Chemistry Books

Book SynopsisDue to its enormous sensitivity and ease of use, mass spectrometry has grown into the analytical tool of choice in most industries and areas of research.Trade Review“In summary, this handbook presents research from a variety of areas tied together by the common thread of mass spectrometry. The authors present their works in a manner that is accessible to beginning researchers and include sufficient references to allow in depth exploration of the topic. More seasoned scientists could also benefit from this book as they venture into new areas of research.” (Journal of American Society for Mass Spectrometry, 6 October 2012)Table of ContentsFOREWORD xi PREFACE xiii CONTRIBUTORS xvii SECTION I BIOTECHNOLOGY/PROTEINS 1 1 Targeted Proteomics Using Immunoaffi nity Purifi cation 3 Karen R. Jonscher, Lei Jin, John C. Cambier, Shaikh M. Rahman, and Jacob E. Friedman 2 Mass Spectrometry-Based Methods to Investigate Posttranslational Protein Modifi cations by Lipid Peroxidation Products 23 Navin Rauniyar and Laszlo Prokai 3 Imaging Mass Spectrometry (IMS) for Biological Application 41 Yuki Sugiura, Ikuko Yao, and Mitsutoshi Setou 4 Methodologies for Identifying Microorganisms and Viruses by Mass Cataloging of RNAs 85 George W. Jackson, Rafal Drabek, Mithil Soni, Roger McNichols, Richard C. Willson, and George E. Fox SECTION II PHARMACEUTICAL 107 5 Preclinical Pharmacokinetics: Industrial Perspective 109 Ayman El-Kattan and Manthena Varma 6 LC-MS in Drug Metabolism and Pharmacokinetics: A Pharmaceutical Industry Perspective 119 Wenying Jian, Wilson Shou, Richard W. Edom, Naidong Weng, and Mingshe Zhu 7 Quantitative Mass Spectrometry in Support of Pharmacokinetic Studies 171 Xiaoying Xu, Wenkui Li, and Francis L.S. Tse 8 Determination of Pharmacokinetic Parameters by HPLC-MS/MS and UPLC-MS/MS 191 Margrét Thorsteinsdóttir, Baldur Bragi Sigurðsson, and Gísli Bragason 9 Methods for Screening Enantioselective Interactions in the Solution Phase Using ESI-MS 209 Kevin A. Schug 10 Hydrogen/Deuterium Exchange Mass Spectrometry (HDX MS) in the Studies of Architecture, Dynamics, and Interactions of Biopharmaceutical Products 227 Igor A. Kaltashov, Cedric E. Bobst, and Rinat R. Abzalimov 11 TOF-SIMS Applications to Bioimaging and Biomolecule Evaluation Methods 243 Satoka Aoyagi 12 Accelerator Mass Spectrometry in Pharmaceutical Development 259 Benjamin J. Stewart, Graham Bench, Bruce A. Buchholz, Kurt W. Haack, Michael A. Malfatti, Ted J. Ognibene, and Kenneth W. Turteltaub SECTION III CLINICAL ANALYSIS 271 13 Mass Spectrometry in Clinical Analysis: Screening for Inborn Errors in Metabolism 273 Donald H. Chace 14 Mass Spectrometry for Steroid Analysis 297 William J. Griffi ths, Michael Ogundare, Anna Meljon, and Yuqin Wang SECTION IV FORENSICS 339 15 Forensic Applications of Isotope Ratio Mass Spectrometry 341 Sarah J. Benson 16 Analysis of Triacetone Triperoxide Explosive by Mass Spectrometry 373 Michael E. Sigman and C. Douglas Clark SECTION V SPACE EXPLORATION 389 17 Mass Spectrometry in Solar System Exploration 391 Paul V. Johnson, Luther W. Beegle, and Isik Kanik 18 Application of GC × GC–TOFMS to the Characterization of Extraterrestrial Organic Matter 407 Jonathan S. Watson SECTION VI HOMELAND SECURITY 417 19 Methods of Mass Spectrometry in Homeland Security Applications 419 Ünige A. Laskay, Erin J. Kaleta, and Vicki H. Wysocki 20 Homeland Security 441 Christina L. Crawford and Herbert H. Hill, Jr. 21 Mass Spectrometry in Homeland Security 477 Yasuaki Takada 22 Measurements of Surface Contaminants and Sorbed Organics Using an Ion Trap Secondary Ion Mass Spectrometer 491 Gary S. Groenewold, Anthony D. Appelhans, Garold L. Gresham, and John E. Olson 23 Determination of Actinides: Determination of Low-Concentration Urine Uranium 235/238 Isotope Ratios 509 R. Steven Pappas SECTION VII FOOD ANALYSIS 529 24 Mass Spectrometry in Agriculture, Food, and Flavors: Selected Applications 531 Maciej Stobiecki, Piotr Kachlicki, and Henryk Jeleñ 25 Top-Down Proteomic Identifi cation of Protein Biomarkers of Food-Borne Pathogens Using MALDI-TOF-TOF-MS/MS 559 Clifton K. Fagerquist and Omar Sultan SECTION VIII ENVIRONMENTAL 575 26 Determination of Dithiocarbamate Fungicides in Food by Hydrophilic Interaction Liquid Chromatography/Mass Spectrometry 577 Wolfgang Schwack 27 Disinfectant and By-Product Analysis in Water Treatment by Membrane Introduction Mass Spectrometry 593 Chongzheng Na and Terese M. Olson 28 Proton Transfer Reaction Mass Spectrometry (PTR-MS) 605 Yujie Wang, Chengyin Shen, Jianquan Li, Haihe Jiang, and Yannan Chu 29 Determination of Chlorinated Compounds in Dialysis Water and in Biological Fluids/Matrices 631 Diana Poli SECTION IX GEOLOGICAL 645 30 Mass Spectrometry Techniques for Analysis of Oil and Gas Trapped in Fluid Inclusions 647 Simon C. George, Herbert Volk, and Adriana Dutkiewicz 31 LA-MC-ICP-MS Applied to U-Pb Zircon Geochronology 675 Alain Cocherie and Michèle Robert 32 Hydrocarbon Processing 707 Maoqi Feng, Thomas Andrews, and Eloy Flores III 33 Hydrocarbon Processing: MALDI-MS of Polydisperse Hydrocarbon Samples 725 Alan A. Herod 34 Renewable Energy: Mass Spectrometry in Biofuel Research 749 Ingvar Eide and Kolbjørn Zahlsen SECTION X ARCHAEOLOGY 763 35 Mass Spectrometry in Archaeology 765 Robert Hedges and James McCullagh 36 Archaeometric Data from Mass Spectrometric Analysis of Organic Materials: Proteins, Lipids, Terpenoid Resins, Lignocellulosic Polymers, and Dyestuff 797 Maria Perla Colombini, Francesca Modugno, and Erika Ribechini 37 Laser Ablation ICP-MS in Archaeology 829 Hector Neff 38 Spatially Resolved MS in the Study of Art and Archaeological Objects 845 Giuseppe Spoto 39 Laser Ablation–Inductively Coupled Plasma Mass Spectrometry for the Investigation of Archaeological Samples 859 Martín Resano, Esperanza García-Ruiz, and Frank Vanhaecke SECTION XI SURFACE ANALYSIS 885 40 Mass Spectrometry in Semiconductor Research 887 Stefan Flege and Wolfgang Ensinger 41 Analysis of Thin and Thick Films 943 Philippe Le Coustumer, Patrick Chapon, Agnès Tempez, Yuriy Popov, George Thompson, Igor Molchan, Nicolas Trigoulet, Peter Skeldon, Antonino Licciardello, Nunzio Tuccitto, Ivan Delfanti, Katrin Fuhrer, Marc Gonin, James Whitby, Markus Hohl, Christian Tanner, Nerea Bordel Garcia, Lara Lobo Revilla, Jorge Pisonero, Rosario Pereiro, Cristina Gonzalez Gago, Alfredo Sanz Medel, Mihai Ganciu Petcu, Ani Surmeian, Constantin Diplasu, Andreea Groza, Norbert Jakubowski, Roland Dorka, Stela Canulescu, Johann Michler, Philippe Belenguer, Thomas Nelis, Abdellatif Zahri, Philippe Guillot, Laurent Thérèse, Arnaud Littner, Richard Vaux, Julien Malherbe, Frédéric Huneau, Fred Stevie, and Hugues François-Saint-Cyr 42 SIMS for Organic Film Analysis 961 Taoufi q Mouhib and Arnaud Delcorte 43 Ceramics: Contribution of Secondary Ion Mass Spectrometry (SIMS) to the Study of Crystal Chemistry of Mica Minerals 1017 Luisa Ottolini, Emanuela Schingaro, and Fernando Scordari SECTION XII POLYMERS 1061 44 ETV-ICPMS for Analysis of Polymers 1063 Maite Aramendía Marzo, Martín Resano, and Frank Vanhaecke 45 Polymers 1079 Maurizio S. Montaudo and Salvatore Battiato 46 Mass Spectroscopy in Polymer Research 1107 Jale Hacaloglu and Talat Yalcin 47 Laser Mass Spectrometry Applied to the Analysis of Polymers 1135 Jérôme Bour and David Ruch SECTION XIII ANALYTICAL TECHNIQUES 1143 48 Measuring Thermodynamic Properties of Metals and Alloys 1145 Evan H. Copland and Nathan S. Jacobson 49 High-Performance Thin-Layer Chromatography–Mass Spectrometry for Analysis of Small Molecules 1181 Gertrud E. Morlock 50 Laser Ionization Mass Spectrometry of Inorganic Ions 1207 Julius Pavlov and Athula B. Attygalle 51 Mass Spectrometry in the SSITKA Studies 1229 L.G. Pinaeva, E.M. Sadovskaya, A.P. Suknev, V.B. Goncharov, and B.S. Bal’zhinimaev 52 Proton Transfer Reaction Mass Spectrometry: Applications in the Life Sciences 1257 Elena Crespo, Marco M.L. Steeghs, Simona M. Cristescu, and Frans J.M. Harren INDEX 1283

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Book SynopsisThis book provides an introduction to chemical engineering topics in an integrated fashion and illustrates the methodology of process design through the processes followed in the text. It provides an all-in-one coverage of topics from process plant interactions to economic analyses and thermodynamic properties of streams.Trade Review“The author, a professor emeritus of chemical engineering at Stevens Institute of Technology, guides readers step by step through the execution of both chemical process analysis and equipment design, allowing readers to master such chemical engineering operations and equipment as separators, reactors, heat exchangers, and more.” (Chemical Engineering Progress, 1 September 2013) Table of ContentsPREFACE xix PART I MACROSCOPIC VIEW 1 1 Chemical Process Perspective 3 1.1 Some Basic Concepts in Chemical Processing, 3 1.2 Acrylic Acid Production, 5 1.3 Biocatalytic Processes—Enzymatic Systems, 21 1.4 Basic Database, 24 Problems, 26 2 Macroscopic Mass Balances 28 2.1 Chemical Processing Systems, 28 2.2 Steady-State Mass Balances Without Chemical Reactions, 37 2.3 Steady-State Mass Balances with Single Chemical Reactions, 41 2.4 Steady-State Mass Balances with Multiple Chemical Reactions, 46 3 Macroscopic Energy and Entropy Balances 53 3.1 Basic Thermodynamic Functions, 53 3.2 Evaluation of H and S for Pure Materials, 55 3.3 Evaluation of H and S Functions for Mixtures, 59 3.4 Energy Flows and the First Law, 62 3.5 Energy Balances Without Reaction, 64 3.6 Energy Balances with Reaction-Ideal Solution, 70 3.7 Entropy Balances, 77 4 Macroscopic Momentum and Mechanical Energy Balances 86 4.1 Momentum Balance, 86 4.2 Mechanical Energy Balance, 88 4.3 Applications to Incompressible Flow Systems, 89 5 Completely Mixed Systems—Equipment Considerations 95 5.1 Mixing and Residence Time Distributions—Definitions, 95 5.2 Measurement and Interpretation of Residence Time Distributions, 97 5.3 Basic Aspects of Stirred Tank Design, 99 6 Separation and Reaction Processes in Completely Mixed Systems 107 6.1 Phase Equilibrium: Single-Stage Separation Operations, 107 6.2 Gas–Liquid Operations, 109 6.3 Flash Vaporization, 133 6.4 Liquid–Liquid Extraction, 145 6.5 Adsorption, 151 6.6 Single-Phase Stirred Tank Reactors, 159 6.7 Chemical Reaction Equilibrium, 174 PART II MICROSCOPIC VIEW 181 7 Multistage Separation and Reactor Operations 183 7.1 Absorption and Stripping, 183 7.2 Distillation, 200 7.3 Liquid–Liquid Extraction, 221 7.4 Multiple Reactor Stages, 235 7.5 Staged Fixed-Bed Converters for Exothermic Gas Phase Reaction, 238 8 Microscopic Equations of Change 243 8.1 Mass Flux: Average Velocities and Diffusion, 244 8.2 Momentum Flux: Stress Tensor, 249 8.3 Energy Flux: Conduction, 250 8.4 Balance Equations, 251 8.5 Entropy Balance and Flux Expressions, 254 8.6 Turbulence, 265 8.7 Application of Balance Equations, 269 9 Nonturbulent Isothermal Momentum Transfer 276 9.1 Rectangular Models, 276 9.2 Cylindrical Systems, 280 9.3 Spherical Systems, 287 9.4 Microfluidics—Gas Phase Systems, 289 10 Nonturbulent Isothermal Mass Transfer 296 10.1 Membranes, 296 10.2 Diffusion Models for Porous Solids, 307 10.3 Heterogeneous Catalysis, 311 10.4 Transient Adsorption by Porous Solid, 316 10.5 Diffusion with Laminar Flow, 318 11 Energy Transfer Under Nonturbulent Conditions 324 11.1 Conduction in Solids–Composite Walls, 325 11.2 Thermal Effects in Porous Catalysts, 327 11.3 Heat Transfer to Falling Film—Short Contact Times, 330 11.4 Moving Boundary Problem, 332 12 Isothermal Mass Transfer Under Turbulent Conditions 335 12.1 Intraphase Mass Transfer Coefficients, 335 12.2 Interphase Mass Transfer Coefficients—Controlling Resistances, 338 12.3 Measurement and Correlation of Mass Transfer Coefficients, 339 12.4 Fixed Beds, 342 12.5 Pipes, 345 12.7 Packed Towers—Gas Absorption, 349 12.8 Applification of Experimental Mass Transfer Coefficients, 357 13 Interphase Momentum Transfer Under Turbulent Conditions 367 13.1 Pressure Drop in Conduits and Fixed Beds, 368 13.2 Flow Over Submerged Spheres, 376 14 Interphase Energy Transfer Under Turbulent Conditions 384 14.1 Heat Transfer Coefficients—Analogy with Mass Transfer, 384 14.2 Heat Exchangers, 385 14.3 Multi-Tubular Catalytic Reactors, 395 15 Microscopic to Macroscopic 400 15.1 Macroscopic Mass Balance, 400 15.2 Macroscopic Energy Balance, 401 15.3 Macroscopic Mechanical Energy Balance, 402 APPENDIX A PERIODIC TABLE 405 APPENDIX B CONVERSION FACTORS 406 APPENDIX C PARTIAL DATABASE FOR ACRYLIC ACID PROCESS 409 APPENDIX D SOME MATHEMATICAL RESULTS 414 APPENDIX E MASS BALANCE IN CYLINDRICAL COORDINATES AND LAMINAR FLOW IN Z DIRECTION 418 NOMENCLATURE 419 REFERENCES 423 INDEX 427

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Book SynopsisIn contrast to the classical books which largely focus on separate, individual physicochemical and biological aspects, this book aims to integrate the frontiers of knowledge on the fundamentals and the impact of physicochemical and biological interactions and processes of AOCs in soil, sediment, water and air. The specific objectives of this book are to address: (1) fundamental biophysico-chemical processes of AOCs in the environment, (2) occurrence and distribution of AOCs in air, water, and soil, and their global cycling, (3) the state-of-the-art analytical techniques of AOCs, and (4) restoration of natural environments contaminated by AOCs. The book also identifies the gaps in knowledge on the subject matter and as such provides future directions to stimulate scientific research to advance the chemical science on biophysico-chemical interfacial reactions in natural habitats. By virtue of complex nature of the interactions of AOCs with different environmental components and matriTable of ContentsSeries Preface. Preface. Contributors. PART I FUNDAMENTAL BIOPHYSICO-CHEMICAL PROCESSES OF ANTHROPOGENIC ORGANIC COMPOUNDS IN THE ENVIRONMENT. 1 Interactions of Anthropogenic Organic Chemicals with Natural Organic Matter and Black Carbon in Environmental Particles (Joseph J. Pignatello). 2 Comprehensive Study of Organic Contaminant Adsorption by Clays: Methodologies, Mechanisms and Environmental Implications (Stephen A. Boyd, Cliff T. Johnston, David A. Laird, B. J. Teppen and Hui Li). 3 The Role of Organic Matter-Mineral Interactions in the Sorption of Organic Contaminants (Myrna J. Simpson and Andre J. Simpson). 4 Photocatalytic Degradation of Organic Contaminants on Mineral Surfaces (Chuncheng Chen, Zhaohui Wang, Wanhong Ma, Hongwei Ji and Jincai Zhao). PART II ANTHROPOGENIC ORGANIC COMPOUNDS IN AIR, WATER, AND SOIL, AND THEIR GLOBAL CYCLING. 5 Sorption of Anthropogenic Organic Compounds to Airborne Particles (Hans Peter H. Arp and Kai–weU. Goss). 6 Measurement and Modeling of Semivolatile Organic Compounds in Local Atmospheres (Songyan Du and Lisa A. Rodenburg). 7 Pharmaceuticals and Personal Care Products in Soils and Sediments (Bo Pan and Baoshan Xing). 8 Fate and Transport of Organic Compounds in (to) the Subsurface Environment (Peter Grathwohl). 9 Pharmaceuticals and Endocrine Disrupting Compounds in Drinking Water (Daniel W. Gerrity, Mark J. Benotti, David A. Reckhow and Shane A. Snyder). 10 Intermedia Transfers and Global Cycling of Persistent Organic Pollutants (Claudia Moeckel and Kevin C. Jones). 11 Emission of Polycyclic Aromatic Hydrocarbons in China (Shu Tao, Bengang G. Li, Yanxu X. Zhang and Huishi Yuan). PART III ANALYTICAL TECHNIQUES. 12 Principles and Guidelines of Sampling, Extraction and Instrumental Analysis Techniques for Measurements or Organic Pollutants in Environmental Matrices (Eddy Yongping Zeng, Zhaohui Wang and O. Samnuel Sojinu). 13 NMR Application in Environmental Research on Anthropogenic Organic Compounds (Robert L. Cook). 14 Synchrotron-Based X-Ray and FTIR Absorption Spectromicroscopies of Organic Contaminants in the Environment (John R. Lawrence and Adam. P. Hitchcock). 15 Application of Solid Phase Microextraction in Determination of Organic Compounds from Complex Environmental Matrices (Sanja Resticevic, Dajana Vuckovic and Janusz Pawliszyn). 16 Application of Biosensors for Environmental Analysis (Marinella Farré, Sandra Pérez, Lina Kantiani and Damiá Barceló). 17 Analyses of Drugs and Pharmaceuticals in the Environment (Imran Ali, Hassan Y. Aboul-Enein and Klaus Kummerer). PART IV RESTORATION OF NATURAL ENVIRONMENTS CONTAMINATED BY ORGANIC POLLUTANTS. 18. Biochemistry of Environmental Contaminant Transformation: Nonylphenolic Compounds and Hexachlorocyclohexanes – Two Case Studies (Hans-Peter E. Kohler). 19. Biodegradation of Anthropogenic Organic Compounds in Natural Environments (Jose-Luis Niqui-Arroyo, Marisa Bueno-Montes and José-Julio Ortega-Calvo). 20. Phytoremediation of Soils Contaminated with Organic Pollutants (Jason C. White and Lee A. Newman). 21. Bioavailability of Hydrophobic Organic Contaminants in Soils and Sediments (Wesley H. Hunter, Jay Gan and Rai S. Kookana). 22. Abiotic and Biotic Factors Affecting the Fate of Organic Pollutants in Soils and Sediments (Richard E. Meggo and Jerald L. Schnoor). Index.

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Book SynopsisNow in its fourth edition, Surfactants and Interfacial Phenomena explains why and how surfactants operate in interfacial processes (such as foaming, wetting, emulsion formation and detergency), and shows the correlations between a surfactant''s chemical structure and its action. Updated and revised to include more modern information, along with additional three chapters on Surfactants in Biology and Biotechnology, Nanotechnology and Surfactants, and Molecular Modeling with Surfactant Systems, this is the premier text on the properties and applications of surfactants. This book provides an easy-to-read, user-friendly resource for industrial chemists and a text for classroom use, and is an unparalleled tool for understanding and applying the latest information on surfactants. Problems are included at the end of each chapter to enhance the reader's understanding, along with many tables of data that are not compiled elsewhere. Only the minimum mathematics is used in the eTrade Review“Written by Milton J. Rosen and Joy T. Kunjappu, two leading authorities in the field, Surfactants and Interfacial Phenomena, Fourth Edition is an unparalleled tool for understanding and applying the latest information on surfactants, and includes unique data tables and end-of-chapter problems designed to enhance the reader’s understanding.” (Chimie Nouvelle, 1 March 2013) “The book is recommended to all who want to enter the interesting and yet further growing field of surfactants at interfaces. It can serve as textbook for graduated students attending courses on surfactants and their applications. The book is also excellent for experts working in fundamental and applied research as they can find the main principles of the modification of interfaces via the impact of surfactants.” (Tenside Surfactants Detergents, 1 May 2012) Table of ContentsPreface xv 1 Characteristic Features of Surfactants 1 I. Conditions under which Interfacial Phenomena and Surfactants Become Significant 2 II. General Structural Features and Behavior of Surfactants 2 A. General Use of Charge Types 4 B. General Effects of the Nature of the Hydrophobic Group 5 1. Length of the Hydrophobic Group 5 2. Branching, Unsaturation 5 3. Aromatic Nucleus 5 4. Polyoxypropylene or Polyoxyethylene (POE) Units 5 5. Perfluoroalkyl or Polysiloxane Group 6 III. Environmental Effects of Surfactants 6 A. Surfactant Biodegradability 6 B. Surfactant Toxicity; Skin Irritation 7 IV. Characteristic Features and Uses of Commercially Available Surfactants 8 A. Anionics 9 1. Carboxylic Acid Salts 9 2. Sulfonic Acid Salts 11 3. Sulfuric Acid Ester Salts 15 4. Phosphoric and Polyphosphoric Acid Esters 17 5. Fluorinated Anionics 18 B. Cationics 19 1. Long-Chain Amines and Their Salts 20 2. Acylated Diamines and Polyamines and Their Salts 20 3. Quaternary Ammonium Salts 20 4. Polyoxyethylenated Long-Chain Amines 22 5. Quaternized POE Long-Chain Amines 22 6. Amine Oxides 22 C. Nonionics 23 1. Polyoxyethylenated Alkylphenols, Alkylphenol "Ethoxylates" 23 2. Polyoxyethylenated Straight-Chain Alcohols 24 3. Polyoxyethylenated Polyoxypropylene Glycols 25 4. Polyoxyethylenated Mercaptans 25 5. Long-Chain Carboxylic Acid Esters 26 6. Alkanolamine "Condensates," Alkanolamides 27 7. Tertiary Acetylenic Glycols and Their "Ethoxylates" 28 8. Polyoxyethylenated Silicones 28 9. N-Alkylpyrrolid(in)ones 29 10. Alkylpolyglycosides 29 D. Zwitterionics 30 1. pH-Sensitive Zwitterionics 30 2. pH-Insensitive Zwitterionics 32 E. Newer Surfactants Based Upon Renewable Raw Materials 32 1. α-Sulfofatty Acid Methyl Esters (SME) 32 2. Acylated Aminoacids 33 3. Nopol Alkoxylates 34 V. Some Useful Generalizations 34 VI. Electronic Searching of the Surfactant Literature 35 References 36 Problems 37 2 Adsorption of Surface-Active Agents at Interfaces: The Electrical Double Layer 39 I. The Electrical Double Layer 40 II. Adsorption at the Solid–Liquid Interface 44 A. Mechanisms of Adsorption and Aggregation 44 B. Adsorption Isotherms 48 1. The Langmuir Adsorption Isotherm 50 C. Adsorption from Aqueous Solution onto Adsorbents with Strongly Charged Sites 53 1. Ionic Surfactants 53 2. Nonionic Surfactants 59 3. pH Change 59 4. Ionic Strength 60 5. Temperature 60 D. Adsorption from Aqueous Solution onto Nonpolar, Hydrophobic Adsorbents 60 E. Adsorption from Aqueous Solution onto Polar Adsorbents without Strongly Charged Sites 63 F. Effects of Adsorption from Aqueous Solution on the Surface Properties of the Solid Adsorbent 63 1. Substrates with Strongly Charged Sites 63 2. Nonpolar Adsorbents 65 G. Adsorption from Nonaqueous Solution 65 H. Determination of the Specific Surface Areas of Solids 66 III. Adsorption at the Liquid–Gas (L/G) and Liquid–Liquid (L/L) Interfaces 66 A. The Gibbs Adsorption Equation 67 B. Calculation of Surface Concentrations and Area Per Molecule at the Interface by Use of the Gibbs Equation 69 C. Effectiveness of Adsorption at the L/G and L/L Interfaces 71 D. The Szyszkowski, Langmuir, and Frumkin Equations 99 E. Efficiency of Adsorption at the L/G and L/L Interfaces 100 F. Calculation of Thermodynamic Parameters of Adsorption at the L/G and L/L Interfaces 104 G. Adsorption from Mixtures of Two Surfactants 113 References 115 Problems 121 3 Micelle Formation by Surfactants 123 I. The Critical Micelle Concentration (CMC) 123 II. Micellar Structure and Shape 126 A. The Packing Parameter 126 B. Surfactant Structure and Micellar Shape 127 C. Liquid Crystals 128 D. Rheology of Surfactant Solutions 131 III. Micellar Aggregation Numbers 132 IV. Factors Affecting the Value of the CMC in Aqueous Media 140 A. Structure of the Surfactant 140 1. The Hydrophobic Group 140 2. The Hydrophilic Group 158 3. The Counterion in Ionic Surfactants; Degree of Binding to the Micelle 160 4. Empirical Equations 164 B. Electrolyte 166 C. Organic Additives 167 1. Class I Materials 167 2. Class II Materials 168 D. The Presence of a Second Liquid Phase 169 E. Temperature 170 V. Micellization in Aqueous Solution and Adsorption at the Aqueous Solution–Air or Aqueous Solution–Hydrocarbon Interface 170 A. The CMC/C20 Ratio 171 VI. CMCs in Nonaqueous Media 179 VII. Equations for the CMC Based on Theoretical Considerations 180 VIII. Thermodynamic Parameters of Micellization 184 IX. Mixed Micelle Formation in Mixtures of Two Surfactants 191 References 192 Problems 200 4 Solubilization by Solutions of Surfactants: Micellar Catalysis 202 I. Solubilization in Aqueous Media 203 A. Locus of Solubilization 203 B. Factors Determining the Extent of Solubilization 206 1. Structure of the Surfactant 207 2. Structure of the Solubilizate 209 3. Effect of Electrolyte 209 4. Effect of Monomeric Organic Additives 210 5. Effect of Polymeric Organic Additives 211 6. Mixed Anionic–Nonionic Micelles 212 7. Effect of Temperature 212 8. Hydrotropy 214 C. Rate of Solubilization 214 II. Solubilization in Nonaqueous Solvents 215 A. Secondary Solubilization 218 III. Some Effects of Solubilization 218 A. Effect of Solubilization on Micellar Structure 218 B. Change in the CPs of Aqueous Solutions of Nonionic Surfactants 219 C. Reduction of the CMC 223 D. Miscellaneous Effects of Solubilization 223 IV. Micellar Catalysis 224 References 229 Problems 233 5 Reduction of Surface and Interfacial Tension by Surfactants 235 I. Efficiency in Surface Tension Reduction 239 II. Effectiveness in Surface Tension Reduction 241 A. The Krafft Point 241 B. Interfacial Parameter and Chemical Structural Effects 242 III. Liquid–Liquid Interfacial Tension Reduction 256 A. Ultralow Interfacial Tension 257 IV. Dynamic Surface Tension Reduction 262 A. Dynamic Regions 262 B. Apparent Diffusion Coefficients of Surfactants 265 References 266 Problems 270 6 Wetting and Its Modification by Surfactants 272 I. Wetting Equilibria 272 A. Spreading Wetting 273 1. The Contact Angle 275 2. Measurement of the Contact Angle 277 B. Adhesional Wetting 278 C. Immersional Wetting 281 D. Adsorption and Wetting 282 II. Modification of Wetting by Surfactants 285 A. General Considerations 285 B. Hard Surface (Equilibrium) Wetting 286 C. Textile (Nonequilibrium) Wetting 288 D. Effect of Additives 299 III. Synergy in Wetting by Mixtures of Surfactants 300 IV. Superspreading (Superwetting) 300 References 303 Problems 306 7 Foaming and Antifoaming by Aqueous Solutions of Surfactants 308 I. Theories of Film Elasticity 309 II. Factors Determining Foam Persistence 313 A. Drainage of Liquid in the Lamellae 313 B. Diffusion of Gas through the Lamellae 314 C. Surface Viscosity 315 D. The Existence and Thickness of the Electrical Double Layer 315 III. The Relation of Surfactant Chemical Structure to Foaming in Aqueous Solution 316 A. Efficiency as a Foaming Agent 317 B. Effectiveness as a Foaming Agent 317 C. Low-Foaming Surfactants 325 IV. Foam-Stabilizing Organic Additives 326 V. Antifoaming 329 VI. Foaming of Aqueous Dispersions of Finely Divided Solids 330 VII. Foaming and Antifoaming in Organic Media 331 References 332 Problems 334 8 Emulsification by Surfactants 336 I. Macroemulsions 337 A. Formation 338 B. Factors Determining Stability 338 1. Physical Nature of the Interfacial Film 339 2. Existence of an Electrical or Steric Barrier to Coalescence on the Dispersed Droplets 341 3. Viscosity of the Continuous Phase 342 4. Size Distribution of Droplets 342 5. Phase Volume Ratio 343 6. Temperature 343 C. Inversion 345 D. Multiple Emulsions 345 E. Theories of Emulsion Type 347 1. Qualitative Theories 347 2. Kinetic Theory of Macroemulsion Type 349 II. Microemulsions 350 III. Nanoemulsions 354 IV. Selection of Surfactants as Emulsifying Agents 355 A. The Hydrophile–Lipophile Balance (HLB) Method 356 B. The PIT Method 358 C. The Hydrophilic Lipophilic Deviation (HLD) Method 361 V. Demulsification 361 References 363 Problems 366 9 Dispersion and Aggregation of Solids in Liquid Media by Surfactants 368 I. Interparticle Forces 368 A. Soft (Electrostatic) and van der Waals Forces: Derjaguin and Landau and Verwey and Overbeek (DLVO) Theory 369 1. Limitations of the DLVO Theory 374 B. Steric Forces 376 II. Role of the Surfactant in the Dispersion Process 378 A. Wetting of the Powder 378 B. Deaggregation of Fragmentation of Particle Clusters 379 C. Prevention of Reaggregation 379 III. Coagulation or Flocculation of Dispersed Solids by Surfactants 379 A. Neutralization or Reduction of the Potential at the Stern Layer of the Dispersed Particles 380 B. Bridging 381 C. Reversible Flocculation 381 IV. The Relation of Surfactant Chemical Structure to Dispersing Properties 382 A. Aqueous Dispersions 382 B. Nonaqueous Dispersions 387 C. Design of New Dispersants 387 References 388 Problems 390 10 Detergency and Its Modification by Surfactants 392 I. Mechanisms of the Cleaning Process 392 A. Removal of Soil from Substrate 393 1. Removal of Liquid Soil 394 2. Removal of Solid Soil 395 B. Suspension of the Soil in the Bath and Prevention of Redeposition 398 1. Solid Particulate Soil: Formation of Electrical and Steric Barriers; Soil Release Agents 398 2. Liquid Oily Soil 399 C. Skin Irritation (see Chapter 1, Section IIIB) 400 D. Dry Cleaning 401 II. Effect of Water Hardness 402 A. Builders 402 B. LSDAs 404 III. Fabric Softeners 405 IV. The Relation of the Chemical Structure of the Surfactant to its Detergency 407 A. Effect of Soil and Substrate 407 1. Oily Soil 407 2. Particulate Soil 409 3. Mixed Soil 410 B. Effect of the Hydrophobic Group of the Surfactant 411 C. Effect of the Hydrophilic Group of the Surfactant 412 D. Dry Cleaning 414 V. Biosurfactants and Enzymes in Detergent Formulations 415 VI. Nanodetergents (see Chapter 14, Section IIIF) 416 References 416 Problems 419 11 Molecular Interactions and Synergism in Mixtures of Two Surfactants 421 I. E valuation of Molecular Interaction Parameters 422 A. Notes on the Use of Equations 11.1–11.4 423 II. Effect of Chemical Structure and Molecular Environment on Molecular Interaction Parameters 427 III. Conditions for the Existence of Synergism 440 A. Synergism or Antagonism (Negative Synergism) in Surface or Interfacial Tension Reduction Efficiency 441 B. Synergism or Antagonism (Negative Synergism) in Mixed Micelle Formation in an Aqueous Medium 442 C. Synergism or Antagonism (Negative Synergism) in Surface or Interfacial Tension Reduction Effectiveness 445 D. Selection of Surfactant Pairs for Optimal Interfacial Properties 447 IV. The Relation between Synergism in Fundamental Surface Properties and Synergism in Surfactant Applications 448 References 453 Problems 456 12 Gemini Surfactants 458 I. Fundamental Properties 459 II. Interaction with Other Surfactants 463 III. Performance Properties 466 References 467 Problems 470 13 Surfactants in Biology 471 I. Biosurfactants and Their Application Areas 471 II. Cell Membranes 480 III. Surfactants in Cell Lysis 486 IV. Protein Denaturing and Electrophoresis with Surfactants 491 V. Pulmonary Surfactants 491 VI. Surfactants in Biotechnology 493 A. Mineral Engineering 494 B. Fermentation 495 C. Enzymatic Deinking 495 D. EOR and Oil Bioremediation 495 E. Enzyme Activity in Surfactant Media 496 F. Carbon Dioxide “Fixing” in Bioreactors 496 G. Soil Remediation 496 H. Effluent Purification 497 I. Surfactants in Horticulture 497 J. Vesicle Manipulation 497 K. Genetic Engineering and Gene Therapy 497 References 498 Problems 501 14 Surfactants in Nanotechnology 502 I. Special Effects of the Nanostate 503 II. Role of Surfactants in the Preparation of Nanostructures 503 A. Bottom-Up Methods 504 1. Surfactant Self-Assembly 504 2. Synthetic Processes 508 B. Top-Down Methods 517 III. Surfactants in Nanotechnology Applications 517 A. Nanomotors 517 B. Other Nanodevices 520 C. Drug Delivery 522 D. Nanostructural Architectural Control of Materials 522 E. Nanotubes 525 F. Nanodetergents 525 G. Surfactant Nanoassemblies in the Origin of Life 526 References 528 Problems 529 15 Surfactants and Molecular Modeling 531 I. Molecular Mechanics Methods 533 A. Parametrization from Experiments 534 B. Classes of FF Methods 534 II. Quantum Mechanical Methods 534 A. Application to the Electronic Problem 536 B. The Hartree Product (HP) Description 537 C. Minimal and Larger Basis Sets 538 D. Electron Correlation Method 539 E. Density Functional Theory (DFT) 540 III. Energy Minimization Procedure 540 IV. Computer Simulation Methods 541 V. Surfactant Systems 542 VI. Five Selected Systems 542 A. Aggregation in a Liquid (i) 542 B. Aggregation in a Liquid (ii) 543 C. Liquid–liquid and Liquid–Gas Interface 545 D. Solid–Liquid Interface 547 E. Solid–Liquid Interface and Aggregation in a Liquid 549 VII. Summary of Representative Modeling Studies 550 General References 568 Problems 568 Answers to Selected Problems 569 Index 576

