Biotechnology Books

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

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Book SynopsisThis book focuses on practical applications for using adult and embryonic stem cells in the pharmaceutical development process. It emphasizes new technologies to help overcome the bottlenecks in developing stem cells as therapeutic agents.Table of ContentsForeword Current state of stem cell field: Overview (Mahendra S. Rao). Chapter 1: Derivation methods for human embryonic stem cells: Past, present & future Necati Findikli. Mohan Vemuri. Chapter 2: Isolation of human ESCs from various stages of the human embryo (Yuri Verlinsky, N. Strelchenko, V. Kukharenko, A. Shkumatov, S. Rechitsky, O. Verlinsky, and A. Kuliev). Chapter 3: Derivation of stem cells from epiblasts (Michal Amit). Chapter 4: Derivation of Embryonic Stem Cells from Parthenogenetic Eggs (Jose Cibelli). Chapter 5: Reprogramming Developmental Potential (Costas A. Lyssiotis Cradley D. Charette, and Luke L. Lairson). Chapter 6: Adult stem cells and their role in endogenous tissue repair (N. Sachewsky and Cindi Morshead). Chapter 7: Greater differentiation potential of adult stem cells (Carlos Clavel and Catherine Verfaillie). Chapter 8: Cancer stem cells (Scott Dylla, In-Kyung Park and Austin L. Gurney). Chapter 9: Large scale production of adult stem cells for clinical use (Kristin Goltry, Brian Hampson, Naia Venturi and Ronnda Bartel). Chapter 10: Genetic and epigenetic features of stem cells (Jonathan Auerbach and Richard Josephson). Chapter 11: Directed differentiation of embryonic stem cells (Marjorie Pick). Chapter 12: Identification of signaling pathways involved during differentiation Takumi Miura. Chapter 13 Media and extracellular matrix requirements for large scale ESC growth (Allan J. Robins and Tom Schultz). Chapter 14: Automated method for culturing ES cells (S. Terstegge and Oliver Brustle). Chapter 15: Quantitative 2D Imaging of Human Embryonic Stem Cells (Steven K.W. Oh, Allen K. Chen, Andre B.H. Choo and Ivan Reading). Chapter 16: Nanobiotechonology for stem cell culture and Maintenance (Minseok S. Kim, Wonhye Lee and Je-Kyun Park). Chapter 17: Engineering Microenvironments to Control Stem Cell Functions (Anielle An-Chi Tsou and Song Li). Chapter 18: Improved lentiviral gene delivery tools for stem cells (Sanjay Vasu, Jian-Ping Yang and Wieslaw Kudlicki). Chapter 19: Sleeping Beauty-mediated Transposition in Stem Cells (Andrew Wilbur, Jakub Tolar, Bruce R Blazar, Catherine M Verfaillie, Uma Lakshmipathy, Dan S Kaufman and Scott McIvor). Chapter 20: PhiC31 Integrase for Modification of Stem Cells (W. Edward Jung and Michelle Calos). Chapter 21: Cell Engineering using Integrase and Recombinase systems (Takefumi Sone, Fumiko Nishi, Kazuhide Yahata, Yukari Sasaki, Hiroe Kishine, Taichi Andoh, Ken Inoue, Bhaskar Thyagarajan, Jonathan D. Chesnut and Fumio Imamoto). Chapter 22: hESC derived cardiomyocytes for cell therapy and drug discovery (William Sun and Robert Zweigerdt). Chapter 23: hESC in Drug discovery (Catharina Ellerstrom, Petter Bjorquist, Peter Sartipy, Johan Hyllner and Raimund Strehl). Chapter 24: Characterization and Culturing of Adipose-Derived Precursor Cells (Dietmar Hutmacher, Joanna Olkowska-Truchanowicz, David Leong, Johannes Reichert and Thiam Chye Lim). Chapter 25: Bringing Mesenchymal stem cells to clinic (Robert Deans).

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

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Book Synopsis* In-depth look created by the unique perspective of the author, the leader in this field. * Serves as a comprehensive collection of current trends, thoughts and emerging hot aspects in the field of metal-fluorophore interactions and applications.Table of ContentsPreface. Contributors. Mental-Enhanced Fluorescence: Progress Towards a Unified Plasmon-Fluorophore Description (Kadir Aslan and Chris D. Geddes). Spectral Profile Modifications In Metal-Enhanced Fluorescence (E. C. Le Ru, J. Grand, N. Félidj, J. Aubard, G. Lévi, A. Hohenau, J. R. Krenn, E. Blackie and P. G. Etchegoin). The Role Of Plasmonic Engineering In Metal-Enhanced Fluorescence (Daniel J. Ross, Nicholas P.W. Pieczonka and R. F. Aroca). Importance of Spectral Overlap: Fluorescence Enhancement by Single Metal Nanoparticles (Keiko Munechika, Yeechi Chen, Jessica M. Smith and.David S. Ginger). Near-IR Metal Enhanced Fluorescence And Controlled Colloidal Aggregation (Jon P. Anderson, Mark Griffiths, John G. Williams, Daniel L. Grone, Dave L. Steffens, and Lyle M. Middendorf). Optimisation Of Plasmonic Enhancement Of Fluorescence For Optical Biosensor Applications (Colette McDonagh, Ondrej Stranik, Robert Nooney and Brian D. MacCraith). Microwave-Accelerated Metal-Enhanced Fluorescence (Kadir Aslan and Chris D. Geddes). Localized Surface Plasmon Coupled Fluorescence Fiber Optic Based Biosensing (Chien Chou, Ja-An Annie Ho, Chii-Chang Chen, Ming-Yaw, Wei-Chih Liu, Ying-Feng Chang, Chen Fu, Si-Han Chen and Ting-Yang Kuo). Surface Plasmon Enhanced Photochemistry (Stephen K. Gray). Metal-Enhanced Generation of Oxygen Rich Species (Yongxia Zhang, Kadir Aslan and Chris D. Geddes). Synthesis Of Anisotropic Noble Metal Nanoparticles (Damian Aherne, Deirdre M. Ledwith and John M. Kelly). Enhanced Fluorescence Detection Enabled By Zinc Oxide Nanomaterials (Jong-in Hahm). ZnO Platforms For Enhanced Directional Fluorescence Applications (H.C. Ong, D.Y. Lei, J. Li and J.B. Xu). E-Beam Lithography And Spontaneous Galvanic Displacement Reactions For Spatially Controlled MEF Applications (Luigi Martiradonna, S. Shiv Shankar and Pier Paolo Pompa). Metal-Enhanced Chemiluminescence (Yongxia Zhang, Kadir Aslan and Chris D. Geddes). Enhanced Fluorescence From Gratings (Chii-Wann Lin, Nan-Fu Chiu, Jiun-Haw Lee and Chih-Kung Lee). Enhancing Fluorescence with Sub-Wavelength Metallic Apertures (Steve Blair and Jérôme Wenger). Enhanced Multi-Photon Excitation of Tryptophan-Silver Colloid (Renato E. de Araujo, Diego Rativa and Anderson S. L. Gomes). Plasmon-enhanced radiative rates and applications to organic electronics (Lewis Rothberg and Shanlin Pan). Fluorescent Quenching Gold Nanoparticles: Potential Biomedical Applications (Xiaohua Huang, Ivan H. El-Sayed, and Mostafa A. El-Sayed). Index.

