i&cacute;, and Milorad Jeremi&cacute;). Chapter 7. Cellular Interactions of Nano Drug Delivery Systems (Rangaramanujam M. Kannan, Omathanu Pillai Perumal, and Sujatha Kannan). Chapter 8. Adapting AFM Techniques for Studies on Living Cells (J. K. Heinrich Hörber) Chapter 9. Intermolecular Forces of Leukocyte Adhesion Molecules (Xiaohui Zhang and Vincent T. Moy). Chapter 10. Mechanisms of Avidity Modulation in Leukocyte Adhesion Studied by AFM (Ewa P. Wojcikiewicz and Vincent T. Moy). Chapter 11. Resolving the Thickness and Micromechanical Properties of Lipid Bilayers and Vesicles Using AFM (Guangzhao Mao and Xuemei Liang). Chapter 12. Imaging Soft Surfaces by SFM (Andreas Janke and Tilo Pompe). Chapter 13. High-Speed Atomic Force Microscopy of Biomolecules in Motion (Tilman E. Schäffer). Chapter 14. Atomic Force Microscopy in Cytogenetics (S. Thalhammer and W. M. Heckl). Chapter 15. Atomic Force Microscopy in the Study of Macromolecular Interactions in Hemostasis and Thrombosis: Utility for Investigation of the Antiphospholipid Syndrome (William J. Montigny, Anthony S. Quinn, Xiao-Xuan Wu, Edwin G. Bovill, Jacob H. Rand, and Douglas J. Taatjes). Index

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Book Synopsis"The biotech industry is a complex, rapidly evolving, and critical industry. The industry holds great commercial and societal promise, but it is also filled with hype, confusion, and risks.Table of ContentsPreface xi Acknowledgments xvii CHAPTER 1 Overview 1 CHAPTER 2 Pharmaceuticals 43 CHAPTER 3 Medicine and Agriculture 77 CHAPTER 4 Computing, Biomaterials, and the Military 105 CHAPTER 5 Infrastructure 142 CHAPTER 6 Financing 175 CHAPTER 7 Regional Analysis 217 CHAPTER 8 Outlook 295 Appendix 319 Glossary 329 Sources and Further Reading 337 Index 347

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Book SynopsisCommercial Biosensors offers professionals an in-depth look at some of the most significant applications of commercially available biosensor-based instrumentation in the medical, bioprocess, and environmental fields. Featuring contributions by an international team of scientists, the book provides readers with an unparalleled opportunity to see how their colleagues around the world are using these powerful new tools. Commercial Biosensors is divided into three sections. In the first, which is devoted to applications of biosensors to clinical samples, the authors explore how biosensors are currently being used for in-home diabetes monitoring, point-of-care diagnostics, and noninvasive sensing, and biomedical research. The second section deals with cutting-edge applications of biosensors in bioprocess control- for example, measuring glucose, sucrose, glutamate, or choline concentrations during food and beverage production and measuring ethanol concentration during beer fermentatTable of ContentsAPPLICATIONS TO CLINICAL SAMPLES. Biosensors for Personal Diabetes Management (T. Henning & D. Cunningham). Microfabricated Sensors and the Commercial Development of the i-Stat Point-of-Care System (G. Davis). Noninvasive Biosensors in Clinical Analysis (G. Palleschi, et al.). Surface Plasmon Resonance (R. Earp & R. Dessy). Biosensors Based on Evanescent Waves (D. Purvis, et al.). APPLICATIONS TO BIOPROCESS SAMPLES. Applications of Biosensor-Based Instruments to the Bioprocess Industry (J. Woodward & R. Spokane). APPLICATIONS TO ENVIRONMENTAL SAMPLES. Application of Biosensors to Environmental Samples (K. Riedel). Index.

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Book SynopsisAnalytical techniques based on separation processes, such aschromatography and electrophoresis, are finding a growing range ofapplications in chemical, pharmaceutical and clinical laboratories.The Wiley Separation Science Series provides the analyst in theselaboratories with well focused books covering individualtechniques, so that they can be applied more efficiently andeffectively to contemporary analytical problems. In biotechnology,biochemistry and molecular biology, the characterization andanalysis of biomolecules such as proteins, oligosaccharides andnucleic acids are of great importance. High performance liquidchromatography (HPLC) has become one of the key analytical tools inthese fields, providing rapid purification and quantitativeanalysis of biomolecules. High Performance Liquid Chromatography: Principles and Methods inBiotechnology covers the most important theoretical and practicalaspects of the application of HPLC to the biosciences, includingsample preparation, Table of ContentsIntroduction to Chromatography in Biotechnology (C. Simpson). The Principles of Separation by High Performance LiquidChromatography (R. Scott). Column Selection in High Performance Liquid Chromatography (R.Eksteen). Detection and Identification in Biochromatography (I. Krull, etal.). Sample Preparation (A. Rizzi & I. Maurer-Fogy). The Preparative HPLC of Biomolecules (G. Cox). The Application of HPLC for Nucleic Acid Analysis (J. Wages &E. Katz). High-pH Anion Exchange Chromatography of Recombinant GlycoproteinGlycans (R. Townsend). The Application of HPLC for Proteins (K. Benedek). Alternative Bioseparation Techniques (P. Righetti, et al.). Index.

