Biotechnology Books

Book SynopsisThe development of sensors at macroscopic or nanometric scales in solid, liquid, or gas phases, contact or noncontact configurations, has driven the research of sensor & detection materials and technology into high gear.Table of ContentsPreface xv Part 1: Principals and Prospective 1 1 Advances in Sensors? Nanotechnology 3 Ida Tiwari and Manorama Singh 1.1 Introduction 3 1.2 What is Nanotechnology? 4 1.3 Significance of Nanotechnology 5 1.4 Synthesis of Nanostructure 5 1.5 Advancements in Sensors’ Research Based on Nanotechnology 5 1.6 Use of Nanoparticles 7 1.7 Use of Nanowires and Nanotubes 8 1.8 Use of Porous Silicon 11 1.9 Use of Self-Assembled Nanostructures 12 1.10 Receptor-Ligand Nanoarrays 12 1.11 Characterization of Nanostructures and Nanomaterials 13 1.12 Commercialization Efforts 14 1.13 Future Perspectives 14 References 15 2 Construction of Nanostructures: A Basic Concept Synthesis and Their Applications 19 Rizwan Wahab, Farheen Khan, Nagendra K. Kaushik, Javed Musarrat and Abdulaziz A.Al-Khedhairy 2.1 Introduction 20 2.2 Formation of Zinc Oxide Quantum Dots (ZnO-QDs) and Their Applications 24 2.3 Needle-Shaped Zinc Oxide Nanostructures and Their Growth Mechanism 30 2.4 Flower-Shaped Zinc Oxide Nanostructures and Their Growth Mechanism 37 2.5 Construction of Mixed Shaped Zinc Oxide Nanostructures and Their Growth Mechanicsm 47 2.6 Summary and Future Directions 56 References 57 3 The Role of the Shape in the Design of New Nanoparticles 61 G. Mayeli Estrada-Villegas and Emilio Bucio 3.1 Introduction 62 3.2 The Importance of Shape as Nanocarries 63 3.3 Influence of Shape on Biological Process 65 3.4 Different Shapes of Polymeric Nanoparticles 67 3.5 Different Shapes of Non-Polymeric Nanoparticles 71 3.6 Different Shapes of Polymeric Nanoparticles: Examples 74 3.7 Another Type of Nanoparticles 76 Acknowledgments 80 References 80 4 Molecularly Imprinted Polymer as Advanced Material for Development of Enantioselective Sensing Devices 87 Mahavir Prasad Tiwari and Bhim Bali Prasad 4.1 Introduction 88 4.2 Molecularly Imprinted Chiral Polymers 90 4.3 MIP-Based Chiral Sensing Devices 91 4.4 Conclusion 105 References 105 5 Role of Microwave Sintering in the Preparation of Ferrites for High Frequency Applications 111 S. Bharadwaj and S.R. Murthy 5.1 Microwaves in General 112 5.2 Microwave-Material Interactions 114 5.3 Microwave Sintering 115 5.4 Microwave Equipment 118 5.5 Kitchen Microwave Oven Basic Principle 122 5.6 Microwave Sintering of Ferrites 126 5.7 Microwave Sintering of Garnets 137 5.8 Microwave Sintering of Nanocomposites 138 References 140 Part 2: New Materials and Methods 147 6 Mesoporous Silica: Making “Sense” of Sensors 149 Surender Duhan and Vijay K. Tomer 6.1 Introduction to Sensors 150 6.2 Fundamentals of Humidity Sensors 153 6.3 Types of Humidity Sensors 154 6.4 Humidity Sensing Materials 156 6.5 Issues with Traditional Materials in Sensing Technology 158 6.6 Introduction to Mesoporous Silica 159 6.7 M41S Materials 160 6.8 SBA Materials 162 6.9 Structure of SBA-15 164 6.10 Structure Directing Agents of SBA-15 165 6.11 Factors Affecting Structural Properties and Morphology of SBA-15 169 6.12 Modification of Mesoporous Silica 174 6.13 