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

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

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Book SynopsisA collection of articles from the Advances in Biomedical and Biomimetic Materials symposium give insight into advances in biomedical and biomimetic materials.Table of ContentsPreface ix BIOCERAMICS Biotribological Characterization of the Bilayer System: HN/ZrO2 on 316LSS 3B. Bermudez-Reyes, I. Espitia-Cabrera, J. Zarate-Medina, M. A. L. Hernandez-Rodrrguez, J. A. Ortega-Saenz, F. J. Espinoza-Beltran, and M. E. Contreras-Garcia Bioinspired Ceramic Microstructures Prepared by Freezing of Suspensions 19Qiang Fu, Mohamed N. Rahaman, B. Sonny Bal, and Fatih Dogan Mechanical Properties Modeling of Porous Calcium Phosphates Ceramics 27Frangois Pecqueux, Franck Tancret, Nathalie Payraudeau, and Jean-Michel Bouler Bone Cement Reinforced with Zirconium Oxide Particles 39H. H. Rodriguez and M. C. Piiia METALLIC IMPLANT MATERIALS Characterization of New Nickel-Titanium Wire for Rotary Endodontic Instruments 49William A. Brantley, Jie Liu, William A.T. Clark, Libor Kovarik, Caesar Buie, Masahiro lijima Satish B. Alapati, and William Ben Johnson Effect of Cold Work on the Behavior of NiTi Shape Memory Alloy 59Mohamed Elwi Mitwally and Mahmoud Farag Microstructure and Mechanical Properties of Ti-6AI-4V for Biomedical and Related Applications Involving Rapid-Layer Powder Manufacturing 71L. E. Murr, S. M. Gaytan, S. A. Quinones, M. I. Lopez, A. Rodela, E. Y. Martinez, D. H. Hernandez, E. Martinez, D. A. Rarnirez, F. Medina, and R. B. Wicker Mechanical Properties of Implant Rods Made of Low-Modulus p-Type Titanium Alloy, Ti-29Nb-13Ta-4.6Zr, for Spinal Fixture 83Kengo Narita, Mitsuo Niinomi, Masaaki Nakai, Toshikazu Akahori, Harumi Tsutsumi, Kazuya Oribe, Takashi Tamura, Shinji Kozuka, and Shizuma Sato Functionality of Porous Titanium Improved by Biopolymer Filling 91Mitsuo Niinomi, Masaaki Nakai, Toshikazu Akahori, Harumi Tsutsumi, Hideaki Yamanoi, Shinichi Itsuno, Naoki Haraguchi, Yoshinori Itoh, Tadashi Ogasawara, Takashi Onishi, and Taku Shindoh SCAFFOLDS FOR TISSUE ENGINEERING Fracture Forces in Femurs Implanted with PMMA 105Dan Dragomir-Daescu, Hilary E. Brown, Nadia Anguiano-Wehde, Sean McEligot, Michael J. Burke, Kevin E. Bennet, James T. Bronk, and Mark E. Bolander Development, Synthesis and Characterization of Porous Biomaterial Scaffolds for Tissue Engineering 115Kajal K. Mallick Engineered Nanofibers with Stem Cells for Biomimetic Tissue Engineering 129Seeram Ramakrishna, Susan Liao, Kun Ma, and Casey K. Chan Preclinic Test of Collagen Membranes 135B. Leon Mancilla and C. Piiia Barba SURFACE MODIFICATION OF BIOMATERIALS Polysiloxane Coatings Containing Tethered Antimicrobial Moieties 143P. Majumdar, S. J. Stafslien, J. Daniels, E. Lee, N. Patel, N. Gubbins, C. J. Thorson, and B. J. Chisholm High-Throughput Microbial Biofilm Assay for the Rapid Discovery of Antimicrobial Coatings and Materials for Biomedical Applications 151S. Stafslien, B. Chisholm, P. Majurndar, J. Bahr, and J. Daniels Chemical--Hydrothermal Combined Synthesis of Bioactive Ti02 and CaTiO, Films on Ti Surfaces 159M. Veda, M. Ikeda, and M. Ogawa Surface Modification of Hydroxyapatite: A Review 171Otto C. Wilson, Jr. MATERIALS FOR DRUG DELIVERY Nanophase Hydroxyapatite in Biodegradable Polymer Composites as Novel Drug-Carrying Implants for Treating Bone Diseases at Targeted Sites 185Huinan Liu and Thomas J. Webster Author Index 193