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Book SynopsisNatural Products, broadly defined as high value chemical entities derived from plants or microbial sources, have been known and exploited for many years. In recent years, as the need for higher potency and predictability of such products has increased, more sophisticated concentration and isolation procedures have been developed. With the passage of time, such procedures have been rationalized in terms of scientific principles but, in general, theory has followed behind practice, leading at any given time to an absence from the literature of methods which are truly state of the art. Downstream Processing of Natural Products: A Practical Handbook is a highly practical manual which addresses this issue, and guides researchers and industrial workers through the many potential pitfalls of natural product isolation. The contributors to this volume, all of whom have wide practical experience in this field, present state-of-the-art techniques and observations. The three main stages of naturalTable of ContentsPartial table of contents: Broth Conditioning and Clarification (D. Mackay). Cell Disruption: A Practical Approach (E. Keshavarz-Moore). Solvent Extraction of Fermentation Broth (L. Weatherley). Chemically Assisted Solvent Extraction (C. King). Process Integration in Biotechnology (J. Asenjo & E.Leser). Displacement Chromatography (D. Wallworth). Affinity Chromatography (S. Burton). High-Performance Liquid Chromatography (P. Shelley). Lyophilization (J. Snowman). Instrumentation and Process Control (J. Noble & K.Robins). Scale-Up Considerations (J. Noble & R. Davies). GMP and Quality Control (D. Sherwood). Index.

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Book SynopsisYeasts are the world''s premier industrial micro-organisms. In addition to their wide exploitation in the production of foods, beverages and pharmaceuticals, yeasts also play significant roles as model eukaryotic cells in furthering our knowledge in the biological and biomedical sciences. In order for modern biotechnology to fully exploit the activities of yeasts, it is essential to appreciate aspects of yeast cell physiology. In recent years, however, our knowledge of yeast physiological phenomena has lagged behind that of yeast genetics and molecular biology. Yeast Physiology and Biotechnology redresses the balance by linking key aspects of yeast physiology with yeast biotechnology. Individual chapters provide broad and timely coverage of yeast cytology, nutrition, growth and metabolism - important aspects of yeast cell physiology which are pertinent to the practical uses of yeasts in industry. The final chapter reviews traditional, modern and emerging biotechnologies in which roles Table of ContentsIntroduction to Yeasts. Yeast Cytology. Yeast Nutrition. Yeast Growth. Yeast Metabolism. Yeast Technology. Index.

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Book SynopsisWritten by an exceptionally experienced author in the area of medical equipment product design, this text presents a comprehensive overview of such sound principles and state-of-the-art techniques covering a whole host of material types, biocompatability, the design process and future trends within this exciting field.Trade Review"This is a handbook of commercially available materials which are commonly used for medical devices" (Aslib Book Guide, Vol. 64, No. 1, January 1999)Table of ContentsMATERIALS. Material Available. Material Selection Processes. Ferrous Metals. Non-Ferrous Metals. Polymers. Poly(vinyl chloride)(PVC). Other Materials. Adhesives. Corrosion and Degradation. Biocompatability. Filters and Membranes. Fibre Optics. Battery Selection. DESIGN. Training and Education for Design. Design Process and Factors. Microengineering. Prototyping. Sterilisation. Standards. Specifications. Packaging. Communication in Design. Product Liability. Patents and Registration. Quality Assurance. Manufacturing Methods. FUTURE TRENDS. Future Trends. Environmental Issues. INFORMATION. Sourcing. Glossary. Index.