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Book SynopsisFor researchers already familiar with biomass conversion technologies and for professionals in other fields, such as agriculture, food, and chemical industries, here is a comprehensive review of the emerging biorefinery industry.Table of ContentsPreface xvii Contributors xix 1 Integrated Biorefi nery for Sustainable Production of Fuels, Chemicals, and Polymers 1 Shang-Tian Yang and Mingrui Yu 2 The Outlook of Sugar and Starch Crops in Biorefinery 27 Klanarong Sriroth and Kuakoon Piyachomkwan 3 Novel and Traditional Oil Crops and Their Biorefinery Potential 47 Johann Vollmann and Margit Laimer 4 Energy Crops 61 Walter Zegada-Lizarazu and Andrea Monti 5 Microalgae as Feedstock for Biofuels and Biochemicals 79 Dong Wei 6 Pretreatment of Lignocellulosic Biomass 91 Tae Hyun Kim 7 Amylases: Characteristics, Sources, Production, and Applications 111 Hesham A. El-Enshasy, Yasser R. Abdel Fattah, and Nor Zalina Othman 8 Cellulases: Characteristics, Sources, Production, and Applications 131 Xiao-Zhou Zhang and Yi-Heng Percival Zhang 9 Xylanases: Characteristics, Sources, Production, and Applications 147 Evangelos Topakas, Gianni Panagiotou, and Paul Christakopoulos 10 Lignin-Degrading Enzymes: An Overview 167 Rajni Hatti-Kaul and Victor Ibrahim 11 Advances in Lignocellulosic Bioethanol 193 Reeta Rani Singhania, Parameswaran Binod, and Ashok Pandey 12 Biodiesel Properties and Alternative Feedstocks 205 Bryan R. Moser 13 Biological Production of Butanol and Higher Alcohols 235 Jingbo Zhao, Congcong Lu, Chih-Chin Chen, and Shang-Tian Yang 14 Advancement of Biohydrogen Production and Its Integration with Fuel Cell Technology 263 Jong-Hwan Shin and Tai Hyun Park 15 Biogas Technology 279 Günter Busch 16 Production of Lactic Acid and Polylactic Acid for Industrial Applications 293 Nuttha Thongchul 17 Production of Succinic Acid from Renewable Resources 317 Jongho Yi, Sol Choi, Min-Sun Han, Jeong Wook Lee, and Sang Yup Lee 18 Propionic Acid Fermentation 331 Zhongqiang Wang, Jianxin Sun, An Zhang, and Shang-Tian Yang 19 Anaerobic Fermentations for the Production of Acetic and Butyric Acids 351 Shang-Tian Yang, Mingrui Yu, Wei-Lun Chang, and I-Ching Tang 20 Production of Citric, Itaconic, Fumaric, and Malic Acids in Filamentous Fungal Fermentations 375 Kun Zhang, Baohua Zhang, and Shang-Tian Yang 21 Biotechnological Development for the Production of 1,3-Propanediol and 2,3-Butanediol 399 Youngsoon Um and Kyung-Duk Kim 22 Production of Polyhydroxyalkanoates in Biomass Refining 415 Jian Yu 23 Microbial Production of Poly-γ-Glutamic Acid 427 Zhinan Xu, Huili Zhang, Hao Chen, Feng Shi, Jin Huang, Shufang Wang, and Cunjiang Song 24 Refining Food Processing By-Products for Value-Added Functional Ingredients 441 Kequan Zhou, Yuting Zhou, and Y. Martin Lo About the Editors 449 Index 451

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Book SynopsisThis series provides the chemical physics field with a forum for critical, authoritative evaluations of advances in every area of the discipline. Topics included in this volume include recent developments in classical density functional theory, nonadiabatic chemical dynamics in intermediate and intense laser fields, and bilayers and their simulation.Table of ContentsRecent Developments in Classical Density Functional Theory (James F. Lutsko). Nondiabatic Chemical Dynamics in Intermediate and Intense Laser Fields (Kazuo Takatsuka and Takehiro Yonehara). Liquid Bilayer and Its Simulation (J. Stecki). Author Index. Subject Index.

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Book SynopsisIonic and Organometallic-Catalyzed Organosilane Reductions provides an up-to-date, comprehensive review of reductions with organosilanes. Both ionic and catalyst-mediated reaction types are included, with appropriate reference to reaction mechanisms where they have been elucidated. The text also provides a wide variety of organic functional group reductions by organosilicon hydrides, and includes a substantial discussion of asymmetric reductions. All known examples have been compiled in thirty-four easily scanned, comprehensive tables compiled from 809 original articles. This is a must-have reference book for all synthetic organic chemists working in academic and industrial laboratories.Trade Review"This is an impressive piece of work." (JACS, 2010) Table of ContentsForeword vii Preface ix Ionic And Organometallic-Catalyzed Organosilane Reductions 1Gerald L. Larson and James L. Fry Index 747

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Book SynopsisThe book provides an account of the totality of fragrance chemistry in one volume. It describes the chemistry of odorous materials, how and why they are produced in nature, how they are produced and used commercially, how they are analyzed and characterized, the chemistry of how we perceive them, and their role in our everyday lives.Trade Review“I cannot recommend this fascinating book highly enough.” (Simon Cotton, Chemistry & Industry, September 2014) “In conclusion: A comprehensive introduction to the world of odours, not only for chemists.” (review in German: Monika Paduch, Gefahrstoffe - Reinhaltung Luft, October 2014)Table of ContentsPreface vii Acknowledgments ix Introduction 1 1 Why Do We Have a Sense of Smell? 4 2 The Mechanism of Olfaction 32 3 Analysis and Characterisation of Odour 188 4 The Sense of Smell in Our Lives 209 5 The Scents of Nature 237 6 Manufacture of Fragrance Ingredients 296 7 The Design of New Fragrance Ingredients 357 8 The Relationship Between Molecular Structure and Odour 388 9 Intellectual Challenges in Fragrance Chemistry and the Future 420 Glossary 428 Index 437

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Book SynopsisThis book guides the reader through FDA regulation guidelines and outlines a comprehensive strategy for cost reduction in regulatory affairs and compliance. This book explains six strategies to cost-effectively comply with FDA regulations while maintaining product safety and improving public access through cost controls. It provides useful and practical guidance through industry case studies from pharmaceutical, biotech, and medical device industries.Table of ContentsPREFACE. Chapter 1. Controlling Regulatory Costs. Chapter 2. Clear Operation Definitions of Requirements. Chapter 3. Pre-Regulatory Audits. Chapter 4. Quality by Design. Chapter 5. Outsourcing. Chapter 6. Electronic Submissions. Chapter 7. EMEA/FDA Inspections. Chapter 8. Managing FDA Inspections. Chapter 9. Risk Assessment. Chapter 10. Cases. Chapter 11. Cost Containment Analysis. Chapter 12. Managing Regulation In Times of Chaos. Chapter 13. International Regulation. Chapter 14. Cost Contained Regulatory Compliance. Chapter 15. Future. BIBLIOGRAPHY. INDEX .

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Book SynopsisThe one-stop resource for rubber-clay nanocomposite information The first comprehensive, single-volume book to compile all the most important data on rubber-clay nanocomposites in one place, Rubber-Clay Nanocomposites: Science, Technology, and Applications reviews rubber-clay nanocomposites in an easy-to-reference format designed for R&D professionals. Including contributions from experts from North America, Europe, and Asia, the book explores the properties of compounds with rubber-clay nanocomposites, including their rheology, curing kinetics, mechanical properties, and many others. Rubber-clay nanocomposites are of growing interest to the scientific and technological community, and have been shown to improve rubber compound reinforcement and impermeability. These natural mineral fillers are of potential interest for large-scale applications and are already making an impact in several major fields. Packed with valuable information about the synthesis, Table of ContentsPREFACE xvii CONTRIBUTORS xxi SECTION I CLAYS FOR NANOCOMPOSITES 1 CLAYS AND CLAY MINERALS 3 1.1 What’s in a Name / 3 1.2 Multiscale Organization of Clay Minerals / 6 1.2.1 Dispersion Versus Aggregation / 6 1.2.2 Delamination/Exfoliation Versus Stacking / 6 1.3 Intimate Organization of the Layer / 8 1.3.1 Cationic and Neutral Clay Minerals / 8 1.3.2 Anionic Clay Minerals (O) / 21 1.4 Most Relevant Physicochemical Properties of Clay Mineral / 22 1.4.1 Surface Area and Porosity / 22 1.4.2 Chemical Landscape of the Clay Surfaces / 24 1.4.3 Cation (and Anion) Exchange Capacity / 24 1.4.4 Intercalation and Confinement in the Interlayer Space / 27 1.4.5 Swelling / 30 1.4.6 Rheology / 31 1.5 Availability of Natural Clays and Synthetic Clay Minerals / 33 1.6 Clays and (Modified) Clay Minerals as Fillers / 35 Acknowledgment / 37 References / 37 2 ORGANOPHILIC CLAY MINERALS 45 2.1 Organophilicity/Lipophilicity and the Hydrophilic/Lipophilic Balance (HLB) / 45 2.2 From Clays to Organoclays in Polymer Technology / 47 2.3 Methods of Organoclay Synthesis / 49 2.3.1 Cation Exchange from Solutions / 49 2.3.2 Solid-State Intercalation / 58 2.3.3 Grafting from Solution / 59 2.3.4 Direct Synthesis of Grafted Organoclays / 62 2.3.5 Postsynthesis Modifications of Organoclays: The “PCH” / 64 2.3.6 An Overview of Commercial Organoclays / 64 2.3.7 One-Pot CPN Formation / 66 2.4 Other Types of Clay Modifications for Clay-Based Nanomaterials / 66 2.4.1 Organo-Pillared Clays / 66 2.4.2 Plasma-Treated Clays / 69 2.5 Fine-Tuning of Organoclays Properties / 69 2.5.1 Maximizing the Dispersion of the Filler: Effect of Surfactant/CEC Ratio / 69 2.5.2 Improving Thermal Stability / 70 2.5.3 Chemical Treatments / 71 2.5.4 Physical Treatments (Freeze-Drying, Sonication, Microwave) / 71 2.6 Some Introductory Reflections on Organoclay Polymer Nanocomposites / 72 References / 75 3 INDUSTRIAL TREATMENTS AND MODIFICATION OF CLAY MINERALS 87 3.1 Bentonite: From Mine to Plant / 87 3.1.1 A Largely Diffused Clay / 87 3.1.2 Geological Occurrence / 89 3.1.3 Mining / 89 3.2 Processing of Bentonite / 90 3.2.1 Modification of Bentonite Properties / 90 3.2.2 Processing Technologies / 91 3.3 Purification of Clay / 93 3.3.1 Influence of Clay Concentration / 94 3.3.2 Influence of Swelling Time / 94 3.3.3 Influence of Temperature / 95 3.4 Reaction of Clay with Organic Substances / 97 3.5 Particle Size Modification / 99 References / 99 4 ALKYLAMMONIUM CHAINS ON LAYERED CLAY MINERAL SURFACES 101 4.1 Structure and Dynamics / 101 4.1.1 Packing Density and Self-Assembly / 102 4.1.2 Dynamics and Diffusion at the Clay–Surfactant Interface / 110 4.1.3 Utility of Molecular Simulation to Obtain Molecular-Level Insight / 111 4.2 Thermal Properties / 111 4.2.1 Reversible Melting Transitions of Alkyl Chains in the Interlayer / 111 4.2.2 Solvent Evaporation and Thermal Elimination of Alkyl Surfactants / 113 4.3 Layer Separation and Miscibility with Polymers / 115 4.3.1 Thermodynamics Model for Exfoliation in Polymer Matrices / 115 4.3.2 Cleavage Energy / 116 4.3.3 Surface Energy / 121 4.4 Mechanical Properties of Clay Minerals / 121 References / 123 5 CHEMISTRY OF RUBBER–ORGANOCLAY NANOCOMPOSITES 127 5.1 Introduction / 127 5.2 Organic Cation Decomposition in Salts, Organoclays and Polymer Nanocomposites / 128 5.2.1 Experimental Techniques / 128 5.2.2 Decomposition of Organoclays Versus Precursor Organic Cation Salts / 133 5.3 Mechanism of Thermal Decomposition of Organoclays / 135 5.4 Role of Organic Cations in Organoclays as Rubber Vulcanization Activators / 137 References / 141 SECTION II PREPARATION AND CHARACTERIZATION OF RUBBER–CLAY NANOCOMPOSITES 6 PROCESSING METHODS FOR THE PREPARATION OF RUBBER–CLAY NANOCOMPOSITES 147 6.1 Introduction / 147 6.2 Latex Compounding Method / 148 6.2.1 Mechanism / 148 6.2.2 Influencing Factors / 149 6.3 Melt Compounding / 157 6.3.1 Mechanism / 157 6.3.2 Influencing Factors / 160 6.4 Solution Intercalation and In Situ Polymerization Intercalation / 170 6.5 Summary and Prospect / 170 Acknowledgment / 171 References / 171 7 MORPHOLOGY OF RUBBER–CLAY NANOCOMPOSITES 181 7.1 Introduction / 181 7.1.1 Focus, Objective and Structure of Chapter 7 / 181 7.1.2 X-Ray Diffraction Analysis for the Investigation of RCN / 182 7.2 Background for the Review of RCN Morphology / 182 7.2.1 Cationic Clays Used for the Preparation of Rubber Nanocomposites / 182 7.2.2 Multiscale Organization of Layered Clays / 184 7.2.3 Clay Distribution and Dispersion / 184 7.2.4 Clay Modification: Intercalation of Low Molecular Mass Substances / 184 7.2.5 Types of Polymer–Clay Composites / 184 7.2.6 Specific Literature on RCN / 186 7.3 Rubber–Clay Nanocomposites with Pristine Clays / 186 7.3.1 Rubber Nanocomposites with Cationic Clays / 187 7.3.2 In a Nutshell / 187 7.3.3 Distribution and Dispersion of a Pristine Clay in a Rubber Matrix / 190 7.3.4 Organization of Aggregated Pristine Clays / 194 7.4 Rubber–Clay Nanocomposites with Clays Modified with Primary Alkenylamines / 197 7.4.1 In a Nutshell / 197 7.4.2 Composites with Montmorillonite and Bentonite / 198 7.4.3 Composites with Fluorohectorite Modified with a Primary Alkenylamine / 202 7.5 Rubber–Clay Nanocomposites with Clays Modified with an Ammonium Cation Having three Methyls and One Long-Chain Alkenyl Substituents / 206 7.5.1 In a Nutshell / 206 7.5.2 Composites with Montmorillonite and Bentonite / 207 7.6 Rubber–Clay Nanocomposites with Montmorillonite Modified with Two Substituents Larger Than Methyl / 212 7.6.1 In a Nutshell / 212 7.6.2 Hydrogenated Tallow and Benzyl Groups as Ammonium Cation Substituents / 213 7.6.3 Hydrogenated Tallow and Ethylhexyl Groups as Ammonium Cation Substituents / 213 7.6.4 Other Long- and Short-Chain Alkenyl Groups as Ammonium Cation Substituents / 215 7.7 Rubber Composites with Montmorillonite Modified with an Ammonium Cation Containing a Polar Group / 215 7.7.1 In a Nutshell / 217 7.7.2 Composites with Diene Rubbers / 217 7.8 Rubber Nanocomposites with Montmorillonite Modified with an Ammonium Cation Containing Two Long-Chain Alkenyl Substituents / 219 7.8.1 In a Nutshell / 220 7.8.2 Composites with Two Talloyl Groups as Ammonium Cation Substituents / 220 7.9 Proposed Mechanisms for the Formation of Rubber–Clay Nanocomposites / 228 7.9.1 Two Mechanisms for the Formation of an Exfoliated Clay / 228 7.9.2 Two Mechanisms for the Formation of an Intercalated Organoclay / 228 7.9.3 Intercalation of Polymer Chains in the Interlayer Space / 229 7.9.4 Intercalation of Low Molecular Mass Substances in the Interlayer Space / 230 Abbreviations / 232 Acknowledgment / 233 References / 233 8 RHEOLOGY OF RUBBER–CLAY NANOCOMPOSITES 241 8.1 Introduction / 241 8.2 Rheological Behavior of Rubber–Clay Nanocomposites / 242 8.2.1 Natural Rubber (NR), Epoxidized Natural Rubber (ENR) and Polyisoprene Rubber (IR)–Clay Nanocomposites / 243 8.2.2 Styrene–Butadiene Rubber (SBR)–Clay Nanocomposites / 246 8.2.3 Polybutadiene Rubber (BR)–Clay Nanocomposites / 247 8.2.4 Acrylonitrile Butadiene Rubber (NBR)–Clay Nanocomposites / 250 8.2.5 Ethylene Propylene Rubber–Clay Nanocomposites / 253 8.2.6 Fluoroelastomer–Clay Nanocomposites / 254 8.2.7 Poly(isobutylene-co-para-methylstyrene) (BIMS) Rubber–Clay Nanocomposites / 257 8.2.8 Poly(ethylene-co-vinylacetate) (EVA) Rubber–Clay Nanocomposites / 257 8.2.9 Polyepichlorohydrin Rubber–Clay Nanocomposites / 259 8.2.10 Thermoplastic Polyurethane (TPU)–Clay Nanocomposites / 261 8.2.11 Styrene–Ethylene–Butylene–Styrene (SEBS) Block Copolymer–Clay Nanocomposites / 262 8.3 General Remarks on Rheology of Rubber–Clay Nanocomposites / 263 8.4 Overview of Rheological Theories of Polymer–Clay Nanocomposites / 269 8.5 Conclusion and Outlook / 270 References / 271 9 VULCANIZATION CHARACTERISTICS AND CURING KINETIC OF RUBBER–ORGANOCLAY NANOCOMPOSITES 275 9.1 Introduction / 275 9.2 Vulcanization Reaction / 276 9.3 Rubber Cross-Linking Systems / 278 9.3.1 Sulfur Vulcanization / 278 9.3.2 Peroxide Vulcanization / 282 9.4 The Role of Organoclay on Vulcanization Reaction / 283 9.4.1 Influence of Organoclay Structural Characteristics on Rubber Vulcanization / 288 9.5 Vulcanization Kinetics of Rubber–Organoclay Nanocomposites / 290 9.6 Conclusions / 297 References / 298 10 MECHANICAL AND FRACTURE MECHANICS PROPERTIES OF RUBBER COMPOSITIONS WITH REINFORCING COMPONENTS 305 10.1 Introduction / 305 10.2 Testing of Viscoelastic and Mechanical Properties of Reinforced Elastomeric Materials / 307 10.2.1 Dynamic–Mechanical Analysis / 307 10.2.2 Tensile Testing / 310 10.2.3 Assessment of Toughness Behavior under Impact-Like Loading Conditions / 313 10.2.4 Hardness Testing / 315 10.2.5 Special Methods / 316 10.3 Characterization of the Fracture Behavior of Elastomers / 319 10.3.1 Fracture Mechanics Concepts / 319 10.3.2 Experimental Methods / 321 10.4 Mechanism of Reinforcement in Rubber–Clay Composites / 328 10.5 Theories and Modeling of Reinforcement / 333 Acknowledgment / 336 References / 336 11 PERMEABILITY OF RUBBER COMPOSITIONS CONTAINING CLAY 343 11.1 Introduction / 343 11.1.1 Butyl Rubbers as Nanocomposite Base Elastomers / 343 11.1.2 Measurement of Tire Innerliner Compound Permeability / 345 11.1.3 Further Improvement in Tire Permeability / 346 11.2 Nanocomposites / 346 11.3 Preparation of Elastomer Nanocomposites / 352 11.4 Temperature and Compound Permeability / 352 11.5 Vulcanization of Nanocomposite Compounds and Permeability / 356 11.6 Thermodynamics and BIMSM Montmorillonite Nanocomposites / 358 11.7 Nanocomposites and Tire Performance / 362 11.8 Summary / 364 References / 364 SECTION III COMPOUNDS WITH RUBBER–CLAY NANOCOMPOSITES 12 RUBBER–CLAY NANOCOMPOSITES BASED ON APOLAR DIENE RUBBER 369 12.1 Introduction / 369 12.2 Preparation Methods / 371 12.2.1 Latex / 371 12.2.2 Solution / 373 12.2.3 Melt Blending / 374 12.3 Cure Characteristics / 377 12.4 Clay Dispersion / 379 12.4.1 Detection / 380 12.4.2 Characterization / 383 12.5 Properties / 387 12.5.1 Mechanical (Dynamic–Mechanical) / 387 12.5.2 Friction/Wear/Abrasion / 392 12.5.3 Barrier / 393 12.5.4 Fire Resistance / 396 12.5.5 Others / 397 12.6 Applications and Future Trends / 398 Acknowledgment / 399 References / 399 13 RUBBER–CLAY NANOCOMPOSITES BASED ON NITRILE RUBBER 409 13.1 Introduction / 409 13.2 Preparation Methods and Clay Dispersion / 410 13.2.1 Solution / 410 13.2.2 Latex / 411 13.2.3 Melt Blending / 412 13.3 Cure Characteristics / 414 13.4 Properties / 416 13.4.1 Mechanical (Dynamic–Mechanical) / 416 13.4.2 Friction/Wear / 421 13.4.3 Barrier / 423 13.4.4 Fire Resistance / 424 13.4.5 Others / 425 13.5 Outlook / 425 Acknowledgment / 426 References / 426 xii CONTENTS FOR SCREEN VIEWING IN DART ONLY 14 RUBBER–CLAY NANOCOMPOSITES BASED ON BUTYL AND HALOBUTYL RUBBERS 431 14.1 Introduction / 431 14.1.1 Butyl Rubber: Key Properties and Applications / 431 14.1.2 Butyl Rubber–Clay Nanocomposites / 433 14.2 Types of Clays Useful in Butyl Rubber–Clay Nanocomposites / 435 14.2.1 Montmorillonite Clays / 435 14.2.2 Hydrotalcite Clays / 435 14.2.3 High Aspect Ratio Talc Fillers / 436 14.2.4 Other Clays / 437 14.3 Compatibilizer Systems for Butyl Rubber–Clay Nanocomposites / 438 14.3.1 Surfactants and Swelling Agents / 439 14.3.2 Butyl Rubber Ionomers / 439 14.3.3 Maleic Anhydride-Grafted Polymers / 443 14.3.4 Low Molecular Weight Polymers and Resins / 444 14.4 Methods of Preparation of Butyl Rubber–Clay Nanocomposites / 444 14.4.1 Melt Method / 445 14.4.2 Solution Method / 445 14.4.3 Latex Method / 447 14.4.4 In Situ Polymerization / 448 14.5 Properties and Applications of Butyl Rubber–Clay Nanocomposites / 449 14.5.1 Air Barrier Properties / 449 14.5.2 Reinforcement Properties / 452 14.5.3 Vulcanization Properties / 454 14.5.4 Adhesion Properties / 456 14.5.5 Other Properties / 457 14.6 Conclusions / 457 References / 458 15 RUBBER–CLAY NANOCOMPOSITES BASED ON OLEFINIC RUBBERS (EPM, EPDM) 465 15.1 Introduction / 465 15.2 Types of Clay Minerals Useful in EPM–, EPDM–Clay Nanocomposites / 466 15.3 Compatibilizer Systems for Olefinic Rubber–Clay Nanocomposites / 467 15.4 Preparation of EPDM–Clay Nanocomposites by an In Situ Intercalation Method / 469 15.5 Characteristics of EPDM–Clay Nanocomposites / 473 15.5.1 Gas Barrier Properties of EPDM–Clay Nanocomposites / 473 15.5.2 Rheological Properties of EPDM–Clay Nanocomposites / 474 15.5.3 Stability of EPDM–Clay Nanocomposites / 475 15.5.4 Swelling Properties of EPDM–Clay Nanocomposites / 475 15.5.5 Mechanical Properties of EPDM–Clay Nanocomposites / 476 15.6 Preparation and Characteristics of EPM–Clay Nanocomposites / 479 15.6.1 Tensile Properties of EPM–CNs / 480 15.6.2 Temperature Dependence of Dynamic Storage Moduli of EPM–CNs / 481 15.6.3 Creep Properties of EPM–CNs / 482 15.6.4 Swelling Properties of EPM–CNs / 483 15.7 Conclusions / 486 References / 486 16 RUBBER–CLAY NANOCOMPOSITES BASED ON THERMOPLASTIC ELASTOMERS 489 16.1 Introduction / 489 16.2 Selection of Materials / 491 16.2.1 Polymer Resin / 491 16.2.2 Nanoparticles / 493 16.3 Experimental / 493 16.3.1 Processing of Thermoplastic Elastomer Nanocomposites / 493 16.3.2 Morphological Characterization / 494 16.3.3 Thermal Properties Characterization / 495 16.3.4 Flammability Properties Characterization / 495 16.3.5 Thermophysical Properties Characterization / 496 16.4 Numerical / 497 16.4.1 Modeling of Decomposition Kinetics / 497 16.5 Discussion of Results / 501 16.5.1 Nanoparticle Dispersion / 501 16.5.2 Thermal Properties / 503 16.5.3 Flammability Properties / 507 16.5.4 Microstructures of Posttest Specimens / 511 16.5.5 Thermophysical Properties / 512 16.5.6 Kinetic Parameters / 513 16.6 Summary and Conclusions / 516 16.7 Nomenclature / 517 Acknowledgments / 518 References / 518 SECTION IV APPLICATIONS OF RUBBER–CLAY NANOCOMPOSITES 17 AUTOMOTIVE APPLICATIONS OF RUBBER–CLAY NANOCOMPOSITES 525 17.1 Introduction / 525 17.2 Automotive Application of Rubber / 526 17.2.1 Automotive Hose / 527 17.2.2 Automotive Seals / 528 17.2.3 Automotive Belts / 529 17.2.4 Automotive Tubing / 529 17.2.5 Door Seal and Window Channels / 529 17.2.6 Diaphragms and Rubber Boots / 529 17.2.7 Tire, Tube and Flap / 529 17.2.8 Other Miscellaneous Rubber Parts / 531 17.3 Prime Requirement of Different Elastomeric Auto Components from Application Point of View / 531 17.4 Elastomeric Nanocomposites and Rubber Industry / 531 17.5 Superiority of Clay/Clay Mineral in Comparison to Other Nanofillers / 534 17.6 Organo-Modified Clay/Clay Minerals / 534 17.7 Scope of Application of Elastomeric Nanocomposites in Automotive Industry / 534 17.7.1 Lighter Weight and Balanced Mechanical Property / 535 17.7.2 Barrier Property or Air Retention Property / 538 17.7.3 Aging and Ozone Resistance / 539 17.7.4 Solvent Resistance / 541 17.7.5 Better Processability / 542 17.7.6 Elastomeric Polyurethane–Organoclay Nanocomposites / 544 17.7.7 Use of Organoclay Nanocomposites in Tire / 545 17.8 Disadvantages of Use of Organoclay Elastomeric Nanocomposites in Automotive Industry / 548 17.9 Conclusion / 549 Acknowledgment / 550 References / 550 18 NONAUTOMOTIVE APPLICATIONS OF RUBBER–CLAY NANOCOMPOSITES 557 18.1 Water-Based Nanocomposites / 557 18.1.1 Barrier Properties / 557 18.1.2 Comparison with Thermally Processed Elastomers / 566 18.2 Applications / 566 18.2.1 Sports Balls and Other Pneumatic Applications / 566 18.2.2 Breakthrough Time Applications / 571 References / 573 INDEX 575

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Book SynopsisThis is a Student Solutions Manual to accompany Physical Chemistry, 5th Edition. Ever since Physical Chemistry was first published in 1913, it has remained a highly effective and relevant learning tool thanks to the efforts of physical chemists from all over the world.Table of ContentsPART ONE THERMODYNAMICS 1. Zeroth Law of Thermodynamics and Equations of State 3 2. First Law of Thermodynamics 31 3. Second and Third Laws of Thermodynamics 74 4. Fundamental Equations of Thermodynamics 102 5. Chemical Equilibrium 132 6. Phase Equilibrium 7. Electrochemical Equilibrium 218 Thermodynamics of Biochemical Reactions PART TWO QUANTUM CHEMISTRY 9. Quantum Theory 295 10. Atomic Structure 348 11. Molecular Electronic Structure 396 12. Symmetry 437 13. Rotational and Vibrational Spectroscopy 458 14. Electronic Spectroscopy of Molecules 502 15. Magnetic Resonance Spectroscopy 537 16. Statistical Mechanics 568 PART THREE KINETICS 17. Kinetic Theory of Gases 613 18. Experimental Kinetics and Gas Reactions 641 19. Chemical Dynamics and Photochemistry 686 20. Kinetics in the Liquid Phase 724 PART FOUR MACROSCOPIC AND MICROSCOPIC STRUCTURES 21. Macromolecules 763 22. Electric and Magnetic Properties of Molecules 786 23. Solid-State Chemistry 803 24. Surface Dynamics 840 APPENDIX A. Physical Quantities and Units 863 B. Values of Physical Constants 867 C. Tables of Physical Chemical Data 868 D. Mathematical Relations 884 E. Greek Alphabet 897 F. Useful Information on the Web 898 G. Symbols for Physical Quantities and Their SI Units 899 H. Answers to Exercises INDEX 933

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Book SynopsisIntegrates solid-phase organic synthesis with palladium chemistry The Wiley Series on Solid-Phase Organic Syntheses keeps researchers current with major accomplishments in solid-phase organic synthesis, providing full experimental details. Following the validated, tested, and proven experimental procedures, readers can easily perform a broad range of complex syntheses needed for their own experiments and industrial applications. The series is conveniently organized into themed volumes according to the specific type of synthesis. This second volume in the series focuses on palladium chemistry in solid-phase synthesis, exploring palladium catalysts and reactions, procedures for preparation and utilization, ligands, and linker reactions. The first part of the volume offers a comprehensive overview of the field. Next, the chapters are organized into three parts: Part Two: Palladium-Mediated Solid-Phase Organic Syntheses Part Three: Immobilized Trade Review“Overall, though, the adoption of an Organic Synthesesstyle is an excellent idea and works very well. Along with other related volumes, this collection serves to demystify polymer-supported methods for palladium-catalysed reactions and provides a very useful collection of clear methods. It will certainly be of interest and use to those new to the fi eld.” (Platinum Metals Review, 1 July 2013) Table of ContentsContributors ix Preface xiii Abbreviations xv PART I INTRODUCTION 1 1. An Introduction to Solid-Phase Palladium Chemistry 3 Carmen Gil PART II PALLADIUM-MEDIATED SPOS 23 2. Pd-Catalyzed Solid-Phase Decoration of the 2(1H)-Pyrazinone Scaffold 25 Vaibhav P. Mehta and Erik V. Van der Eycken 3. One-Step Palladium- and Phenylsilane-Activated Amidation of Solid-Supported Ally Esters 35 Zheming Ruan, Katy Van Kirk, Christopher B. Cooper, R. Michael Lawrence, and Michael Poss 4. Solid-Phase Reactions of Polymer-Bound Arenesulfonates with Aryl Grignard Reagents 41 Kwangyong Park and Chul-Hee Cho 5. Fluorous Synthesis of 3-Aminoimidazo[1,2-a]-Pyridine/Pyrazine Library 51 Wei Zhang and Yimin Lu 6. Resin-to-Resin Transfer Reactions (RRTR) via Sonogashira Coupling 59 Judit Tulla-Puche, Rita S. Majerle, Fernando Albericio, and George Barany PART III IMMOBILIZED CATALYSTS AND LIGANDS 67 7. Polymer-supported Palladium Catalysts for Suzuki and Heck Reactions 69 Peter Styring 8. Solid-Phase Catalytic Activity of a Polymer-Supported Palladium Complex 79 Maria M. Dell’Anna, Piero Mastrorilli, and Cosimo F. Nobile 9. Polyaniline-immobilized Palladium for Suzuki-Miyaura Coupling Reaction in Water 87 Moumita Roy, Pravin R. Likhar, and M. Lakshmi Kantam 10. Synthesis of Polymer-Supported Aryldicyclohexylphosphine for an Efficient Recycling in Suzuki-Miyaura Reactions 91 Katarzyna Glegola and Eric Framery 11. C–C or C–N Reactions Catalyzed by Diadamanthylphosphine Palladium-Based Catalyst Supported on Dab-Dendrimers 97 Karine Heuzé, Agnés Fougeret, Julietta Lemo, and Daniel Rosario-Amorin PART IV PALLADIUM-MEDIATED MULTIFUNCTIONAL CLEAVAGE 105 12. Solid-Phase Reactions of Resin-Supported Boronic Acids 107 François Carreaux, Bertrand Carboni, Herve Deleuze, and Christelle Pourbaix-L’Ebraly 13. A Simple Diversity Linker Strategy Using Immobilized Enol Phosphonates as Electrophiles for Suzuki-Miyaura Reactions 119 Tom M. Woods 14. Heck Cleavage of Resin-bound Triazenes 129 Sylvia Vanderheiden, Nicole Jung, and Stefan Bräse 15. Pd-Mediated Cleavage from Tetrafluoroarylsulfonate Linker Units 139 Andrew N. Cammidge and Zainab Ngaini 16. Palladium-Catalyzed Solid-Phase Synthesis of Allylic Amines 145 Richard C. D. Brown and Martin L. Fisher 17. Palladium-Catalyzed Solid-Phase Synthesis of 4-Methylene Pyrrolidines 157 Lynda J. Brown, Richard C. D. Brown, and Martin L. Fisher Index 167