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

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

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

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

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Book SynopsisThis book helps students and practicing scientists alike understand that a comprehensive knowledge about the friction and wear properties of advanced materials is essential to further design and development of new materials. With important introductory chapters on the fundamentals, processing, and applications of tribology, the book then examines in detail the nature and properties of materials, the friction and wear of structural ceramics, bioceramics, biocomposites, and nanoceramics, as well as lightweight composites and the friction and wear of ceramics in a cryogenic environment.Table of ContentsPREFACE xvii FOREWORD BY PROF. IAN HUTCHINGS xxi FOREWORD BY PROF. KARL-HEINZ ZUM GAHR xxiii ABOUT THE AUTHORS xxv SECTION I FUNDAMENTALS CHAPTER 1 INTRODUCTION 3 References 6 CHAPTER 2 OVERVIEW: TRIBOLOGICAL MATERIALS 7 2.1 Introduction 7 2.2 Definition and Classification of Ceramics 8 2.3 Properties of Structural Ceramics 9 2.4 Applications of Structural Ceramics 11 2.5 Closing Remarks 14 References 16 CHAPTER 3 OVERVIEW: MECHANICAL PROPERTIES OF CERAMICS 18 3.1 Theory of Brittle Fracture 18 3.2 Cracking in Brittle Materials 23 3.3 Definition and Measurement of Basic Mechanical Properties 24 3.4 Toughening Mechanisms 33 3.5 Closing Remarks 37 References 37 CHAPTER 4 SURFACES AND CONTACTS 39 4.1 Surface Roughness 39 4.2 Surface Topography and Asperities 41 4.3 Real Contact Area 42 4.4 Contact Load Distribution and Hertzian Stresses 44 4.5 Closing Remarks 47 References 48 CHAPTER 5 FRICTION 49 5.1 Introduction 49 5.2 Laws of Friction 49 5.3 Friction Mechanisms 51 5.4 Friction of Common Engineering Materials 54 5.5 Closing Remarks 58 References 59 CHAPTER 6 FRICTIONAL HEATING AND CONTACT TEMPERATURE 60 6.1 Tribological Process and Contact Temperature 60 6.2 Concept of “Bulk” and “Flash” Temperature 61 6.3 Importance and Relevance of Some Ready-to-Use Analytical Models 63 6.4 Review of Some Frequently Employed Ready-to-Use Models 64 References 68 CHAPTER 7 WEAR MECHANISMS 70 7.1 Introduction 70 7.2 Classification of Wear Mechanisms 72 7.3 Closing Remarks 98 References 99 CHAPTER 8 LUBRICATION 101 8.1 Lubrication Regimes 101 8.2 Stribeck Curve 107 References 109 SECTION II FRICTION AND WEAR OF STRUCTURAL CERAMICS CHAPTER 9 OVERVIEW: STRUCTURAL CERAMICS 113 9.1 Introduction 113 9.2 Zirconia Crystal Structures and Transformation Characteristics of Tetragonal Zirconia 114 9.3 Transformation Toughening 116 9.4 Stabilization of Tetragonal Zirconia 117 9.5 Different Factors Infl uencing Transformation Toughening 118 9.6 Stress-Induced Microcracking 125 9.7 Development of SiAlON Ceramics 126 9.8 Microstructure of S-sialon Ceramics 127 9.9 Mechanical Properties and Crack Bridging of SiAlON Ceramic 129 9.10 Properties of Titanium Diboride Ceramics 132 References 138 CHAPTER 10 CASE STUDY: TRANSFORMATION-TOUGHENED ZIRCONIA 142 10.1 Background 142 10.2 Wear Resistance 144 10.3 Morphological Characterization of the Worn Surfaces 146 10.4 Zirconia Phase Transformation and Wear Behavior 149 10.5 Wear Mechanisms 152 10.6 Relationship among Microstructure, Toughness, and Wear 154 10.7 Infl uence of Humidity on Tribological Properties of Self-Mated Zirconia 156 10.8 Wear Mechanisms in Different Humidity 157 10.9 Tribochemical Wear in High Humidity 160 10.10 Closing Remarks 163 References 164 CHAPTER 11 CASE STUDY: SIALON CERAMICS 167 11.1 Introduction 167 11.2 Materials and Experiments 168 11.3 Tribological Properties of Compositionally Tailored Sialon versus β-Sialon 172 11.4 Tribological Properties of S-Sialon Ceramic 179 11.5 Concluding Remarks 182 References 183 CHAPTER 12 CASE STUDY: MAX PHASE—TI3SIC2 185 12.1 Background 185 12.2 Frictional Behavior 188 12.3 Wear Resistance and Wear Mechanisms 188 12.4 Raman Spectroscopy and Atomic Force Microscopy Analysis 190 12.5 Transition in Wear Mechanisms 193 12.6 Summary 194 References 195 CHAPTER 13 CASE STUDY: TITANIUM DIBORIDE CERAMICS AND COMPOSITES 197 13.1 Introduction 197 13.2 Materials and Experiments 198 13.3 Tribological Properties of TiB2–MoSi2 Ceramics 200 13.4 Tribological Properties of TiB2–TiSi2 Ceramics 204 13.5 Closing Remarks 206 References 208 SECTION III FRICTION AND WEAR OF BIOCERAMICS AND BIOCOMPOSITES CHAPTER 14 OVERVIEW: BIOCERAMICS AND BIOCOMPOSITES 213 14.1 Introduction 213 14.2 Some Useful Definitions and Their Implications 215 14.3 Experimental Evaluation of Biocompatibility 217 14.4 Wear of Implants 221 14.5 Coating on Metals 223 14.6 Glass-Ceramics 224 14.7 Biocompatible Ceramics 226 14.8 Outlook 228 References 229 CHAPTER 15 CASE STUDY: POLYMER-CERAMIC BIOCOMPOSITES 233 15.1 Introduction 233 15.2 Materials and Experiments 235 15.3 Frictional Behavior 237 15.4 Wear-Resistance Properties 240 15.5 Wear Mechanisms 242 15.6 Correlation among Wear Resistance, Wear Mechanisms, Material Properties, and Contact Pressure 247 15.7 Concluding Remarks 248 References 249 CHAPTER 16 CASE STUDY: NATURAL TOOTH AND DENTAL RESTORATIVE MATERIALS 251 16.1 Introduction 251 16.2 Materials and Methods 254 16.3 Tribological Tests on Tooth Material 255 16.4 