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Book SynopsisThe manufacture and commercialization of optically-active products and intermediates is a rapidly evolving field. There have been significant new developments since the first volume of Chirality in Industry was published.Table of ContentsPartial table of contents: Chiral Drugs: Regulatory Aspects (J. Blumenstein). Synthesis of Enantiomerically Pure Nucleosides (B. Bray, etal.). PHYSICAL METHODS AND CLASSICAL RESOLUTION. Crystal Science Techniques in the Manufacture of Chiral Compounds(W. Wood). BIOLOGICAL METHODS AND CHIRAL POOL SYNTHESES. Development of a Multi-Stage Chemical and Biological Process for anOptically Active Intermediate for an Anti-Glaucoma Drug (A. Blacker& R. Holt). ASYMMETRIC SYNTHESES BY CHEMICAL METHODS. Asymmetric Hydrocyanation of Vinylarenes (A. Casalnuovo & T.Rajanbabu). Sharpless Asymmetric Epoxidation: Scale-up and IndustrialProduction (W. Shum & M. Cannarsa). Index.

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Book SynopsisIn Biology Is Technology, author Robert Carlson offers a uniquely informed perspective on the endeavors that contribute to current progress in the science of biological systems and the technology used to manipulate them.Trade ReviewA thoughtful attempt to put what we think we know about biotechnology into a larger context, by a physicist-turned-bioentrepreneur. * The Economist *Biology Is Technology is essential reading for anyone who wishes to understand the current state of biotechnology and the opportunities and dangers it may create. -- Alex Soojung-Kim Pang * American Scientist *[Carlson] presents an informative view of the future prospects for biotechnology and its regulation. -- Michael A. Goldman * Nature *In this new book, bioengineer Robert H. Carlson forecasts the rise of the cell and the subsequent emergence of biological techniques for making fuels, synthetic DNA that builds new organisms, and reverse-engineered viruses for making vaccines. Biologists, Carlson says, are the new engineers, and the future is in remodeling life as we know it. * Wired *Since Rob Carlson is the authoritative tracker of progress in biotech, this book is the most complete—and exciting—chronicle of the technological revolution that promises to dominate this century. -- Stewart Brand, author of Whole Earth Discipline: An Ecopragmatist ManifestoCarlson clearly frames a fresh future for biotechnology. Each chapter, from technology trends to property rights and biosecurity conundrums, invites close reading and vibrant discussion. -- Drew Endy, Department of Bioengineering, Stanford University, and the BioBricks FoundationBiology Is Technology makes a tremendous contribution to public analysis of a very important emerging field. Although various commentators have discussed particular aspects of synthetic biology (e.g., risk regulation, intellectual property considerations), I am not aware of a book that encapsulates all of the varying strands of the debate. In addition, the book takes a set of provocative and interesting stances on the subjects that it addresses. It is obviously written by someone who has been a longstanding participant in, and commentator on, the field. Although I do not necessarily agree with all of the positions taken by the book, they are well-defended and thought through. -- Arti K. Rai, Duke Law SchoolTable of Contents* Acknowledgments * What Is Biology? * Building with Biological Parts * Learning to Fly (or Yeast, Geese, and 747s) * The Second Coming of Synthetic Biology * A Future History of Biological Engineering * The Pace of Change in Biological Technologies * The International Genetically Engineered Machines Competition (iGEM) * Reprogramming Cells and Building Genomes * The Promise and Peril of Biological Technologies * The Sources of Innovation and the Effects of Existing and Proposed Regulations * Laying the Foundations for a Bio-Economy * Of Straightjackets and Springboards for Innovation * Open Source Biology, or Open Biology? * What Makes a Revolution? * Notes * Index

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Book SynopsisEugene Goldfield lays out principles of engineering found in the natural world, with a focus on how components of coordinated structures organize themselves into autonomous functional systems. This self-organizing capacity is one of many qualities which can be harnessed to design technologies that can interact seamlessly with human bodies.Trade ReviewThe book is fact-packed and beautifully crafted… Bioinspired Devices provides a fascinating way into one of biomedicine’s most complex fields. While Goldfield writes with both erudition and elegance, he has a wonderfully popular touch and a keen sense of humor that has him drawing on Wallace and Gromit and Star Trek (and more) to help with key explanations. It is a book that will not only leave you with a deep respect for research into copying nature, but also in awe of nature itself and how it does so much with so little. -- Adrian Barnett * New Scientist *Bioinspired Devices: Emulating Nature’s Assembly and Repair Process is a reliquary of nature’s wonders, exploring how cells, organisms, and living systems form and function. Goldfield explains how new insights about these natural building processes are now being leveraged to create ‘biologically inspired’ engineering innovations, from medical devices to robot swarms. After reading this book, you will look at the world in an entirely new way. -- Donald E. Ingber, Wyss Institute for Biologically Inspired Engineering, Harvard UniversityBioinspired Devices takes us on a fascinating journey between nature and engineering. Goldfield extracts key principles for how living systems grow and function and proposes that they be applied to the design of better machines and prostheses. Combining an incredibly rich set of observations from neuroscience, bioengineering, biomechanics, ecology, and more, this book is a stimulating read for anyone interested in living systems and the construction of biologically-inspired devices. -- Auke Ijspeert, Swiss Federal Institute of Technology at LausanneBioinspired Devices explores modern bioengineering’s dance between technology and nature, illuminating how the concepts of resiliency, self-repair, and environmental harmony are more evident today than ever before. -- Ravi Bellamkonda, Duke UniversityBioinspired Devices presents an original, erudite perspective on how to emulate fundamental characteristics of living systems—self repair, robustness, development, and emergence—in order to engineer bioinspired solutions to neurological disorders. Goldfield builds on his extensive experience with dynamical systems, at Boston Children’s Hospital and via collaborations with Harvard’s Wyss Institute, to discuss challenges and opportunities in unravelling and emulating nature’s principles to build neuroprosthetic devices and pathways to rehabilitation. -- Marc-Olivier Coppens, University College London