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Book SynopsisThe definitive book on the neutralization of recombinant biopharmaceuticals Recombinant biopharmaceuticals are an important tool for treating a range of illnesses; however, their efficacy can be severely impaired by their immunogenicity. When introduced into the body, these pharmaceuticals can cause the immune system to produce anti-drug antibodies (ADAs) that neutralize their effects. The first and only book to cover neutralization in connection with biopharmaceuticals and the measurement and application of neutralizing antibodies in modern medicine at any real length, Detection and Quantification of Antibodies to Biopharmaceuticals: Practical and Applied Considerations offers a comprehensive and in-depth look at all the principal aspects of the detection and quantification of antibodies that are essential to understanding and responding to the challenges they present. Bringing together a large-scale review of neutralization and biopharmaceuticals and the abiliTable of ContentsINTRODUCTION: A PERSPECTIVE ix Michael G. Tovey CONTRIBUTORS xxi PART I RISK-BASED STRATEGIES 1 1 Principles of Risk Assessment and Monitoring of Antibody Responses to Biopharmaceuticals 3 Eugen Koren, Erik Foehr, and Charles A. O’Neill PART II REGULATORY REQUIREMENTS 13 2 Immunogenicity of Therapeutic Proteins: A Regulatory Perspective 15 Susan Kirshner 3 Guidance on Immunogenicity Assessment of Biologically Derived Therapeutic Proteins: A European Perspective 37 Meenu Wadhwa and Robin Thorpe 4 Japanese Regulatory Perspective on Immunogenicity 57 Takao Hayakawa and Akiko Ishii-Watabe PART III PRINCIPAL TECHNOLOGIES EMPLOYED FOR THE QUANTIFICATION OF ANTI-DRUG ANTIBODIES 81 5 Enzyme Immunoassays and Radioimmunoassays for Quantification of Anti-TNF Biopharmaceuticals and Anti-Drug Antibodies 83 Klaus Bendtzen and Morten Svenson 6 Confirmatory Immunogenicity Assays 103 Eric Wakshull and Daniel Coleman 7 The Use of Pharmacodynamics as a Surrogate Marker for the Detection of Anti-Drug Neutralizing Antibodies 119 Florian Deisenhammer 8 Cell-Based Assays for the Detection of Neutralizing Antibodies to Interferon Beta (IFN-β) and Tumor Necrosis Factor Alpha (TNF-α) Inhibitors 133 Anthony Meager 9 Detection of Neutralizing Antibodies against Interferon Beta by Real-Time RT-PCR 157 Francesca Gilli and Antonio Bertolotto 10 Competitive Ligand-Binding Assays for the Detection of Neutralizing Antibodies 175 Bonnie W. Wu, George R. Gunn III, and Gopi Shankar 11 The Use of Surface Plasmon Resonance for the Detection and Characterization of Antibodies 193 Steven J. Swanson and Daniel Mytych 12 Hypersensitivity Reactions to Biopharmaceuticals: Detection and Quantification of Drug-Specific IgE Antibodies 211 Jörgen Dahlström and Lennart Venemalm PART IV ASSAY STANDARDIZATION AND VALIDATION 233 13 Standardization and Validation of Immunoassays 235 Daniel Kramer 14 Standardization and Validation of Cell-Based Assays for the Detection of Neutralizing Anti-Drug Antibodies 243 Deborah Finco-Kent and Amy Grenham 15 Standardization of Neutralizing Antibody Unitage by Bioassay Design: Constant Antigen and Constant Antibody Methodology 269 Sidney E. Grossberg, Yoshimi Kawade, and Leslie D. Grossberg PART V STATISTICAL CONSIDERATIONS 287 16 Cut Points and Performance Characteristics for Anti-Drug Antibody Assays 289 Viswanath Devanarayan and Michael G. Tovey 17 Dilutional Linearity for Neutralizing Antibody Assays 309 David Lansky and Carrie Wager PART VI ADAPTATION OF ANTI-DRUG ANTIBODY ASSAYS TO CHALLENGING CONDITIONS 319 18 Detection of Antibodies to Biopharmaceuticals in the Presence of High Levels of Circulating Drug 321 Arno Kromminga and Michael G. Tovey 19 Antibody Assays in Animal Research 331 Vera Brinks, Francesca Gilli, Melody Sauerborn, and Huub Schellekens 20 Immunogenicity of Microbial Digestive Enzymes for Oral Replacement Therapy in Pancreatic Exocrine Insufficiency 343 Claudia Berger and Uwe Niesner PART VII NOVEL TECHNOLOGIES FOR THE QUANTIFICATION OF NEUTRALIZING ANTIBODIES 369 21 Measurement of Biologically Active Drug as an Approach to Detection of Anti-Drug Neutralizing Antibodies 371 Yao Zhuang and Shalini Gupta 22 A Novel One-Step Cell-Based Assay for Quantification of Neutralizing Antibodies to Biopharmaceuticals 383 Christophe Lallemand and Michael G. Tovey INDEX 399

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Book SynopsisThis book reviews advances in understanding phosphodiesterases within the central nervous system and theirtherapeutic applications. A range of expert authors from both academia and industry describe these, then focus on the areas of greatest scientific and medical interest to provide more detailed coverage. Therapeutic and drug discovery applications are covered for diseasesincluding Alzheimer''s, Parkinson''s, schizophrenia, erectile dysfunction, and spinal cord injuries. There is also a chapter on drug discovery tools such as in vitro assays and X-ray structures for medicinal chemistry studies.Table of ContentsPREFACE vii CONTRIBUTORS ix 1 PHOSPHODIESTERASES AND CYCLIC NUCLEOTIDE SIGNALING IN THE CNS 1 Marco Conti and Wito Richter 2 PUTTING TOGETHER THE PIECES OF PHOSPHODIESTERASE DISTRIBUTION PATTERNS IN THE BRAIN: A JIGSAW PUZZLE OF CYCLIC NUCLEOTIDE REGULATION 47 Michy P. Kelly 3 COMPARTMENTALIZATION AND REGULATION OF CYCLIC NUCLEOTIDE SIGNALING IN THE CNS 59 Manuela Zaccolo and Alessandra Stangherlin 4 PHARMACOLOGICAL MANIPULATION OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASE SIGNALING FOR THE TREATMENT OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS IN THE BRAIN 77 Frank S. Menniti, Niels Plath, Niels Svenstrup, and Christopher J. Schmidt 5 RECENT RESULTS IN PHOSPHODIESTERASE INHIBITOR DEVELOPMENT AND CNS APPLICATIONS 115 David P. Rotella 6 CRYSTAL STRUCTURES OF PHOSPHODIESTERASES AND IMPLICATION ON DISCOVERY OF INHIBITORS 145 Hengming Ke, Huanchen Wang, Mengchun Ye, and Yingchun Huang 7 INHIBITION OF CYCLIC NUCLEOTIDE PHOSPHODIESTERASES TO REGULATE MEMORY 171 Han-Ting Zhang, Ying Xu, and James O’Donnell 8 EMERGING ROLE FOR PDE4 IN NEUROPSYCHIATRIC DISORDERS: TRANSLATING ADVANCES FROM GENETIC STUDIES INTO RELEVANT THERAPEUTIC STRATEGIES 211 Sandra P. Zoubovsky, Nicholas J. Brandon, and Akira Sawa 9 BEYOND ERECTILE DYSFUNCTION: UNDERSTANDING PDE5 ACTIVITY IN THE CENTRAL NERVOUS SYSTEM 223 Eva P.P. Bollen, Kris Rutten, Olga A.H. Reneerkens, Harry M.W. Steinbusch, and Jos Prickaerts 10 MOLECULAR AND CELLULAR UNDERSTANDING OF PDE10A: A DUAL-SUBSTRATE PHOSPHODIESTERASE WITH THERAPEUTIC POTENTIAL TO MODULATE BASAL GANGLIA FUNCTION 247 Erik I. Charych and Nicholas J. Brandon 11 ROLE OF CYCLIC NUCLEOTIDE SIGNALING AND PHOSPHODIESTERASE ACTIVATION IN THE MODULATION OF ELECTROPHYSIOLOGICAL ACTIVITY OF CENTRAL NEURONS 269 Sarah Threlfell and Anthony R. West 12 THE ROLE OF PHOSPHODIESTERASES IN DOPAMINE SYSTEMS GOVERNING MOTIVATED BEHAVIOR 303 Gretchen L. Snyder, Joseph P. Hendrick, and Akinori Nishi 13 INHIBITION OF PHOSPHODIESTERASES AS A STRATEGY FOR TREATMENT OF SPINAL CORD INJURY 353 Elena Nikulina and Marie T. Filbin INDEX 375

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Book Synopsis Heterocyclic chemistry is of prime importance as a sub-discipline of Organic Chemistry, as millions of heterocyclic compounds are known with more being synthesized regularly Introduces students to heterocyclic chemistry and synthesis with practical examples of applied methodology Emphasizes natural product and pharmaceutical applications Provides graduate students and researchers in the pharmaceutical and related sciences with a background in the field Includes problem sets with several chapters Trade Review"Provides graduate students and researchers in the pharmaceutical and related sciences with a background in the field." (Trading Charts, 22 February 2011)Table of ContentsPREFACE. ACKNOWLEDGMENT. Chapter 1 THE SCOPE OF THE FIELD OF HETEROCYCLIC CHEMISTRY. References. Appendix. Chapter 2 COMMON RING SYSTEMS AND THE NAMING OF HETEROCYCLIC COMPOUNDS. 2.1. General. 2.2. Naming Simple Monocyclic Compounds. 2.3. Handling the "Extra Hydrogen". 2.4. Substituted Monocyclic Compounds. 2.5. Rings With More Than One Heteroatom. 2.6. Bicyclic Compounds. 2.7. Multicyclic Systems. 2.8. The Replacement Nomenclature System. 2.9. Saturated Bridged Ring Systems. References. Review Exercises. Chapter 3 NATURE AS A SOURCE OF HETEROCYCLIC COMPOUNDS. 3.1. General. 3.2. Naturally Occurring Nitrogen Heterocyclic Compounds. 3.3. Oxygen Compounds. 3.4. Sulfur and Phosphorus Heterocyclic Compounds in Nature. References. Chapter 4 PRINCIPLES OF SYNTHESIS OF AROMATIC HETEROCYCLES BY INTRAMOLECULAR CYCLIZATION. 4.1. General. 4.2. Some of the Classic Synthetic Methods. 4.3. Cyclizations Involving Metallic Complexes as Catalysts. 4.4. Cyclizations with Radical Intermediates. 4.5. Cyclizations by Intramolecular Wittig Reactions. 4.6. Synthesis of Heterocycles by the Alkene Metathesis Reaction. References. Review Exercises. Chapter 5 SYNTHESIS OF HETEROCYCLIC SYSTEMS BY CYCLOADDITION REACTIONS. 5.1. The Diels–Alder Reaction. 5.2. Dipolar Cycloadditions. 5.3. [2 + 2] Cycloadditions. References. Review Exercises. Chapter 6 AROMATICITY AND OTHER SPECIAL PROPERTIES OF HETEROCYCLES: PI-DEFICIENT RING SYSTEMS. 6.1. General. 6.2. Review of the Aromaticity of Benzene. 6.3. Pi-Deficient Aromatic Heterocycles. References. Review Exercises. Chapter 7 AROMATICITY AND OTHER SPECIAL PROPERTIES OF HETEROCYCLES: PI-EXCESSIVE RING SYSTEMS AND MESOIONIC RING SYSTEMS. 7.1. Pi-Excessive Aromatic Heterocycles. 7.2. Mesoionic Heterocycles. References. Review Exercises. Chapter 8 THE IMPORTANCE OF HETEROCYCLES IN MEDICINE. 8.1. General. 8.2. Historical. 8.3. Pyridines. 8.4. Indoles. 8.5. Quinolines. 8.6. Azepines. 8.7. Pyrimidines. 8.8. Concluding Remarks. References. Chapter 9 SYNTHETIC METHODS FOR SOME PROMINENT HETEROCYCLIC FAMILIES: EXAMPLES OF PHARMACEUTICALS SYNTHESIS. 9.1. Scope of the Chapter. 9.2. Pyrroles. 9.3. Furans. 9.4. Thiophenes. 9.5. 1,3-Thiazoles. 9.6. 1,3-Oxazoles. 9.7. Imidazoles. 9.8. Pyrazoles. 9.9. 1,2,4-Triazoles. 9.10. Tetrazoles. 9.11. 1,3,4-Thiadiazoles and other 5-Membered Systems. 9.12. Indole. 9.13. Pyridines. 9.14. Quinolines and Isoquinolines. 9.15. Benzodiazepines. 9.16. Pyrimidines. 9.17. Fused Pyrimidines: Purines and Pteridines. 9.18. 1,3,5-Triazines. 9.19. Multicyclic Compounds. References. Review Exercises. Chapter 10 GEOMETRIC AND STEREOCHEMICAL ASPECTS OF NONAROMATIC HETEROCYCLES. 10.1. General. 10.2. Special Properties of Three-Membered Rings. 10.3. Closing Heterocyclic Rings: Baldwin’s Rules. 10.4. Conformations of Heterocyclic Rings. 10.5. Chirality Effects on Biological Properties of Heterocycles. References. Review Exercises. Chapter 11 SYNTHETIC HETEROCYCLIC COMPOUNDS IN AGRICULTURAL AND OTHER APPLICATIONS. 11.1. Heterocyclic Agrochemicals. 11.2. Applications of Heterocyclic Compounds in Commercial Fields. References. Appendix UNIFIED AROMATICITY INDICES (IA) OF BIRD. INDEX.

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Book Synopsis* Examines the variety of roles that chaperones play in neurodegenerative diseases such as Huntington s disease and Parkinson s disease. * Caters to the ever-growing, global aging population.Table of ContentsPreface. Introduction. Contributors. 1 Intrinsically Disordered Chaperones and Neurodegeneration (Vladimir N. Uversky). 2 Redox Regulation of Protein Misfolding, Synaptic Damage, and Neuronal Loss in Neurodegenerative Diseases (Tomohiro Nakamura and Stuart A. Lipton). 3 Chaperone-Mediated Autophagy and Parkinson’s Disease (Marta Martinez-Vicente and Ester Wong). 4 Chaperone and Anti-Chaperone Properties of Synuclein: Implications for Development, Aging, and Neurodegenerative Disease (Makoto Hashimoto, Kazuanri Sekiyama, Akio Sekigawa, and Masayo Fujita). 5 The Ubiquitin–Proteasome System in Neurodegenerative Diseases: More than the Usual Suspects (Anne Bertolotti). 6 Regulation of the Polyglutamine Androgen Receptor by the Hsp90/Hsp70-Based Chaperone Machinery (Andrew P. Lieberman and William B. Pratt). 7 Amyloid Remodeling by Hsp104 (James Shorter). 8 Chaperone-Dependent Amyloid Assembly and Prion Toxicity (Daniel W. Summers, Katie J. Wolfe, and Douglas M. Cyr). 9 Modulation of Amyloid Propagation in Yeast by Hsp70 and its Regulators and Chaperone Partners (Daniel C. Masison). 10 ALS and the Copper Chaperone CCS (Marjatta Son and Jeffrey L. Elliott). 11 Emerging Area: TorsinA, a Novel ATP-Dependent Factor Linked to Dystonia (Michal Zolkiewski and Hui-Chuan Wu). 12 Therapeutics: Harnessing the Power of Molecular and Pharmacological Chaperones (David S. Gross, Ronald L. Klein and Stephan N. Witt). Index.

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Book SynopsisProcess safety metrics is a topic of frequent conversation within chemical industry associations. Guidelines for Process Safety Metrics provides basic information on process safety performance indicators, including a comprehensive list of metrics for measuring performance and examples as to how they can be successfully applied over both the short and long term. For engineers, insurers, corporate traininers, military personnel, government officials, students, and managers involved in production, product and process development, Guidelines for Process Safety Metrics can help determine appropriate metrics useful in monitoring performance and improving process safety programs. Note: CD-ROM/DVD and other supplementary materials are not included as part of eBook file.Table of ContentsItems on The CD Accompanying This Book xi Acronyms and Abbreviations xiii Glossary xv Acknowledgments xix Preface xxi INTRODUCTION 1 1.1 An Introduction to Process Safety and Metrics 1 1.2 Purpose of This Book 3 1.3 Key Audiences for the Guidelines 5 1.4 An Organization's Personnel Hierarchy 6 1.5 Organization of This Guideline 7 1.6 Using This Guideline 7 WHY IMPLEMENT PROCESS SAFETY METRICS 9 2.1 Preventing Process Safety Incidents 11 2.2 Benefits from Measuring Performance 13 2.3 Tracking Operational Performance and Process Safety Performance 16 2.4 Avoiding Complacency 17 2.5 Conclusion 17 PROCESS SAFETY MANAGEMENT METRICS 19 3.1 Metrics and the Process Safety Models 19 3.2 Other Metric Dimensions 24 3.3 Forms of Metrics 26 3.4 Characteristics of Good Metrics 27 3.5 Conclusion 30 CHOOSING APPROPRIATE METRICS 33 4.1 Process Safety Goals and Objectives 33 4.2. Define the Process Safety Goals 35 4.3 Define Process Safety Objectives 37 4.4 Develop the Metrics Strategy for Improving the Process Safety System 42 4.5 Select Metrics 46 4.6 Conclusion 51 IMPLEMENTING A METRICS PROGRAM 53 5.1 Management Support and Leadership 53 5.2 Develop an Implementation Strategy 53 5.3 Develop the Framework for the Metrics Implementation Strategy 56 5.4 Implementation Analysis 61 5.5 Prepare for Rollout 69 5.6 Rollout 72 5.7 Reevaluate Metrics Based Upon Experience 75 5.8 Conclusion 75 COMMUNICATING RESULTS 77 6.1 Communication Analysis 78 6.2 Select Appropriate Communication Characteristics 82 6.3 Report Appropriate Data to Different Audiences 85 6.4 Tools for Communicating Metrics 90 6.5 Conclusion 93 USING METRICS TO DRIVE PERFORMANCE IMPROVEMENTS 97 7.1 Identify Weaknesses and Deficiencies in Process Safety Performance 98 7.2 Leadership Commitment to Process Safety Performance 99 7.3 Hold Responsible Parties Accountable 99 7.4 Engage the Public 102 7.5 Conduct Periodic Management Reviews 103 7.6 Cultivate a Positive Process Safety Culture 105 7.7 Communicate Process Safety and Other Organizational Successes 107 7.8 Conclusion 108 IMPROVING INDUSTRY-WIDE PERFORMANCE 111 8.1 Performance Benchmarking 111 8.2 Metrics Allow Performance Comparisons for Multiple Parties 112 8.3 Sharing Data Across Industry Leads to Improved Performance 114 8.4 Conclusion 118 FUTURE TRENDS IN THE DEVELOPMENT AND USE OF PROCESS SAFETY METRICS 121 9.1 Improving Process Safety 121 9.2 Societal Interests 126 APPENDIX I: LISTING OF POTENTIAL PROCESS SAFETY METRICS TO CONSIDER (BASED ON THE RISK BASED PROCESS SAFETY ELEMENTS) 131 APPENDIX II: PROCESS SAFETY PERFORMANCE INDICATORS: BP CHEMICALS HULL CASE STUDY 163 APPENDIX III: NOVA CHEMICALS UNCONTROLLED PROCESS FIRE AND LOPC METRICS 171 INDEX 173

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Book SynopsisExplores the benefits and limitations of the latest capillary electrophoresis techniques Capillary electrophoresis and microchip capillary electrophoresis are powerful analytical tools that are particularly suited for separating and analyzing biomolecules. In comparison with traditional analytical techniques, capillary electrophoresis and microchip capillary electrophoresis offer the benefits of speed, small sample and solvent consumption, low cost, and the possibility of miniaturization. With contributions from a team of leading analytical scientists, Capillary Electrophoresis and Microchip Capillary Electrophoresis explains how researchers can take full advantage of all the latest techniques, emphasizing applications in which capillary electrophoresis has proven superiority over other analytical approaches. The authors not only explore the benefits of each technique, but also the limitations, enabling readers to choose the most appropriate technique to Table of ContentsPREFACE xvii ACKNOWLEDGMENTS xix CONTRIBUTORS xxi 1 Critical Evaluation of the Use of Surfactants in Capillary Electrophoresis 1 Jessica L. Felhofer, Karin Y. Chumbimuni-Torres, Maria F. Mora, Gabrielle G. Haby, and Carlos D. Garcý´a 1.1 Introduction 1 1.2 Surfactants for Wall Coatings 4 1.2.1 Controlling the Electroosmotic Flow 4 1.2.2 Preventing Adsorption to the Capillary 5 1.3 Surfactants as Buffer Additives 6 1.3.1 Micellar Electrokinetic Chromatography 6 1.3.2 Microemulsion Electrokinetic Chromatography 8 1.3.3 Nonaqueous Capillary Electrophoresis with Added Surfactants 9 1.4 Surfactants for Analyte Preconcentration 9 1.4.1 Sweeping 10 1.4.2 Transient Trapping 11 1.4.3 Analyte Focusing by Micelle Collapse 12 1.4.4 Micelle to Solvent Stacking 12 1.4.5 Combinations of Preconcentration Methods 12 1.4.6 Cloud Point Extraction 12 1.5 Surfactants and Detection in CE 14 1.5.1 Mass Spectrometry 14 1.5.2 Electrochemical Detection 15 1.6 Conclusions 16 References 17 2 Sample Stacking: A Versatile Approach for Analyte Enrichment in CE and Microchip-CE 23 Bruno Perlatti, Emanuel Carrilho, and Fernando Armani Aguiar 2.1 Introduction 23 2.2 Isotachophoresis 24 2.3 Chromatography-Based Sample Stacking 25 2.4 Methods Based on Electrophoretic Mobility and Velocity Manipulation (Electrophoretic Methods) 26 2.4.1 Field-Enhanced Sample Stacking (FESS) 27 2.4.2 Field-Enhanced Sample Injection (FESI) 27 2.4.3 Large-Volume Sample Stacking (LVSS) 28 2.4.4 Dynamic pH Junction 28 2.5 Sample Stacking in Pseudo-Stationary Phases 29 2.5.1 Field-Enhanced Sample Stacking 29 2.5.2 Hydrodynamic Injection Techniques 30 2.5.2.1 Normal Stacking Mode (NSM) 30 2.5.2.2 Reverse Electrode Polarity Stacking Mode (REPSM) 30 2.5.2.3 Stacking with Reverse Migrating Micelles (SRMM) 30 2.5.2.4 Stacking Using Reverse Migrating Micelles and a Water Plug (SRW) 31 2.5.2.5 High-Conductivity Sample Stacking (HCSS) 31 2.5.3 Electrokinetic Injection Techniques 32 2.5.3.1 Field-Enhanced Sample Injection (FESI–MEKC) 32 2.5.3.2 Field-Enhanced Sample Injection with Reverse Migrating Micelles (FESI–RMM) 32 2.5.4 Sweeping 32 2.5.5 Combined Techniques 33 2.5.5.1 Dynamic pH Junction: Sweeping 33 2.5.5.2 Selective Exhaustive Injection (SEI) 33 2.5.6 New Techniques 33 2.6 Stacking Techniques in Microchips 33 2.7 Concluding Remarks 36 References 37 3 Sampling and Quantitative Analysis in Capillary Electrophoresis 41 Petr Kuba´9n, Andrus Seiman, and Mihkel Kaljurand 3.1 Introduction 41 3.2 Injection Techniques in CE 42 3.2.1 Hydrodynamic Sample Injection 43 3.2.1.1 Principle 43 3.2.1.2 Advantages and Performance 44 3.2.1.3 Disadvantages 44 3.2.2 Electrokinetic Sample Injection 44 3.2.2.1 Principle 44 3.2.2.2 Advantages and Performance 45 3.2.2.3 Disadvantages 45 3.2.3 Bias-Free Electrokinetic Injection 45 3.2.4 Extraneous Sample Introduction Accompanying Injections in CE 46 3.2.5 Sample Stacking 48 3.2.5.1 Principle 48 3.2.5.2 Advantages and Performance 49 3.2.5.3 Disadvantages 50 3.2.6 Alternative Batch Sample Injection Techniques 50 3.2.6.1 Rotary-Type Injectors for CE 50 3.2.6.2 Hydrodynamic Sample Splitting as Injection Method for CE 51 3.2.6.3 Electrokinetic Sample Splitting as Injection Method for CE 52 3.2.6.4 Dual-Opposite End Injection in CE 52 3.3 Micromachined/Microchip Injection Devices 53 3.3.1 Droplet Sampler Based on Digital Microfluidics 53 3.3.2 Wire Loop Injection 54 3.4 Automated Flow Sample Injection and Hyphenated Systems 55 3.4.1 Introduction 55 3.4.2 Advantages and Performance 56 3.4.3 Disadvantages 57 3.5 Computerized Sampling and Data Analysis 57 3.6 Sampling in Portable CE Instrumentation 58 3.7 Quantitative Analysis in CE 59 3.7.1 Introduction 59 3.7.2 Quantitative Analysis with HD Injection 59 3.7.3 Quantitative Analysis with EK Injection 60 3.7.4 Validation of the Developed CE Methods 61 3.7.5 Computer Data Treatment in Quantitative Analysis 61 3.8 Conclusions 62 References 62 4 Practical Considerations for the Design and Implementation of High-Voltage Power Supplies for Capillary and Microchip Capillary Electrophoresis 67 Lucas Blanes, Wendell Karlos Tomazelli Coltro, Renata Mayumi Saito, Claudimir Lucio do Lago, Claude Roux, and Philip Doble 4.1 Introduction 67 4.1.1 High-Voltage Fundamentals 67 4.1.2 Electroosmotic Flow Control 68 4.1.3 Technical Aspects 70 4.1.4 Construction of Bipolar HVPS from Unipolar HVPS 70 4.1.5 Safety Considerations 71 4.1.6 HVPS Commercially Available 71 4.1.7 Practical Considerations 72 4.1.8 Alternative Sources of HV 72 4.1.9 HVPS Controllers for MCE 72 4.2 High-Voltage Measurement 73 4.3 Concluding Remarks 74 References 74 5 Artificial Neural Networks in Capillary Electrophoresis 77 Josef Havel, Eladia Marýa Pe~na-Mendez, and Alberto Rojas-Hernandez 5.1 Introduction 77 5.2 Optimization in CE: From Single Variable Approach Toward Artificial Neural Networks 77 5.2.1 Limitations of “Traditional” Single Variable Approach 79 5.2.2 Multivariate Approach with Experimental Design and Response Surface Modeling 79 5.2.2.1 Experimental Design 79 5.2.2.2 Response Surface Modeling 80 5.3 Artificial Neural Networks in Electromigration Methods 81 5.3.1 Introduction—Basic Principles of ANN 81 5.3.2 Optimization Using a Combination of ED and ANN 82 5.3.2.1 Testing of ED–ANN Algorithm 83 5.3.2.2 Practical Applications of ED–ANN 83 5.3.3 Quantitative CE Analysis and Determination from Overlapped Peaks 84 5.3.3.1 Evaluation of Calibration Plots in CE Using ANN to Increase Precision of Analysis 84 5.3.3.2 ANN in Quantitative CE Analysis from Overlapped Peaks 86 5.3.4 ANN in CEC and MEKC 86 5.3.5 ANN for Peptides Modeling 88 5.3.6 Classification and Fingerprinting 88 5.3.7 Other Applications 90 5.4 Conclusions 90 Acknowledgments 91 References 91 6 Improving the Separation in Microchip Electrophoresis by Surface Modification 95 M. Teresa Fernandez-Abedul, Isabel Alvarez-Martos, Francisco Javier Garcýa Alonso, and Agustýn Costa-Garcýa 6.1 Introduction 95 6.2 Strategies for Improving Separation 96 6.2.1 Selection of an Adequate Technique: ME 96 6.2.2 Microchannel Design 96 6.2.3 Selection of an Appropriate ME Material 96 6.2.4 Optimization of the Working Conditions 97 6.2.5 Surface Modification 97 6.2.5.1 Surface Micro- and Nanostructuring 98 6.2.5.2 Employment of Energy Sources 99 6.2.5.3 Chemical Surface Modification 99 6.3 Chemical Modifiers 102 6.3.1 Surfactants 104 6.3.2 Ionic Liquids 105 6.3.3 Nanoparticles 108 6.3.4 Polymers 110 6.4 Conclusions 119 Acknowledgments 120 References 120 7 Capillary Electrophoretic Reactor and Microchip Capillary Electrophoretic Reactor: Dissociation Kinetic Analysis Method for “Complexes” Using Capillary Electrophoretic Separation Process 127 Toru Takahashi and Nobuhiko Iki 7.1 Introduction 127 7.2 Basic Concept of CER 128 7.3 Dissociation Kinetic Analysis of Metal Complexes Using a CER 129 7.3.1 Determination of the Rate Constants of Dissociation of 1:2 Complexes of Al3þ and Ga3þ with an Azo Dye Ligand 2,20-Dihydroxyazobenzene-5,50-Disulfonate in a CER 130 7.4 Expanding the Scope of the CER to Measurements of Fast Dissociation Kinetics with a Half-Life from Seconds to Dozens of Seconds: Dissociation Kinetic Analysis of Metal Complexes Using a Microchip Capillary Electrophoretic Reactor (mCER) 133 7.5 Expanding the Scope of the CER to the Measurement of Slow Dissociation Kinetics with a Half-Life of Hours 135 7.5.1 Principle of LS-CER 135 7.5.2 Application of LS-CER to the Ti(IV)–Catechin Complex 136 7.5.3 Application of LS-CER to the Ti(IV)–Tiron Complex 138 7.6 Expanding the Scope of CER to Measurement of the Dissociation Kinetics of Biomolecular Complexes 139 7.6.1 Dissociation Kinetic Analysis of [SSB–ssDNA] Using CER 139 7.7 Conclusions 142 References 142 8 Capacitively Coupled Contactless Conductivity Detection (C4D) Applied to Capillary Electrophoresis (CE) and Microchip Electrophoresis (MCE) 145 Jose Alberto Fracassi da Silva, Claudimir Lucio do Lago, Dosil Pereira de Jesus, and Wendell Karlos Tomazelli Coltro 8.1 Introduction 145 8.2 Theory of C4D 145 8.2.1 Basic Principles of C4D 145 8.2.2 Simulation 146 8.2.3 Basic Equation for Sensitivity 147 8.2.4 Equivalent Circuit of a CE-C4D System 147 8.2.5 Practical Guidelines 148 8.3 C4D Applied to Capillary Electrophoresis 148 8.3.1 Instrumental Aspects in CE 149 8.3.2 Coupling C4D with UV–Vis Photometric Detectors in CE 149 8.3.3 Fundamental Studies in Capillary Electrophoresis Using C4D 149 8.3.4 Fundamental Studies on C4D 149 8.3.5 Applications 150 8.4 C4D Applied to Microchip Capillary Electrophoresis 151 8.4.1 Geometry of the Detection Electrodes 151 8.4.1.1 Embedded Electrodes 151 8.4.1.2 Attached Electrodes 153 8.4.1.3 External Electrodes 153 8.4.2 Applications 154 8.4.2.1 Bioanalytical Applications 154 8.4.2.2 On-Chip Enzymatic Reactions 155 8.4.2.3 Food Analysis 155 8.4.2.4 Explosives and Chemical Warfare Agents 155 8.4.2.5 Other Applications 156 8.5 Concluding Remarks 156 Acknowledgments 157 References 157 9 Capillary Electrophoresis with Electrochemical Detection 161 Blanaid White 9.1 Principles of Electrochemical Detection 161 9.1.1 Amperometric Detection 161 9.1.2 Potentiometric Detection 162 9.1.3 Conductivity Detection 162 9.2 Interfacing Amperometric Detection to Capillary Electrophoresis 163 9.2.1 Off-Column Detection 163 9.2.2 End-Column Detection 164 9.2.3 Use of Multiple Detection Electrodes 165 9.2.4 Pulsed Amperometric Detection 166 9.2.5 Nonaqueous EC Detection 166 9.2.6 Electrode Material 166 9.2.7 Dual Conductivity and Amperometric Detection 167 9.3 Interfacing Electrochemical Detection to Microfluidic Capillary Electrophoresis 168 9.3.1 End-Column Detection 168 9.3.2 Pulsed Amperometric Detection 169 9.3.3 Off-Channel Detection 169 9.3.4 Electrode Material 170 9.3.5 Portable CE and MCE Systems 170 9.3.6 Applications of CE–MCE with AD 171 9.3.7 Future Directions for CE–MCE with EC Detection 173 References 173 10 Overcoming Challenges in Using Microchip Electrophoresis for Extended Monitoring Applications 177 Scott D. Noblitt and Charles S. Henry 10.1 Introduction 177 10.2 Background Electrolyte (BGE) Longevity 179 10.3 Achieving Rapid Sequential Injections 186 10.4 Robust Quantitation 192 10.5 Conclusions 197 References 198 11 Distinction of Coexisting Protein Conformations by Capillary Electrophoresis 201 Hanno Stutz 11.1 Introduction 201 11.1.1 Theoretical Aspects of in vivo Protein Folding 202 11.2 Protein Misfolding and Induction of Unfolding 203 11.3 Conformational Pathologies 204 11.4 Distinction Between Conformations 205 11.5 Relevance of Conformations for Biotechnological Products 206 11.6 Conformational Elucidation—An Overview of Alternative Methods to CE 206 11.7 HPLC in Conformational Distinction 207 11.7.1 Intact Proteins 207 11.7.1.1 Reversed-Phase (RP)–HPLC 207 11.7.1.2 Size Exclusion (SEC)–HPLC 208 11.7.1.3 Ion-Exchange–HPLC 208 11.7.2 HPLC with Detectors Sensitive for Conformations and Aggregates 208 11.7.3 Peptides as Model Compounds for Hydrophobic Stationary Phases in HPLC 208 11.8 Capillary Electrophoresis (CE) in Conformational Separations 209 11.8.1 Fundamental Aspects and Survey of Pitfalls 209 11.8.2 Electrophoretic Mobility of Proteins 210 11.8.3 Peak Profiles and Derivable Thermodynamic Aspects of Protein Re-/Unfolding 211 11.8.4 Dipeptides as a Case Study for Isomerization 213 11.8.5 Denaturation Factors and Strategies Applied in CE 214 11.8.5.1 Separation Electrolyte, Injection Solution, and Sample Storage 215 11.8.5.2 Denaturation by Urea, Dithiothreitol, and GdmCl 215 11.8.5.3 Effects of pH and Organic Solvents 216 11.8.5.4 Temperature 216 11.8.5.5 Electrical Field 218 11.8.5.6 Detergents 218 11.8.5.7 Ligands and Ions—Case Studies on Potential Amyloidogenic b2m 221 11.8.6 b-Amyloid Peptides 222 11.8.6.1 Prions 223 11.9 Comparison Between CE and HPLC 223 11.10 Conclusive Discussion and Method Evaluation 223 11.10.1 General Aspects 223 11.10.2 HPLC 224 11.10.3 CE 224 References 225 12 Capillary Electromigration Techniques for the Analysis of Drugs and Metabolites in Biological Matrices: A Critical Appraisal 229 Cristiane Masetto de Gaitani, Anderson Rodrigo Moraes de Oliveira, and Pierina Sueli Bonato 12.1 Introduction 229 12.2 Strategies to Obtain Reliable Capillary Electromigration Methods for the Bioanalysis of Drugs and Metabolites 230 12.2.1 Selectivity and Detectability 230 12.2.1.1 Efficiency 232 12.2.1.2 Sample Preparation 233 12.2.1.3 Detectors 235 12.2.2 Repeatability 236 12.3 Selected Applications of Capillary Electromigration Techniques in Bioanalysis 238 12.3.1 Pharmacokinetics and Metabolism Studies 238 12.3.2 Enantioselective Analysis of Drugs and Metabolites 240 12.3.3 Biopharmaceuticals or Biotechnology-Derived Pharmaceuticals 240 12.3.4 Therapeutic Drug Monitoring 241 12.3.5 Clinical and Forensic Toxicology 242 12.4 Concluding Remarks 243 References 243 13 Capillary Electrophoresis and Multicolor Fluorescent DNA Analysis in an Optofluidic Chip 247 Chaitanya Dongre, Hugo J.W.M. Hoekstra, and Markus Pollnau 13.1 Introduction 247 13.2 Optofluidic Integration in an Electrophoretic Microchip 248 13.2.1 Sample Fabrication 248 13.2.2 Optofluidic Characterization 248 13.3 Fluorescence Monitoring of On-Chip DNA Separation 249 13.3.1 Experimental Materials and Methods 249 13.3.2 Experimental Results and Analysis 250 13.4 Toward Ultrasensitive Fluorescence Detection 253 13.4.1 Optimization of the Experimental Setup 253 13.4.2 All-Numerical Postprocessed Noise Filtering 253 13.5 Multicolor Fluorescent DNA Analysis 255 13.5.1 Dual-Point, Dual-Wavelength Fluorescence Monitoring 256 13.5.2 Modulation-Frequency Encoded Multiwavelength Fluorescence Sensing 259 13.5.3 Application to Multiplex Ligation-Dependent Probe Amplification 260 13.6 Conclusions and Outlook 263 Acknowledgments 264 References 264 14 Capillary Electrophoresis of Intact Unfractionated Heparin and Related Impurities 267 Robert Weinberger 14.1 Introduction 267 14.2 Capillary Electrophoresis and Heparin 269 14.3 Method Development in Capillary Electrophoresis 269 14.4 Common Impurities Found in Heparin 272 14.5 The United States Pharmacoepia and CE of Heparin 273 14.6 Interlaboratory Collaborative Study 274 14.7 Conclusions 275 References 275 15 Microchip Capillary Electrophoresis for In Situ Planetary Exploration 277 Peter A. Willis and Amanda M. Stockton 15.1 Introduction 277 15.2 Instrument Design 279 15.3 Instrumentation External to the Microdevice 280 15.4 Microdevice Basics 282 15.4.1 All-Glass Devices for Microchip Capillary Electrophoresis 282 15.4.2 Three-Layer Hybrid Substrate Glass–PDMS Devices for Fluidic Manipulation 284 15.4.3 Integrating Fluidic Manipulation with Electrophoresis 285 15.5 Microdevices and their Applications 285 15.5.1 Microdevices with Bus-Valve Control of Microfluidic Manipulation 285 15.5.2 Automaton Devices for Programmable Microfluidic Manipulation 288 15.6 Conclusions 289 Acknowledgments 290 References 290 16 Rapid Analysis of Charge Heterogeneity of Monoclonal Antibodies by Capillary Zone Electrophoresis and Imaged Capillary Isoelectric Focusing 293 Yan He, Jim Mo, Xiaoping He, and Margaret Ruesch 16.1 Introduction 293 16.2 Capillary Zone Electrophoresis 295 16.2.1 Separation and Detection Strategy 295 16.2.1.1 Capillary Construction 295 16.2.1.2 Buffer Composition 295 16.2.1.3 Separation Voltage and Field Strength 297 16.2.1.4 Detection 297 16.2.2 Applications 297 16.3 Imaged Capillary Isoelectric Focusing 299 16.3.1 Method Development and Optimization 299 16.3.1.1 Carrier Ampholyte 300 16.3.1.2 Additives 300 16.3.1.3 Focusing Time and Voltage 300 16.3.1.4 Salt Concentration 303 16.3.1.5 Protein Concentration 303 16.3.2 iCE Method Validation 303 16.3.3 Applications 304 16.3.3.1 Cell Line Development Support 304 16.3.3.2 Formulation Screening 304 16.3.3.3 Characterization of Acidic Species 305 16.4 Summary 306 References 307 17 Application of Capillary Electrophoresis for High-Throughput Screening of Drug Metabolism 309 Roman 9Remý´nek, Jochen Pauwels, Xu Wang, Jos Hoogmartens, Zden9ek Glatz, and Ann Van Schepdael 17.1 Introduction 309 17.2 Sample Deproteinization 310 17.3 On-line Preconcentration 311 17.4 Method Development 312 17.4.1 Dynamic Coating of Inner Capillary Wall 312 17.4.2 Short-End Injection 313 17.4.3 Strong Rinsing Procedure 313 17.4.4 Optimized Method 313 17.5 Method Validation 314 17.6 Method Applications 315 17.6.1 Drug Stability Screening 315 17.6.2 Kinetic Study 316 17.7 Conclusions 316 Acknowledgments 317 References 317 18 Electrokinetic Transport of Microparticles in the Microfluidic Enclosure Domain 319 Qian Liang, Chun Yang, and Jianmin Miao 18.1 Introduction 319 18.2 Numerical Model 320 18.2.1 Problem Description 320 18.2.2 Mathematical Model 320 18.3 Numerical Simulation 322 18.4 Results and Discussion 322 18.4.1 Particle Transport in the Bulk Flow 322 18.4.1.1 The Particle Velocity in the Confined Domain 322 18.4.1.2 The Trajectory of Particle Transport within the Confined Domain 323 18.4.1.3 The Effect of Sidewall Zeta Potential on the Particle Motion 324 18.4.2 Particle Transport Near the Bottom Surface 325 18.4.2.1 The Effect of the EDLThickness on the Near Wall Motion of the Particle 325 18.4.2.2 The Effect of Surface Charge on the Near Wall Transport of the Particle 325 18.5 Model Application 325 18.6 Conclusions 326 References 326 19 Integration of Nanomaterials in Capillary and Microchip Electrophoresis as a Flexible Tool 327 Germa´n A. Messina, Roberto A. Olsina, and Patricia W. Stege 19.1 Introduction 327 19.1.1 Historical Overview of Nanotechnology 327 19.1.2 Nanomaterials 329 19.1.2.1 Carbon-Based Nanomaterials 329 19.1.2.2 Metal-Based Nanomaterials 329 19.1.2.3 Dendrimers 331 19.1.2.4 Composites 331 19.2 Nanomaterials in Analytical Chemistry 332 19.3 Nanoparticles in Capillary Electrophoresis 333 19.3.1 Nanoparticles in Capillary Electrochromatography 334 19.3.1.1 Organic Nanoparticles 334 19.3.1.2 Inorganic Particles 338 19.3.2 Nanoparticles in Electrokinetic Chromatography 342 19.3.2.1 Organic Nanoparticles 343 19.3.2.2 Inorganic Particles 347 19.3.3 Nanoparticles in Microchip Electrochromatography 349 19.4 Conclusions 352 References 353 20 Microchip Capillary Electrophoresis to Study the Binding of Ligands to Teicoplanin Derivatized on Magnetic Beads 359 Toni Ann Riveros, Roger Lo, Xiaojun Liu, Marisol Salgado, Hector Carmona, and Frank A. Gomez 20.1 Introduction 359 20.2 Experimental Section 359 20.2.1 Materials and Methods 359 20.2.1.1 Equipment and Fabrication of the Microchips 360 20.2.1.2 Surface Coating 360 20.2.1.3 Teic Immobilization on Magnetic Microbeads 360 20.2.2 Procedures 360 20.2.2.1 FAMCE Studies 360 20.2.2.2 MFAC Studies 361 20.3 Results and Discussion 361 20.3.1 FAMCE Studies 361 20.3.1.1 Nonspecific Adsorption Resistance 361 20.3.1.2 The Binding of DA3 to Teic-Beads 362 20.3.2 MFAC Studies 363 20.4 Conclusions 364 Acknowledgments 365 References 365 21 Glycomic Profiling Through Capillary Electrophoresis and Microchip Capillary Electrophoresis 367 Yehia Mechref 21.1 Introduction 367 21.1.1 Release of N-Glycans from Glycoproteins 368 21.1.1.1 Chemical Release 368 21.1.1.2 Enzymatic Release 368 21.1.2 Release of O-Glycans from Glycoproteins 368 21.1.2.1 Chemical Release 368 21.1.2.2 Enzymatic Release 369 21.2 General Considerations of Capillary Electrophoresis and Microchip Capillary Electrophoresis of Glycans 369 21.2.1 Capillary Electrophoresis–Laser-Induced Fluorescence (CE–LIF) Analysis of Glycans 369 21.2.2 Interfacing Capillary Electrophoresis and Capillary Electrochromatography to Mass Spectrometry 372 21.2.2.1 ESI Interfaces for Capillary Electrophoresis 372 21.2.2.2 Sheathless-Flow Interface 372 21.2.2.3 Sheath-Flow Interface 373 21.2.2.4 Liquid Junction Interface 373 21.2.2.5 MALDI Interfaces for Capillary Electrophoresis 373 21.2.2.6 CE–MS Analysis of Glycans 374 21.2.2.7 Glycomic Analysis by CEC–MS 376 21.3 Microchip Capillary Electrophoresis 377 21.4 Conclusions 380 References 381 INDEX 385