Production and Characterization of Glass-Ceramics 255 16.5 Wear Experiments on Glass-Ceramics 256 16.6 Microstructure and Hardness of Human Tooth Material 257 16.7 Tribological Properties of Human Tooth Material 260 16.8 Wear Properties of Glass-Ceramics 262 16.9 Discussion of Wear Mechanisms of Glass-Ceramics 266 16.10 Comparison with Existing Glass-Ceramic Materials 271 16.11 Concluding Remarks 273 References 274 CHAPTER 17 CASE STUDY: GLASS-INFILTRATED ALUMINA 276 17.1 Introduction 276 17.2 Materials and Experiments 277 17.3 Frictional Properties 278 17.4 Wear Resistance and Wear Mechanisms 278 17.5 Wear Debris Analysis and Tribochemical Reactions 282 17.6 Influence of Glass Infi ltration on Wear Properties 283 17.7 Concluding Remarks 284 References 285 CHAPTER 18 TRIBOLOGICAL PROPERTIES OF CERAMIC BIOCOMPOSITES 287 18.1 Background 287 18.2 Tribological Properties of Mullite-Reinforced Hydroxyapatite 288 18.3 Friction and Wear Rate 288 18.4 Concluding Remarks 298 References 302 SECTION IV FRICTION AND WEAR OF NANOCERAMICS CHAPTER 19 OVERVIEW: NANOCERAMIC COMPOSITES 307 19.1 Introduction 307 19.2 Processing of Bulk Nanocrystalline Ceramics 309 19.3 Overview of Developed Nanoceramics and Ceramic Nanocomposites 309 19.4 Overview of Tribological Properties of Ceramic Nanocomposites 318 19.5 Concluding Remarks 320 References 322 CHAPTER 20 CASE STUDY: NANOCRYSTALLINE YTTRIA-STABILIZED TETRAGONAL ZIRCONIA POLYCRYSTALLINE CERAMICS 325 20.1 Introduction 325 20.2 Materials and Experiments 327 20.3 Tribological Properties 329 20.4 Tribomechanical Wear of Yttria-Stabilized Zirconia Nanoceramic with Varying Yttria Dopant 330 20.5 Comparison with Other Stabilized Zirconia Ceramics 335 20.6 Concluding Remarks 335 References 336 CHAPTER 21 CASE STUDY: NANOSTRUCTURED TUNGSTEN CARBIDE–ZIRCONIA NANOCOMPOSITES 338 21.1 Introduction 338 21.2 Materials and Experiments 339 21.3 Friction and Wear Characteristics 340 21.4 Wear Mechanisms 345 21.5 Explanation of High Wear Resistance of Ceramic Nanocomposites 347 21.6 Concluding Remarks 349 References 349 SECTION V LIGHTWEIGHT COMPOSITES AND CERMETS CHAPTER 22 OVERVIEW: LIGHTWEIGHT METAL MATRIX COMPOSITES AND CERMETS 353 22.1 Development of Metal Matrix Composites 353 22.2 Development of Cermets 356 References 358 CHAPTER 23 CASE STUDY: MAGNESIUM–SILICON CARBIDE PARTICULATEREINFORCED COMPOSITES 362 23.1 Introduction 362 23.2 Materials and Experiments 363 23.3 Load-Dependent Friction and Wear Properties 363 23.4 Fretting-Duration-Dependent Tribological Properties 366 23.5 Tribochemical Wear of Magnesium–Silicon Carbide Particulate-Reinforced Composites 371 23.6 Concluding Remarks 375 References 376 CHAPTER 24 CASE STUDY: TITANIUM CARBONITRIDE–NICKELBASED CERMETS 377 24.1 Introduction 377 24.2 Materials and Experiments 379 24.3 Energy Dissipation and Abrasion at Low Load 381 24.4 Influence of Type of Secondary Carbides on Sliding Wear of Titanium Carbonitride–Nickel Cermets 386 24.5 Tribochemical Wear of Titanium Carbonitride–Based Cermets 387 24.6 Influence of Tungsten Carbide Content on Load-Dependent Sliding Wear Properties 393 24.7 High Temperature Wear of Titanium Carbonitride–Nickel Cermets 397 24.8 Summary of Key Results 403 References 404 CHAPTER 25 CASE STUDY: (W,Ti)C–CO CERMETS 407 25.1 Introduction 407 25.2 Materials and Experiments 408 25.3 Microstructure and Mechanical Properties 409 25.4 Wear Properties 410 25.5 Correlation between Mechanical Properties and Wear Resistance 413 25.6 Concluding Remarks 418 References 419 SECTION VI FRICTION AND WEAR OF CERAMICS IN A CRYOGENIC ENVIRONMENT CHAPTER 26 OVERVIEW: CRYOGENIC WEAR PROPERTIES OF MATERIALS 423 26.1 Background 423 26.2 Designing a High-Speed Cryogenic Wear Tester 425 26.3 Summary of Results Obtained with Ductile Metals 427 26.4 Summary 437 References 437 CHAPTER 27 CASE STUDY: SLIDING WEAR OF ALUMINA IN A CRYOGENIC ENVIRONMENT 439 27.1 Background 439 27.2 Materials and Experiments 440 27.3 Tribological Properties of Self-Mated Alumina 442 27.4 Genesis of Tribological Behavior in a Cryogenic Environment 449 27.5 Concluding Remarks 452 References 452 CHAPTER 28 CASE STUDY: SLIDING WEAR OF SELF-MATED TETRAGONAL ZIRCONIA CERAMICS IN LIQUID NITROGEN 454 28.1 Introduction 454 28.2 Materials and Experiments 456 28.3 Friction of Self-Mated Y-TZP Material in LN2 456 28.4 Cryogenic Wear of Zirconia 459 28.5 Cryogenic Sliding-Induced Zirconia Phase Transformation 460 28.6 Wear Mechanisms of Zirconia in LN2 464 28.7 Concluding Remarks 466 References 467 CHAPTER 29 CASE STUDY: SLIDING WEAR OF SILICON CARBIDE IN A CRYOGENIC ENVIRONMENT 469 29.1 Introduction 469 29.2 Materials and Experiments 470 29.3 Friction and Wear Properties 470 29.4 Thermal Aspect and Limited Tribochemical Wear 473 29.5 Tribomechanical Stress-Assisted Deformation and Damage 479 29.6 Comparison with Sliding Wear Properties of Oxide Ceramics 481 29.7 Concluding Remarks 482 References 483 SECTION VII WATER-LUBRICATED WEAR OF CERAMICS CHAPTER 30 FRICTION AND WEAR OF OXIDE CERAMICS IN AN AQUEOUS ENVIRONMENT 487 30.1 Background 487 30.2 Tribological Behavior of Alumina in an Aqueous Solution 488 30.3 Tribological Behavior of Self-Mated Zirconia in an Aqueous Environment 493 30.4 Concluding Remarks 499 References 500 SECTION VIII CLOSURE CHAPTER 31 PERSPECTIVE FOR DESIGNING MATERIALS FOR TRIBOLOGICAL APPLICATIONS 505 INDEX 509