Characterization Techniques for Mesoporous Materials 177 6.14 Humidity Sensing of SBA-15 184 6.15 Extended Family of Mesoporous Silica 185 6.16 Other Applications of SBA-15 188 6.17 Conclusion 190 References 191 7 Towards Improving the Functionalities of Porous TiO2-Au/Ag Based Materials 193 Monica Baia, Virginia Danciu, Zsolt Pap and Lucian Baia 7.1 Porous Nanostructures Based on Tio2 and Au/Ag Nanoparticles for Environmental Applications 194 7.2 Morphological Particularities of the TiO2-based Aerogels 199 7.3 Designing the TiO2 Porous Nano-architectures for Multiple Applications 201 7.4 Evaluating the Photocatalytic Performances of the TiO2-Au/Ag Porous Nanocomposites for Destroying Water Chemical Pollutants 208 7.5 Testing the Effectiveness of the TiO2-Au/Ag Porous Nanocomposites for Sensing Water Chemical Pollutants by SERS 210 7.6 In-depth Investigations of the Most Efficient Multifunctional TiO2-Au/Ag Porous Nanocomposites 216 7.7 Conclusions 221 Acknowledgments 223 References 223 8 Ferroelectric Glass-Ceramics 229 Viswanathan Kumar 8.1 Introduction 230 8.2 (Ba1-xSrx)TiO3 [BST] Glass-Ceramics 232 8.3 Glass-Ceramic System (1-y) BST: y (B2O3: x SiO2) 234 8.4 Glass-Ceramic System (1-y) BST: y (BaO: Al2O3: 2SiO2) 245 8.5 Comparision of the Two BST Glass-Ceramic Systems 254 8.6 Pb(ZrxTi1-x)TiO3[PZT] Glass-Ceramics 256 References 263 9 NASICON: Synthesis, Structure and Electrical Characterization 265 Umaru Ahmadu 9.1 Introduction 265 9.2 Theretical Survey of Superionic Conduction 268 9.3 NASICON Synthesis 271 9.4 NASICON Structure and Properties 273 9.5 Characterization Techniques 278 9.6 Experimental Results 291 9.7 Problems, Applications, and Prospects 299 9.8 Conclusion 300 Acknowledgments 300 References 300 10 Ionic Liquids 309 Arnab De, Manika Dewan and Subho Mozumdar 10.1 Ionic Liquids: What Are They? 309 10.2 Historical Background 310 10.3 Classification of Ionic Liquids 311 10.4 Properties of Ionic Liquids, Physical and Chemical 314 10.5 Synthesis Methods of Ionic Liquids 323 10.6 Characterization of Ionic Liquids 329 10.7 Major Applications of ILs 330 10.8 ILs in Organic Transformations 331 10.9 ILs for Synthesis and Stabilization of Metal Nanoparticles 339 10.10 Challenges with Ionic Liquids 344 References 346 11 Dendrimers and Hyperbranched Polymers 369 Jyotishmoy Borah and Niranjan Karak 11.1 Introduction 369 11.2 Synthesis of Dendritic Polymers 372 11.3 Characterization 385 11.4 Properties 391 11.5 Applications 398 11.6 Conclusion 403 References 404 Part 3: Advanced Structures and Properties 413 12 Theoretical Investigation of Superconducting State Parameters of Bulk Metallic Glasses 415 Aditya M. Vora 12.1 Introduction 415 12.2 Computational Methodology 417 12.3 Results and Discussion 421 12.4 Conclusions 434 References 434 13 Macroscopic Polarization and Thermal Conductivity of Binary Wurtzite Nitrides 439 Bijaya Kumar Sahoo 13.1 Introduction 440 13.2 The Macroscopic Polarization 441 13.3 Effective Elastic Constant, C44 442 13.4 Group Velocity of Phonons 443 13.5 Phonon Scattering Rates 444 13.6 Thermal Conductivity of InN 445 13.7 Summary 449 References 450 14 Experimental and Theoretical Background to Study Materials 453 Arnab De, Manika Dewan and Subho Mozumdar 14.1 Quasi-Elastic