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Book Synopsis* Part of the Essential Engineering Calculations Series, this book presents step-by-step solutions of the basic principles of mass transfer operations. * Covers specific mass transfer operations such as distillation, absorption and stripping, and adsorption.Table of ContentsPreface. Part One Introduction. 1. History of Chemical Engineering and Mass Transfer Operations. References. 2. Transport Phenomena vs Unit Operations Approach. References. 3. Basic Calculations. Introduction. Units and Dimensions. Conversion of Units. The Gravitational Constant gc. Significant Figures and Scientific Notation. References. 4. Process Variables. Introduction. Temperature. Pressure. Moles and Molecular Weight. Mass, Volume, and Density. Viscosity. Reynolds Number. pH. Vapor Pressure. Ideal Gas Law. References. 5. Equilibrium vs Rate Considerations. Introduction. Equilibrium. Rate. Chemical Reactions. References. 6. Phase Equilibrium Principles. Introduction. Gibb’s Phase Rule. Raoult’s Law. Henry’s Law. Raoult’s Law vs Henry’s Law. Vapor-Liquid Equilibrium in Nonideal Solutions. Vapor-Solid Equilibrium. Liquid-Solid Equilibrium. References. 7. Rate Principles. Introduction. The Operating Line. Fick’s Law. Diffusion in Gases. Diffusion in Liquids. Mass Transfer Coefficients. Individual Mass Transfer Coefficients. Equimolar Counterdiffusion. Diffusion of Component A Through Non-diffusing Component B. Overall Mass Transfer Coefficients. Equimolar Counterdiffusion and/or Diffusion in Dilute Solutions. Gas Phase Resistance Controlling. Liquid Phase Resistance Controlling. Experimental Mass Transfer Coefficients. References. Part Two Applications: Component and Phase Separation Processes. 8. Introduction to Mass Transfer Operations. Introduction. Classification of Mass Transfer Operations. Contact of Immiscible Phases. Miscible Phases Separated by a Membrane. Direct Contact of Miscible Phases. Mass Transfer Equipment. Distillation. Absorption. Adsorption. Extraction. Humidification and Drying. Other Mass Transfer Unit Operations. The Selection Decision. Characteristics of Mass Transfer Operations. Unsteady-State vs Steady-State Operation. Flow Pattern. Stagewise vs Continuous Operation. References. 9. Distillation. Introduction. Flash Distillation. Batch Distillation. Continuous Distillation with Reflux. Equipment and Operation. Equilibrium Considerations. Binary Distillation Design: McCabe-Thiele Graphical Method. Multicomponent Distillation: Fenske-Underwood-Gilliland (FUG) Method. Packed Column Distillation. References. 10. Absorption and Stripping. Introduction. Description of Equipment. Packed Columns. Plate Columns. Design and Performance Equations?Packed Columns. Liquid Rate. Column Diameter. Column Height. Pressure Drop. Design and Performance Equations-Plate Columns. Stripping. Packed vs Plate Tower Comparison. Summary of Key Equations. References. 11. Adsorption. Introduction. Adsorption Classification. Activated Carbon. Activated Alumina. Silica Gel. Molecular Sieves. Adsorption Equilibria. Freundlich Equation. Langmuir Isotherms. Description of Equipment. Design and Performance Equations. Regeneration. References. 12. Liquid-Liquid and Solid-Liquid Extraction. Introduction. Liquid-Liquid Extraction. The Extraction Process. Equipment. Solvent Selection. Equilibrium. Graphical Procedures. Analytical Procedures. Solid-Liquid Extraction (Leaching). Process Variables. Equipment and Operation. Design and Predictive Equations. References. 13. Humidification and Drying. Introduction. Psychrometry and the Psychrometric Chart. Humidification. Equipment. Describing Equations. Drying. Rotary Dryers. Spray Dryers. References. 14. Crystallization. Introduction. Phase Diagrams. The Crystallization Process. Crystal Physical Characteristics. Equipment. Describing Equations. Design Considerations. References. 15. Membrane Separation Processes. Introduction. Reverse Osmosis. Describing Equations. Ultrafiltration. Describing Equations. Microfiltration. Describing Equations. Gas Permeation. Describing Equations. References. 16. Phase Separation Equipment. Introduction. Fluid-Particle Dynamics. Gas-Solid (G-S) Equipment. Gravity Settlers. Cyclones. Electrostatic Precipitators. Venturi Scrubbers. Baghouses. Gas-Liquid (G-L) Equipment. Liquid-Solid (L-S) Equipment. Sedimentation. Centrifugation. Flotation. Liquid-Liquid (L-L) Equipment. Solid-Solid (S?S) Equipment. High-Gradient Magnetic Separation. Solidification. References. Part Three Other Topics. 17. Other and Novel Separation Processes. Freeze Crystallization. Ion Exchange. Liquid Ion Exchange. Resin Adsorption. Evaporation. Foam Fractionation. Dissociation Extraction. Electrophoresis. Vibrating Screens. References. 18. Economics and Finance. Introduction. The Need for Economic Analyses. Definitions. Simple Interest. Compound Interest. Present Worth. Evaluation of Sums of Money. Depreciation. Fabricated Equipment Cost Index. Capital Recovery Factor. Present Net Worth. Perpetual Life. Break-Even Point. Approximate Rate of Return. Exact Rate of Return. Bonds. Incremental Cost. Principles of Accounting. Applications. References. 19. Numerical Methods. Introduction. Applications. References. 20. Open-Ended Problems. Introduction. Developing Students’ Power of Critical Thinking. Creativity. Brainstorming. Inquiring Minds. Failure, Uncertainty, Success: Are They Related? Angels on a Pin. Applications. References. 21. Ethics. Introduction. Teaching Ethics. Case Study Approach. Integrity. Moral Issues. Guardianship. Engineering and Environmental Ethics. Future Trends. Applications. References. 22. Environmental Management and Safety Issues. Introduction. Environmental Issues of Concern. Health Risk Assessment. Risk Evaluation Process for Health. Hazard Risk Assessment. Risk Evaluation Process for Accidents. Applications. References. Appendix. Appendix A. Units. A.1 The Metric System. A.2 The SI System. A.3 Seven Base Units. A.4 Two Supplementary Units. A.5 SI Multiples and Prefixes. A.6 Conversion Constants (SI). A.7 Selected Common Abbreviations. Appendix B. Miscellaneous Tables. Appendix C. Steam Tables. Index.

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Book SynopsisThis book takes a comprehensive look at bioenergetics, the energy flow in living systems, discussing ion exchange and electron transfer processes in biological membranes and artificial bio-films, and how these processes contribute to developing modern biosensor and ion-sensor technology, as well as biofuel cells.Table of ContentsContributors vii Preface ix 1 Modeling of Relations between Ionic Fluxes and Membrane Potential in Artificial Membranes 1Agata Michalska and Krzysztof Maksymiuk 2 Transmembrane Ion Fluxes for Lowering Detection Limits of Ion-Selective Electrodes 23Tomasz Sokalski 3 Ion Transport and (Selected) Ion Channels in Biological Membranes in Health and Pathology 61Krzysztof Do³owy 4 Electrical Coupling through Gap Junctions between Electrically Excitable Cells 83Yarra Lefler and Marylka Yoe Uusisaari 5 Enzyme Film Electrochemistry 105Julea N. Butt, Andrew J. Gates, Sophie J. Marritt and David J. Richardson 6 Plant Photosystem II as an Example of a Natural Photovoltaic Device 121Wies³aw I. Gruszecki 7 Electrochemical Activation of Cytochrome P450 133Andrew K. Udit, Michael G. Hill and Harry B. Gray 8 Molecular Properties and Reaction Mechanism of Multicopper Oxidases Related to Their Use in Biofuel Cells 169Edward I. Solomon, Christian H. Kjaergaard and David E. Heppner 9 Electrochemical Monitoring of the Well-Being of Cells 213Kalle Levon, Qi Zhang, Yanyan Wang, Aabhas Martur and Ramya Kolli 10 Electrochemical Systems Controlled by Enzyme-Based Logic Networks: Toward Biochemically Controlled Bioelectronics 231Jan Halámek and Evgeny Katz Index 000

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Book SynopsisThis book provides a description of the generalized two layer surface complexation model, data treatment procedures, and thermodynamic constants for sorption of metal cations and anions on gibbsite, the most common form of aluminum oxide found in nature and one of the most abundant minerals in soils, sediments, and natural waters. The book provides a synopsis of aluminum oxide forms and a clearly defined nomenclature. Compilations of available data for sorption of metal cations and anions on gibbsite are presented, and the results of surface complexation model fitting of these data are given. The consistency of the thermodynamic surface complexation constants extracted from the data is examined through development of linear free energy relationships which are also used to predict thermodynamic constants for ions for which insufficient data are available to extract constants. The book concludes with a comparison of constants extracted from data for sorption on gibbsite with those determTable of ContentsForeword xi Preface xiii 1 Aluminum Oxides and Hydroxides under Environmental Conditions 1 1.1 Introduction 1 1.2 Occurrence of Aluminum Oxides and Hydroxides in the Subsurface 2 1.3 Occurrence of Aluminum Oxides and Hydroxides in Surface Water 4 1.4 Use of Aluminum Hydroxide in Water Treatment 6 1.5 Summary 7 2 Formation and Properties of Gibbsite and Closely Related Minerals 9 2.1 Al Polymerization Models 9 2.1.1 The “Core-Links” Model 10 2.1.2 The “Cage-Like” (Keggin-Al 13 Structure) Model 10 2.1.3 The “Continuous” Model 11 2.2 Formation of Gibbsite and Other Al Hydroxides and Oxyhydroxides 12 2.3 Aluminum Hydroxide Polymorphs: Structure and Nomenclature 15 2.4 Gibbsite 19 2.4.1 Kinetics of Precipitation and Crystal Growth 19 2.4.2 Structure 21 2.4.3 Common Techniques of Synthesis 21 2.4.4 Synthesized Gibbsite and Differences from Natural Gibbsite 24 2.5 Bayerite 25 2.5.1 Kinetics of Precipitation and Crystal Growth 25 2.5.2 Structure 26 2.5.3 Differences from Gibbsite 26 2.5.4 Synthesized Bayerite and Transformation to Gibbsite 27 2.6 Nordstrandite 27 2.7 Doyleite 28 2.8 Other Forms of Aluminum Oxides and Oxyhydroxides 28 2.8.1 Corundum (a-Al 2 O 3) 28 2.8.2 Boehmite (g-AlOOH) 29 2.8.3 Diaspore (a-AlOOH) 29 2.9 Other Forms Manufactured under High Temperature and Pressure 30 3 Types of Available Data 33 3.1 Gibbsite Structure Verification 33 3.2 Physical–Chemical Properties 34 3.2.1 Specific Surface Area 34 3.2.2 Surface Site Characterization 35 3.2.2.1 Hydroxyl Surface Sites 35 3.2.2.2 Surface Site Density 36 3.3 Acid–Base Titration Data 37 3.4 Cation and Anion-Sorption Data 40 3.5 Spectroscopic Data for Sorption on Gibbsite 41 3.6 Proton ReleaseUptake Data 43 3.7 Electrokinetic Data 43 3.8 Summary 44 4 Data Compilation and Treatment Methods 45 4.1 Collection of Data 45 4.2 Assessment of Data Quality 46 4.2.1 Solid Preparation Method 46 4.2.2 Type of Reaction Vessel 47 4.2.3 Nature of Background Electrolyte 47 4.2.4 Sorption Kinetics 48 4.2.4.1 Proton Sorption Kinetics 48 4.2.4.2 Cation and Anion Sorption Kinetics 49 4.2.5 Method of Solid–Liquid Separation 49 4.2.6 CO 2 Exclusion 50 4.2.7 Experimental Temperature 51 4.3 Compilation of Surface Properties 51 4.4 Extraction of Equilibrium Sorption Constants 51 4.4.1 Solution Activity Coefficients 52 4.4.2 Fiteql 52 4.4.3 Data Grouping 54 4.4.4 Selection of Surface Species 54 4.4.5 Selection of Best Estimates 55 4.5 Optimal-Fit Simulations 56 4.6 Presentation of Results 56 5 Surface Properties of Gibbsite 59 5.1 Surface Area 59 5.2 Site Density 62 5.3 Point of Zero Charge 64 5.4 Surface Acid–Base Chemistry 65 5.5 Effects of Dissolution on Gibbsite Surface Acid–Base Chemistry 76 5.6 Summary 80 6 Cation Sorption on Gibbsite 81 6.1 Modeling Methodology and Reactions 81 6.2 Available Spectroscopic Data and Use in Modeling 86 6.2.1 Copper 86 6.2.2 Lead 87 6.2.3 Cobalt 88 6.2.4 Cadmium 88 6.2.5 Manganese 88 6.2.6 Iron(II) 88 6.2.7 Calcium 88 6.2.8 Zinc 89 6.2.9 Mercury 89 6.2.10 Uranium 90 6.2.11 Thorium 91 6.3 Copper 92 6.4 Lead 99 6.5 Cobalt 107 6.6 Cadmium 117 6.7 Manganese 126 6.8 Iron (II) 127 6.9 Calcium 128 6.10 Zinc 130 6.11 Mercury 132 6.12 Uranium 142 6.13 Thorium 145 7 Anion Sorption on Gibbsite 149 7.1 Modeling Methodology and Reactions 149 7.2 Available Spectroscopic Data and Use in Modeling 153 7.2.1 Phosphate 153 7.2.2 Arsenate 154 7.2.3 Arsenite 154 7.2.4 Molybdate 155 7.2.5 Selenate 155 7.2.6 Chromate 155 7.2.7 Borate 155 7.2.8 Sulfate 156 7.2.9 Fluoride 156 7.2.10 Silicate 156 7.3 Phosphate 157 7.4 Arsenate 164 7.5 Arsenite 176 7.6 Molybdate 182 7.7 Selenate 185 7.8 Chromate 187 7.9 Borate 188 7.10 Sulfate 192 7.11 Fluoride 195 7.12 Silicate 197 8 Coherence and Extrapolation of the Results 199 8.1 Cation Sorption on Gibbsite 199 8.2 Anion Sorption on Gibbsite 204 8.3 Comparison of Gibbsite Surface-Complexation Constants with Those of Goethite, Hydrous Ferric Oxide, and Hydrous Manganese Oxide 208 8.4 Summary 213 References 219 Appendix A: Summary of Experimental Details 241 Author Index 283 Subject Index 289

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Book SynopsisMethods for more planet-friendly process engineering Our earth is just one big, complex Process Facility with limited air, water, and mineral resources. It responds to a number of process variablesamong them, humanity and the environmental effects of our carbon consumption. What can professionals in the Hydrocarbon Process Industry do to retard environmental degradation? Rather than looking to exotic technology for solutions, Process Engineering for a Small Planet details ready-at-hand methods that the process engineer can employ to help combat the environmental crisis. Drawing from the author''s professional experience working with petroleum refineries petroleum refineries, petrochemical plants, and natural gas wells, this handbook explains how to operate and retrofit process facilities to: Reuse existing process equipment Save energy Reduce greenhouse gas emissions Expand plant capacity without installing new equipment Table of ContentsForeword xv Preface xvii Introduction: Turning of the Tide 1 1. Expanding Fractionator and Compressor Capacity 3 Reuse of Existing Fractionator Changing Tray Deck Panels Alternates to New Compressor Keeping Compressor Rotor Clean Calculating Liquid Injection Rates to Compressor 2. Vacuum Tower Heater Expansion 17 Entrainment Velocity Limitations Missing Tray Deck Manways Heater Draft Limitation Improving Ejector Performance Velocity Steam in Heater Passes 3. Natural-Draft-Fired Heaters 27 Control Excess Air O2 and Combustible Analyzers Improving Air–Fuel Mixing Convective Section Air Leaks Air Preheater Leaks Indirect Air Preheat 4. Crude Pre-Flash Towers 37 Pre-Flash Tower Flooding Energy Saving with Pre-Flash Towers Capacity Benefits Pre-Flash Tower External Reflux 5. Amine Regeneration and Sulfur Recovery 47 Amine Capacity Expansion Sulfur Plant Capacity Expansion Rich Amine Flash Drum Design Cascaded Seal Legs Sulfur Recovery from Sour Water Stripper Off-Gas Acid Gas of High CO2 Content Sulfur Plant Oxygen Enrichment 6. Treating and Drying Hydrocarbons 59 Jet Fuel Treating Salt Dryer Operation Water-Washing Sodium Naphthanates from Jet Fuel Pipe Distributor Design Treating Sour Naphtha Converting Mercaptans to Disulfides 7. Minimizing Process Water Consumption 71 Two-Stage Wastewater Stripper Steam Condensate Recovery Condensate Drum Balance Line Location Water Hammer Measuring Condensate Recovery Cooling Tower Cycles of Concentration 8. Incremental Expansion Design Concept: Reprocessing Waste Lube Oil 79 Reprocessing Waste Lube Oil Vacuum Tower Design Wash Oil Grid Coking Vapor Horn Design in Vacuum Towers Stripping Tray Efficiency Precondenser Fouling Pump NPSH Limit in Vacuum Service Exchanger Fouling in Waste Oil Service Transfer-Line Sonic Velocity 9. Improving Fractionation Efficiency in Complex Fractionators 91 Pre-Flash Tower Concept Intermediate Reflux Stripping Tray Efficiency Maximizing Diesel Recovery from Crude Picket Weirs Adjusting Pump-arounds Pressure Optimization 10. Increasing Centrifugal Pump Capacity and Efficiency 103 Hydraulic Limitations Worn Impeller-to-Case Clearances Impeller Wear Ring Upgrading Impeller Size Marginal Cavitation Viscosity Effects on Efficiency NPSH Limited Condition 11. Eliminating Process Control Valves Using Variable-Speed Drivers 113 Frequency Control of Motors Eliminating Control Valves on Pump Discharge Direct Speed Control of Steam Turbine Variable-Speed Compressors Spill-backs Waste Energy Calculating Incentive for Variable-Speed Drivers Floating Tower Pressure Control 12. Expanding Refrigeration Capacity 123 Centrifugal Compressor Head vs. Flow Curve Calculating Compression Work Horsepower vs. Suction Pressure Limited Effect of Increasing Suction Pressure Reducing Refrigerant Condenser Fouling Effect of Noncondensibles Condensate Backup in Condenser 13. Oversizing Equipment Pitfalls 135 Amine H2 S Scrubber Optimizing Number of Trays in Absorbers Consequences of Overdesign Use of Demister in Knockout Drum Low Demister Velocity Promotes Mist Entrainment 14. Optimizing Use of Steam Pressure to Minimize Consumption of Energy 145 Preserving the Potential of Steam to Do Work Power Recovery from Steam to a Reboiler Use of the Mollier Diagram Cogeneration Plants Extracting Work from Reboiler Steam Using Existing Equipment Understanding Thermodynamics of Flowing Steam Steam Turbine Efficiency Checklist 15. Expanding Compressor Capacity and Efficiency 157 Reciprocating Compressors Pulsation Dampener Plates Adjustable Head-End Unloaders Natural Gas Engines Axial Compressor Rotor Fouling of Axial Air Compressor Centrifugal Compressors Cleaning Centrifugal Compressor Rotor 16. Vapor–Liquid Separator Entrainment Problems 171 Effect of Foam on Indicated Liquid Levels Hydrogen-Heavy Gas Oil Separtors Foam Induced Carry-Over Enhancing De-Entrainment Rates Vapor Distribution Aids De-Entrainment 17. Retrofitting Shell-and-Tube Heat Exchangers for Greater Efficiency 179 Running Slops Without Fouling Floating Suction in Charge Tanks Exchanger Online Spalling Effect of Feed Interruptions Tube Velocity and Surface Roughness Shell-Side Seal Strips Cooling High-Viscosity Fluids Expanding Water Cooler Capacity Hydrocarbon Losses to Cooling Towers 18. Reducing Sulfur and Hydrocarbon Emissions 189 Sulfur Plant Waste Heat Boiler Modifications Hydrocarbon Leaks in Seawater Cooling Systems Incinerator Back-Fire in Sulfur Plant Main Reaction Furnace Loss of Draft Due to Air Leaks Global Emissions in Perspective 19. Hydrocarbon Leaks to the Environment 201 Measuring Leaks Through Valves Fixing Leaking Valves On-Stream Detecting Leaking Relief Valves On-Stream Repair of Leaking Relief Valves Measuring Flows in Flare Lines Leaks into Cooling Water Air Cooler Leaks Valve Stem Packing Leaking Pump Mechanical Seal and Improper Use of Seal Flush Fixing Weld Leaks On-Stream 20. Composition-Induced Flooding in Packed Towers: FCU Fractionator Expansion 209 Fluid Cracking Unit Fractionator Expansion Flooding of Slurry Oil P/A Sections FCU Fractionator Vapor Line Quench Multipump Piping Stress Analysis Perception vs. Reality in Process Design 21. Maintenance for Longer Run Lengths 219 Sulfuric Acid Regeneration Importance of Reactor Insulation On-Stream Piping Repairs Preserving Pump Mechanical Seals Concept of Avoiding Unit Shutdowns 22. Instrument Malfunctions 229 Control Valve Loss Due to Instrument Air Pressure Signal Stuck Flow Control Valve Stem Mislocated Liquid-Level Tap Reducing Load to Vacuum System by Correcting False Level Indication 23. Summary Checklist for Reuse of Process Equipment 237 Fired Heaters Heat Exchangers Fin-Fan Air Coolers Distillation Tower Trays Vapor–Liquid Separators Centrifugal Pumps Fixed-Bed Reactors Electric Motors Gas and Steam Turbines Reciprocating and Centrifugal Compressors Air Blowers Water–Hydrocarbon Separators Overcoming Utility System Limits 24. Water–Hydrocarbon Separation: Corrosive Effects of Water 245 Water–Oil Separators Corrosive Elements from Cracking Plants Water Traps in Strippers Current CO2 Levels Environmental Overview Appendix: Solar Power Potential 257 Index 259