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Book SynopsisTrade ReviewHendee’s Physics of Medical Imaging, 5th Edition is written with clear and focused academic language…and will be very useful both for students and lecturers on the subject. Congratulations to both authors for the excellent textbook. - Slavik Tabakov, King’s College London, UK, Immediate Past President IOMP (International Organization of Medical Physics)Table of ContentsForeword ix Commentary by William Hendee xi Clarification and Acknowledgment xiii Introduction: The Role of Imaging in Medicine xv 1 Physics of Radiation and Matter 1 2 Anatomy, Physiology, and Pathology in Imaging 55 3 Imaging Science 89 4 Radiobiology, Dosimetry, and Protection 143 5 Imaging Operation and Infrastructure 181 6 Projection X-ray Imaging 217 7 Volumetric X-ray Imaging 243 8 Nuclear Medicine 271 9 Ultrasonography 305 10 Magnetic Resonance Imaging 339 Index 453

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

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

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

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

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

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

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

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Book SynopsisPresents the synthesis, technology and processing details of a large range of polymers derived from renewable resources It has been a long-term desire to replace polymers from fossil fuels with the more environmentally friendly polymers generated from renewable resources.Table of ContentsPreface xii List of Contributors xv 1. Polymers from renewable Resources 1 V. Mittal 1.1 Introduction 1 1.2 Naturally Renewable Methylene Butyrolactones 4 1.3 Renewable Rosin Acid-Degradable Caprolactone Block Copolymers 6 1.4 Plant Oils as Platform Chemicals for Polymer Synthesis 7 1.5 Biosourced Sterecontrolled Polytriazoles 9 1.6 Polymers from Naturally Occurring Monoterpene 10 1.7 Polymerization of Biosourced 2- (Methacryloyloxy) ethyl Tiglate 11 1.8 Oxypropylation of Repeseed Cake Residue 12 1.9 Copolymerization of Naturally Occurring Limonene 13 1.10 Polymerization of Lactides 14 1.11 Nanocomposites Using Renewable Polymers 19 1.12 Castor Oil Based Thermosets 19 References 22 2. Design, Synthesis, Property, and Application of Plant Oil Polymers 23 Keshar Prassain and Duy H. Hua 2.1 Introduction 24 2.2 Triglyceride Polymers 25 2.3 Summary 65 Reference 65 3. Advances in Acid Mediated Polymerizations 69 Stewart P. Lewis and R. Mathers 3.1 Introduction 70 3.2 Problems Inherent to Cationic Ole. N Polymerization 72 3.3 Progress Toward Cleaner Cationic Polymerization 75 3.4 Environmental Bene. Ts via New Process Conditions 158 3.5 Cationic Polymerization of Monomers Derived from Renewable Resources 161 3.6 Sustainable Synthesis of Monomers for Cationic Polymerization 163 References 164 4. Olive Oil Wastewater as a Renewable Resource for Production of Polyhydroxyalkanoates 175 Francesco Valentino, Marianna Villano, Lorenzo Bertin, Mario Beccari, and Mauro Majone 4.1 Polyhydroxyalkanoates (PHAs): Structure, Properties, and Applications 175 4.2 PHA Production Processes Employing Pure Microbial Cultures 177 4.3 PHA Production Processes Employing Mixed Microbial Cultures 178 4.4 Olive Oil Mill Ef. Uents (OMEs) as a Possible Feedstock for PHA Production 197 4.5 OMEs as Feedstock for PHA Production 206 4.6 Concluding Remarks 211 References 212 5. Atom Transfer Radical Polymerization (ATRP) for Production of Polymers from Renewable Resources 221 Kattimuttathu I. Suresh 5.1 Introduction 221 5.2 Atom Transfer Radical Polymerization (ATRP) 222 5.3 Synthetic Strategies to Develop Functional Material Based on Renewable Resources – Composition, Topologies and Functionalities 227 5.4 Sustainable Sources for Monomers with a Potential for Making Novel Renewable Polymers 231 5.5 Conclusions and Outlook 241 References 242 6. Renewable Polymers in Transgenic Crop Plants 247 Tina Hausmann and Inge Broer 6.1 Natural Plant Polymers 248 6.2 De Novo Synthesis of Polymers in Plants 269 6.3 Conclusion 289 References 291 7. Polyesters, Polycarbonates and Polyamides Based on Renewable Resources 305 Bart A. J. Noordover 7.1 Introduction 306 7.2 Biomass-Based Monomers 307 7.3 Polyesters Based on Renewable Resources 308 7.4 Polycarbonates Based on Renewable Resources 332 7.5 Polyamides Based on Renewable Resources 344 7.6 Conclusions 349 References 350 8. Succinic Acid: Synthesis of Biobased Polymers from Renewable Resources 355 Stephen Kabasci and Inna Bretz 8.1 Introduction 355 8.2 Polymerization 359 8.3 Conclusions 371 References 372 9. 5-Hydroxymethylfurfural Based Polymers 381 Ananda S. Amarasekara 9.1 Introduction 381 9.2 5-Hydroxymethylfurfural 382 9.3 5-Hydroxymethylfurfural Derivatives 393 9.4 Polymers from 5-Hydroxymethylfurfural Derivatives 398 9.5 Conclusion 421 References 422 10. Natural Polymers-A Boon for Drug Delivery Rajesh. N. Uma, and Valluru Ravi 10.1 Introduction 429 10.2 Acacia 429 10.3 Agar 431 10.4 Alginate 433 10.5 Carrageenan 436 10.6 Cellulose 438 10.7 Chitosan 440 10.8 Dextrin 444 10.9 Dextrin 445 10.10 Gellan Gum 447 10.11 Guar Gum 448 10.12 Inulin 451 10.13 Karaya Gum 454 10.14 Konjac Glucomannan 453 10.15 Locust Bean Gum 454 10.16 Locust Gum 455 10.17 Pectin 455 10.18 Psyllium Husk 457 10.19 Scleroglucan 457 10.20 Starch 460 10.21 Xanthan Gum 462 References 465 Index 473