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Book SynopsisThe life sciences deal with a vast array of problems at different spatial, temporal, and organizational scales. The mathematics necessary to describe, model, and analyze these problems is similarly diverse, incorporating quantitative techniques that are rarely taught in standard undergraduate courses. This textbook provides an accessible introductiTrade Review"Textbooks are not always fun, but this one is... The engaging, colourful and sharp style of Mathematics for the Life Sciences makes it a refreshing new entry into the world of bioscience textbooks."--George Pryn Ford, The Biologist

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Book SynopsisA critical look at the social, environmental, and economic impacts of agricultural biotechnology in Canada.Table of ContentsIntroduction1 Canadian Biotechnology Policy and Its Critics2 Enclosure and Resistance on the BioCommons3 Battles to Reclaim and Maintain the BioCommons4 Intellectual Property Rights: Facilitating Capital’s Command over Biotechnology5 Regulatory Capture and Its Critics6 Capture and Control of Biotechnology Discourse in CanadaConclusionNotesBibliographyIndex

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Book SynopsisA critical look at the social, environmental, and economic impacts of agricultural biotechnology in Canada.Table of ContentsIntroduction1 Canadian Biotechnology Policy and Its Critics2 Enclosure and Resistance on the BioCommons3 Battles to Reclaim and Maintain the BioCommons4 Intellectual Property Rights: Facilitating Capital’s Command over Biotechnology5 Regulatory Capture and Its Critics6 Capture and Control of Biotechnology Discourse in CanadaConclusionNotesBibliographyIndex