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Book SynopsisThe ultimate reference guide to the synthesis of radiopharmaceuticals The Radiochemical Syntheses series provides scientists and professionals with a comprehensive reference to proven synthetic methods for radiochemical reactions, along with step-by-step guidance on how to replicate these syntheses in the laboratory. Volume 1 in the series focuses on the synthesis and purification of radiopharmaceuticals in clinical use today. It brings together in one complete, self-contained volume a collection of monographs containing a wealth of practical information from across the literature, demonstrating in meticulous detail how to prepare radiopharmaceuticals for positron emission tomography (PET) imaging, especially in tumor studies, cardiology, and neuroscience. Readers have key experimental details culled from the literature at their fingertips, greatly simplifying the process of qualifying a site for the clinical production of new radiopharmaceuticals.Table of ContentsContributors ix Foreword xvii Preface xix Abbreviations xxi Part I Fluorine-18 Labeled Radiopharmaceuticals 1 1. Synthesis of [18F]-Fluorodeoxyglucose ([18F]FDG) 3Michelle L. Richards and Peter J. H. Scott 2. Synthesis of Sodium [18F]Fluoride (Na[18F]F) 15Brian G. Hockley and Peter J. H. Scott 3. Radiosynthesis of 3_-Deoxy-3_-[18F]Fluorothymidine ([18F]FLT) 21Hartmuth C. Kolb, Henry C. Padgett, Steve Zigler, Jim Patanella, Fanrong Mu, Umesh B. Gangadharmath, Vani P. Mocharla, Peter J. H. Scott, and Joseph C. Walsh 4. Synthesis of [18F]Fluoroazomycin Arabinoside ([18F]FAZA) 31Brian G. Hockley and Peter J. H. Scott 5. Synthesis of [18F]Fluoromisonidazole (1-(2-Hydroxy-3-[18F]Fluoropropyl)-2-Nitroimidazole, [18F]FMISO) 41Patrick J. Riss, Valentina Ferrari, Robert Bielik, Roberto Canales-Candela, Rob Smith, and Franklin I. Aigbirhio 6. Synthesis of [18F]FPPRGD2 51Shuanglong Liu, Frederick T. Chin, Zhen Cheng, and Xiaoyuan Chen 7. Synthesis of [18F]Fluorocholine ([18F]FCH) 61David Kryza 8. Clinical Manufacturing of [18F]-16-α-Fluoroestradiol ([18F]FES) 69Piyush Kumar and John R. Mercer 9. Synthesis of N-Succinimidyl 4-[18F]Fluorobenzoate ([18F]SFB) 81Xia Shao 10. Synthesis of 4-(2_-Methoxyphenyl)-1-[2_-(N-2__Pyridinyl)-p-[18F]Fluorobenzamido]Ethylpiperazine [18F]MPPF 87Marion Alvarez and Didier Le Bars 11. Synthesis of [18F]-Fallypride 95Laurent Brichard, Valentina Ferrari, Rob Smith, and Franklin I. Aigbirhio 12. Synthesis of [18F]Fluoroethyltyrosine (18F-FET) 103Yi Zhao, Amar Alfteimi, and Maaz Zuhayra 13. Synthesis of [18F]Flumazenil ([18F]FZ) 111Ralf Schirrmacher, Alexey Kostikov, Gassan Massaweh, Miriam Kovacevic, Carmen Wängler, and Alexander Thiel 14. Synthesis of 6-[18F]Fluorodopamine (6-[18F]FDA) 125Michael A. Channing, John L. Musachio, and Jozef J. Kusmierz 15. Synthesis of 2-([18F]Fluoro)-3-[(2S)-2-Azetidinylmethoxy]Pyridine ([18F]2FA) 139Hayden T. Ravert, Daniel P. Holt, and Robert F. Dannals 16. Synthesis of [18F]-Substance-P Antagonist-Receptor Quantifier ([18F]SPA-RQ) 155Sofie Celen, Kim Serdons, Tjibbe de Groot, Terence G. Hamill, and Guy Bormans Part II Carbon-11 Labeled Radiopharmaceuticals 167 17. Synthesis of [11C]Choline Chloride ([11C]CHL) 169Brian G. Hockley, Bradford Henderson, and Xia Shao 18. Synthesis of 2-(4-N-[11C]Methylaminophenyl)-6-Hydroxybenzothiazole ([11C]6-OH-BTA-1; [11C]PIB) 177Cécile Philippe, Markus Mitterhauser, and Wolfgang Wadsak 19. Synthesis of [11C]-meta-Hydroxyephedrine ([11C]MHED) 191Filippo Lodi, Assunta Carpinelli, Claudio Malizia, and Stefano Boschi 20. Synthesis of l-[methyl-11C]Methionine ([11C]MET) 199Amy L. Vāvere and Scott E. Snyder 21. Synthesis of (+)-α-[11C]Dihydrotetrabenazine ([11C]DTBZ) 213Michael R. Kilbourn 22. Synthesis of [11C]Flumazenil([11C]FMZ) 221Roberto Canales-Candela, Patrick J. Riss, and Franklin I. Aigbirhio 23. Synthesis of [11C]Hexadecanoic Acid ([11C]Palmitic Acid) 233Adam C. Runkle, Xia Shao, and Peter J. H. Scott 24. Synthesis of O-methyl-11C]Metomidate ([11C]-MTO) 245István Boros and Franklin I. Aigbirhio 25. Synthesis of [11C]Carfentanil ([11C]CFN) 257Louis Tluczek and Xia Shao 26. Synthesis of [carbonyl-11C]Way-100635 265Jan D. Andersson, Sangram Nag, Raisa N. Krasikova, Victor W. Pike, and Christer Halldin 27. Synthesis of [11C]Raclopride 275Xia Shao 28. Synthesis of 3-Amino-4-[2-(N-Methyl-N-[11C]Methyl-Amino-Methyl)Phenylsulfanyl]-Benzonitrile ([11C]Dasb) 285Daniela Haeusler, Markus Mitterhauser, and Wolfgang Wadsak 29. Synthesis of [11C] Acetate 297Filippo Lodi, Claudio Malizia, and Stefano Boschi 30. Synthesis of N-(2-[11C]Methoxybenzyl)-N-(4-Phenoxypyridin-3-yl)Acetamide ([11C]PBR28) 305Qi-Huang Zheng, Min Wang, and Bruce H. Mock Part III Other Radiopharmaceuticals 313 31. Synthesis of [13N]Ammonia ([13N]NH3) 315Peter J. H. Scott 32. Synthesis of [68GA]Gallium Dota-(TYR3)-Octreotide Acetate ([68GA]-Dotatoc) 321Harald Eidherr, Friedrich Girschele, Markus Mitterhauser, and Wolfgang Wadsak Appendix 1 Supplier Information 335 Index 339

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Book SynopsisThis book isa comprehensive and up-to-date review and evaluation of the contemporary status of telomerase research. Chapters in this volume cover the basic structure, mechanisms, and diversity of the essential and regulatory subunits of telomerase. Other topics include telomerase biogenesis, transcriptional and post-translational regulation, off-telomere functions of telomerase and the role of telomerase in cellular senescence, aging and cancer. Its relationship to retrotransposons, a class of mobile genetic elements that shares similarities with telomerase and serves as telomeres in selected organisms, are also reviewed. Table of ContentsPreface vii Contributors ix 1 The Telomerase Complex: An Overview 1 Johanna Mancini and Chantal Autexier 2 Telomerase RNA: Structure, Function, and Molecular Mechanisms 23 Yehuda Tzfati and Julian J.-L. Chen 3 TERT Structure, Function, and Molecular Mechanisms 53 Emmanuel Skordalakes and Neal F. Lue 4 Telomerase Biogenesis: RNA Processing, Trafficking, and Protein Interactions 79 Tara Beattie and Pascal Chartrand 5 Transcriptional Regulation of Human Telomerase 105 Antonella Farsetti and Yu-Sheng Cong 6 Telomerase Regulation and Telomere-Length Homeostasis 135 Joachim Lingner and David Shore 7 Telomere Structure in Telomerase Regulation 157 Momchil D. Vodenicharov and Raymund J. Wellinger 8 Off-Telomere Functions of Telomerase 201 Kenkichi Masutomi and William C. Hahn 9 Murine Models of Dysfunctional Telomeres and Telomerase 213 Yie Liu and Lea Harrington 10 Cellular Senescence, Telomerase, and Cancer in Human Cells 243 Phillip G. Smiraldo, Jun Tang, Jerry W. Shay, and Woodring E. Wright 11 Telomerase, Retrotransposons, and Evolution 265 Irina R. Arkhipova Index 301

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Book SynopsisThere are plenty of books on specialized risk topics but few that deal with the broad diversity and daily applicability of this subject. Risk applications require a robust knowledge of many attributes of this seemingly simple subject. This book teaches the reader through examples and case studies the fundamental (and subtle) aspects of risk - regardless of the specific situation. The text allows the reader to understand the concept of risk analysis while not getting too involved in the mathematics; in this method the reader can apply these techniques across a wide range of situations. The second edition includes new examples from NASA and several other industries as well as new case studies from legal databases. The many real-life discussion topics enable the reader to form an understanding of the concepts of risk and risk management and apply them to day-to-day issues.Table of ContentsPreface ix Acknowledgments xi 1. Risk: Life’s Question Mark 1 2. Measurement: The Alchemist’s Base 15 3. Statistics: Numbers Looking for an Argument 41 4. The Value of Life and Limb, Statistically Speaking 69 5. The Evolution of Risk 93 6. Frequency and Severity: Weighing the Risk 107 7. What’s in a Risk? Perception Creates Risk Reality 128 8. Risk, Regulation, and Reason 151 9. Earth, Air, and Water: The Not-So-Bare Essentials 176 10. Food . . . for Thought 210 11. Flying: The Not-So-Wild Blue Yonder 249 12. Risk on the Roads 278 13. An Incomplete List of Life’s Risks 315 Index 337

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Book SynopsisBiomedical applications of Polymers from Scaffolds to Nanostructures The ability of polymers to span wide ranges of mechanical properties and morph into desired shapes makes them useful for a variety of applications, including scaffolds, self-assembling materials, and nanomedicines. With an interdisciplinary list of subjects and contributors, this book overviews the biomedical applications of polymers and focuses on the aspect of regenerative medicine. Chapters also cover fundamentals, theories, and tools for scientists to apply polymers in the following ways: Matrix protein interactions with synthetic surfaces Methods and materials for cell scaffolds Complex cell-materials microenvironments in bioreactors Polymer therapeutics as nano-sized medicines for tissue repair Functionalized mesoporous materials for controlled delivery Nucleic acid delivery nanocarriers Concepts include macro and nano requiTable of ContentsPreface xi Contributors xvii Part A Methods for Synthetic Extracellular Matrices and Scaffolds 1 1 Polymers as Materials for Tissue Engineering Scaffolds 3 Ana Vallés Lluch Dunia Mercedes García Cruz Jorge Luis Escobar Ivirico Cristina Martínez Ramos and Manuel Monleón Pradas 1.1 The Requirements Imposed by Application on Material Structures Intended as Tissue Engineering Scaffolds 3 1.2 Composition and Function 5 1.2.1 General Considerations 5 1.2.2 Some Families of Polymers for Tissue Engineering Scaffolds 8 1.2.3 Composite Scaffold Matrices 12 1.3 Structure and Function 14 1.3.1 General Considerations 14 1.3.2 Structuring Polymer Matrices 15 1.4 Properties of Scaffolds Relevant for Tissue Engineering Applications 24 1.4.1 Porous Architecture 24 1.4.2 Solid State Properties: Glass Transition Crystallinity 25 1.4.3 Mechanical and Structural Properties 26 1.4.4 Swelling Properties 28 1.4.5 Degradation Properties 29 1.4.6 Diffusion and Permeation 30 1.4.7 Surface Tension and Contact Angle 31 1.4.8 Biological Properties 31 1.5 Compound Multicomponent Constructs 32 1.5.1 Scaffold-Cum-Gel Constructs 32 1.5.2 Scaffolds and Membranes Containing Microparticles 34 1.5.3 Other Multicomponent Scaffold Constructs 34 1.6 Questions Arising from Manipulation and Final Use 35 1.6.1 Sterilization 35 1.6.2 Cell Seeding Cell Culture Analysis 36 1.6.3 In the Surgeon’s Hands 37 References 37 2 Natural-Based and Stimuli-Responsive Polymers for Tissue Engineering and Regenerative Medicine 49 Mariana B. Oliveira and João F. Mano 2.1 Introduction 49 2.2 Natural Polymers and Their Application in TE & RM 52 2.2.1 Polysaccharides 52 2.2.2 Protein-Based Polymers 60 2.2.3 Polyesters 65 2.3 Natural Polymers in Stimuli-Responsive Systems 65 2.3.1 pH-Sensitive Natural Polymers 67 2.3.2 Temperature Sensitive Natural Polymers 67 2.3.3 Natural Polymers Modified to Show Thermoresponsive Behavior—Modifying Responsive Polymers and Agents 71 2.3.4 Light-Sensitive Polymers—Potential Use of Azobenzene/α-Cyclodextrin Inclusion Complexes 72 2.4 Conclusions 73 References 74 3 Matrix Proteins Interactions with Synthetic Surfaces 91 Patricia Rico Marco Cantini George Altankov and Manuel Salmerón-Sánchez 3.1 Introduction 91 3.2 Protein Adsorption 92 3.2.1 Cell Adhesion Proteins 93 3.2.2 Experimental Techniques to Follow Protein Adsorption 94 3.2.3 Effect of Surface Properties on Protein Adsorption 97 3.3 Cell Adhesion 109 3.3.1 Experimental Techniques to Characterize Cell Adhesion 112 3.3.2 Cell Adhesion at Cell–Material Interface 115 3.4 Remodeling of the Adsorbed Proteins 122 3.4.1 Protein Reorganization and Secretion at the Cell–Material Interface 122 3.4.2 Proteolytic Remodeling at Cell–Materials Interface 126 References 128 4 Focal Adhesion Kinase in Cell–Material Interactions 147 Cristina González-García Manuel Salmerón-Sánchez and Andrés J. García 4.1 Introduction 147 4.2 Role of FAK in Cell Proliferation 149 4.3 Role of FAK in Migratory and Mechanosensing Responses 150 4.4 Role of FAK in the Generation of Adhesives Forces 152 4.5 Influence of Material Surface Properties on FAK Signaling 156 4.5.1 Effect of Mechanical Properties on FAK Signaling 156 4.5.2 Effect of Surface Topography on FAK Signaling 160 4.5.3 Effect of Surface Chemistry on FAK Signaling 163 4.5.4 Effect of Surface Functionalization in FAK Expression 165 References 168 5 Complex Cell–Materials Microenvironments in Bioreactors 177 Stergios C. Dermenoudis and Yannis F. Missirlis 5.1 Introduction 177 5.2 Cell–ECM Interactions 178 5.2.1 ECM Chemistry 179 5.2.2 ECM Topography 181 5.2.3 ECM Mechanical Properties 183 5.2.4 ECM 3D Structure 184 5.2.5 ECM-Induced Mechanical Stimuli 186 5.3 Cell–Nutrient Medium 187 5.3.1 Composition and Volume-Related Phenomena 188 5.3.2 Mechanical Stresses Induced by Nutrient Medium 191 5.4 Other Aspects of Interaction 194 5.4.1 Co-Culture Systems 195 5.4.2 Material Interactions 196 5.5 Conclusions 197 References 197 Part B N anostructures for Tissue Engineering 207 6 Self-Curing Systems for Regenerative Medicine 209 Julio San Román Blanca Vázquez and María Rosa Aguilar 6.1 Introduction 209 6.2 Self-Curing Systems for Hard Tissue Regeneration 210 6.2.1 Antimicrobial Self-Curing Formulations 211 6.2.2 Self-Curing Formulations for Osteoporotic Bone 214 6.2.3 Antineoplastic Drug-Loaded Self-Curing Formulations 216 6.2.4 Nonsteroidal Anti-Inflammatory Drug-Loaded Formulations 217 6.2.5 Self-Curing Formulations with Biodegradable Components 218 6.3 Self-Curing Hydrogels for Soft Tissue Regeneration 219 6.3.1 Chemically Cross-Linked Hydrogels 220 6.3.2 Chemically and Physically Cross-Linked Hydrogels 225 6.4 Expectative and Future Directions 226 References 226 7 Self-Assembling Peptides as Synthetic Extracellular Matrices 235 M.T. Fernandez Muiños and C.E. Semino 7.1 Introduction 235 7.2 In Vitro Applications 238 7.3 In Vivo Applications 242 References 245 8 Polymer Therapeutics as Nano-Sized Medicines for Tissue Regeneration and Repair 249 Ana Armiñán Pilar Sepúlveda and María J. Vicent 8.1 Polymer Therapeutics as Nano-Sized Medicines 249 8.1.1 The Concept and Biological Rationale behind Polymer Therapeutics 249 8.1.2 Current Status and Future Trends 252 8.2 Polymer Therapeutics for Tissue Regeneration and Repair 254 8.2.1 Ischemia/Reperfusion Injuries 255 8.2.2 Wound Healing/Repair 260 8.2.3 Musculoskeletal Disorders 263 8.2.4 Diseases of the Central Nervous System 267 8.3 Conclusions and Future Perspectives 272 References 273 9 How Regenerative Medicine Can Benefit from Nucleic Acids Delivery Nanocarriers? 285 Erea Borrajo Anxo Vidal Maria J. Alonso and Marcos Garcia-Fuentes 9.1 Introduction 285 9.1.1 Learning from Viruses: How to Overcome Cellular Barriers 286 9.2 Nanotechnology in Gene Delivery 292 9.2.1 Lipid Nanocarriers 292 9.2.2 Polymeric Nanocarriers 294 9.2.3 Inorganic Nanoparticles 300 9.3 Nanotechnology in Regenerative Medicine 302 9.3.1 Bone Regeneration 303 9.3.2 Cartilage Regeneration 305 9.3.3 Tendon Regeneration 308 9.3.4 Myocardium Regeneration 309 9.3.5 Neurological Tissue 311 9.4 Conclusions 313 References 313 10 Functionalized Mesoporous Materials with Gate-Like Scaffoldings for Controlled Delivery 337 Elena Aznar Estela Climent Laura Mondragon Félix Sancenón and Ramón Martínez-Máñez 10.1 Introduction 337 10.2 Mesoporous Silica Materials with Gate-Like Scaffoldings 339 10.2.1 Controlled Delivery by pH Changes 339 10.2.2 Controlled Delivery Using Redox Reactions 345 10.2.3 Controlled Delivery Using Photochemical Reactions 349 10.2.4 Controlled Delivery via Temperature Changes 352 10.2.5 Controlled Delivery Using Small Molecules 355 10.2.6 Controlled Delivery Using Biomolecules 356 10.3 Concluding Remarks 360 References 361 11 Where Are We Going? Future Trends and Challenges 367 Sang Jin Lee and Anthony Atala 11.1 Introduction 367 11.2 Classification of Biomaterials in Tissue Engineering and Regenerative Medicine 368 11.2.1 N aturally Derived Materials 368 11.2.2 Biodegradable Synthetic Polymers 370 11.2.3 Tissue Matrices 372 11.3 Basic Principles of Biomaterials in Tissue Engineering 373 11.4 Development of Smart Biomaterials 374 11.5 Scaffold Fabrication Technologies 376 11.5.1 Injectable Hydrogels 376 11.5.2 Electrospinning 377 11.5.3 Computer-Aided Scaffold Fabrication 378 11.5.4 Functionalization of Tissue-Engineered Biomaterial Scaffolds 379 11.6 Summary and Future Directions 381 References 384 Index 391

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Book SynopsisThe accessible compendium of polymers in carbon nanotubes (CNTs) Carbon nanotubes (CNTs)?extremely thin tubes only a few nanometers in diameter but able to attain lengths thousands of times greater?are prime candidates for use in the development of polymer composite materials. Bringing together thousands of disparate research works, Carbon Nanotube-Polymer Composites: Manufacture, Properties, and Applications covers CNT-polymers from synthesis to potential applications, presenting the basic science and engineering of this dynamic and complex area in an accessible, readable way. Designed to be of use to polymer scientists, engineers, chemists, physicists, and materials scientists, the book covers carbon nanotube fundamentals to help polymer experts understand CNTs, and polymer physics to help those in the CNT field, making it an invaluable resource for anyone working with CNT-polymer composites. Detailed chapters describe the mechanical, rheological, electrical, and theTable of ContentsPREFACE ix CHAPTER 1 INTRODUCTION 1 1.1 Similarities Between Polymers and Nanotubes 1 1.2 Organization of the Book 3 1.3 Why Write This Book? 7 References 9 CHAPTER 2 CARBON NANOTUBES 11 2.1 Overview 11 2.2 Synthesis 16 2.2.1 Arc Discharge 19 2.2.2 Visible Light Vaporization 21 2.2.3 Chemical Vapor Deposition 22 2.3 Purification 25 2.4 Properties 26 2.4.1 Mechanical Properties 27 2.4.2 Electronic, Magnetic, and Thermal Properties 29 2.4.3 Optical Properties 32 2.5 Chemistry 36 2.5.1 Characterizing the Nature of Functionalization 38 2.5.2 Common Functionalization Chemistries 40 2.5.3 Polymer Covalently Bonded to Nanotubes: “Grafting From” 42 2.5.4 Polymer Covalently Bonded to Nanotubes: “Grafting To” 44 2.6 Challenges 44 References 45 CHAPTER 3 DISPERSION, ORIENTATION, AND LENGTHS OF CARBON NANOTUBES IN POLYMERS 59 3.1 Overview 59 3.2 Dispersion Characterization 66 3.2.1 Microscopy 67 3.2.2 Spectroscopy 72 3.3 Methods to Disperse Nanotubes into Low-Viscosity Liquids, Including Monomers 77 3.3.1 Mixing Protocols: Sonication and High-Shear Mixing 79 3.3.2 Dispersions of Nanotubes in Water 81 3.3.3 Dispersions of Nanotubes in Other Solvents 86 3.4 Polymer–Nanotube Dispersions: Solution Methods 88 3.4.1 Dispersion–Reaction 88 3.4.2 Dissolution–Dispersion–Precipitation 90 3.4.3 Dispersion–Dispersion–Evaporation 93 3.5 Polymer–Nanotube Dispersions: Melt Mixing 94 3.6 Polymer–Nanotube Dispersions: No Fluid Mixing 96 3.7 Polymer–Nanotube Dispersions: Impregnation/Infusion 97 3.7.1 Nanotube Fiber–Polymer Composites 97 3.7.2 Nanotube Sheet–Polymer Composites 99 3.7.3 Nanotube Forests–Polymer Composites 101 3.7.4 Nanotubes on Already Existing Fibers 101 3.8 Challenges 102 References 103 CHAPTER 4 EFFECTS OF CARBON NANOTUBES ON POLYMER PHYSICS 119 4.1 Overview 119 4.2 Amorphous Polymers 122 4.2.1 Statics: Adsorption and Chain Configuration 122 4.2.2 Dynamics: Glass Transition and Diffusion Coefficient 129 4.3 Semicrystalline Polymers 142 4.3.1 Statics: Unit Cells, Lamellae, Spherulites, and Shish-Kebabs 147 4.3.2 Rate Effects: Glass Transition, Crystal Nucleation, and Growth 169 4.4 Blends and Block Copolymers 174 4.5 Challenges 176 References 177 CHAPTER 5 MECHANICAL AND RHEOLOGICAL PROPERTIES 191 5.1 Overview 191 5.2 Rheological Properties (Measurement of Melt and Solution Properties) 200 5.2.1 Nonoscillatory Measurements 204 5.2.2 Oscillatory Measurements and the Percolation Threshold 208 5.3 Mechanical Properties (Measurement of Solid Properties) 212 5.3.1 Interfacial Shear Strength 214 5.3.2 Tensile, Compressive, and Bending Properties 216 5.3.3 Fracture Toughness and Crack Propagation 228 5.3.4 Impact Energy 230 5.3.5 Oscillatory Measurements 230 5.3.6 Other Mechanical Properties 232 5.4 Challenges 232 References 233 CHAPTER 6 ELECTRICAL PROPERTIES 249 6.1 Overview 249 6.2 Mixed Composites 252 6.2.1 Maximum or Plateau Conductivity 260 6.2.2 Broadness of Percolation Region (Critical Exponent) 264 6.2.3 Percolation Threshold 264 6.2.4 Dielectric Constant 268 6.3 Impregnated/Infused Composites 269 6.4 Composites with Electrically Conducting Polymers 271 6.5 Challenges 274 References 275 CHAPTER 7 THERMAL CONDUCTIVITY 283 7.1 Overview 283 7.2 Interfacial Resistance and Thermal Conductivity 292 7.3 Dispersion, Percolation, and Thermal Conductivity 295 7.4 Effects of Other Variables on Thermal Conductivity 296 7.5 Challenges 299 References 299 CHAPTER 8 APPLICATIONS OF POLYMER–NANOTUBE COMPOSITES 305 8.1 Overview 305 8.2 Electrical Conductivity: EMI Shielding, ESD, and Transparent Electrodes 305 8.2.1 Electromagnetic Shielding 306 8.2.2 Electrostatic Dissipation 308 8.2.3 Transparent Electrodes 310 8.2.4 Other Applications Based on Nanotube Conductivity on Polymeric Substrates 312 8.3 Thermal Properties: Flame Retardancy 312 8.4 Electromechanical Properties: Strain Sensing and Actuators 315 8.4.1 Electromechanical Actuation 316 8.4.2 Strain Sensing 318 8.5 Other Applications 320 8.6 Challenges 322 References 322 GLOSSARY 331 INDEX 337

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Book SynopsisThe physical and chemical properties of polymeric materials influence their processing and use, so it is essential to be familiar with the properties and behavior to ensure proper utilization of such polymers.Trade Review"The articles provide comprehensive, current information on the physical properties of polymers and the resulting characteristics and behaviour." (Materials and Corrosion, 2011) Table of ContentsVolume 1. Acoustic Properties. Adhesion. Adsorption. Aging, Physical. Conformation and Configuration. Cryogenic properties. Degradation. Depolymerization. Drag Reduction. Elasticity, Rubber-like. Electrical Active Polymers. Flammability. Glass Transition. Hardness. Impact Resistance. Magnetic Polymers. Mechanical Performance of Plastics. Micromechanical Properties. Microstructure. Miscibility. Modeling of Polymer Processing and Properties. Volume 2. Networks, Elastomeric. Nonlinear Optical Properties. Optical Properties. Orientation. Photorefraction. Rheology and Rheological Measurements. Scratch Behavior of Polymers. Self-healing polymers. Solubility of Polymers. Surface Mechanical Damage and Wear of Polymers. Surface Properties. Thermal Properties. Thermodynamic Properties of Polymers. Transitions and Relaxations. Transport Properties. Viscoelasticity. Weathering. Yield and Crazing. Index.

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Book SynopsisMetal- and metalloid-containing macromolecules are defined as large molecules (i.e., polymers, DNA, proteins) that contain a metal or metalloid group affiliated with the molecule. This volume describes what is possible with metal-containing polymers where the metal is an essential ingredient in obtaining desired optical and electronic properties. Covering applications in nonlinear optical materials, solar cells, light-emitting diodes, photovoltaic cells, field-effect transistors, chemosensing devices, and biosensing devices, this indispensible guide focuses on the photochemistry and photophysics of metal-containing polymers, with chapters by leading contributors to the core advances in this field.Table of ContentsPreface. Series Preface. 1. Introduction to Photophysics and Photochemistry (Shawkat M. Aly, Charles E. Carraher Jr., and Pierre D. Harvey). I. General. II. Photophysics and Photochemistry. III. Light Absorption. IV. Luminescence. V. Emission Lifetime. VI. Ground and Excited State Molecular Interactions. A. Energy and Electron Transfer (Excited State Interactions and Reactions). B. Energy Transfer. C. Electron Transfer. VII. Nonlinear Optical Behavior. VIII. Photoconductive and Photonic Polymers. IX. Photosynthesis. A. Purple Photosynthetic Bacteria. B. Green Sulfur Bacteria. X. Organometallic Polymers and Synthetic Photosynthesis Systems. XI. Summary. XII. References Additional Readings. XIII. References. 2. Luminescent Organometallic Coordination Polymers Built on Isocyanide Bridging Ligands (Pierre D. Harvey, Sébastien Clément, Michael Knorr, and Jerome Husson). I. Introduction. II. Luminescent Organometallic Polynuclear Systems and Coordination Polymers Containing a Terminal Isocyanide Ligand. III. Luminescent Polymeric Systems Containing an Isocyanide Ligand Assembled via M...M Interactions. IV. Luminescent Organometallic Polymetallic Systems and Coordination Polymers Containing Bridging Isocyanides. V. Conclusion. VI. Acknowledgments. VII. References. 3. Luminescent Oligomeric and Polymeric Copper Coordination Compounds Assembled by Thioether Ligands (Michael Knorr and Fabrice Guyon). I. Introduction. II. Background Informations. III. Luminescent Copper Polymers Assembled by Thioether Ligands. A. Copper Polymers Assembled by Monothioether Ligands RSR. B. Copper Polymers Assembled by Aromatic Dithioether Ligands. C. Copper Polymers Assembled by Aliphatic Dithioether and Polythioether Ligands. D. Copper Polymers Assembled by Dithioether and Polythioether Ligands Bearing Heteroelements in the Spacer Unit. IV. Conclusion. V. Acknowledgments. VI. References. 4. Applications of Metal Containing Polymers in Organic Solar Cells (Chris S. K. Mak and Wai Kin Chan). I. Introduction. II. Types of Organic Solar Cells. A. Dye-Sensitized Solar Cells. B. Organic Thin Film Solar cells. III. Solar Cell Characterizations. IV. Metal Containing Polymers in Solar Cells. A. Dye-Sensitized Solar Cells. B. Organic Thin Film Solar Cells. V. Summary. VI. Acknowledgments. VII. References. 5. Functional Silole-Containing Polymers (Junwu Chen, Yong Cao, and Ben Zhong Tang). I. Introduction. II. Electronic Transition and Band Gap. III. Light Emission. A. Photoluminescence. B. Electroluminescence. IV. Bulk-Heterojuction Photovoltaic Cells. V. Field Effect Transistors. VI. Aggregation-Induced Emission. VII. Chemosensors. VIII. Conductivity. IX. Optical Limiting. X. Summary. XI. Acknowledgments. XII. References. 6. Photophysics and Photochemistry of Polysilanes for Electronic Applications (Starr Dostie, Cetin Aktik, and Mihai Scarlete). I. Introduction. II. Synthesis of Electronic-Grade Polysilanes. III. Band Structure. IV. Photophysics. A. Influence of the Backbone Structure. B. Side Groups. C. Nanostructured Polysilanes. D. PL Quenching by Doping. E. Energy Transfer. F. Electroluminescence. G. Cathodoluminescence. H. Interaction with Photoelectrons. V. Photochemistry. A. Photo-Oxidation. VI. Polysilane Thin Films for Electronic Devices. A. LED. B. Photoconductors. C. Photovoltaics. D. Lithography. E. Electron Beam. VII. Polysilane Films for Optical Devices. A. NLO. VIII. Summary. IX. References. 7. Polymers with Metal-Metal Bonds as Models in Mechanistic Studies of Polymer Photodegradation (David R. Tyler, Bevin Daglen, and Ginger Shultz). I. Introduction. II. Experimental Strategies. III. Synthesis of Polymers with Metal-Metal Bonds along their Backbones. A. Step-Growth Polymers. B. ADMET Polymerization. C. Chain-Growth Polymers. IV. Photochemical Reactions of the Polymers in Solution. V. Photochemistry in the Solid State. VI. Factors Controlling the Rate of Polymer Photochemical Degradation in the Solid State. A. Temperature Effects. B. Interpreting the Kinetics of Polymer Degradation in the Solid State. C. Photodegradation Rate Dependence on Polymer Curing Time. D. The Effects of Stress on Polymer Degradation. VII. Kinetics of Polymer Formation. VIII. Concluding Remarks on the Importance of Radical-Radical Recombination on the Efficiency of Polymer Photochemical Degradation. IX. Acknowledgments. X. References. 8. Optical Properties and Photophysics of Platinum-Containing Poly (aryleneethynylene)s (Wai-Yeung Wong). I. Introduction. II. Synthetic Methods and Materials Characterization. III. Optical and Photophysical Properties. A. Energy Gap Law for Triplet States. B. Phosphorescence Color Tuning of Metallopolyynes. C. Roles of Metallopolyynes in Optoelectronic and Photonic Devices. IV. Summary. V. Acknowledgments. VI. References. 9. Luminescence in Polymetallic Gold-Heteronuclear Derivatives (Antonio Laguna and Jose M. López-de-Luzuriaga). I. Introduction and Background. II. Luminescent Gold-Silver Derivatives. A. Supramolecular Gold-Silver Complexes with Bidentate Ligands. B. Supramolecular Gold-Silver Complexes with Tridentate Ligands. C. Supramolecular Gold-Silver Complexes Built with Metallic Cationic and Anionic Counterparts. III. Luminescent Gold-Copper Derivatives. IV. Luminescent Gold-Thallium Derivatives. A. Supramolecular Gold-Thallium Complexes with Bidentate Ligands. B. Supramolecular Gold-Thallium Complexes through Acid-Base Reactions. V. Luminescent Gold-Lead Derivatives. VI. Luminescent Gold-Platinum Derivatives. VII. Luminescent Gold-Mercury Derivatives. VIII. Conclusion. IX. References. 10. Functional Self-Assembled Zinc(II) Coordination Polymers (Chi-Chung Kwok and Chi-Ming Che). I. Introduction. II. Zinc(II) Terpyridine Polymers. III. Zinc(II) Schiff Base Polymer. IV. Summary. V. Acknowledgment. VI. References. 11. Redox and Photo Functions of Metal Complex Oligomer and Polymer Wires on the Electrode (Mariko Miyachi and Hiroshi Nishihara). I. Introduction. II. Bottom-Up Fabrication of Redox-Conducting Metal Complex Oligomers on an Electrode Surface and Their Redox Conduction Behavior. A. Bottom-Up Fabrication of Metal Complex Oligomer and Polymer Wires. B. Electron Transport Behavior of the Molecular Wires on the Electrode. III. Photoelectric Conversion System Using Porphyrin and Redox-Conducting Metal Complex Wires. A. Bottom-Up Fabrication of the Porphyrin-Terminated Redox-Conducting Metal Complex Film on ITO. B. Photoelectrochemical Properties of the Porphyrin-Terminated Redox-Conducting Metal Complex Film on ITO. IV. Biophotosensor and Biophotoelectrode Composed of Cyanobacterial Photosystem I and Molecular Wires. A. Biophotosensor Composed of Cyanobacterial Photosystem I, Molecular Wire, Gold Nanoparticle, and Transistor. B. Biophotoelectrode Composed of Cyanobacterial Photosystem I and Molecular Wires. V. Conclusion. VI. References. Index.