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Book SynopsisChitosan is a linear polysaccharide commercially produced by the deacetylation of chitin. It is non-toxic, biodegradable, biocompatible, and acts as a bioadhesive with otherwise unstable biomolecules - making it a valuable component in the formulation of biopharmaceutical drugs. Chitosan-Based Systems for Biopharmaceuticals provides an extensive overview of the application of chitosan and its derivatives in the development and optimisation of biopharmaceuticals. The book is divided in four different parts. Part I discusses general aspects of chitosan and its derivatives, with particular emphasis on issues related to the development of biopharmaceutical chitosan-based systems. Part II deals with the use of chitosan and derivatives in the formulation and delivery of biopharmaceuticals, and focuses on the synergistic effects between chitosan and this particular subset of pharmaceuticals. Part III discusses specific applications of chitosan and its derivatives for biopharmaceutiTable of ContentsList of Contributors xvii Foreword xxiii Marıa Jose Alonso Preface xxv Acknowledgments xxvii Part One General Aspects of Chitosan 1 1 Chemical and Technological Advances in Chitins and Chitosans Useful for the Formulation of Biopharmaceuticals 3 Riccardo A. A. Muzzarelli 1.1 Introduction 3 1.2 Safety of Chitins and Chitosans 4 1.3 Ionic Liquids: New Solvents and Reaction Media 5 1.4 Chitin and Chitosan Nanofibrils 8 1.5 Electrospun Nanofibers 10 1.6 Polyelectrolyte Complexes and Mucoadhesion 12 1.7 Conclusions and Future Perspectives 16 2 Physical Properties of Chitosan and Derivatives in Sol and Gel States 23 Marguerite Rinaudo 2.1 Introduction 23 2.2 Chitin 24 2.3 Chitosan 28 2.4 Conclusions and Future Perspectives 36 3 Absorption Promotion Properties of Chitosan and Derivatives 45 Akira Yamamoto 3.1 Introduction 45 3.2 Effect of Chitosan on the Intestinal Absorption of Poorly Absorbable Drugs 47 3.3 Effect of Chitosan Derivatives on the Intestinal Absorption of Poorly Absorbable Drugs 47 3.4 Effect of Chitosan Oligomers on the Intestinal Absorption of Poorly Absorbable Drugs 48 3.5 Colon-Specific Delivery of Insulin Using Chitosan Capsules 51 3.6 Conclusions and Future Perspectives 54 4 Biocompatibility and Biodegradation of Chitosan and Derivatives 57 Ahmad Sukari Halim, Lim Chin Keong, Ismail Zainol, and Ahmad Hazri Abdul Rashid 4.1 Introduction 57 4.2 Biocompatibility Evaluation of Chitosan and Derivatives 58 4.3 Biodegradation of Chitosan and Derivatives 65 4.4 Conclusions and Future Perspectives 69 5 Biological and Pharmacological Activity of Chitosan and Derivatives 75 Teresa Cunha, Branca Teixeira, Barbara Santos, Marlene Almeida, Gustavo Dias, and Jose das Neves 5.1 Introduction 75 5.2 Biological Activity 76 5.3 Chitosan's Usefulness in Therapy and Alternative Medicine 82 5.4 Conclusions and Future Perspectives 84 6 Biological, Chemical, and Physical Compatibility of Chitosan and Biopharmaceuticals 93 Masayuki Ishihara, Masanori Fujita, Satoko Kishimoto, Hidemi Hattori, and Yasuhiro Kanatani 6.1 Introduction 93 6.2 Structural Features of Chitosan and Its Derivatives 94 6.3 Biocompatibility for Chitosan and Its Derivatives 95 6.4 Biocompatibility of Photo-Cross-Linkable Chitosan Hydrogel 98 6.5 Physical and Chemical Compatibility of Chitosan and Its Derivatives 100 6.6 Conclusions and Future Perspectives 102 7 Approaches for Functional Modification or Cross-Linking of Chitosan 107 A. Anitha, N. Sanoj Rejinold, Joel D. Bumgardner, Shanti V. Nair, and Rangasamy Jayakumar 7.1 Introduction 107 7.2 General Awareness of Chitosan Cross-Linking Methods 108 7.3 Modified Chitosan: Synthesis and Characterization 112 7.4 Applications of Modified Chitosan and Its Derivatives in Drug Delivery 118 7.5 Conclusions and Future Perspectives 118 Part Two Biopharmaceuticals Formulation and Delivery Aspects Using Chitosan and Derivatives 125 8 Use of Chitosan and Derivatives in Conventional Biopharmaceutical Dosage Forms Formulation 127 Teofilo Vasconcelos, Pedro Barrocas, and Rui Cerdeira 8.1 Introduction 127 8.2 Advantageous Properties of Chitosan and Its Derivatives 128 8.3 Oral Administration 129 8.4 Buccal Administration 131 8.5 Nasal Administration 132 8.6 Pulmonary Administration 132 8.7 Transdermal Administration 133 8.8 Conclusions and Future Perspectives 133 9 Manufacture Techniques of Chitosan-Based Microparticles and Nanoparticles for Biopharmaceuticals 137 Franca Ferrari, M. Cristina Bonferoni, Silvia Rossi, Giuseppina Sandri, and Carla M. Caramella 9.1 Introduction 137 9.2 Water-in-Oil Emulsion and Chemical Cross-linking 138 9.3 Drying Techniques 141 9.4 Ionic Cross-linking Methods 144 9.5 Coacervation and Precipitation Method 151 9.6 Direct Interaction between Chitosan and Biopharmaceuticals 152 9.7 Conclusions and Future Perspectives 153 10 Chitosan and Derivatives for Biopharmaceutical Use: Mucoadhesive Properties 159 Katharina Leithner and Andreas Bernkop-Schnurch 10.1 Introduction 159 10.2 Mucoadhesion 160 10.3 Chitosan and Its Derivatives 161 10.4 Biopharmaceutical Use of Chitosan and Its Derivatives 171 10.5 Conclusions and Future Perspectives 175 11 Chitosan-Based Systems for Mucosal Delivery of Biopharmaceuticals 181 Sonia Al-Qadi, Ana Grenha, and Carmen Remunan-Lopez 11.1 Introduction 181 11.2 Important Challenges for the Delivery of Biopharmaceuticals by Mucosal Routes 182 11.3 Interest in Chitosan for Mucosal Delivery of Biopharmaceuticals 184 11.4 Chitosan-Based Delivery Nanosystems for Mucosal Delivery of Biopharmaceuticals 188 11.5 Conclusions and Future Perspectives 200 12 Chitosan-Based Delivery Systems for Mucosal Vaccination 211 Gerrit Borchard, Farnaz Esmaeili, and Simon Heuking 12.1 Introduction 211 12.2 Adjuvant Properties of Chitosan 212 12.3 Chitosan in the Delivery of Protein and Subunit Vaccines 213 12.4 Chitosan-Based Formulations of DNAVaccines 215 12.5 Vaccine Formulations Using Chitosan in Combination with Other Polymers 216 12.6 Chitosan Derivatives in Vaccine Carrier Design 217 12.7 Conclusions and Future Perspectives 220 13 Chitosan-Based Nanoparticulates for Oral Delivery of Biopharmaceuticals 225 Filipa Antunes, Fernanda Andrade, and Bruno Sarmento 13.1 Introduction 225 13.2 Challenges on the Oral Delivery of Therapeutic Proteins 226 13.3 Challenges on the Oral Delivery of Genetic Material 227 13.4 Role of Chitosan in the Protection of Biopharmaceuticals in the Gastrointestinal Tract 229 13.5 Chitosan-Based Nanoparticles for Oral Delivery of Therapeutic Proteins 232 13.6 Chitosan-Based Nanoparticles for Oral Delivery of Genetic Material 234 13.7 Conclusions and Future Perspectives 236 14 Chitosan-Based