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Book SynopsisCoverage of basic Anaerobic Biotechnology principles Practical applications of principles and processes Thorough coverage of cost-effective and sustainable means of treating waste water and resource reclamation.Table of ContentsCONTRIBUTORS, xi PREFACE, xiii 1 OVERVIEW OF ANAEROBIC BIOTECHNOLOGY, 1 Samir Kumar Khanal 1.1 Anaerobic Biotechnology and Bioenergy Recovery, 1 1.2 Historical Development, 3 1.3 Importance of Anaerobic Biotechnology in Overall Waste Treatment, 5 1.4 Definition and Principle of Anaerobic Processes, 6 1.5 Important Considerations in Anaerobic Biotechnology, 8 1.6 Merits of Anaerobic Biotechnology, 15 1.7 Limitations of Anaerobic Process, 22 References, 25 2 MICROBIOLOGY AND BIOCHEMISTRY OF ANAEROBIC BIOTECHNOLOGY, 29 Samir Kumar Khanal 2.1 Background, 29 2.2 Organics Conversion in Anaerobic Systems, 29 2.3 Process Microbiology, 32 References, 41 3 ENVIRONMENTAL FACTORS, 43 Samir Kumar Khanal 3.1 Background, 43 3.2 Temperature, 43 3.3 Operating pH and Alkalinity, 47 3.4 Nutrients, 55 3.5 Toxic Materials, 56 3.6 Redox Potential or Oxidation–Reduction Potential, 59 References, 61 4 KINETICS AND MODELING IN ANAEROBIC PROCESSES, 65 Keshab Raj Sharma 4.1 Background, 65 4.2 Basic Elements, 66 4.3 Stepwise Approach to Modeling, 69 4.4 Modeling of pH Change, 79 4.5 Modeling of Energy Generation, 87 References, 92 5 ANAEROBIC REACTOR CONFIGURATIONS FOR BIOENERGY PRODUCTION, 93 Samir Kumar Khanal 5.1 Background, 93 5.2 Strategies for Decoupling HRT and SRT, 93 5.3 Classification of Anaerobic Bioreactors, 94 5.4 Membrane Technology for Syngas Fermentation to Ethanol, 112 References, 114 6 MOLECULAR TECHNIQUES IN ANAEROBIC BIOTECHNOLOGY: APPLICATION IN BIOENERGY GENERATION, 115 Srisuda Dhamwichukorn 6.1 Background, 115 6.2 Molecular Techniques in Anaerobic Biotechnology, 115 6.3 Fundamentals of Molecular Techniques, 116 6.4 Phylogenetic Analysis, 117 6.5 Molecular Techniques for Microbial Community Structure Analysis: DNA Fingerprinting, Clone Library, and Fluorescent in Situ Hybridization, 118 6.6 Molecular Techniques for Functional Analysis, 121 6.7 Nucleic Acid Extraction of Anaerobic Cells/Isolates and Sludge, 123 6.8 Molecular Techniques for Structure and Function Analysis, 123 6.9 Postgenomic Approaches for Bioenergy Research, 128 References, 130 7 BIOENERGY RECOVERY FROM SULFATE-RICH WASTE STREAMS AND STRATEGIES FOR SULFIDE REMOVAL, 133 Samir Kumar Khanal 7.1 Background, 133 7.2 Sulfate-Reducing Bacteria, 133 7.3 High-Strength Sulfate-Rich Wastewater, 135 7.4 Methane Recovery from High-Strength Sulfate-Laden Wastewater, 135 7.5 Important Considerations in Treatment and Methane Recovery from High-Strength Sulfate-Laden Wastewater, 137 7.6 Interactions between MPB and SRB, 143 7.7 Sulfide Removal, 149 References, 157 8 BIOENERGY GENERATION FROM RESIDUES OF BIOFUEL INDUSTRIES, 161 Samir Kumar Khanal 8.1 Background, 161 8.2 Bioethanol Feedstocks, 162 8.3 Biodiesel Feedstocks, 163 8.4 Ethanol Production, 163 8.5 Thin Stillage Characterization, 171 8.6 Cassava-Based Ethanol Production, 183 8.7 Cellulose-Based Ethanol Production, 185 8.8 Bioenergy Recovery from Crude Glycerin, 186 References, 187 9 BIOHYDROGEN PRODUCTION: FUNDAMENTALS, CHALLENGES, AND OPERATION STRATEGIES FOR ENHANCED YIELD, 189 Samir Kumar Khanal 9.1 Background, 189 9.2 Biological Hydrogen Production, 190 9.3 Microbiology of Dark Fermentation, 191 9.4 Hydrogen Production Pathway through Dark Fermentation, 192 9.5 Suppression of Hydrogen Consumers, 196 9.6 Hydrogen Yield, 199 9.7 Important Considerations in Biohydrogen Production, 200 9.8 Limitations of Dark Fermentation and Potential Remedial Options, 210 9.9 Technoeconomic Analysis of Hydrogen Fermentation, 213 References, 215 10 MICROBIAL FUEL CELL: NOVEL ANAEROBIC BIOTECHNOLOGY FOR ENERGY GENERATION FROM WASTEWATER, 221 Hong Liu 10.1 Background, 221 10.2 How Does a Microbial Fuel Cell Work?, 222 10.3 Stoichiometry and Energetics, 223 10.4 Electrochemically Active Microbes and Electron Transfer Mechanisms, 225 10.5 Evaluation of MFC Performance, 228 10.6 MFC Designs and Electrode Materials, 231 10.7 Operational Factors Affecting MFC Performance, 239 10.8 Opportunities and Challenges for MFCs in Wastewater Treatment, 242 References, 243 11 PRETREATMENT OF HIGH-SOLIDS WASTES/RESIDUES TO ENHANCE BIOENERGY RECOVERY, 247 Santha Harikishan 11.1 Background, 247 11.2 Efficiency of Sludge Pretreatment, 248 11.3 Ultrasound Pretreatment, 250 11.4 Chemical and Physical Pretreatment, 257 11.5 Thermal Hydrolysis, 261 11.6 Impact of Improved Digestibility on Overall Process Economics, 264 References, 264 12 BIOGAS PROCESSING AND UTILIZATION AS AN ENERGY SOURCE, 267 Santha Harikishan 12.1 Background, 267 12.2 Biogas Production, 267 12.3 Factors Affecting Digester Gas Production, 269 12.4 Biogas Composition, 270 12.5 Biogas Impurities, 272 12.6 Biogas Cleaning for Effective Utilization, 274 12.7 Biogas Utilization, 279 12.8 Future of Biogas as a Renewable Resource, 290 References, 291 INDEX, 293

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