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Book SynopsisPresents both the fundamental concepts and the most recent applications in solid-phase organic synthesis With its emphasis on basic concepts, Solid-Phase Organic Synthesis guides readers through all the steps needed to design and perform successful solid-phase organic syntheses. The authors focus on the fundamentals of heterogeneous supports in the synthesis of organic molecules, explaining the use of a solid material to facilitate organic synthesis. This comprehensive text not only presents the fundamentals, but also reviews the most recent research findings and applications, offering readers everything needed to conduct their own state-of-the-art science experiments. Featuring chapters written by leading researchers in the field, Solid-Phase Organic Synthesis is divided into two parts: Part One, Concepts and Strategies, discusses the linker groups used to attach the synthesis substrate to the solid support, colorimetric tests to Table of Contents Preface xv Acknowledgments xvii Contributors xix Part I Concepts and Strategies 1 1 Linker Strategies in Modern Solid-Phase Organic Synthesis 3Peter J. H. Scott 1.1 Introduction 3 1.2 Classical Linker Strategies 5 1.3 Multifunctional Linker Strategies 28 1.4 Conclusions 73 References 73 2 Colorimetric Test For Solid-Phase Organic Synthesis 83Yan Teng and Patrick H. Toy 2.1 Introduction 83 2.2 Functional Group Tests 84 2.3 Conclusions 92 References 92 3 Practical Aspects of Combinatorial Solid-Phase Synthesis 95Jan Hlavac, Miroslav Soural, and Viktor Krchnak 3.1 Introduction 95 3.2 Strategies in Combinatorial Solid-Phase Synthesis 101 3.3 Equipment and Instrumentation 112 3.4 Characterization and Purification 118 3.5 Conclusions 121 Acknowledgments 121 References 121 4 Diversity-Oriented Synthesis 131Kieron M. G. O’Connell, Warren R. J. D Galloway, Brett M. Ibbeson, Albert Isidro-Llobet, Cornelius J. O’Connor, and David R. Spring 4.1 Introduction 131 4.2 Small Molecules and Biology 131 4.3 Diversity-Oriented Synthesis, Target-Oriented Synthesis, and Combinatorial Chemistry 133 4.4 Molecular Diversity 134 4.5 Diversity-Oriented Synthesis on Solid Phase 137 4.6 Diversity-Oriented Synthesis Around Privileged Scaffolds 146 4.7 Diversity Linker Units in Solid-Phase Organic Synthesis 147 4.8 Conclusions 148 References 149 5 Diversity-Oriented Synthesis of Privileged Heterocycles Using Divergent Strategy 151Seung Bum Park and Jonghoon Kim 5.1 Introduction 151 5.2 Divergent Synthesis of Natural Product-Like Polyheterocycles Using a Cyclic Iminium as a Single Key Intermediate 153 5.3 Conclusions 168 References 168 6 Chemo- and Regioselectivity Enhancement in Solid-Supported Reactions 171Douglas D. Young and Alexander Deiters 6.1 Introduction 171 6.2 Transition Metal-Mediated Solid-Supported Reactions 172 6.3 Non-transition Metal-Mediated Solid-Supported Reactions 186 6.4 Traceless Cleavage 192 6.5 Conclusions 201 References 201 Part II Applications 205 7 Asymmetric Synthesis On Solid Support 207Baburaj Baskar and Kamal Kumar 7.1 Introduction 207 7.2 Asymmetric Chemical Transformations of Solid-Supported Substrates 208 7.3 Asymmetric Transformations Using Resin-Bound Chiral Catalysts and Auxiliaries 219 7.4 Conclusions 227 References 227 8 Recent Advances in Microwave-Assisted Solid-Phase Synthesis of Heterocycles 231Prasad Appukkuttan, Vaibhav, P. Mehta, and Erik Van der Eycken 8.1 Introduction 231 8.2 Fused 1,3-oxazin-6-ones 232 8.3 Thiazolo[4,5-d]pyrimidine-5,7-diones 233 8.4 Pyrazoles 234 8.5 HSP70 Modulators 234 8.6 Benzimidazo[2,1-b]quinazolin-12(5H)-ones 236 8.7 Imidazoles 237 8.8 1,4-Naphthoquinones 238 8.9 Phthalocyanines 238 8.10 1,2,3,4-Tetrahydroquinolines 242 8.11 1,2,3-Triazoles 243 8.12 2,8-Diaminopurines 244 8.13 Imidazolidin-4-ones 245 8.14 Indoles 247 8.15 1,2,3,4-Tetrahydroquinolines Using a SmI2-Cleavable Linker 248 8.16 Hydantoins 249 8.17 Imatinib 250 8.18 Isoindolines 252 8.19 2-(Benzylthio)imidazo[1,2a]-pyrimidin-5-ones 253 8.20 2-Aminobenzothiazoles 254 8.21 Pyrimidines, Pyrazoles, and Isoxazoles 255 8.22 Quinolin-2(1H)-ones and Coumarins 256 8.23 Benzofurans 257 8.24 i-Condensed Purines 258 8.25 2(1H)-Pyrazinones 259 8.26 Conclusions 260 References 261 9 Solid-Phase Synthesis of Heterocycles From Peptides and Amino Acids 269Zhi Li, Marc Giulianotti, Wenteng Chen, Richard A. Houghten, and Yongping Yu 9.1 Introduction 269 9.2 Synthesis of Various Heterocycles 269 References 316 10 Generation of Drug-Like Five-Membered Heterocyclic Libraries Using Carbon Disulfide and Merrifield Resin 319Young-Dae Gong and Taeho Lee 10.1 Introduction 319 10.2 Solid-Phase Synthesis of Related Thiazole Compounds 320 10.3 Solid-Phase Synthesis of Benzoxazoles 333 10.4 Solid-Phase Synthesis of Related Pyrazole Compounds and 1,3,4-Triazoles via a Dithiocarbazate Linker 334 10.5 Solid-Phase Synthesis of 1,3,4-Oxadiazoles and 1,3,4-Thiadiazoles via Selective Cyclization 342 10.6 Solid-Phase Synthesis of 1,2,4-Thiadiazoles 347 10.7 Summary 350 References 350 11 Recent Advances in Solid-Phase 1,3-Dipolar Cycloaddition Reactions 355Kirsi Harju and Jari Yli-Kauhaluoma 11.1 Introduction 355 11.2 Solid-Phase Synthesis of Pyrrolidines, Pyrrolines, and Pyrroles 356 11.3 Synthesis of Pyrazolines and Pyrazoles 361 11.4 Solid-Phase Synthesis of Imidazoles, 1,2,4-Triazoles, and 1,2,3-Triazoles 364 11.5 Solid-Phase Synthesis of Isoxazolidines, Isoxazolines, and Isoxazoles 369 11.6 Conclusions 378 References 378 12 Sulfones in Solid-Phase Heterocycle Synthesis 383Chai Hoon Soh and Yulin Lam 12.1 Introduction 383 12.2 Linkers 384 12.3 Conclusions 411 References 411 13 Solid-Phase Organic Radiosynthesis 415Raphael Hoareau and Peter J. H. Scott 13.1 Introduction 415 13.2 Solid-Phase Organic Radiosynthesis with Fluorine-18 416 13.3 Solid-Phase Organic Radiosynthesis with Carbon-11 421 13.4 Solid-Phase Organic Radiosynthesis with Other Radioisotopes 422 13.5 Conclusions 424 References 424 14 Solid-Phase Synthesis of Dyes and Their Application As Sensors and Bioimaging Probes 427Marc Vendrell, Hyung-Ho Ha, Sung Chan Lee, and Young-Tae Chang 14.1 Introduction 427 14.2 On-Bead Sensors 428 14.3 Solid-Phase Approaches in Fluorescent Labeling 429 14.4 Solid-Phase Derivatization of Fluorescent Scaffolds 430 14.5 Diversity-Oriented Fluorescent Libraries 433 14.6 Conclusions 437 14.7 Acknowledgments 437 References 437 15 Dendritic Molecules On Solid Support: Solid-Phase Synthesis and Applications 441Kerem Goren and Moshe Portnoy 15.1 Introduction 441 15.2 Synthesis 442 15.3 Applications of Dendronized Supports 464 15.4 Conclusions 480 References 482 16 Oligosaccharide Synthesis On Solid, Soluble Polymer, and Tag Supports 489Katsunori Tanaka and Koichi Fukase 16.1 Introduction 489 16.2 Solid-Phase Methods for Synthesis of Oligosaccharides 490 16.3 Polymer-Supported and Tag-Assisted Oligosaccharide Synthesis in Solution 516 16.4 Conclusions 526 16.5 Acknowledgments 527 References 527 Index 531

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Book SynopsisUsing case studies of successful drug discoveries and launches, this book helps master the necessary knowledge of the drug discovery process. It includes pharmacology, drug metabolism, biology, drug development, and clinical studies.Trade Review“This book will enrich the collection of medicinal chemists or pharmacologists involved in active drug discovery research, as well as students with a passion for pursuing a career in drug discovery.” (Doody’s, 22 February 2013) "A well-made glossary is available in the appendix, which defines the dozens of terms that a medicinal chemist will encounter in his/her career. . . This book demonstrates yet again the need for new, better medicines and the reasons for the high cost of drug research. An enjoyable read!.” (ChemMedChem, 1 January 2013)Table of ContentsPreface xv Contributors xvii Chapter 1 Introduction: Drug Discovery in Difficult Times 1Malcolm MacCoss Chapter 2 Discovery and Development of The DPP-4 Inhibitor Januvia® (SITA-GLIPTIN) 10Emma R. Parmee, Ranabir SinhaRoy, Feng Xu, Jeffrey C. Givand, and Lawrence A. Rosen 2.1 Introduction 10 2.2 DPP-4 Inhibition as a Therapy for Type 2 Diabetes: Identification of Key Determinants for Efficacy and Safety 10 2.2.1 Incretin-Based Therapy for T2DM 10 2.2.2 Biological Rationale: DPP-4 is a Key Regulator of Incretin Activity 11 2.2.3 Injectable GLP-1 Mimetics for the Treatment of T2DM 12 2.2.4 DPP-4 Inhibition as Oral Incretin-Based Therapy for T2DM 12 2.2.5 Investigation of DPP-4 Biology: Identification of Candidate Substrates 13 2.2.6 Preclinical Toxicities of In-Licensed DPP-4 Inhibitors 15 2.2.7 Correlation of Preclinical Toxicity with Off-Target Inhibition of Pro-Specific Dipeptidase Activity 16 2.2.8 Identification of Pro-Specific Dipeptidases Differentially Inhibited by the Probiodrug Compounds 17 2.2.9 A Highly Selective DPP-4 Inhibitor is Safe and Well Tolerated in Preclinical Species 19 2.2.10 A Highly Selective DPP-4 Inhibitor Does Not Inhibit T-Cell Proliferation in vitro 19 2.2.11 DPP-4 Inhibitor Selectivity as a Key Parameter for Drug Development 20 2.3 Medicinal Chemistry Program 20 2.3.1 Lead Generation Approaches 20 2.3.2 Cyclohexyl Glycine α-Amino Acid Series of DPP-4 Inhibitors 20 2.3.3 Improving Selectivity of theα-Amino Acid Series 22 2.3.4 Identification and Optimization of the β-Amino Acid Series 22 2.4 Synthetic and Manufacturing Routes to Sitagliptin 27 2.4.1 Medicinal Chemistry Route to Sitagliptin and Early Modifications 27 2.4.2 An Asymmetric Hydrogenation Manufacturing Route to Sitagliptin 28 2.4.3 A “Greener” Manufacturing Route to Sitagliptin Employing Biocatalytic Transamination 31 2.5 Drug Product Development 33 2.5.1 Overview 33 2.5.2 Composition Development 33 2.5.3 Manufacturing Process Development 33 2.6 Clinical Studies 36 2.6.1 Preclinical PD Studies and Early Clinical Development of Sitagliptin 36 2.6.2 Summary of Phase II/III Clinical Trials 38 2.7 Summary 39 References 39 Chapter 3 Olmesartan Medoxomil: An Angiotensin II Receptor Blocker 45Hiroaki Yanagisawa, Hiroyuki Koike, and Shin-ichiro Miura 3.1 Background 45 3.1.1 Introduction 45 3.1.2 Prototype of Orally Active ARBs 46 3.2 The Discovery of Olmesartan Medoxomil (Benicar) 47 3.2.1 Lead Generation 47 3.2.2 Lead Optimization 49 3.3 Characteristics of Olmesartan 53 3.4 Binding Sites of Omlersartan to the AT1 Receptor and Its Inverse Agonoist Activity 56 3.4.1 Binding Sites of Olmesartan to the AT1 Receptor 56 3.4.2 Inverse Agonist Activity of Olmesartan 56 3.4.3 Molecular Model of the Interaction between Olmesartan and the AT1 Receptor 57 3.5 Practical Preparation of Olmesartan Medoxomil 58 3.6 Preclinical Studies 58 3.6.1 AT1 Receptor Blocking Action 58 3.6.2 Inhibition of Ang II-Induced Vascular Contraction 59 3.6.3 Inhibition of the Pressor Response to Ang II 60 3.6.4 Blood Pressure Lowering Effects 60 3.6.5 Organ Protection 61 3.7 Clinical Studies 62 3.7.1 Antihypertensive Efficacy and Safety 62 3.7.2 Organ Protection 63 3.8 Conclusion 63 References 64 Chapter 4 Discovery of Heterocyclic Phosphonic Acids as Novelampmimics That Are Potent and Selective Fructose-1,6-Bisphosphatase Inhibitors and Elicit Potent Glucose-Lowering Effects in Diabetic Animals and Humans 67Qun Dang and Mark D. Erion 4.1 Introduction 67 4.2 The Discovery of MB06322 69 4.2.1 Research Operation Plan 69 4.2.2 Discovery of Nonnucleotide AMP Mimics as FBPase Inhibitors 69 4.2.3 Discovery of Benzimidazole Phosphonic Acids as FBPase Inhibitors 74 4.2.4 Discovery of Thiazole Phosphonic Acids as Potent and Selective FBPase Inhibitors 77 4.2.5 The Discovery of MB06322 Through Prodrug Strategy 80 4.3 Pharmacokinetic Studies of MB06322 82 4.4 Synthetic Routes to MB06322 83 4.5 Clinical Studies of MB06322 83 4.5.1 Efficacy Study of Thiazole 12.6 in Rodent Models of T2DM 83 4.5.2 Phase I/II Clinical Studies 84 4.6 Summary 84 References 85 Chapter 5 Setting The Paradigm of Targeted Drugs for The Treatment of Cancer: Imatinib and Nilotinib, Therapies for Chronic Myelogenous Leukemia 88Paul W. Manley and Jurg Zimmermann 5.1 Introduction 88 5.2 Chronic Myelogenous Leukemia (CML) and Early Treatment of the Disease 89 5.3 Imatinib: A Treatment for Chronic Myelogenous Leukemia (CML) 92 5.4 The Need for New Inhibitorts of BCR-ABL1 and Development of Nilotinib 94 5.5 Conclusion 99 References 100 Chapter 6 Amrubicin, A Completely Synthetic 9-Aminoanthracycline for Extensive-Disease Small-Cell Lung Cancer 103Mitsuharu Hanada 6.1 Introduction 103 6.2 The Discovery of Amrubicin: The First Completely Synthetic Anthracycline 106 6.3 Toxicological Profile of Amrubicin 107 6.4 DNA Topoisomerase II Inhibition and Apoptosis Induction by Amrubicin 110 6.5 Amrubicin Metabolism: The Discovery of Amrubicinol 113 6.5.1 Amrubicinol Functions as an Active Metabolite of Amrubicin 113 6.5.2 Tumor-Selective Metabolism of Amrubicin to Amrubicinol 115 6.6 Improved Usage of Amrubicin 116 6.7 Clinical Trials 118 6.7.1 Clinical Trials of Amrubicin as First-line Therapy in Patients with ED-SCLC 118 6.7.2 Clinical Trials of Amrubicin as Second-Line Therapy in Patients with ED-SCLC 121 6.8 Conclusions 122 References 123 Chapter 7 The Discovery of Dual IGF-1R and IR Inhibitor FQIT for the Treatment of Cancer 127Meizhong Jin, Elizabeth Buck, and Mark J. Mulvihill 7.1 Biological Rational for Targeting the IGF-1R/IR Pathway for Anti-Cancer Therapy 127 7.2 Discovery of OSI-906 128 7.2.1 Summary of OSI-906 Discovery 128 7.2.2 OSI-906 Clinical Aspects 129 7.3 OSI-906 Back Up Efforts 131 7.4 The Discovery of FQIT 131 7.4.1 Lead Generation Strategy 131 7.4.2 Small Molecule Dual IGF-1R/IR Inhibitor Drug Discovery Cascade 133 7.4.3 Initial Proof-of-Concept Compounds 134 7.4.4 Synthesis of 5,7-Disubstituted Imidazo[5,1-f][1,2,4] Triazines 135 7.4.5 Lead Imidazo[5,1-f][1,2,4] Triazine IGF-1R/IR Inhibitors and Emergence of FQIT 139 7.5 In Vitro Profile of FQIT 140 7.5.1 Cellular and Antiproliferative Effects as a Result of IGF-1R and IR Inhibition 140 7.5.2 Cellular Potency in the Presence of Plasma Proteins 141 7.5.3 In Vitro Metabolism and CYP450 Profile 143 7.6 Pharmacokinetic Properties of FQIT 144 7.6.1 formulation and Salt Study 144 7.6.2 Pharmacokinetics Following Intravenous Administration 144 7.6.3 Pharmacokinetics Following Oral Administration 145 7.7 In Vivo Profile of FQIT 146 7.7.1 In Vivo Pharmacodynamic and PK/PD Correlation 146 7.7.2 In Vivo Efficacy 146 7.8 Safety Assessment and Selectivity Profile of FQIT 148 7.8.1 Effects on Blood Glucose and Insulin Levels 148 7.8.2 Oral Glucose Tolerance Test 148 7.8.3 Ames, Rodent, and Nonrodent Toxicology Studies 149 7.8.4 Selectivity Profile of FQIT 149 7.9 Summary 150 Acknowledgments 151 References 151 Chapter 8 Discovery and Development of Montelukast (Singulair®) 154Robert N. Young 8.1 Introduction 154 8.2 Drug Development Strategies 158 8.3 LTD4 Antagonist Program 159 8.3.1 Lead Generation and Optimization 159 8.3.2 In Vitro and In Vivo Assays 159 8.4 The Discovery of Montelukast (Singulair®) 160 8.4.1 First-Generation Antagonists (Figure 8.3) 160 8.4.2 Discovery of MK-571 163 8.4.3 Discovery of MK-0679 (29) 168 8.4.4 Discovery of Montelukast (L-706,631, MK-0476, Singulair®) 171 8.5 Synthesis of Montelukast 174 8.5.1 Medicinal Chemistry Synthesis 174 8.5.2 Process Chemistry Synthesis [104, 105] (Schemes 8.5 and 8.6) 176 8.6 ADME Studies with MK-0476 (Montelukast) 179 8.7 Safety Assessment of Montelukast 180 8.8 Clinical Development of Montelukast 180 8.8.1 Human Pharmacokinetics, Safety, and Tolerability 180 8.8.2 Human Pharmacology 181 8.8.3 Phase 2 Studies in Asthma 182 8.8.4 Phase 3 Studies in Asthma 182 8.8.5 Effects of Montelukast on Inflammation 185 8.8.6 Montelukast and Allergic Rhinitis 185 8.9 Summary 185 8.9.1 Impact on Society 185 8.9.2 Lessons Learned 186 8.10 Personal Impact 187 References 188 Chapter 9 Discovery and Development of Maraviroc, A CCR5 Antagonist for the Treatment of HIV Infection 196Patrick Dorr, Blanda Stammen, and Elna van der Ryst 9.1 Background and Rationale 196 9.2 The Discovery of Maraviroc 199 9.2.1 HTS and Biological Screening to Guide Medicinal Chemistry 199 9.2.2 Hit Optimization 200 9.2.3 Overcoming Binding to hERG 201 9.3 Preclinical Studies 201 9.3.1 Metabolism and Pharmacokinetic Characteristics of Maraviroc 201 9.3.2 Maraviroc Preclinical Pharmacology 202 9.3.3 Preclinical Investigations into HIV Resistance 202 9.3.4 Binding of Maraviroc to CCR5 204 9.4 The Synthesis of Maraviroc 205 9.5 Nonclinical Safety and Toxicity Studies 206 9.5.1 Safety Pharmacology 206 9.5.2 Immuno- and Mechanistic Toxicity 206 9.6 Clinical Development of Maraviroc 207 9.6.1 Phase 1 Studies 207 9.6.2 Phase 2a Studies 209 9.6.3 Phase 2b/3 Studies 210 9.6.4 Development of Resistance to CCR5 Antagonists In Vivo 213 9.7 Summary, Future Directions, and Challenges 214 Acknowledgments 217 References 217 Chapter 10 Discovery of Antimalarial Drug Artemisinin and Beyond 227Weiwei Mao, Yu Zhang, and Ao Zhang 10.1 Introduction: Natural Products in Drug Discovery 227 10.2 Natural Product Drug Discovery in China 227 10.3 Discovery of Artemisinin: Background, Structural Elucidation and Pharmacological Evaluation 228 10.3.1 Background and Biological Rationale 228 10.3.2 The Discovery of Artemisinin through Nontraditional Drug Discovery Process 229 10.3.3 Structural Determination of Artemisinin 231 10.3.4 Pharmacological Evaluation and Clinical Trial Summary of Artemisinin 231 10.4 The Synthesis of Artemisinin 232 10.4.1 Synthesis of Artemisinin using Photooxidation of Cyclic or Acyclic Enol Ether as the Key Step 233 10.4.2 Synthesis of Artemisinin by Photooxidation of Dihydroarteannuic Acid 236 10.4.3 Synthesis of Artemisinin by Ozonolysis of a Vinylsilane Intermediate 236 10.5 SAR Studies of Structural Derivatives of Artemisinin: The Discovery of Artemether 238 10.5.1 C-10-Derived Artemisinin Analogs 240 10.5.2 C-9 and C-9,10 Double Substituted Analogs 245 10.5.3 C-3 Substituted Analogs 246 10.5.4 C-6 or C-7 Substituted Derivatives 246 10.5.5 C-11-Substituted Analogs 247 10.6 Development of Artemether 248 10.6.1 Profile and Synthesis of Artemether 248 10.6.2 Clinical Studies Aspects of Artemether 249 10.7 Conclusion and Perspective 250 Acknowledgment 250 References 251 Chapter 11 Discovery and Process Development of MK-4965, A Potent Nonnucleoside Reverse Transcriptase Inhibitor 257Yong-Li Zhong, Thomas J. Tucker, and Jingjun Yin 11.1 Introduction 257 11.2 The Discovery of MK-4965 260 11.2.1 Background Information 260 11.2.2 SAR Studies Leading to the Discovery of MK-4965 262 11.3 Preclinical and Clinical Studies of MK-4965 (19) 266 11.4 Summary of Back-Up SAR Studies of MK-4965 Series 266 11.5 Process Development of MK-4965 (19) 267 11.5.1 Medicinal Chemistry Route 267 11.5.2 Process Development 269 11.6 Conclusion 290 11.6.1 Lessons Learned from the Medicinal Chemistry Effort of MK-4965 Discovery 290 11.6.2 Summary and Lessons Learned from the Process Development of MK-4965 291 Acknowledgments 291 References 291 Chapter 12 Discovery of Boceprevir and Narlaprevir: The First and Second Generation of HCV NS3 Protease Inhibitors 296Kevin X. Chen and F. George Njoroge 12.1 Introduction 296 12.2 HCV NS3 Protease Inhibitors 298 12.3 Research Operation Plan and Biological Assays 302 12.3.1 Research Operation Plan 302 12.3.2 Enzyme Assay 302 12.3.3 Replicon Assay 302 12.3.4 Measure of Selectivity 303 12.4 Discovery of Boceprevir 303 12.4.1 Initial Lead Generation Through Structure-Based Drug Design 303 12.4.2 SAR Studies Focusing on Truncation, Depeptization, and Macrocyclisation 304 12.4.3 Individual Amino Acid Residue Modifications 307 12.4.4 Correlations Between P1, P3, and P3 Capping: The Identification of Boceprevir 315 12.5 Profile of Boceprevir 317 12.5.1 In Vitro Characterization of Boceprevir 317 12.5.2 Pharmacokinetics of Boceprevir 317 12.5.3 The Interaction of Boceprevir with NS3 Protease 318 12.6 Clinical Development and Approval of Boceprevir 319 12.7 Synthesis of Boceprevir 319 12.8 Discovery of Narlaprevir 322 12.8.1 Criteria for the Back-up Program of Boceprevir 322 12.8.2 SAR Studies 322 12.8.3 Profile of Narlaprevir 326 12.8.4 Clinical Development Aspects of Narlaprevir 327 12.8.5 Synthesis of Narlaprevir 327 12.9 Summary 329 References 330 Chapter 13 The Discoveryofsamsca® (Tolvaptan): Thefirst Oral Nonpeptide Vasopressin Receptor Antagonist 336Kazumi Kondo and Yoshitaka Yamamura 13.1 Background Information about the Disease 336 13.2 Biological Rational 337 13.3 Lead Generation Strategies: The Discovery of Mozavaptan 338 13.4 Lead Optimization: From Mozavaptan to Tolvaptan 347 13.5 Pharmacological Profiles of Tolvaptan 350 13.5.1 Antagonistic Affinities of Tolvaptan for AVP Receptors 350 13.5.2 Aquaretic Effect Following a Single Dose in Conscious Rats 352 13.6 Drug Development 353 13.6.1 Synthetic Route of Discovery and Commercial Synthesis [10a] 353 13.6.2 Nonclinical Toxicology 353 13.6.3 Clinical Studies 355 13.7 Summary Focusing on Lessons Learned 356 Acknowledgments 357 References 357 Chapter 14 Silodosin (Urief®, Rapaflo®, Thrupas®, Urorec®, Silodix®): A Selective α1A Adrenoceptor Antagonist for the Treatment of Benign Prostatic Hyperplasia 360Masaki Yoshida, Imao Mikoshiba, Katsuyoshi Akiyama, and Junzo Kudoh 14.1 Background Information 360 14.1.1 Benign Prostatic Hyperplasia 360 14.1.2 α1-Adrenergic Receptors 361 14.2 The Discovery of Silodosin 362 14.2.1 Medicinal Chemistry 362 14.2.2 The Synthesis of Silodosin (Discovery Route) 363 14.2.3 Receptor Binding Studies 365 14.3 Pharmacology of Silodosin 369 14.3.1 Action Against Noradrenalin-Induced Contraction of Lower Urinary Tract Tissue 369 14.3.2 Actions Against Phenylephrine-Induced Increase in Intraurethral Pressure and Blood Pressure 371 14.3.3 Actions Against Intraurethral Pressure Increased by Stimulating Hypogastric Nerve and Blood Pressure in Dogs with Benign Prostatic Hyperplasia 372 14.3.4 Safety Pharmacology 373 14.4 Metabolism of Silodosin 373 14.5 Pharmacokinetics of Silodosin 376 14.5.1 Absorption 376 14.5.2 Organ Distribution 377 14.5.3 Excretion 378 14.6 Toxicology of Silodosin 379 14.7 Clinical Trials 382 14.7.1 Phase I Studies 382 14.7.2 Phase III Randomized, Placebo-Controlled, Double-Blind Study 383 14.7.3 Long-Term Administration Study 385 14.8 Summary: Key Lessons Learned 388 References 389 Chapter 15 Raloxifene: A Selective Estrogen Receptor Modulator (SERM) 392Jeffrey A. Dodge and Henry U. Bryant 15.1 Introduction: SERMs 392 15.2 The Benzothiophene Scaffold: A New Class of SERMs 394 15.3 Assays for Biological Evaluation of Tissue Selectivity 394 15.4 Benzothiophene Structure Activity 395 15.5 The Synthesis of Raloxifene 401 15.6 SERM Mechanism 402 15.7 Raloxifene Pharmacology 405 15.7.1 Skeletal System 405 15.7.2 Reproductive System—Uterus 407 15.7.3 Reproductive System—Mammary 408 15.7.4 General Safety Profile and Other Pharmacological Considerations 410 15.8 Summary 411 References 411 Appendix I Small Molecule Drug Discovery and Development Paradigm 417 Appendix II Glossary 419 Appendix III Abbreviations 432 Index 443

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Book SynopsisThis book provides a thorough and up-to-date overview of the aryl hydrocarbon receptor (AHR) and its unique dual role in toxicology and biology. The coverage includes epigenetic mechanisms, gene expression, reproductive and developmental toxicity, signal transduction, and transgenic animal models.Trade Review Table of ContentsPreface. A. Historical background. 1. History of Research on the AHR (Thomas A. Gasiewocz and Ellen C. Henry). B. AHR as a ligand-activated transcription factor. 2. Overview of AHR functional domains and the classical signaling pathway: induction of drug-metabolizing enzymes (Qiang Ma). 3. Role of chaperone proteins in AHR function (Iain A. Murray and Gary H. Perdew). 4. AHR Ligands: Promiscuity in Binding and Diversity in Response (Danica DeGroot, Guochun He, Domenico Fraccalvieri, Laura Bonati, Allesandro Pandin and Michael S. Denison). 5. Dioxin response elements and regulation of gene transcription (Hollie Swanson). 6. The AHR/ARNT dimer and transcriptional coactivators (Oliver Hankinson). 7. Regulation of AHR by the AHR repressor (AHRR) (Yoshiaki Fujii-Kuriyama and Kaname Kawajiri). 8. Influence of HIF-1α and Nrf2 signaling on AHR-mediated gene expression, toxicity and biological functions (Thomas Haarmann-Stemmann and Josef Abel). 9. Functional interactions of AHR with other receptors (Sara Brunnberg, Elin Swedenborg and Jan-Åke Gustafsson). 10. The E3 ubiquitin ligase activity of transcription factor AHR permits non-genomic regulation of biological pathways (Fumiaki Ohtake and Shigeaki Kato). 11. Epigenetic mechanisms in AHR function (Chia-I Ko and Alvaro Puga). C. AHR as a mediator of xenobiotic toxicities: dioxins as a key example. 12. Role of the AHR and its structure in TCDD toxicity (Raimo Pohjanvirta, Merja Korkalainen, Ivy D. Moffat, Paul C. Boutros, Allan B. Okey). 13. Nongenomic route of action of TCDD: Identity, characteristics and toxicological significance (Fumio Matsumura). 14. Inter-species heterogeneity in the hepatic transcriptomic response to AHR activation by dioxin (Paul Boutros). 15. Dioxin-activated AHR: toxic responses and the induction of oxidative stress (Sidney J. Stohs and Ezdihar A. Hassoun). 16. Dioxin-activated AHR and cancer in laboratory animals (Dieter Schrenk and Martin Chopra). 17. Teratogenic impact of dioxin-activated AHR in laboratory animals (Barbara D. Abbott). 18. The developmental toxicity of dioxin to the developing male reproductive system in the rat; relevance of the AHR for risk assessment (David R. Bell). 19. TCDD, AHR and immune regulation (Nancy I. Kerkvliet). 20. Effects of dioxins on teeth and bone: the role of AHR (Matti Viluksela, Hanna M. Miettinen and Merja Korkalainen). 21. Impacts of dioxin-activated AHR signaling in fish and birds (Michael T. Simonich and Robert L. Tangray). 22. Adverse Health Outcomes Caused By Dioxin-Activated AHR in Humans (Sally S. White, Suzanne E. Fenton, and Linda S. Birnbaum). 23. The toxic equivalency principle and its application in dioxin risk assessment (Jouko Tuomisto). 24. AHR-active compounds in the human diet (Stephen Safe, Gayathri Chadalapaka and Indira Jutooru). 25. Modulation of AHR function by heavy metals and disease states (Anwar Anwar-Mohammed and Ayman O.S. El-Kadi). 26. Transgenic mice with a constitutively active AHR: a model for human exposure to dioxin an other AHR ligands (Patrik Andersson, Sara Brunnberg, Carolina Wejheden, Lorenz Poellinger and Annika Hanberg). D. AHR as a physiological regulator. 27. Structural and functional diversification of AHRs during metazoan evolution (Mark E. Hahn and Sibel I. Karchner). 28. Invertebrate AHR homologs: Ancestral functions in sensory systems (Jo Anne Powell-Coffman and Hongtao Qin). 29. Role of AHR in the development of the liver and blood vessels (Sahoko Ichihara). 30. Involvement of the AHR in cardiac function and regulation of blood pressure (Jason A. Scott and Mary K. Walker). 31. Involvement of the AHR in development and functioning of the female and male reproductive systems (Bethany N. Karman, Isabel Hernández-Ochoa, Ayelet Ziv-Gal, Jodi A. Flaws). 32. The AHR in the control of cell cycle and apoptosis (Cornelia Dietrich). 33. The AHR regulates cell adhesion and migration by interacting with oncogene and growth factor-dependent signaling (Angel Carlos Roman, Jose M. Carvajal-Gonzalez, Sonia Mulero-Navarro, Aurea Gomez-Duran, Eva M. Rico-Leo and Pedro M. Fernandez-Salguero). 34. The physiological role of AHR in the mouse immune system (Charlotte Esser). 35. AHR and the circadian clock (Shelley A. Tischkau).

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Book Synopsis* Includes easy-to-understand and easy-to-implement costreduction concepts organized into five general areas (labour,material, design, process, and overhead), with several chapters ineach. * Each chapter gets to the point without a lot of extraneousdata, providing proven tactics for cutting costs.Table of ContentsIntroduction. Chapter 1: Organizing a Cost-Reduction Program. Part I Labor. Chapter 2: Head Count. Chapter 3: Time Standards. Chapter 4: Efficiency. Chapter 5: Utilization. Chapter 6: Overtime. Chapter 7: Multiple Shifts. Chapter 8: Lost Time. Chapter 9: The Learning Curve. Part II Material. Chapter 10: Make-versus-Buy Determinations. Chapter 11: Inventory Minimization. Chapter 12: Material Utilization. Chapter 13: Minimizing Supplier Costs. Chapter 14: Supplier Negotiation. Chapter 15: Supplier Competition. Part III Process. Chapter 16: Work-Flow Optimization. Chapter 17: Setup Time Reduction. Chapter 18: Material-Handling Improvements. Chapter 19: Scrap and Rework Reduction. Chapter 20: Cleanliness. Part IV Design. Chapter 21: The Design Approach. Chapter 22: Requirements Relaxation. Chapter 23: Tolerance Relaxation. Chapter 24: Materials Substitution. Chapter 25: Packaging. Part V Overhead. Chapter 26: General Overhead Expenses. Chapter 27: Travel. Chapter 28: Inspection. Part VI Gaining Disciples and Measuring Progress. Chapter 29: Suggestion Programs. Chapter 30: Measuring Progress. Index.