Light Scattering (Photon Correlation Spectroscopy) 453 14.2 Transmission Electron Microscopy (TEM) 456 14.3 Scanning Electron Microscopy [2] 457 14.4 X-ray Diffraction (XRD) 459 14.5 UV-visible Spectroscopy 461 14.6 FT-IR Spectroscopy 462 14.7 NMR Spectroscopy 463 14.8 Mass Spectrometry 464 14.9 Vibrating Sample Magnetometer 465 References 466 15 Graphene and Its Nanocomposites for Gas Sensing Applications 467 Parveen Saini, Tapas Kuila, Sanjit Saha and Naresh Chandra Murmu 15.1 Introduction 468 15.2 Principles of Chemical Sensing by Conducting Nanocomposite Materials 470 15.3 Synthesis of Graphene and Its Nanocomposites 472 15.4 Characterization of Graphene and Its Nanocomposites 473 15.5 Chemical Sensing of Graphene and Its Nanocomposites 477 15.6 Conclusion and Future Aspects 493 Acknowledgements 494 References 494 Index 501

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Book SynopsisWith the needed mathematical and computational tools, this book provides a solid foundation in formulating and solving real-world PDE numerical and analytical problems in various fields from applied mathematics, engineering, and computer science to biology and medicine.Table of ContentsPreface ix 1. Introduction to Partial Differentiation Equation Analysis: Chemotaxis 1 2. Pattern Formation 43 3. Belousov–Zhabotinskii Reaction System 103 4. Hodgkin–Huxley and Fitzhugh–Nagumo Models 127 5. Anesthesia Spatiotemporal Distribution 163 6. Influenza with Vaccination and Diffusion 207 7. Drug Release Tracking 243 8. Temperature Distributions in Cryosurgery 287 Index 323 Preface ix 1. Introduction to Ordinary Differential Equation Analysis: Bioreactor Dynamics 1 2. Diabetes Glucose Tolerance Test 79 3. Apoptosis 145 4. Dynamic Neuron Model 191 5. Stem Cell Differentiation 217 6. Acetylcholine Neurocycle 241 7. Tuberculosis with Differential Infectivity 321 8. Corneal Curvature 337 Appendix A1: Stiff ODE Integration 375 Index 417

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Book SynopsisTable of ContentsForeword 1 xxix Foreword 2 xxxi Foreword 3 xxxiii Preface to the Third Edition xxxv Preface to the Second Edition xxxix Acknowledgments xliii H.K. Huang Short Biography xlv List of Acronyms xlvii Part 1 The Beginning: Retrospective 1 1 Medical Imaging, PACS and Imaging Informatics: Retrospective 3 PART I TECHNOLOGY DEVELOPMENT AND PIONEERS 4 1.1 Medical Imaging 4 1.2 PACS and its Development 8 1.3 Key Technologies: Computer and Software, Storage, and Communication Networks 15 1.4 Key Technologies: Medical Imaging Related 17 PART II COLLABORATIONS AND SUPPORTS 22 1.5 Collaboration with Government Agencies, Industry and Medical Imaging Associations 22 1.6 Medical Imaging Informatics 29 1.7 Summary 32 1.8 Acknowledgments 34 References 35 Part 2 Medical Imaging, Industrial Guidelines, Standards, and Compliance 37 2 Digital Medical Imaging 39 2.1 Digital Medical Imaging Fundamentals 39 2.2 Two-Dimensional Medical Imaging 46 2.3 Three-Dimensional Medical Imaging 55 2.4 Four-Dimensional, Multimodality, and Fusion Imaging 78 2.5 Image Compression 85 Further Reading 93 3 PACS Fundamentals 97 3.1 PACS Components and Network 97 3.2 PACS Infrastructure Design Concept 101 3.3 Generic PACS-Based Multimedia