Systems for Ocular Delivery of Biopharmaceuticals 243 Suresh P. Vyas, Rishi Paliwal, and Shivani Rai Paliwal 14.1 Introduction 243 14.2 Ocular Delivery of Biopharmaceuticals 244 14.3 Chitosan: A Suitable Biomaterial for Ocular Therapeutics 244 14.4 Chitosan-Based Systems for Ocular Delivery of Biomacromolecules 245 14.5 Toxicological and Compatibility Aspects of Chitosan-Based Ocular Systems 249 14.6 Conclusions and Future Perspectives 250 15 Chemical Modification of Chitosan for Delivery of DNA and siRNA 255 You-Kyoung Kim, Hu-Lin Jiang, Ding-Ding Guo, Yun-Jaie Choi, Myung-Haing Cho, Toshihiro Akaike, and Chong-Su Cho 15.1 Introduction 255 15.2 Hydrophilic Modification 256 15.3 Hydrophobic Modification 257 15.4 Specific Ligand Modification 259 15.5 pH-Sensitive Modification 264 15.6 Conclusions and Future Perspectives 269 Part Three Advanced Application of Chitosan and Derivatives for Biopharmaceuticals 275 16 Target-Specific Chitosan-Based Nanoparticle Systems for Nucleic Acid Delivery 277 Shardool Jain and Mansoor Amiji 16.1 Introduction 277 16.2 Chitosan-Based Nanoparticle Delivery Systems 283 16.3 Illustrative Examples of DNAVaccine Delivery 286 16.4 Illustrative Examples of Nucleic Acid Delivery Systems for Cancer Therapy 288 16.5 Illustrative Examples of Nucleic Acid Delivery Systems for Anti-Inflammatory Therapy 291 16.6 Conclusions and Future Perspectives 294 17 Functional PEGylated Chitosan Systems for Biopharmaceuticals 301 Hee-Jeong Cho, Goen Kim, Hyeok-Seung Kwon, and Yu-Kyoung Oh 17.1 Introduction 301 17.2 PEGylated Chitosan for the Delivery of Proteins and Peptides 304 17.3 PEGylated Chitosan for Delivery of Nucleic Acids 308 17.4 PEGylated Chitosan for Delivery of Other Macromolecular Biopharmaceuticals 311 17.5 PEGylated Chitosan Used for Cellular Scaffolds 313 17.6 Conclusions and Future Perspectives 313 18 Stimuli-Sensitive Chitosan-Based Systems for Biopharmaceuticals 319 Cuiping Zhai, Jinfang Yuan, and Qingyu Gao 18.1 Introduction 319 18.2 pH-Sensitive Chitosan-Based Systems 319 18.3 Thermosensitive Chitosan-Based Systems 321 18.4 pH-Sensitive and Thermosensitive Chitosan-Based Systems 323 18.5 pH- and Ionic-Sensitive Chitosan-Based Systems 325 18.6 Photo-Sensitive Chitosan-Based Systems 325 18.7 Electrical-Sensitive Chitosan-Based Systems 326 18.8 Magnetic-Sensitive Chitosan-Based Systems 326 18.9 Chemical Substance-Sensitive Chitosan-Based Systems 327 18.10 Conclusions and Future Perspectives 327 19 Chitosan Copolymers for Biopharmaceuticals 333 Ramon Novoa-Carballal, Ricardo Riguera, and Eduardo Fernandez-Megia 19.1 Introduction 333 19.2 Chitosan-g-Poly(Ethylene Glycol) 337 19.3 Chitosan-g-Polyethylenimine 347 19.4 Other Copolymers of Chitosan 357 19.5 Copolymers of Chitosan with Promising Applications 363 19.6 Conclusions and Future Perspectives 368 20 Application of Chitosan for Anticancer Biopharmaceutical Delivery 381 Claudia Philippi, Brigitta Loretz, Ulrich F. Schaefer, and Claus-Michael Lehr 20.1 Introduction 381 20.2 Chitosan and Cancer: Intrinsic Antitumor Activity of the Polymer Itself 382 20.3 Chitosan Formulations Developed for Classic Anticancer Drugs 383 20.4 Biopharmaceuticals Delivered by Chitosan Preparations 384 20.5 Active Targeting Strategies and Multifunctional Chitosan Formulations 388 20.6 Conclusions and Future Perspectives 389 21 Chitosan-Based Biopharmaceutical Scaffolds in Tissue Engineering and Regenerative Medicine 393 Tao Jiang, Meng Deng, Wafa I. Abdel- Fattah, and Cato T. Laurencin 21.1 Introduction 393 21.2 Fabrication of Chitosan-Based Biopharmaceuticals Scaffolds 395 21.3 Applications of Chitosan-Based Biopharmaceutical Scaffolds in Tissue Engineering and Regenerative Medicine 403 21.4 Future Trends: Regenerative Engineering 416 21.5 Conclusions and Future Perspectives 417 22 Wound-Healing Properties of Chitosan and Its Use in Wound Dressing Biopharmaceuticals 429 Tyler G. St. Denis, Tianhong Dai, Ying-Ying Huang, and Michael R. Hamblin 22.1 Introduction 429 22.2 Brief Review of Wound Repair 430 22.3 Wound-Healing Effects of Chitosan 433 22.4 Chitosan for Wound Therapeutics Delivery 440 22.5 Conclusions and Future Perspectives 444 Part Four Regulatory Status, Toxicological Issues, and Clinical Perspectives 451 23 Toxicological Properties of Chitosan and Derivatives for Biopharmaceutical Applications 453 Thomas J. Kean and Maya Thanou 23.1 Introduction 453 23.2 In Vitro Toxicity of Chitosan and Derivatives 454 23.3 In Vivo Toxicity of Chitosan and Derivatives 457 23.4 Conclusions and Future Perspectives 459 24 Regulatory Status of Chitosan and Derivatives 463 Michael Dornish, David S. Kaplan, and Sambasiva R. Arepalli 24.1 Introduction 463 24.2 Source 464 24.3 Characterization 464 24.4 Purity 465 24.5 Applications of Advanced Uses of Chitosan 466 24.6 Regulatory Considerations for Chitosan and Chitosan Derivatives in the European Union, and Medical Devices or Combination Products with Medical Device (CDRH) Lead 468 24.7 Regulatory Pathways 469 24.8 Chitosan Medical Products: US Regulatory Review Processes for Medical Devices or Combination Products with CDRH Lead 469 24.9 Chitosan Wound Dressings 470 24.10 The European Regulatory System: The European Medicines Agency (EMA) and European Directorate for the Quality of Medicines (EDQM) 474 24.11 Further Regulatory Considerations 475 24.12 Conclusions and Future Perspectives 477 24.13 Disclaimer 478 25 Patentability and Intellectual Property Issues Related to Chitosan-Based Biopharmaceutical Products 483 Mafalda Videira and Rogerio Gaspar 25.1 Introduction 483 25.2 Setting the Scene: The Role of Chitosan as a Pharmaceutical Excipient 484 25.3 Addressing the Drivers for Scientific Progress on Chitosan: Innovation and Inventability 495 25.4 Conclusions and Future Perspectives 496 26 Quality Control and Good Manufacturing Practice (GMP) for Chitosan-Based Biopharmaceutical Products 503 Torsten Richter, Maika Gulich, and Katja Richter 26.1 Introduction 504 26.2 Regulatory Requirements for Production 505 26.3 Manufacturing GMP: Fundamental Considerations 508 26.4 Requirements for Rooms, Personnel, and Equipment 511 26.5 Qualification and Validation 511 26.6 Quality Control 513 26.7 Monitoring and Maintenance of a GMP System 519 26.8 Conclusions and Future Perspectives 522 27 Preclinical and Clinical Use of Chitosan and Derivatives for Biopharmaceuticals: From Preclinical Research to the Bedside 525 David A. Zaharoff, Michael Heffernan, Jonathan Fallon, and John W. Greiner 27.1 Introduction 525 27.2 Chitosan as a Parenteral (Subcutaneous) Vaccine Platform 526 27.3 Chitosan as an Immunotherapeutic Platform 530 27.4 Conclusions and Future Perspectives 537 References 539 Index 543