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Book SynopsisThis book covers various aspects of antibody mediated drug delivery systems theoretical aspects, processing, viral and non-viral vectors, and fields where these systems find and /or are being evaluated for applications as therapeutics and diagnostic treatment. Chapters discuss actual applications of techniques used for formulation and characterization. Applications areas include cancer, pulmonary, ocular diseases; brain drug delivery; and vaccine delivery. The contributing authors represent over 10 different countries, covering recent developments happening around the globe.Table of ContentsCONTRIBUTORS xv PREFACE xix CHAPTER 1 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEMS: GENERAL REVIEW AND APPLICATIONS Navdeep Kaur, Karthikeyan Subramani, and Yashwant Pathak 1 1 Historical Perspective 1 2 Antibodies 2 3 Antibody Mediation 3 4 Antibody-Mediated Drug Delivery Systems 4 5 Applications 6 6 Recent Trends 9 7 Future Trends 10 CHAPTER 2 IMMUNOLIPOSOMES FOR CARDIOVASCULAR TARGETING Tatyana Levchenko, William Hartner, and Vladimir P. Torchilin 13 1 Introduction 13 2 Immunoliposome Targeting to Pathological Regions of the Vessel Wall 14 3 Liposome Internalization by Endothelial Cells 15 4 Targeting of Atherosclerotic Lesions for Tomographic Imaging 17 5 Antibody-Mediated Liposomes for Diagnosis of Thrombosis 17 6 Thrombolytic Therapy with Immunoliposomes 18 7 Targeted Sealing of Cell Membrane Lesions: Preservation of Cell Viability 19 8 Accumulation of Liposomes and Immunoliposomes in the Ischemic Heart 21 9 Immunoliposomes as a Drug and Gene Delivery Vehicle to the Infarcted Heart 26 CHAPTER 3 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEMS FOR BREAST CANCER THERAPEUTICS Leonor Munoz Alcivar and Yashwant Pathak 35 1 Introduction 35 2 Breast Cancer 35 3 Drug Delivery Systems 36 4 Monoclonal Antibodies 37 5 Human Epidermal Growth Factor Receptor 2 40 6 Antibody-Mediated Drug Delivery System 43 7 Targets for the Treatment of Breast Cancer 45 8 Breast Cancer Therapies 46 9 The Future of Breast Cancer Therapeutics 49 10 Other Treatment Strategies 50 11 Nanotechnology 51 12 Conclusions 52 CHAPTER 4 DEVELOPMENT OF IMMUNONCONJUGATES FOR IN VIVO DELIVERY: CANCER DIAGNOSIS, IMAGING, AND THERAPY Arutselvan Natarajan 57 1 Introduction 57 2 Immunoconjugates 61 3 Immunoconjugates in Cancer Therapy 62 4 Immunoconjugates for Imaging 69 5 Immunoconjugates in Diagnostic Applications 71 6 Immunoconjugates’ Promising Future and Challenges 72 7 Summary 73 CHAPTER 5 MATHEMATICAL MODELS OF ANTI-TNF THERAPIES AND THEIR CORRELATION WITH TUBERCULOSIS Simeone Marino, Mohammad Fallahi-Sichani, Jennifer J. Linderman, and Denise E. Kirschner 83 1 Introduction 83 2 Tuberculosis, TNF, and Anti-TNF Drugs 84 3 Theoretical Models To Study TB Infection 88 4 Present and Future Work 96 CHAPTER 6 TARGETED NANOPARTICLES IN RADIOTHERAPY Misty Muscarella and Yashwant Pathak 105 1 Introduction 105 2 Nanoparticles 106 3 Radiotherapy 110 4 Nanoparticles in Radiotherapy 111 5 Current and Future Developments with Nanotechnology in Radiotherapy 123 6 Conclusions 124 CHAPTER 7 ELECTRICALLY-ENHANCED DELIVERY OF DRUGS AND CONJUGATES FOR CANCER TREATMENT Arutselvan Natarajan, Luca Campana, and Raji Sundararajan 129 1 Introduction 129 2 Electroporation Mechanisms to Permeabilize the Drugs and DNAs in Cells 130 3 Electroporation-Aided Drug Delivery for Preclinical Studies 133 4 EP applications for Human Patient Studies 136 5 Future Perspectives 138 6 Summary 139 CHAPTER 8 CHARACTERIZATION OF MONOCLONAL ANTIBODY VARIANTS AND GLYCOSYLATION Ting Zheng, Srinivasa Rao, Jeff Rohrer, and Chris Pohl 145 1 Characterization of Monoclonal Antibody Heterogeneity by HPLC Analysis 145 2 Analysis of Monoclonal Antibody Glycosylation 150 CHAPTER 9 ANTIBODY-MEDIATED DRUG DELIVERY SYSTEM FOR LYMPHATIC TARGETING TREATMENT Fang Wu, Hong Ding, and Zhirong Zhang 169 1 Introduction 169 2 Lymphatic Disorders and Their Normal Treatment 170 3 Antibody-Mediated Drug Delivery Systems for Lymphatic Targeting Treatment 172 4 Conclusions and Future Perspectives 183 CHAPTER 10 METHODS FOR NANOPARTICLE CONJUGATION TO MONOCLONAL ANTIBODIES Junling Li and Chin K. Ng 191 1 Introduction 191 2 Current Nanoparticle Systems used for Conjugation with mAbs 191 3 Conjugation Methods 192 4 Conclusions 202 CHAPTER 11 SINGLE-USE SYSTEMS IN ANIMAL CELL–BASED BIOPRODUCTION William G. Whitford 209 1 Introduction 209 2 Component Offerings 214 3 Characteristics of Single-Use Systems and Their Applications 218 CHAPTER 12 IMMUNOLIPOSOMES FOR SPECIFIC DRUG DELIVERY Manuela Calin 229 1 Introduction: Advances in Liposome Formulation 229 2 Design of Immunoliposomes for Site-Specific Drug Delivery 230 3 Cellular-Specific Targeting of Immunoliposomes 242 4 Cellular-Specific Internalization of Immunoliposomes 246 5 Immunoliposomes in Diagnosis and Therapy 247 6 Clinical Use of Immunoliposomes 251 7 Conclusions and Perspectives 252 CHAPTER 13 GENE THERAPY TARGETING KIDNEY DISEASES: ROUTES AND VEHICLES Yoshitaka Isaka, Yoshitsugu Takabatake, and Hiromi Rakugi 267 1 Introduction 267 2 Rationale for Successful Gene Targeting 268 3 Site-Specific Gene Delivery 268 4 Nuclear Import of Gene Material 270 5 Targeting the Glomerulus 270 6 Targeting the Tubule 272 7 Targeting the Interstitium 274 8 Targeting Muscle 274 9 Conclusions 275 CHAPTER 14 DETECTION OF ANTIBODIES TO POLY(ETHYLENE GLYCOL) POLYMERS USING DOUBLE-ANTIGEN-BRIDGING IMMUNOGENICITY ELISA Yijuan Liu, Helen Reidler, Jing Pan, David Milunic, Dujie Qin, Dave Chen, Yli Remo Vallejo, and Ray Yin 279 1 Introduction 279 2 Methods 280 3 Results 283 4 Discussion 286 CHAPTER 15 ANTIBODIES IN NANOMEDICINE AND MICROIMAGING METHODS Rakesh Sharma 291 1 Introduction: Antibody Molecules and Nanoparticles 291 2 Antibody-Based Nanoparticles in Microimaging 292 3 Troponin T: Newer Magnetic Immunoassay Method 317 4 Gold Nanoparticles as an Antigen Carrier and Adjuvant 330 5 Immunochemical Biosensors, Nanomedicine, and Disease 339 6 Future Directions and Conclusions 341 CHAPTER 16 METHODS FOR POLYMERIC NANOPARTICLE CONJUGATION TO MONOCLONAL ANTIBODIES Uyen Minh Le, Hieu Tran, and Yashwant Pathak 351 1 Introduction 351 2 Conjugation of mAb and Polyethylenimine Nanoparticles 353 3 Conjugation of mAb to Poly(Lactide-CO-Glycolide) Nanoparticles 357 4 Conjugation of mAb to Poly(Lactic Acid) and its Derivatives 359 5 Conjugation of mAb to Other Polymeric Nanoparticles 360 6 Summary 361 CHAPTER 17 PLANT-DERIVED ANTIBODIES FOR ACADEMIC, INDUSTRIAL, AND THERAPEUTIC APPLICATIONS Slavko Komarnytsky and Nikolai Borisjuk 365 1 Historical Perspective 365 2 Plant-Based Production of Recombinant Proteins 366 3 Expression in an Entire Plant Versus a Plant Organ 367 4 ER Targeting and Secretion of Recombinant Proteins 368 5 Expression in Seeds 370 6 Transient Expression 371 7 Glycosylation 373 8 Recent Examples of Plant-Derived Antibodies Effective in Mammalian Systems 375 9 Conclusions 376 CHAPTER 18 MONOCLONAL ANTIBODIES AS BIOPHARMACEUTICALS Girish J. Kotwal 383 1 Historical Perspective 383 2 Introduction 384 3 Structure and Types of mAbs 385 4 Mechanism of Action 385 5 FDA-approved mAb Biopharmaceuticals in Current Use 386 6 Future of Monoclonal Antibodies as Biopharmaceuticals 389 CHAPTER 19 PULMONARY TARGETING OF NANOPARTICLES AND MONOCLONAL ANTIBODIES Weiyuan Chang 391 1 Introduction 391 2 Attributes of mAbs as Therapeutics for Pulmonary Diseases 392 3 Antibody-Conjugated Nanoparticles for Lung Targeting 393 4 Monoclonal Antibodies in the Treatment of Asthma 394 5 Monoclonal Antibodies in the Treatment of COPD 398 6 Challenges in Pulmonary Disease 400 7 Conclusions 402 CHAPTER 20 ANTIBODY-MEDIATED ARTHRITIS AND NEW THERAPEUTIC AVENUES Kutty Selva Nandakumar 407 1 Autoantibodies in Rheumatoid Arthritis 407 2 Role of Cartilage Antigen-Specific Antibodies in Inducing Arthritis 408 3 Arthritis Mediation Through Antibodies Recognizing Citrullinated Antigens 413 4 Regulation at the Effector Level 414 5 Cartilage Damage Independent of Inflammatory Mediators 414 6 pathogenicity of GPI-Specific Antibodies 415 7 Therapeutic Cleavage of Arthritogenic Antibodies 415 8 Arthritis Attenuation Though Removal of Specific Sugars on IgG 417 CHAPTER 21 IMMUNONANOPARTICLES FOR NUCLEAR IMAGING AND RADIOTHERAPY Oren Giladi and Simon Benita 427 1 Radioisotopes and Radiopharmaceuticals 427 2 Radiolabeled Antibodies 432 3 Radiolabeled Nanoparticles 437 4 Future Perspectives and Conclusions 449 CHAPTER 22 MONOCLONAL ANTIBODIES IN THE TREATMENT OF ASTHMA Glenn J. Whelan 457 1 Introduction 457 2 IgE 458 3 TNFα 460 4 IL-5 462 5 IL-9 464 6 IL-4 and IL-13 465 7 Targeting the T-cell 467 8 Conclusions 468 References 469 INDEX 473

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Book Synopsis With addiction a key target for drug discovery efforts, this book fills an important and timely need for medicinal chemists who need to understand complex neuroscience issues. The author illustrates medicinal chemistry''s prominent role in treating addiction and covers specific drugs of abuse including narcotics, stimulants, depressants, nicotine, and marijuana. Interprets complex neuro- biological and pharmacological information, like the drug-reward system, for medicinal chemists Emphasizes neurotransmitters and neurochemical mechanisms of addictive drugs Pulls together information on the many potential drug targets for treating addiction Stresses unique medicinal chemistry problems when describing pharmacology testing methods and drug developmentTable of ContentsPreface xiii 1 What Is Drug Addiction? 1 1.1 Definitions 2 1.2 The Drugs of Abuse 4 1.3 Schedule of Controlled Substances 5 1.4 Some Facts From 2012 NSDUH Study 6 1.5 The Addictive State 8 1.6 Theories of Addiction 12 1.7 Comorbidity 13 1.8 Genetic Aspects of Addiction 13 1.9 Approved Medications for the Treatment of Substance Abuse and Addiction 16 2 Physiological Basis of Addiction—A Chemist's Interpretation 18 2.1 The Reward System 19 2.2 Neuroanatomy of the Reward System 21 2.3 Brief Review of the Central Nervous System and Addiction 22 2.4 Neurotransmitters and Their Targets 25 2.5 Neurocircuitry and Neurotransmitters in Addiction 32 2.6 Location of Receptors 62 2.7 An Example 64 2.8 Use of Biological Markers 65 2.9 Memories and Addiction 68 2.10 Stress the HPA Axis and Addiction 72 3 Behavioral Pharmacology and Addiction 76 3.1 Animal Models of Addiction 76 3.2 Self-Administration 80 3.3 Conditioned Place Preference 85 3.4 Tolerance 86 3.5 Extinction/Withdrawal 87 3.6 Reinstatement (Animal Models of Relapse) 87 3.7 Drug Discrimination 89 3.8 Operant Sensation Seeking Model 92 3.9 Use of Animal Behavioral Models 92 Acknowledgments 93 4 Medication Development for the Treatment of Drug Addiction 94 4.1 Lead Discovery 95 4.1.1 NIDA Addiction Treatment Discovery Program 96 4.2 Pharmacological Assays 103 4.3 Partial Agonist Approach 110 4.4 Allosteric Modulators 110 4.5 Functional Interactions Between Receptors 114 4.6 Multi-Target Drugs 121 4.7 Physicochemical Properties of CNS Drugs and Blood-Brain Barrier 124 4.8 Brain Imaging Agents 131 4.9 QT Prolongation 135 5 Medication Development for Narcotic Addiction 137 5.1 Pharmacology of Narcotic Addiction and Pain 138 5.2 Prescription Drug Addiction 139 5.3 Approved Medications 140 5.4 Medication Development 151 6 Medication Development for Stimulant Addiction 160 6.1 Pharmacology of Cocaine Addiction 160 6.2 Pharmacology of Methamphetamine Addiction 163 6.3 Medication Development 166 7 Medication Development for Depressant Addiction 213 7.1 Pharmacology of Alcohol Addiction 213 7.2 Approved Medications 214 7.3 Medication Development 219 7.4 Benzodiazepines 228 7.5 Barbiturates 229 8 Medication Development for Nicotine Addiction 230 8.1 Pharmacology of Nicotine Addiction 230 8.2 Approved Medications 232 8.3 Medication Development 237 9 Medication Development for Marijuana Addiction 240 9.1 Pharmacology of Marijuana Addiction 241 9.2 CB1 Antagonist: Rimonabant 243 9.3 Medication Development 244 10 Designer Drugs 252 10.1 Cathinone Drugs 253 10.2 MDMA—ECSTASY 256 10.3 Cannabinoid Designer Drugs 257 Conclusion 259 Appendix A Further Reading for Chemists Interested in a More Detailed Understanding of Addiction and the Central Nervous System 261 Appendix B Public Databases and Sources of Information of Interest to Medicinal Chemistry Addiction Researchers 262 Appendix C Glossary of Terms Used in Addiction Research 263 Appendix D Glossary of Terms Used in Medicinal Chemistry 271 References 290 Index 335

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Book SynopsisAn overview of the new technologies that have revolutionized organic chemistry and allowed easy access to complex bioactives, this book brings modern synthetic techniques and bioactives together. The synthesis of structurally complex molecules has become a real challenge for the synthetic community.Table of ContentsFOREWORD vii PREFACE ix CONTRIBUTORS xi CHAPTER 1 C–H FUNCTIONALIZATION: A NEW STRATEGY FOR THE SYNTHESIS OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS 1 Sophie Rousseaux, Benoýˆt Lie´gault, and Keith Fagnou CHAPTER 2 THE NEGISHI CROSS-COUPLING IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOACTIVE MOLECULES 33 Evelina Colacino, Jean Martinez, and Fre´de´ric Lamaty CHAPTER 3 METAL-CATALYZED C–HETEROATOM CROSS-COUPLING REACTIONS 77 Renata Marcia de Figueiredo, Jean Marc Campagne, and Damien Prim CHAPTER 4 GOLDEN OPPORTUNITIES IN THE SYNTHESIS OF NATURAL PRODUCTS AND BIOLOGICALLY ACTIVE COMPOUNDS 111 Fabien Gagosz CHAPTER 5 METATHESIS-BASED SYNTHESIS OF COMPLEX BIOACTIVES 155 Jean-Alexandre Richard, Sin Yee Ng, and David Y.-K. Chen CHAPTER 6 ENANTIOSELECTIVE ORGANOCATALYSIS: A POWERFUL TOOL FOR THE SYNTHESIS OF BIOACTIVE MOLECULES 189 Mitsuru Shoji and Yujiro Hayashi CHAPTER 7 ASYMMETRIC PHASE-TRANSFER CATALYSIS 213 Seiji Shirakawa, Shin A. Moteki, and Keiji Maruoka CHAPTER 8 REARRANGEMENTS IN NATURAL PRODUCT SYNTHESIS 243 Jose´ Marco-Contelles and Elena Soriano CHAPTER 9 DOMINO REACTIONS IN THE ENANTIOSELECTIVE SYNTHESIS OF BIOACTIVE NATURAL PRODUCTS 271 Lutz F. Tietze, Scott G. Stewart, and Alexander Du¨fert CHAPTER 10 FLUOROUS LINKER-FACILITATED SYNTHESIS OF BIOLOGICALLY INTERESTING MOLECULES 335 Wei Zhang CHAPTER 11 THE EVOLUTION OF IMMOBILIZED REAGENTS AND THEIR APPLICATION IN FLOW CHEMISTRY FOR THE SYNTHESIS OF NATURAL PRODUCTS AND PHARMACEUTICAL COMPOUNDS 359 Rebecca M. Myers, Kimberley A. Roper, Ian R. Baxendale, and Steven V. Ley CHAPTER 12 SYNTHETIC APPROACHES TO BIOACTIVE CARBOHYDRATES 395 Xavier Guinchard, Se´bastien Picard, and David Crich CHAPTER 13 AMMONIUM YLIDES AS BUILDING BLOCKS FOR ALKALOID SYNTHESIS 433 Scott Bur and Albert Padwa CHAPTER 14 PRECURSOR-DIRECTED BIOSYNTHESIS OF POLYKETIDE AND NONRIBOSOMAL PEPTIDE NATURAL PRODUCTS 485 Colin J. B. Harvey and Chaitan Khosla CHAPTER 15 TARGET-ORIENTED AND DIVERSITY-ORIENTED ORGANIC SYNTHESIS 513 Raphae¨l Rodriguez CHAPTER 16 DNA AS A TOOL FOR MOLECULAR DISCOVERY 539 Michael Smietana, Jean-Jacques Vasseur, Janine Cossy, and Stellios Arseniyadis INDEX 557

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Book SynopsisFirst published over 40 years ago, this was the first text on the identification of organic compounds using spectroscopy. This text presents a unified approach to the structure determination of organic compounds based largely on mass spectrometry, infrared (IR) spectroscopy, as well as multinuclear and multidimensional nuclear magnetic resonance (NMR) spectroscopy. The key strength of this text is the extensive set of practice and real-data problems (in Chapters 7 and 8). Even professional chemists use these spectra as reference data. Spectrometric Identification of Organic Compounds is written by and for organic chemists, and emphasizes the synergistic effect resulting from the interplay of spectra. This text is characterized by its problem-solving approach with numerous practice problems and extensive reference charts and tables.Table of ContentsCHAPTER 1 MASS SPECTROMETRY 1 1.1 Introduction 1 1.2 Instrumentation 2 1.3 Ionization Methods 3 1.4 Mass Analyzers 8 1.5 Interpretation of EI Mass Spectra 12 1.6 Mass Spectra of Some Chemical Classes 18 References 37 Student Exercises 37 Appendices 46 A Formula Masses (FM) for Various Combinations of Carbon, Hydrogen, Nitrogen, and Oxygen 46 B Common Fragment Ions 67 C Common Fragments Lost 69 CHAPTER 2 INFRARED SPECTROSCOPY 71 2.1 Introduction 71 2.2 Theory 71 2.3 Instrumentation 76 2.4 Sample Handling 77 2.5 Interpretation of Spectra 78 2.6 Characteristic Group Absorptions of Organic Molecules 81 References 108 Student Exercises 108 Appendices 118 A Transparent Regions of Solvents and Mulling Oils 118 B Characteristic Group Absorptions 119 C Absorptions for Alkenes 124 D Absorptions for Phosphorus Compounds 125 E Absorptions for Heteroaromatics 125 CHAPTER 3 PROTON (1H) MAGNETIC RESONANCE SPECTROSCOPY 126 3.1 Introduction 126 3.2 Theory 126 3.3 Instrumentation and Sample Handling 129 3.4 Chemical Shift 132 3.5 Spin-Spin Coupling, Multiplets, and Spin Systems 137 3.6 Protons on Oxygen, Nitrogen, and Sulfur Atoms:Exchangeable Protons 144 3.7 Coupling of Protons to Other Important Nuclei (19F, D (2H), 31P, 29Si, and 13C) 149 3.8 Chemical Equivalence 150 3.9 Magnetic Equivalence 154 3.10 AMX, ABX, and ABC Rigid Systems with Three Coupling Constants 155 3.11 Weakly and Strongly Coupled Systems: Virtual Coupling 156 3.12 Chirality 158 3.13 Magnitude of Vicinal and Geminal Coupling Constants 160 3.14 Long-Range Coupling 162 3.15 Selective Spin Decoupling: Double Resonance 162 3.16 Nuclear Overhauser Effect 162 3.17 Conclusion 163 References 164 Student Exercises 164 Appendices 175 A Chart A.1: Chemical Shifts of Protons on a Carbon Atom Adjacent (𝛼 Position) to a Functional Group in Aliphatic Compounds (M–Y) 175 Chart A.2: Chemical Shifts of Protons on a Carbon Atom Once Removed (𝛽 Position) from a Functional Group in Aliphatic Compounds (M–C–Y) 177 B Effect on Chemical Shifts by Two or Three Directly Attached Functional Groups 178 C Chemical Shifts in Alicyclic and Heterocyclic Rings 180 D Chemical Shifts in Unsaturated and Aromatic Systems 181 Chart D.1: Chemical Shifts of Protons on Monosubstituted Benzene Rings 183 E Protons Subject to Hydrogen-Bonding Effects (Protons on Heteroatoms) 184 F Proton Spin-Spin Coupling Constants 185 G Chemical Shifts and Multiplicities of Residual Protons in Commercially Available Deuterated Solvents 187 H Chemical Shifts of Common Laboratory Solvents as Trace Impurities 188 I Proton NMR Chemical Shifts of Amino Acids in D2O 190 CHAPTER 4 CARBON-13 NMR SPECTROSCOPY 191 4.1 Introduction 191 4.2 Theory 191 4.3 Interpretation of a Simple 13C NMR Spectrum: Diethyl Phthalate 198 4.4 Quantitative 13C Analysis 198 4.5 Chemical Equivalence 200 4.6 DEPT 200 4.7 Chemical Classes and Chemical Shifts 203 4.7.1 Alkanes 204 4.7.1.1 Linear and Branched Alkanes 204 4.7.1.2 Effect of Substituents on Alkanes 205 4.7.1.3 Cycloalkanes and Saturated Heterocyclics 205 4.7.2 Alkenes 206 4.7.3 Alkynes 208 4.7.4 Aromatic Compounds 208 4.7.5 Heteroaromatic Compounds 209 4.7.6 Alcohols 209 4.7.7 Ethers, Acetals, and Epoxides 209 4.7.8 Halides 211 4.7.9 Amines 211 4.7.10 Thiols, Sulfides, and Disulfides 211 4.7.11 Functional Groups Containing Carbon 211 4.7.11.1 Ketones and Aldehydes 212 4.7.11.2 Carboxylic Acids, Esters, Chlorides, Anhydrides, Amides, and Nitriles 214 4.7.11.3 Oximes 214 References 214 Student Exercises 214 Appendices 225 A The 13C Chemical Shifts, Coupling Constants, and Peak Multiplicities of Common Deuterated NMR Solvents 225 B 13C Chemical Shifts of Common Laboratory Solvents as Trace Impurities in Selected Deuterated NMR Solvents 226 C 13C Chemical Shift Ranges for Chemical Classes 227 D 13C Chemical Shifts (ppm) for Several Natural Products 229 CHAPTER 5 TWO-DIMENSIONAL NMR SPECTROSCOPY 230 5.1 Introduction 230 5.2 Theory 231 5.3 Correlation Spectroscopy 233 5.3.1 1H-1H Correlation: COSY 235 5.4 Ipsenol: 1H-1H COSY 235 5.4.1 Ipsenol: Double Quantum Filtered 1H-1H COSY 238 5.4.2 Carbon Detected 13C-1H COSY: HETCOR 238 5.4.3 Proton Detected 1H-13C COSY: HMQC 239 5.4.4 Ipsenol: HETCOR and HMQC 239 5.4.5 Ipsenol: Proton-Detected, Long-Range 1H-13C Heteronuclear Correlation: HMBC 241 5.5 Caryophyllene Oxide 243 5.5.1 Caryophyllene Oxide: DQF-COSY 243 5.5.2 Caryophyllene Oxide: HMQC 243 5.5.3 Caryophyllene Oxide: HMBC 247 5.6 13C-13C Correlations: INADEQUATE 249 5.6.1 INADEQUATE: Caryophyllene Oxide 251 5.7 Lactose 251 5.7.1 DQF-COSY: Lactose 251 5.7.2 HMQC: Lactose 254 5.7.3 HMBC: Lactose 254 5.8 Relayed Coherence Transfer: TOCSY 254 5.8.1 2D TOCSY: Lactose 254 5.8.2 1D TOCSY: Lactose 257 5.9 HMQC-TOCSY 259 5.9.1 HMQC-TOCSY: Lactose 259 5.10 ROESY 259 5.10.1 ROESY: Lactose 259 5.11 VGSE 262 5.11.1 COSY: VGSE 262 5.11.2 TOCSY: VGSE 262 5.11.3 HMQC: VGSE 262 5.11.4 HMBC: VGSE 264 5.11.5 ROESY: VGSE 265 5.12 Pulsed Field Gradient NMR 265 References 268 Student Exercises 268 CHAPTER 6 MULTINUCLEAR MAGNETIC RESONANCE SPECTROSCOPY 298 6.1 Introduction and General Considerations 298 6.2 15N Nuclear Magnetic Resonance 299 6.3 19F Nuclear Magnetic Resonance 306 6.4 29Si Nuclear Magnetic Resonance 309 6.5 31P Nuclear Magnetic Resonance 312 6.6 Conclusions 315 References 315 Student Exercises 315 Appendix 320 A Properties of Magnetically Active Nuclei 320 CHAPTER 7 SOLVED PROBLEMS 325 7.1 Introduction 325 Problem 7.1 Discussion 329 Problem 7.2 Discussion 333 Problem 7.3 Discussion 337 Problem 7.4 Discussion 344 Problem 7.5 Discussion 350 Problem 7.6 Discussion 356 Student Exercises 357 CHAPTER 8 ASSIGNED PROBLEMS 364 8.1 Introduction 364 INDEX 453

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Book SynopsisA unique approach to the challenges of complex environmental systems Environmental Transport Processes, Second Edition provides much-needed guidance on mass transfer principles in environmental engineering. It focuses on working with uncontrolled conditions involving biological and physical systems, offering examples from diverse fields, including mass transport, kinetics, wastewater treatment, and unit processes. This new edition is fully revised and updated, incorporating modern approaches and practice problems at the end of chapters, making the Second Edition more concise, accessible, and easy to use. The book discusses the fundamentals of transport processes occurring in natural environments, with special emphasis on working at the biological?physical interface. It considers transport and kinetics in terms of systems that involve microorganisms, along with in-depth coverage of particles, size spectra, and calculations for particles that can be considered eitTrade Review“It also would be useful for people that work with these issues. Environmental Transport Processes can be recommended both to undergraduate and graduate students seeking to gain a good comprehension of environmental transport processes.” (Environ Earth Science, 19 October 2012) Table of ContentsPreface xi 1. Introduction 1 2. Equilibrium Calculations 18 3. Diffusive Transport 43 4. The Constitutive Transport Equation 79 5. Concentration Profiles And Chemical Fluxes 95 6. Mass Transport Correlations: From Theory To Empiricism 120 7. Transport In Sheared Reactors 140 8. Suspended Unattached And Aggregated Microorganisms 167 9. Biofilms 194 10. Disperson 232 11. Rivers, Lakes, And Oceans 264 12. Chemical Transport In Porous Media 292 13. Particles And Fractals 331 14. Coagulation In Natural, and Engineered Systems 362 15. Particle Transport In Porous Media 408 Appendicies 445 Index 475

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Book Synopsis Using a collaborative and interdisciplinary author base with experience in the pharmaceutical industry and academia, this book is a practical resource for high content (HC) techniques. Instructs readers on the fundamentals of high content screening (HCS) techniques Focuses on practical and widely-used techniques like image processing and multiparametric assays Breaks down HCS into individual modules for training and connects them at the end Includes a tutorial chapter that works through sample HCS assays, glossary, and detailed appendicesTable of ContentsPREFACE xvii CONTRIBUTORS xix 1 Introduction 1 Steven A. Haney 1.1 The Beginning of High Content Screening, 1 1.2 Six Skill Sets Essential for Running HCS Experiments, 4 1.3 Integrating Skill Sets into a Team, 7 1.4 A Few Words on Experimental Design, 8 1.5 Conclusions, 9 Key Points, 9 Further Reading, 10 References, 10 SECTION I FIRST PRINCIPLES 11 2 Fluorescence and Cell Labeling 13 Anthony Davies and Steven A. Haney 2.1 Introduction, 13 2.2 Anatomy of Fluorescent Probes, Labels, and Dyes, 14 2.3 Stokes’ Shift and Biological Fluorophores, 15 2.4 Fluorophore Properties, 16 2.5 Localization of Fluorophores Within Cells, 18 2.6 Multiplexing Fluorescent Reagents, 26 2.7 Specialized Imaging Applications Derived from Complex Properties of Fluorescence, 27 2.8 Conclusions, 30 Key Points, 31 Further Reading, 31 References, 31 3 Microscopy Fundamentals 33 Steven A. Haney, Anthony Davies, and Douglas Bowman 3.1 Introducing HCS Hardware, 33 3.2 Deconstructing Light Microscopy, 37 3.3 Using the Imager to Collect Data, 43 3.4 Conclusions, 45 Key Points, 45 Further Reading, 46 References, 46 4 Image Processing 47 John Bradley, Douglas Bowman, and Arijit Chakravarty 4.1 Overview of Image Processing and Image Analysis in HCS, 47 4.2 What is a Digital Image?, 48 4.3 “Addressing” Pixel Values in Image Analysis Algorithms, 48 4.4 Image Analysis Workflow, 49 4.5 Conclusions, 60 Key Points, 60 Further Reading, 60 References, 60 SECTION II GETTING STARTED 63 5 A General Guide to Selecting and Setting Up a High Content Imaging Platform 65 Craig Furman, Douglas Bowman, Anthony Davies, Caroline Shamu, and Steven A. Haney 5.1 Determining Expectations of the HCS System, 65 5.2 Establishing an HC Platform Acquisition Team, 66 5.3 Basic Hardware Decisions, 67 5.4 Data Generation, Analysis, and Retention, 72 5.5 Installation, 73 5.6 Managing the System, 75 5.7 Setting Up Workflows for Researchers, 77 5.8 Conclusions, 78 Key Points, 79 Further Reading, 79 6 Informatics Considerations 81 Jay Copeland and Caroline Shamu 6.1 Informatics Infrastructure for High Content Screening, 81 6.2 Using Databases to Store HCS Data, 86 6.3 Mechanics of an Informatics Solution, 89 6.4 Developing Image Analysis Pipelines: Data Management Considerations, 95 6.5 Compliance With Emerging Data Standards, 99 6.6 Conclusions, 101 Key Points, 102 Further Reading, 102 References, 102 7 Basic High Content Assay Development 103 Steven A. Haney and Douglas Bowman 7.1 Introduction, 103 7.2 Initial Technical Considerations for Developing a High Content Assay, 103 7.3 A Simple Protocol to Fix and Stain Cells, 107 7.4 Image Capture and Examining Images, 109 7.5 Conclusions, 111 Key Points, 112 Further Reading, 112 Reference, 112 SECTION III ANALYZING DATA 113 8 Designing Metrics for High Content Assays 115 Arijit Chakravarty, Steven A. Haney, and Douglas Bowman 8.1 Introduction: Features, Metrics, Results, 115 8.2 Looking at Features, 116 8.3 Metrics and Results: The Metric is the Message, 120 8.4 Types of High Content Assays and Their Metrics, 121 8.5 Metrics to Results: Putting it all Together, 126 8.6 Conclusions, 128 Key Points, 128 Further Reading, 129 References, 129 9 Analyzing Well-Level Data 131 Steven A Haney and John Ringeling 9.1 Introduction, 131 9.2 Reviewing Data, 132 9.3 Plate and Control Normalizations of Data, 134 9.4 Calculation of Assay Statistics, 135 9.5 Data Analysis: Hit Selection, 138 9.6 IC 50 Determinations, 139 9.7 Conclusions, 143 Key Points, 143 Further Reading, 143 References, 144 10 Analyzing Cell-Level Data 145 Steven A. Haney, Lin Guey, and Arijit Chakravarty 10.1 Introduction, 145 10.2 Understanding General Statistical Terms and Concepts, 146 10.3 Examining Data, 149 10.4 Developing a Data Analysis Plan, 155 10.5 Cell-Level Data Analysis: Comparing Distributions Through Inferential Statistics, 158 10.6 Analyzing Normal (or Transformed) Data, 159 10.7 Analyzing Non-Normal Data, 160 10.8 When to Call For Help, 162 10.9 Conclusions, 162 Key Points, 162 Further Reading, 163 References, 163 SECTION IV ADVANCED WORK 165 11 Designing Robust Assays 167 Arijit Chakravarty, Douglas Bowman, Anthony Davies, Steven A. Haney, and Caroline Shamu 11.1 Introduction, 167 11.2 Common Technical Issues in High Content Assays, 167 11.3 Designing Assays to Minimize Trouble, 172 11.4 Looking for Trouble: Building in Quality Control, 177 11.5 Conclusions, 179 Key Points, 180 Further Reading, 180 References, 180 12 Automation and Screening 181 John Ringeling, John Donovan, Arijit Chakravarty, Anthony Davies, Steven A Haney, Douglas Bowman, and Ben Knight 12.1 Introduction, 181 12.2 Some Preliminary Considerations, 181 12.3 Laboratory Options, 183 12.4 The Automated HCS Laboratory, 186 12.5 Conclusions, 192 Key Points, 192 Further Reading, 193 13 High Content Analysis for Tissue Samples 195 Kristine Burke, Vaishali Shinde, Alice McDonald, Douglas Bowman, and Arijit Chakravarty 13.1 Introduction, 195 13.2 Design Choices in Setting Up a High Content Assay in Tissue, 196 13.3 System Configuration: Aspects Unique to Tissue-Based HCS, 199 13.4 Data Analysis, 203 13.5 Conclusions, 207 Key Points, 207 Further Reading, 207 References, 208 SECTION V HIGH CONTENT ANALYTICS 209 14 Factoring and Clustering High Content Data 211 Steven A. Haney 14.1 Introduction, 211 14.2 Common Unsupervised Learning Methods, 212 14.3 Preparing for an Unsupervised Learning Study, 218 14.4 Conclusions, 228 Key Points, 228 Further Reading, 228 References, 229 15 Supervised Machine Learning 231 Jeff Palmer and Arijit Chakravarty 15.1 Introduction, 231 15.2 Foundational Concepts, 232 15.3 Choosing a Machine Learning Algorithm, 234 15.4 When Do You Need Machine Learning, and How Do You Use IT?, 243 15.5 Conclusions, 244 Key Points, 244 Further Reading, 244 Appendix A Websites and Additional Information on Instruments, Reagents, and Instruction 247 Appendix B A Few Words About One Letter: Using R to Quickly Analyze HCS Data 249 Steven A. Haney B.1 Introduction, 249 B.2 Setting Up R, 250 B.3 Analyzing Data in R, 253 B.4 Where to Go Next, 261 Further Reading, 263 Appendix C Hypothesis Testing for High Content Data: A Refresher 265 Lin Guey and Arijit Chakravarty C.1 Introduction, 265 C.2 Defining Simple Hypothesis Testing, 266 C.3 Simple Statistical Tests to Compare Two Groups, 269 C.4 Statistical Tests on Groups of Samples, 276 C.5 Introduction to Regression Models, 280 C.6 Conclusions, 285 Key Concepts, 286 Further Reading, 286 GLOSSARY 287 TUTORIAL 295 INDEX 323

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Book SynopsisDemystifies the largest volume manmade synthetic polymer by distillingthe fundamentals of what polyethylene is, how it''s made and processed,and what happens to it after its useful life is over. Endorsement for Introduction to Industrial Polyethylene I found this to be a straightforward, easy-to-read, and useful introductory text on polyethylene, which will be helpful for chemists, engineers, and students who need to learn more about this complex topic. The author is a senior polyethylene specialist and I believe we can all benefit from his distillation of knowledge and insight to quickly grasp the key learnings. R.E. King III; Ciba Corporation (part of the BASF group) Jargon used in industrial polyethylene technology can often be bewildering to newcomers. Introduction to Industrial Polyethylene educates readers on terminology commonly used in the industry and demystifies the chemistry of catalysts and cocatalysts employed in the manuTrade Review"This concise primer reviews the history of polyethylene and introduces basic features and nomenclatures for this versatile polymer." (Forbes.com, 1 November 2010)Table of ContentsPreface ix List of Tables xiii List of Figures xv Chapter 1 Introduction to Polymers of Ethylene 1 Chapter 2 Free Radical Polymerization of Ethylene 23 Chapter 3 Ziegler-Natta Catalysts 33 Chapter 4 Metal Alkyls in Polyethylene Catalyst Systems 45 Chapter 5 Chromium Catalysts 61 Chapter 6 Single Site Catalysts 71 Chapter 7 An Overview of Industrial Polyethylene Processes 85 Chapter 8 Downstream Aspects of Polyethylene 99 Glossary 117 Trade Name Index 125 Index 127