Architecture and Workflow 103 3.4 PACS-Based Architectures 105 3.5 Communication and Networks 110 Further Reading 121 4 Industrial Standards: Health Level 7 (HL7), Digital Imaging and Communications in Medicine (DICOM) and Integrating the Healthcare Enterprise (IHE) 123 4.1 Industrial Standards 124 4.2 The Health Level 7 (HL7) Standard 124 4.3 From ACR-NEMA to DICOM 127 4.4 DICOM 3.0 Standard 129 4.5 Examples of Using DICOM 136 4.6 DICOM Organizational Structure and New Features 138 4.7 IHE (Integrating the Healthcare Enterprise) 142 4.8 Some Operating Systems and Programming Languages useful to HL7, DICOM and IHE 151 4.9 Summary of Industrial Standards: HL7, DICOM and IHE 153 References 153 Further Reading 154 5 DICOM-Compliant Image Acquisition Gateway and Integration of HIS, RIS, PACS and ePR 155 5.1 DICOM Acquisition Gateway 156 5.2 DICOM-Compliant Image Acquisition Gateway 157 5.3 Automatic Image Data Recovery Scheme for DICOM Conformance Device 162 5.4 Interface PACS Modalities with the Gateway Computer 164 5.5 DICOM Compliance PACS Broker 166 5.6 Image Preprocessing and Display 167 5.7 Clinical Operation and Reliability of the Gateway 168 5.8 Hospital Information System (HIS), Radiology Information System (RIS), and PACS 169 References 178 6 Web-Based Data Management and Image Distribution 179 6.1 Distributed Image File Server: PACS-Based Data Management 179 6.2 Distributed Image File Server 179 6.3 Web Server 181 6.4 Component-based Web Server for Image Distribution and Display 183 6.5 Performance Evaluation 188 6.6 Summary of PACS Data Management and Web]based Image Distribution 189 Further Reading 189 7 Medical Image Sharing for Collaborative Healthcare Based on IHE XDS-I Profile 191 7.1 Introduction 192 7.2 Brief Description of IHE XDS/XDS-I Profiles 193 7.3 Pilot Studies of Medical Image Sharing and Exchanging for a Variety of Healthcare Services 194 7.4 Results 206 7.5 Discussion 209 Acknowledgements 212 References 212 Part 3 Informatics, Data Grid, Workstation, Radiotherapy, Simulators, Molecular Imaging, Archive Server, and Cloud Computing 215 8 Data Grid for PACS and Medical Imaging Informatics 217 8.1 Distributed Computing 217 8.2 Grid Computing 219 8.3 Data Grid 222 8.4 Fault-Tolerant Data Grid for PACS Archive and Backup, Query/Retrieval, and Disaster Recovery 226 References 230 Further Reading 230 9 Data Grid for Clinical Applications 233 9.1 Clinical Trials and the Data Grid 233 9.2 Dedicated Breast MRI Enterprise Data Grid 239 9.3 Administrating the Data Grid 247 9.4 Summary 250 References 251 Further Reading 251 10 Display Workstations 253 10.1 PACS-Based Display Workstation 254 10.2 Various Types of Image Workstation 260 10.3 Image Display and Measurement Functions 263 10.4 Workstation Graphic User Interface (GUI) and Basic Display Functions 267 10.5 DICOM PC-Based Display Workstation Software 269 10.6 Post-Processing Workflow, PACS-Based Multidimensional Display, and Specialized Post-Processing Workstation 276 10.7 DICOM-Based Workstations in Progress 277 References 289 11 Multimedia Electronic Patient Record (EPR) System in Radiotherapy (RT) 291 11.1 Multimodality 2-D and 3-D Imaging in Radiotherapy 292 11.2 Multimedia ePR System in Radiation Treatment 298 11.3 Radiotherapy