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

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

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

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Book SynopsisSince the early 1990s, research and discovery collaborations between biotechnology and pharmaceutical companies have increased to the point that they now provide more than half of the total capital invested in the biotechnology sector. Although smaller biotechnology companies may be engaged in only a few alliances at a time, some of the most active pharmaceutical players may be engaged in anywhere from thirty to forty alliances at once. Any single alliance relationship may be the lifeblood for a small biotechnology company, while the same relationship may be just one of many for the pharmaceutical partner. Research alliances with small, close-to-the-science companies are the source of many of the innovative ideas of today and the future, but they present formidable challenges. Successful collaboration depends not only on the solution of scientific and technical problems, but also on the successful resolution of many leadership and organizational problems. Leading Biotechnology Trade Review"...a discussion of the business of biotechnology..." (Journal of Proteome Research, Vol. 1, No. 2, March, April 2002)Table of ContentsTROUBLE IN ALLIANCE LAND. A Case in Point: The Lucida-Pharma Alliance Cast of Characters. The General Case: Many Alliances, Many Problems. ASYMMETRIC RELATIONSHIPS, LOPSIDED RESPONSIBILITY. Contrasting Cultures. Partner Differences and Disparities. LAYING THE GROUNDWORK. Preparing the Organization. Individual and Organizational Due Diligence. The First Meetings. THE ALLIANCE LIFE CYCLE: LEADING DIFFERENTLY OVER TIME. To the First Milestone. Managing Growth and Maturity. Ending: Completion, or Termination. Readiness, Learning, and Alliance Effectiveness: A Road Map. If We Could Turn Back the Clock...(A Hypothetical Coda to the Lucida-Pharma Sciences Case).

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Book SynopsisThis is one volume ''library'' of information on molecular biology, molecular medicine, and the theory and techniques for understanding, modifying, manipulating, expressing, and synthesizing biological molecules, conformations, and aggregates. The purpose is to assist the expanding number of scientists entering molecular biology research and biotechnology applications from diverse backgrounds, including biology and medicine, as well as physics, chemistry, mathematics, and engineering.Table of ContentsArticles. Glossary of Basic Terms. Index.

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

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

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

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

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

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

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Book SynopsisThis important reference is the first work on Plant Biotechnology. Written by an international team of experienced researchers and professionals from both academia and industry, it will bring together the principles and practice of contemporary plant biotechnology to include: * the techniques of plant genetic modification - applications of plant biotechnology, crop improvement in agriculture and a production system for pharmaceutical proteins * ethics and safety issues - public perception, public relations, scale-up and testing, and legislation within the business of plant biotechnology.Trade Review"...provides a comprehensive survey of the state of the field of plant biotechnology." (American Reference Books Annual, 2005) "...this book should be a valuable reference and useful handbook for the near future." (CHOICE, February 2005) "...an excellent getup, layout and print of text, figures, graphs and tables at an opportune, justifiable price may be attested to the Wiley-VCH publisher." (Starke, 2004; Vol 56; No. 10) "These two volumes are published at an ideal time. Researchers, faculty, students, anyone active in plant sciences or the food industry will find this reference valuable." (E-STREAMS, November 2004) "...will certainly help students and practitioners to understand its potentials, limitations and diverse applications..." (Plant Pathology, Vol. 53, No.5, October 2004) "...a comprehensive guide to plant biotechnology..." (Food Science & Technology Abstracts, Vol 37 (9) 2005)Table of ContentsPreface. List of Contributors. PART ONE: INTRODUCTION TO PLANT BIOTECHNOLOGY. PART TWO: PLANT GENETIC MODIFICATION: TRANSGENES AND TRANSFORMATION. Section One: Plant Gene Isolation and Characterization: Non-Genomic Sequences. Section Two: Molecular Assisted Breeding for Multi-Genic Traits. Section Three: Plant Genomics. PART THREE: PLANT GENETIC MODIFICATION: GENE ISOLATION. PART FOUR: AGRONOMIC TRAITS. PART FIVE: QUALITY AND YIELD. PART SIX: DEVELOPMENTAL TRAITS. PART SEVEN: A PRODUCTION SYSTEM FOR INDUSTRIAL AND PHARMACEUTICAL PROTEINS. PART EIGHT: NON-FOOD CROPS. PART NINE: RISK ASSESSMENT OF TRANSGENIC CROPS. PART TEN: COMMERCIALISATION. Section One: Perspectives on Proprietry Technology and Patents. Section Two: Customer and Consumer Perspectives. Section Three: Product Commercialisation Examples. PART ELEVEN: PLANT BIOTECHNOLOGY IN DEVELOPING COUNTRIES. Appendix A: Plant Biotechnology Commercial Products. Appendix B: Key Plant Biotechnology Patents. Index.

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

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

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

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

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

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