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Book SynopsisFor engineering and scientific endeavors to progress there must be generally accepted ethical guidelines in place to which engineers and scientists must adhere. This book explores the various scientific and engineering disciplines, examining the potential for unethical behavior by professionals.Trade Review“Overall, Speight and Foote present a wide-ranging discussion of ethics from a theoretical and applied perspective making Ethics in Science and Engineering a valuable reference book.” (Journal of Chemical Education, 30 November 2012)Table of ContentsPreface ix 1. Explaining Ethics 1 1.1 Introduction 1 1.2 The Impact of Science and Engineering 8 1.3 The Framework of Ethics 12 1.4 Ethics in Professional Life 19 References 24 2. Scientists and Engineers 27 2.1 Introduction 27 2.2 Definitions 32 2.3 Scientific Disciplines 35 2.4 Engineering Disciplines 39 2.5 Expert Witness 41 2.6 Professionalism 43 References 50 3. The Psychology and Philosophy of Ethics 53 3.1 Introduction 53 3.2 Ethical Responsibilities in Research 56 3.3 Ethics in Science and Engineering 63 3.4 A Phenomenological Theory of Ethics 72 3.5 Conflicts of Interest 76 References 82 4. Education of Scientists and Engineers 85 4.1 Introduction 85 4.2 The High School Experience 87 4.3 The Baccalaureate Experience 91 4.4 The Graduate Degree Experience 102 4.5 Postdoctoral Education 106 4.6 Morals and Values 108 4.7 Evaluating Scientists and Engineers 113 4.8 Intellectual Property 114 References 119 5. Scientific and Engineering Societies 123 5.1 Introduction 123 5.2 Scientific Societies 127 5.3 Engineering Societies 131 5.4 Codes of Ethics and Ethical Standards 134 5.5 Promoting Research Integrity 138 5.6 The Effectiveness of Society Activities 140 5.7 Academic Freedom 148 References 153 6. Codes of Ethics and Ethical Standards 157 6.1 Introduction 157 6.2 Ethics 166 6.3 Codes of Ethics 179 6.4 The Premise Behind Codes of Ethics 184 6.5 Codes of Ethics and Peer Reviews 188 References 191 7. Integrity in Research 195 7.1 Introduction 195 7.2 The Nature and Conduct of Research 205 7.3 Collecting Research Data 216 7.4 The Controls 226 References 231 8. Publication and Communication 235 8.1 Introduction 235 8.2 The Scientific and Engineering Literature 241 8.3 The Journals 242 8.4 Data Manipulation for Publication 247 8.5 Detecting Falsified Data 248 8.6 Peer Reviewers and Their Duties 249 8.7 Duties and Responsibilities of a Journal Editor 252 References 257 9. Enforcement of Codes of Ethics 259 9.1 Introduction 259 9.2 Following a Code of Ethics 262 9.3 Enforcing a Code of Ethics 264 9.4 Reporting Misconduct 274 9.5 Published Examples of Unethical Behavior 280 References 288 Glossary 291 Index 301

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Book SynopsisThe pharmaceutical industry is one of the most important industries in the world, offering new medicines, vaccines, and cures to a global population. It is a massive industry, worthy of a deep and thorough examination of its processes and chemistry, with a view toward sustainability. The authors describe what is and isn''t truly sustainable, offering a new approach and a new definition of the sustainability of pharmaceutical and chemical engineering and the science behind it. This is a cutting-edge work, aimed at engineers, scientists, researchers, chemists, and students.Table of ContentsPreface xvii 1 Introduction 1 1.1 Opening Remarks 1 1.2 Are We Trained to Develop Contempt for Conscience and Addiction to Selfi shness? 4 1.3 Metadata 5 1.4 INTRODUCING CHAPTER TWO: What’s Behind Giving Up Honey and Promoting Aspartame as the Cure, i.e., Dumping the Natural Option in Favour of the Artifi cial One? 8 1.5 INTRODUCING CHAPTER THREE: Are the Premises of New Science Suffi cient For Uncovering or Establishing The Cause of Anything? 25 1.6 INTRODUCING CHAPTER FOUR: For How Long We Have Been Lied To? 28 1.7 INTRODUCING CHAPTER FIVE: A Starting-Point for Society-Wide Corruption 29 1.8 INTRODUCING CHAPTER SIX: Deconstruction of the Foundations of Aphenomenal Science in the Works of Newton (Part A) and Einstein (Part B) 30 1.9 INTRODUCING VOLUME TWO: The Way Out 41 1.10 INTRODUCING CHAPTER SEVEN: Concluding the Discussion-So-Far 48 1.11 INTRODUCING CHAPTER EIGHT: About the References and Bibliography, or: Now Previous Knowledge Can Help 50 Appendix 1.1 51 PART ONE The Political Economy of U.S. Government-led Struggles to Control or Suppress Alcohol, Tobacco and Drug Addiction 51 Appendix 1.2 60 PART TWO Delinearizing the Anti-Colonial Origins of the Corporatized American State and Its Consequences for Contemporary Science and Technology 60 2 Current State of the World of Big Pharma 65 2.1 Summary 65 2.2 Introduction 66 2.3 How We Got Here: A Delinearized History of the Information Age 70 2.4 Sociological Degeneration 90 2.5 The Deadliest 10 Diseases 94 2.6 Paradox and New Science 114 2.7 The Cost Of Drugs 128 2.8 “Non-Prescription” Drugs 131 3 HSS®A® Degradation in New Science 143 3.1 Summary 143 3.2 Introduction 144 3.3 The HSS®A® (Honey → Sugar → Saccharin® → Aspartame®) Pathway 147 3.4 The Sugar Culture and Beyond 172 3.5 The Culture of the Artifi cial Sweetener 177 3.6 The Culture of Aspartame 194 3.7 The Honey-Sugar-Saccharin-Aspartame Degradation in Everything 227 4 The Hopelessness of New Science 291 4.1 Summary 291 4.2 Introduction 292 4.3 Colony Collapse Disorder (CDC) 294 4.4 Incurable Disease 325 4.5 Diseases with Implications for Fundamental Theoretical Concerns (Mass, Energy and HTM) 384 4.6 The Need for the Science of Intangibles 397 4.7 The Need for Studying the Time Dimension in Implicit Form 404 4.8 Assessing the Overall Performance of a Process 411 4.9 Aphenomenal Theories of Modern Era 422 4.10 The Law of Conservation of Mass and Energy 425 4.11 Toward Uncovering Knowledge 432 4.12 Conclusions 435 5 Mass, Energy and Time: A Delinearized History 437 5.1 Summary 437 5.2 Introduction 438 5.3 The Energy Crisis 440 5.4 Gas Hydrates 485 5.5 Science of Healthy Energy and Mass 507 Appendix 548 6 Newton & Einstein: A Delinearized Deconstruction 591 6.1 Summary 591 6.2 Introduction 591 6.3 Historical Context 595 6.4 Time Conceptions, Tangible-Intangible Nexus, and Social Roles of Knowledge 610 6.5 What is New Versus what is Permitted: Science and the Establishment? 630 6.6 Deconstruction of Einstein’s concept of reality, mass, time, and energy 648 6.7 Conclusions 662 7 The Nature-Science Approach: Conclusions of Book I 665 7.1 Summary 665 7.2 Introduction 667 7.3 Struggle for Social Reform: Internal and External Factors 674 7.4 Consequences of Nature-Science for Classical Set Theory and Conventional Notions of Mensuration 676 7.5 Conclusions 678 7.6 The Need for Change 709 7.7 The Nature Science Approach 710 References and Bibliography 713 Index 773

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Book SynopsisNow updated - the authoritative reference on one of the most exciting and challenging areas of the modern chemical industry This highly readable and informative reference continues to take a comprehensive, in-depth view of the products, markets, and technology of the fine chemicals industry and business. Dr.Trade ReviewNamed CHOICE Outstanding Title for 2012 "I would recommend it to anyone working with or within the fine chemicals industry." (Chemistry & Industry, 5 December 2011) Table of ContentsPreface to the Second Edition. Preface to the First Edition. Acknowledgments. Part I The Industry. 1. What Fine Chemicals Are. 2. The Fine Chemical Industry. 3. Products. 4. Technologies. 5. Facilities and Plants. 6. Research and Development. 7. Cost Calculation. 8. Management Aspects. Bibliography. Part II The Business. 9. Market Size and Structure. 10. The Business Condition. 11. Customer Base. 12. Marketing. Bibliography. Part III Outlook. 13. General Trends and Growth Drivers. 14. Globalization. 15. Biotechnology. 16. Ethical Pharmaceutical Industry. 17. Generics. 18. Other Life Science Industries. 19. Contract Research Organizations. 20. Conclusion: Who is Fittest for the Future? Bibliography. Abbreviations. Appendices. A.1 Information Sources/Life Sciences. A.2 Checklist for New Product Evaluation. A.3 Product Schedule, Custom Manufacturing Product. A.4 Company Scorecard. A.5 Job Description for Business Development Manager. A.6 Checklist for the Selection of Outsourcing Partners. A.7 Checklist for the Manufacture of Nonregulated (or Basic GMP) Fine Chemicals. A.8 Checklist for Customer Visit. A.9 Outline for a Company Presentation. A.10 Overseas Expansion of Indian Pharm and Fine Chemical Companies. A.11 Asian Expansion of Western Fine Chemical Companies. Index. Note.

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Book SynopsisThis book presents a balance of theoretical considerations and practical problem solving of electrochemical impedance spectroscopy.Table of ContentsPreface ix 1. Fundamentals of electrochemical impedance spectroscopy 1 2. Graphical representation of impedance spectroscopy data 23 3. Equivalent-circuit elements and modeling of the impedance phenomenon 37 4. Examples of ideal equivalent circuit models 49 5. Impedance representation of bulk-material and electrode processes 59 6. Distributed impedance models 97 7. Impedance analysis of complex systems 113 8. Impedance Instrumentation, testing, and data validation 163 9. Selected examples of impedance-analysis applications: electroactive polymer films 205 10. Selected examples of EIS analysis applications: industrial colloids and lubricants 219 11. Selected examples of EIS analysis applications: cell suspensions, protein adsorption, and implantable biomedical devices 247 12. Selected examples of impedance-analysis applications 281 13. Impedance-spectroscopy modifications 319 14. Conclusions and perspectives of EIS 333 Abbreviations and Symbols 335 Index 345

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Book SynopsisThis book focuses on the drug discovery and development applications of transition metal catalyzed processes, which can efficiently create preclinical and clinical drug candidates as well as marketed drugs. The authors pay particular attention to the challenges of transitioning academically-developed reactions into scalable industrial processes. Additionally, the book lays the groundwork for how continued development of transition metal catalyzed processes can deliver new drug candidates. This work provides a unique perspective on the applications of transition metal catalysis in drug discovery and development it is a guide, a historical prospective, a practical compendium, and a source of future direction for the field.Trade Review“The book will be particularly appreciated by young scientists, especially those aspiring to a future in the pharmaceutical industry, because it shows what kind of problems they will be asked to solve once they start their industrial career.” (ChemMedChem, 1 March 2013) “All chapters are well-written and comprehensive with lots of examples from OPR and D. The book is highly recommended to all process chemists.” (Organic Process Research & Development Journal, 1 November 2012)Table of ContentsPreface vii Contributors ix About the Authors xi 1 Transition Metal Catalysis in the Pharmaceutical Industry 1Carl A. Busacca, Daniel R. Fandrick, Jinhua J. Song, and Chris H. Senanayake (Boehringer Ingelheim Pharmaceuticals) 2 Selected Applications of Transition Metal-Catalyzed Carbon–Carbon Cross-Coupling Reactions in the Pharmaceutical Industry 25Hong C. Shen (Roche) 3 Selected Applications of Pd- and Cu-Catalyzed Carbon–Heteroatom Cross-Coupling Reactions in the Pharmaceutical Industry 97Jingjun Yin (Merck) 4 Asymmetric Cross-Coupling Reactions 165Vince Yeh (Novartis) and William A. Szabo (Consultant in Drug Development) 5 Metathesis Reactions 215Oliver R. Thiel (Amgen) 6 Transition Metal-Catalyzed Synthesis of Five- and Six-Membered Heterocycles 257Cheol K. Chung (Merck) and Matthew L. Crawley (Main Line Health) 7 Oxidative Catalysis 277Lamont Terrell (GlaxoSmithKline) 8 Industrial Asymmetric Hydrogenation 315Hans-Ulrich Blaser (Solvias) Index 243

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Book SynopsisBennett's Transport by Advection and Diffusion provides a focused foundation for the principles of transport at the senior or graduate level, with illustrations from a wide range of topics. The text uses an integrated approach to teaching transport phenomena, but widens coverage to include topics such as transport in compressible flows and in open channel flows. Transport by Advection and Diffusion helps students develop the requisite math skills as well as the conceptual understanding needed to succeed in research and education. It presents analytical and numerical tools to aid problem solving in each topic area. The text is designed for senior or graduate level courses for chemical and mechanical engineering, environmental studies, earth science, materials science, and physics, but it will also appeal to practitioners.Table of ContentsChapter 1 Thermodynamic Preliminaries 1 1.1 The First and Second Laws of Thermodynamics 1 1.2 Fundamental Equations 2 1.3 Ideal Gas 7 1.4 Constant Density Solid or Liquid 8 1.5 Properties of Mixtures 9 1.6 Summary of Thermodynamic Results 9 1.7 Problems 10 Chapter 2 Fundamentals of Transport 12 2.1 Physics of Advection and Diffusion 12 2.2 Advection Fluxes 14 2.3 Diffusion Fluxes 17 2.4 Reversible vs. Irreversible Transport 22 2.5 Looking Ahead 23 2.6 Problems 23 Chapter 3 Index Notation 25 3.1 Indices 25 3.2 Representation of Cartesian Differential Equations 26 3.3 Special Operators 27 3.4 Operators in Non-Cartesian Coordinates 31 3.5 Problems 34 Chapter 4 Transport by Advection and Diffusion 36 4.1 Continuity Equation 37 4.2 Transport of Species 39 4.3 Transport of Heat 42 4.4 Transport of Momentum 43 4.5 Summary of Transport Equations without Sources 44 4.6 Conservation Statements from a Finite Volume 44 4.7 Eulerian and Lagrangian Coordinates and the Substantial Derivative 46 4.8 Problems 48 Chapter 5 Transport with Source Terms 50 5.1 Continuity Equation 51 5.2 Species Equation 51 5.3 Heat Equation (without Viscous Heating) 52 5.4 Momentum Equation 54 5.5 Kinetic Energy Equation 55 5.6 Heat Equation (with Viscous Heating) 57 5.7 Entropy Generation in Irreversible Flows 58 5.8 Conservation Statements Derived from a Finite Volume 59 5.9 Leibniz’s Theorem 62 5.10 Looking Ahead 63 5.11 Problems 64 Chapter 6 Specification of Transport Problems 66 6.1 Classification of Equations 66 6.2 Boundary Conditions 67 6.3 Elementary Linear Examples 69 6.4 Nonlinear Example 73 6.5 Scaling Estimates 75 6.6 Problems 78 Chapter 7 Transient One-Dimensional Diffusion 82 7.1 Separation of Time and Space Variables 83 7.2 Silicon Doping 89 7.3 Plane Wall With Heat Generation 93 7.4 Transient Groundwater Contamination 97 7.5 Problems 101 Chapter 8 Steady Two-Dimensional Diffusion 103 8.1 Separation of Two Spatial Variables 103 8.2 Nonhomogeneous Conditions on Nonadjoining Boundaries 105 8.3 Nonhomogeneous Conditions on Adjoining Boundaries 107 8.4 Nonhomogeneous Condition in Governing Equation 111 8.5 Looking Ahead 115 8.6 Problems 115 Chapter 9 Eigenfunction Expansion 119 9.1 Method of Eigenfunction Expansion 119 9.2 Non-Cartesian Coordinate Systems 127 9.3 Transport in Non-Cartesian Coordinates 130 9.4 Problems 139 Chapter 10 Similarity Solution 140 10.1 The Similarity Variable 140 10.2 Laser Heating of a Semi-Infinite Solid 142 10.3 Transient Evaporation 146 10.4 Power Series Solution 148 10.5 Mass Transfer with Time-Dependent Boundary Condition 152 10.6 Problems 157 Chapter 11 Superposition of Solutions 159 11.1 Superposition in Time 159 11.2 Superposition in Space 164 11.3 Problems 169 Chapter 12 Diffusion-Driven Boundaries 172 12.1 Thermal Oxidation 172 12.2 Solidification of an Undercooled Liquid 174 12.3 Solidification of a Binary Alloy from an Undercooled Liquid 178 12.4 Melting of a Solid Initially at the Melting Point 183 12.5 Problems 186 Chapter 13 Lubrication Theory 188 13.1 Lubrication Flows Governed by Diffusion 188 13.2 Scaling Arguments for Squeeze Flow 189 13.3 Squeeze Flow Damping in an Accelerometer Design 191 13.4 Coating Extrusion 194 13.5 Coating Extrusion on a Porous Surface 198 13.6 Reynolds Equation for Lubrication Theory 202 13.7 Problems 203 Chapter 14 Inviscid Flow 206 14.1 The Reynolds Number 207 14.2 Inviscid Momentum Equation 208 14.3 Ideal Plane Flow 209 14.4 Steady Potential Flow through a Box with Staggered Inlet and Exit 210 14.5 Advection of Species through a Box with Staggered Inlet and Exit 215 14.6 Spherical Bubble Dynamics 217 14.7 Problems 221 Chapter 15 Catalog of Ideal Plane Flows 224 15.1 Superposition of Simple Plane Flows 224 15.2 Potential Flow over an Aircraft Fuselage 225 15.3 Force on a Line Vortex in a Uniform Stream 227 15.4 Flow Circulation 229 15.5 Potential Flow over Wedges 231 15.6 Problems 233 Chapter 16 Complex Variable Methods 234 16.1 Brief Review of Complex Numbers 234 16.2 Complex Representation of Potential Flows 235 16.3 The Joukowski Transform 236 16.4 Joukowski Symmetric Airfoils 238 16.5 Joukowski Cambered Airfoils 240 16.6 Heat Transfer between Nonconcentric Cylinders 242 16.7 Transport with Temporally Periodic Conditions 244 16.8 Problems 246 Chapter 17 MacCormack Integration 249 17.1 Flux-Conservative Equations 249 17.2 MacCormack Integration 250 17.3 Transient Convection 255 17.4 Steady-State Solution of Coupled Equations 259 17.5 Problems 262 Chapter 18 Open Channel Flow 265 18.1 Analysis of Open Channel Flows 265 18.2 Simple Surface Waves 267 18.3 Depression and Elevation Waves 268 18.4 The Hydraulic Jump 269 18.5 Energy Conservation 271 18.6 Dam-Break Example 273 18.7 Tracer Transport in the Dam-Break Problem 280 18.8 Problems 280 Chapter 19 Open Channel Flow with Friction 284 19.1 The Saint-Venant Equations 284 19.2 The Friction Slope 286 19.3 Flow through a Sluice Gate 287 19.4 Problems 293 Chapter 20 Compressible Flow 296 20.1 General Equations of Momentum and Energy Transport 296 20.2 Reversible Flows 298 20.3 Sound Waves 299 20.4 Propagation of Expansion and Compression Waves 300 20.5 Shock Wave (Normal to Flow) 302 20.6 Shock Tube Analytic Description 304 20.7 Shock Tube Numerical Description 307 20.8 Shock Tube Problem with Dissimilar Gases 311 20.9 Problems 312 Chapter 21 Quasi-One-Dimensional Compressible Flows 315 21.1 Quasi-One-Dimensional Flow Equations 315 21.2 Quasi-One-Dimensional Steady Flow Equations without Friction 318 21.3 Numerical Solution to Quasi-One-Dimensional Steady Flow 323 21.4 Problems 330 Chapter 22 Two-Dimensional Compressible Flows 333 22.1 Flow through a Diverging Nozzle 333 22.2 Problems 342 Chapter 23 Runge-Kutta Integration 344 23.1 Fourth-Order Runge-Kutta Integration of First-Order Equations 344 23.2 Runge-Kutta Integration of Higher Order Equations 347 23.3 Numerical Integration of Bubble Dynamics 349 23.4 Numerical Integration with Shooting 351 23.5 Problems 355 Chapter 24 Boundary Layer Convection 359 24.1 Scanning Laser Heat Treatment 359 24.2 Convection to an Inviscid Flow 363 24.3 Species Transfer to a Vertically Conveyed Liquid Film 369 24.4 Problems 374 Chapter 25 Convection into Developing Laminar Flows 376 25.1 Boundary Layer Flow over a Flat Plate (Blasius Flow) 376 25.2 Species Transfer across the Boundary Layer 383 25.3 Heat Transfer across the Boundary Layer 387 25.4 A Correlation for Forced Heat Convection from a Flat Plate 389 25.5 Transport Analogies 390 25.6 Boundary Layers Developing on a Wedge (Falkner-Skan Flow) 392 25.7 Viscous Heating in the Boundary Layer 394 25.8 Problems 396 Chapter 26 Natural Convection 399 26.1 Buoyancy 399 26.2 Natural Convection from a Vertical Plate 400 26.3 Scaling Natural Convection from a Vertical Plate 401 26.4 Exact Solution to Natural Convection Boundary Layer Equations 404 26.5 Problems 411 Chapter 27 Internal Flow 412 27.1 Entrance Region 412 27.2 Heat Transport in an Internal Flow 414 27.3 Entrance Region of Plug Flow between Plates of Constant Heat Flux 415 27.4 Plug Flow between Plates of Constant Temperature 417 27.5 Fully Developed Transport Profiles 419 27.6 Fully Developed Heat Transport in Plug Flow between Plates of Constant Heat Flux 421 27.7 Fully Developed Species Transport in Plug Flow Between Surfaces of Constant Concentration 424 27.8 Problems 426 Chapter 28 Fully Developed Transport in Internal Flows 429 28.1 Momentum Transport in a Fully Developed Flow 429 28.2 Heat Transport in a Fully Developed Flow 430 28.3 Species Transport in a Fully Developed Flow 441 28.4 Problems 444 Chapter 29 Influence of Temperature-Dependent Properties 447 29.1 Temperature-Dependent Conductivity in a Solid 447 29.2 Temperature-Dependent Diffusivity in Internal Convection 451 29.3 Temperature-Dependent Gas Properties in Boundary Layer Flow 457 29.4 Problems 462 Chapter 30 Turbulence 465 30.1 The Transition to Turbulence 466 30.2 Reynolds Decomposition 468 30.3 Decomposition of the Continuity Equation 469 30.4 Decomposition of the Momentum Equation 470 30.5 The Mixing Length Model of Prandtl 471 30.6 Regions in a Wall Boundary Layer 473 30.7 Parameters of the Mixing Length Model 476 30.8 Problems 477 Chapter 31 Fully Developed Turbulent Flow 479 31.1 Turbulent Poiseuille Flow Between Smooth Parallel Plates 480 31.2 Turbulent Couette Flow between Smooth Parallel Plates 485 31.3 Turbulent Poiseuille Flow in a Smooth-Wall Pipe 488 31.4 Utility of the Hydraulic Diameter 490 31.5 Turbulent Poiseuille Flow in a Smooth Annular Pipe 490 31.6 Reichardt’s Formula for Turbulent Diffusivity 495 31.7 Poiseuille Flow with Blowing between Walls 497 31.8 Problems 504 Chapter 32 Turbulent Heat and Species Transfer 507 32.1 Reynolds Decomposition of the Heat Equation 507 32.2 The Reynolds Analogy 508 32.3 Thermal Profile Near the Wall 510 32.4 Mixing Length Model for Heat Transfer 513 32.5 Mixing Length Model for Species Transfer 514 32.6 Problems 515 Chapter 33 Fully Developed Transport in Turbulent Flows 517 33.1 Chemical Vapor Deposition in Turbulent Tube Flow with Generation 517 33.2 Heat Transfer in a Fully Developed Internal Turbulent Flow 522 33.3 Heat Transfer in a Turbulent Poiseuille Flow between Smooth Parallel Plates 523 33.4 Fully Developed Transport in a Turbulent Flow of a Binary Mixture 532 33.5 Problems 543 Chapter 34 Turbulence over Rough Surfaces 545 34.1 Turbulence over a Fully Rough Surface 546 34.2 Turbulent Heat and Species Transfer from a Fully Rough Surface 547 34.3 Application of the Rough Surface Mixing Length Model 549 34.4 Application of Reichardt’s Formula to Rough Surfaces 553 34.5 Problems 563 Chapter 35 Turbulent Boundary Layer 565 35.1 Formulation of Transport in Turbulent Boundary Layer 565 35.2 Formulation of Heat Transport in the Turbulent Boundary Layer 575 35.3 Problems 580 Chapter 36 The K-Epsilon Model of Turbulence 581 36.1 Turbulent Kinetic Energy Equation 581 36.2 Dissipation Equation for Turbulent Kinetic Energy 585 36.3 The Standard K-Epsilon Model 586 36.4 Problems 587 Chapter 37 The K-Epsilon Model Applied to Fully Developed Flows 589 37.1 K-Epsilon Model for Poiseuille Flow between Smooth Parallel Plates 589 37.2 Transition Point between Mixing Length and K-Epsilon Models 591 37.3 Solving the K and E Equations 593 37.4 Solution of the Momentum Equation with the K-Epsilon Model 597 37.5 Turbulent Diffusivity Approaching the Centerline of the Flow 598 37.6 Turbulent Heat Transfer with Constant Temperature Boundary 601 37.7 Problems 604 Appendix A 606 Index 611

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Book SynopsisCost-effective strategies for designing novel drug delivery systems that target a broad range of disease conditions In vivo imaging has become an important tool for the development of new drug delivery systems, shedding new light on the pharmacokinetics, biodistribution, bioavailability, local concentration, and clearance of drug substances for the treatment of human disease, most notably cancer. Written by a team of international experts, this book examines the use of quantitative imaging techniques in designing and evaluating novel drug delivery systems and applications. Drug Delivery Applications of Noninvasive Imaging offers a full arsenal of tested and proven methods, practices and guidance, enabling readers to overcome the many challenges in creating successful new drug delivery systems. The book begins with an introduction to molecular imaging. Next, it covers: In vivo imaging techniques and quantitative analysis Table of ContentsPreface ix contributors xi 1 Introduction to Molecular Imaging 1 Vikas Kundra 2 PET/SPECT: Instrumentation and Imaging Techniques 12 Yuan-Chuan Tai 3 Photoacoustic Tomography and Its Applications in Drug Delivery and Photothermal Therapy 45 Liang Song and Lihong V. Wang 4 Raman Microspectral Imaging for Label-Free Detection of Nanoparticle-Mediated Cellular and Subcellular Drug Delivery 70 Tatyana Chernenko, Lara Milane, Christian Matthäus, Max Diem, and Mansoor Amiji 5 A natomical and Functional MRI91 Edward F. Jackson 6 Quantitative Imaging in Drug Delivery 125 Kooresh I. Shoghi 7 PET Imaging of the Pharmacokinetics of Small Molecular-Weight Drugs 147 Stephen M. Moerlein and Zhude Tu 8 Imaging Peptides, Proteins, and Antibody Delivery 192 Frederik L. Giesel and Clemens Kratochwil 9 In Vivo Imaging and Delivery of siRNA199 Zdravka Medarova and Anna Moore 10 Imaging Cell Therapy 223 Yajie Liang and Jeff W. M. Bulte 11 Radiolabeled Liposomes as Drug Delivery Nanotheranostics 252 William T. Phillips, Ande Bao, Keitaro Sou, Shihong Li, and Beth Goins 12 Polymeric Micelles as Imaging Agents and Drug Delivery Systems 268 Jun Zhao and Chun Li 13 Perfluorocarbon Nanoparticles: Translating Bench Opportunities to the Clinic 296 G. M. Lanza, P. M. Winter, S. D. Caruthers, A. H. Schmieder, and S. A. Wickline 14 Cancer Theranostics with Hollow Gold Nanospheres 308 Wei Lu and Chun Li 15 Imaging Pulmonary Drug Delivery 333 Stephen P. Newman 16 In Vivo Imaging for Validation of Oral Dose Performance 367 Fiona J. McInnes and Howard N. E. Stevens 17 Role of Large Animal Models in Translational Studies of Imaging and Targeted Drug Delivery 389 Rajesh K. Uthamanthil and Mei Tian 18 Imaging Transcatheter Delivery to Liver Tumors 412 Adil Al-Nahhas, Meeran Naji, and Imene Zerizer 19 Direct Visualization of Therapeutic Radionuclide Distribution Using Nuclear Medicine Imaging: I-131 in Metastatic Thyroid Carcinoma 426 Ho Young Lee, June-Key Chung, So Won Oh, Jong Jin Lee, Keon Wook Kang, Do Joon Park, Bo Youn Cho, and Myung Chul Lee 20 Imaging Drug Delivery to the CNS Using Translational Positron Emission Tomography Studies 432 Chi-Ming Lee, Katarina Varnäs, and Lars Farde Index 449

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Book SynopsisThe first part of this book (Chapters 1 and 2) provides an introduction and discusses basic concepts. Chapter 3 deals with the use of the basic human senses for identifying hazards. Chapter 4 deals with different classes and categories of hazards.Trade Review"This book comes with a CD-ROM which includes a variety of helpful resources, including additional pictures, special hazard identification presentations, worksheets, and checklists. Moreover, case studies show how the concepts and techniques discussed in the book can be applied in real-world situations." (RoSPA Occupational Safety & Health Journal, 1 April 2011)Table of ContentsPreface xi Acknowledgment xiii Items on CD xv 1 INTRODUCTION i 1.1 Intended Audience 9 1.2 How to Use This Book 11 1.3 References 12 2 BASIC CONCEPTS 13 2.1 Hazard and Risk 14 2.2 Accident Model 16 2.3 Physical and Process Hazards 17 2.4 Benefits of Hazard Identification 34 2.5 Hazards Types by Industry 34 2.6 References 43 3 IDENTIFY HAZARDS 45 3.1 Concept of Recognition 50 3.2 Basic Human Senses 51 3.2.1 Vision 53 3.2.2 Hearing 68 3.2.3 Smell 73 3.2.4 Touch 74 3.2.5 Taste 76 3.3 Relationship Between Senses and Higher Order Processes 76 3.4 Influence of Human Capabilities and Limitations on Hazard Identification 79 3.4.1 Visual Detection 79 3.4.2 Sound Detection 81 3.4.3 Odor Detection 81 3.4.4 Touch Detection 82 3.4.5 Hazard Recognition 82 3.5 What Causes Hazards? 84 3.5.1 Example 1 84 3.5.2 Example 2 87 3.5.3 Example 3 89 3.6 References 90 4 TYPES OF HAZARDS 93 4.1 Explosion Hazards 95 4.1.1 Reactive Explosion Hazards 95 4.1.2 Flammable Explosion Hazards 98 4.1.3 Physical Explosion Hazards 101 4.2 Chemical Hazards 105 4.2.1 Toxic Chemical Hazards 105 4.2.2 Fire Hazards Ill 4.2.3 Corrosive Chemical Hazards 116 4.3 Electrical Hazards 118 4.3.1 Shock/Short Circuit 118 4.3.2 Fire 121 4.3.3 Lightning Strikes 122 4.3.4 Static Electrical Discharge 122 4.3.5 Loss of Power 123 4.4 Excavation Hazards 124 4.5 Asphyxiation Hazards 126 4.6 Elevation Hazards 127 4.7 Thermal Hazards 130 4.7.1 Heat 130 4.7.2 Cold 132 4.8 Vibration Hazards ..132 4.9 Mechanical Failure Hazards 133 4.10 Mechanical Hazards 134 4.11 Corrosion Hazards 135 4.12 Noise Hazards 137 4.13 Radiation Hazards 138 4.13.1 Ionizing Radiation Hazards 138 4.13.2 Non-ionizing Radiation Hazards 139 4.14 Impact Hazards 140 4.15 Struck Against Hazards 142 4.16 Visibility Hazards 143 4.17 Weather Phenomena Hazards 144 4.17.1 Temperature Extreme Hazards 144 4.17.2 Hurricane 147 4.17.3 Flood 147 4.17.4 Wind 149 4.18 References 149 5 EVALUATE HAZARDS 151 5.1 Field Surveys 154 5.1.1 Behavior Observation 154 5.1.2 Facility Walkthrough Checklists 458 5.2 Pre-Job Assessments 164 5.2.1 Job Hazard Analysis 164 5.2.2 Pre-Job Planning and Permitting 175 5.2.3 Ad Hoc Risk Assessment 176 5.3 Facility Assessments 182 5.3.1 Preliminary Hazard Analysis 182 5.3.2 Critical Task Identification Analysis 190 5.4 Incident and Near-Miss Reporting 201 5.4.1 Hazard Trending and Analysis 202 5.4.2 Hazard Mapping 204 5.5 Hazard Identification and Analysis Training 206 5.6 References 207 6 MAKE RISK-BASED DECISIONS 211 6.1 Hazard Ranking 215 6.2 Understanding Risk 217 6.3 Risk Ranking 218 6.3.1 Severity 222 6.3.2 Hierarchy of Safeguards or Layers of Protection 223 6.3.3 Likelihood 228 6.3.4 Risk Ranking 230 6.3.5 Example 1 - Flammable/Explosive Hazard 231 6.3.6 Example 2 - Flammable Hazard 234 6.3.7 More Detailed Matrices 238 6.3.8 Similarities Between More Sophisticated Process Hazard Evaluation Techniques 238 6.4 References 240 7 FOLLOW-UP AND CALL TO ACTION 241 7.1 Safety Culture 242 7.2 Management Commitment 243 7.3 Employee Ownership 243 7.4 Implement an Effective Hazard Management Program 245 7.4.1 Written Procedures and Training 245 7.4.2 Resolving Recommendations for Risk Reduction 245 7.4.3 Concepts to Strengthen Protective Systems 247 7.5 Hazard Communication 249 7.6 Call to Action 251 7.7 References 252 8 LEARNING AND CONTINUOUS IMPROVEMENT 253 8.1 Case Study - Oil Refinery Fire, 2007 253 8.2 Importance of Managing Change 256 8.3 Published Accident Databases and Resources 261 8.4 Revitalizing Lessons Learned 262 8.5 Transfer of Knowledge 263 8.5.1 Identifying and Collecting Information 264 8.5.2 Storing Information 264 8.5.3 Transferring Information 265 8.5.4 Managing the Process 265 8.5.5 Applying What You've Learned 265 8.6 Learning from Incidents 267 8.7 References 269 List of Figures 271 List of Tables 277 Index 278

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