Planning and Treatment 301 11.4 Radiotherapy Workflow 302 11.5 The ePR Data Model and DICOM-RT Objects 303 11.6 Infrastructure, Workflow and Components of the Multimedia ePR in RT 306 11.7 Database Schema 309 11.8 Graphical User Interface Design 311 11.9 Validation of the Concept of Multimedia ePR System in RT 312 11.10 Advantages of the Multimedia ePR system in RT for Daily Clinical Practice 319 11.11 Use of the Multimedia ePR System in RT For Image-Assisted Knowledge Discovery and Decision Making 320 11.12 Summary 321 Acknowledgement 321 References 321 12 PACS-Based Imaging Informatics Simulators 325 12.1 Why Imaging Informatics Simulators? 326 12.2 PACS–ePR Simulator 328 12.3 Data Grid Simulator 329 12.4 CAD–PACS Simulator 331 12.5 Radiotherapy (RT) ePR Simulator 335 12.6 Image]assisted Surgery (IAS) ePR Simulator 338 12.7 Summary 344 Acknowledgements 344 References 344 13 Molecular Imaging Data Grid (MIDG) 347 13.1 Introduction 348 13.2 Molecular Imaging 348 13.3 Methodology 351 13.4 Results 358 13.5 Discussion 360 13.6 Summary 361 Acknowledgements 361 References 362 14 A DICOM-Based Second-Generation Molecular Imaging Data Grid (MIDG) with the IHE XDS-i Integration Profile 365 14.1 Introduction 366 14.2 Methodology 369 14.3 System Implementation 371 14.4 Data Collection and Normalization 375 14.5 System Performance 378 14.6 Data Transmission, MIDG Implementation, Workflow and System Potential 380 14.7 Summary 383 Acknowledgements 386 References 386 15 PACS-Based Archive Server and Cloud Computing 389 15.1 PACS-Based Multimedia Biomedical Imaging Informatics 390 15.2 PACS-Based Server and Archive 390 15.3 PACS-Based Archive Server System Operations 396 15.4 DICOM-Compliant PACS-Based Archive Server 397 15.5 DICOM PACS-Based Archive Server Hardware and Software 399 15.6 Backup Archive Server and Data Grid 400 15.7 Cloud Computing and Archive Server 403 Acknowledgements 414 References 414 Part 4 Multimedia Imaging Informatics, Computer-Aided Diagnosis (CAD), Image-Guide Decision Support, Proton Therapy, Minimally Invasive Multimedia Image-Assisted Surgery, Big Data 417 Prologue – Chapters 16, 17 and 18 417 16 DICOM-Based Medical Imaging Informatics and CAD 419 16.1 Computer]Aided Diagnosis (CAD) 420 16.2 Integration of CAD with PACS-Based Multimedia Informatics 425 16.3 The CAD–PACS Integration Toolkit 429 16.4 Data Flow of the three CAD–PACS Editions Integration Toolkit 432 References 433 Further Reading 434 17 DICOM-Based CAD: Acute Intracranial Hemorrhage and Multiple Sclerosis 435 17.1 Computer]Aided Detection (CAD) of Small Acute Intracranial Hemorrhage on CT of the brain 435 17.2 Development of the CAD Algorithm for AIH on CT 436 17.3 CAD-PACS Integration 452 17.4 Multiple Sclerosis (MS) on MRI 456 References 461 Further Reading 461 18 PACS-Based CAD: Digital Hand Atlas and Bone Age Assessment of children 463 18.1 Average Bone Age of a Child 464 18.2 Bone Age Assessment of Children 466 18.3 Method of Analysis 473 18.4 Integration of CAD with PACS-Based Multimedia Informatics for Bone Age Assessment of Children: The CAD System 479 18.5 Validation of the CAD and the Comparison of CAD Result with Radiologists’ Assessment 483 18.6 Clinical Evaluation of the CAD System for Bone Age Assessment (BAA) 489 18.7 Integrating CAD for Bone Age Assessment with Other Informatics Systems 493 18.8 Research and Development Trends in CAD–PACS Integration 497 Acknowledgements 499 References 499 Further Reading 500 19 Intelligent ePR System for Evidence-Based Research in Radiotherapy 503 19.1 Introduction 503 19.2 Proton Therapy Clinical Workflow and Data 506 19.3 Proton Therapy ePR System 508 19.4 System Implementation 511 19.5 Results 512 19.6 Conclusion and Discussion 520 Acknowledgements 522 References 522 20 Multimedia Electronic Patient Record System for Minimally Invasive Image]Assisted Spinal Surgery 525 20.1 Integration of Medical Diagnosis with Image]Assisted Surgery Treatment 526 20.2 Minimally Invasive Spinal Surgery Workflow 535 20.3 Multimedia ePR System for Image]Assisted MISS Workflow and Data Model 536 20.4 ePR MISS System Architecture 538 20.5 Pre-Op Authoring Module 543 20.6 Intra-Op Module 547 20.7 Post-Op Module 553 20.8 System Deployment, User Training and Support 554 20.9 Summary 557 References 557 21 From Minimally Invasive Spinal Surgery to Integrated Image-Assisted Surgery in Translational Medicine 559 21.1 Introduction 560 21.2 Integrated Image-Assisted Minimally Invasive Spinal Surgery 561 21.3 IIA-MISS EMR System Evaluation 565 21.4 To Fulfill some Translational Medicine Aims 569 21.5 Summary 571 21.6 Contribution from Colleagues 572 Acknowledgement 572 References 572 22 Big Data in PACS-Based Multimedia Medical Imaging Informatics 575 22.1 Big Data in PACS-Based Multimedia Medical Imaging Informatics 575 22.2 Characters and Challenges of Medical Image Big Data 577 22.3 Possible and Potential Solutions of Big Data in DICOM PACS-Based Medical Imaging and Informatics 581 22.4 Research Projects Related to Medical Imaging Big Data 586 22.5 Summary of Big Data 587 Acknowledgements 588 References 588 Index 591

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Book SynopsisTechnological advances have greatly increased the potential for, and practicability of, using medical neurotechnologies to revolutionize how a wide array of neurological and nervous system diseases and dysfunctions are treated.Table of Contents1. The Historical Foundation of Bionics Nick Donaldson and Giles.S. Brindley 1.1 Bionics Past & Future 1.2 History in 1973 1.2.1 Biomaterials 1.2.2 Nerve Stimulation & Recording 1.2.3 Transistors 1.2.4 Conclusion 1.3 Anaesthesia 1.4 Aseptic Surgery 1.5 Clinical Observation & Experiments 1.6 Hermetic Packages 1.6.1 Vacuum Methods 1.6.2 Welding 1.6.3 Glass 1.6.4 Glass Ceramics & Solder Glasses 1.6.5 Ceramics 1.6.6 Microcircuit Technologies 1.6.7 Leak Testing 1.7 Encapsulation (Electrical Insulation) 1.7.1 Insulation 1.7.2 Under-water insulation 1.7.3 Silicones 1.7.4 Primers 1.8 Early Implanted Devices 1.9 Afterword References 2. Development of Stable Long-Term Electrode Tissue Interfaces for Recording and Stimulation Jens Schouenborg 2.1 Introduction 2.2 Tissue responses in the brain to an implanted foreign body 2.2.1 Acute tissue responses 2.2.2 Chronic tissue responses 2.2.3 On the importance of physiological conditions 2.3 Brain Computer Interfaces (BCI) - state of the art 2.4 Biocompatibility of BCI – on the importance of mechanical compliance 2.5 Novel electrode constructs and implantation procedures 2.5.1 Methods to implant ultraflexible electrodes 2.5.2 Surface configurations 2.5.3 Matrix embedded electrodes 2.5.4 Electrode arrays encorporating drugs 2.6 Concluding remarks Acknowledgements References 3. Electrochemical Principles of Safe Charge Injection Stuart F. Cogan, David J. Garrett and Rylie A. Green 3.1 Introduction 3.2 Charge Injection Requirements 3.2.1 Stimulation Levels for Functional Responses 3.2.2 Tissue damage thresholds 3.2.3 Charge Injection Processes 3.2.4 Capacitive Charge Injection 3.2.5 Faradaic Charge Injection 3.2.6 Stimulation Waveforms 3.2.7 Voltage Transient Analysis 3.3 Electrode Materials 3.3.1 Non-noble Metal Electrodes 3.3.2 Noble metals 3.3.3 High Surface Area Capacitor Electrodes 3.3.4 Three-dimensional Noble Metal Oxide Films 3.4 Factors Influencing Electrode Reversibility 3.4.1 In vivo versus saline charge injection limits 3.4.2 Degradation Mechanisms and Irreversible Reactions 3.5 Emerging Electrode Materials 3.5.1 Intrinsically conductive polymers 3.5.2 Carbon Nanotubes and Conductive Diamond 3.6 Conclusion References 4. Principles of Recording from an Electrical Stimulation of Neural Tissue James B. Fallon and Paul M. Carter 4.1 Introduction 4.2 Anatomy and physiology of neural tissue 4.2.1 Active Neurons 4.3 Physiological principles of recording from neural tissue 4.3.1 Theory of recording 4.3.2 Recording electrodes 4.3.3 Amplification 4.3.4 Imaging 4.4 Principles of Stimulation of Neural Tissue 4.4.1 Introduction 4.4.2 Principles of Neural Stimulator Design 4.4.3 Modelling Nerve Stimulation 4.4.4 The Activating Function 4.4.5 Properties of Nerves Under Electrical Stimulation 4.5 Safety of Electrical Stimulation 4.5.1 Safe Stimulation Limits 4.5.2 Metabolic Stress 4.5.3 Electrochemical Stress 4.6 Conclusion References 5. Wireless Neurotechnology for Neural Prostheses Arto Nurmikko, David Borton and Ming Yin 5.1 Introduction 5.2 Rationale and overview of Technical Challenges Associated with Wireless Neuroelectronic Interfaces 5.3 Wireless Brain Interfaces Require Specialized Microelectronics 5.3.1 Lessons learned from Cabled Neural Interfaces 5.3.2 Special Demands for Compact Wireless Neural Interfaces 5.4 Illustrative Microsystems for High Data Rate Wireless Brain Interfaces in Primates 5.5 Power Supply and Management for Wireless Neural Interfaces 5.6 Packaging and Challenges in Hermetic Sealing 5.7 Deployment of High Data Rate Wireless Recording in Freely Moving Large Animals 5.8 Summary and Prospects for High Data Rate Brain Interfaces for Neural Prostheses Acknowledgements References 6. Preclinical Testing of Neural Prostheses Douglas McCreery 6.1 Introduction 6.2 Biocompatibility testing of neural implants 6.3 Testing for mechanical and electrical integrity 6.4 In vitro accelerated testing and accelerated aging of neural implants 6.5 In vivo testing of neural prostheses 6.6 Conclusion References 7. Auditory and Visual Neural Prostheses Robert K. Shepherd, Peter M. Seligman, Mohit N. Shivdasani 7.1 Introduction 7.2 Auditory prostheses 7.2.1 The Auditory system 7.2.2 Hearing loss 7.2.3 Cochlear implants 7.2.4 Central auditory prostheses 7.2.5 Combined electric and acoustic stimulation 7.2.6 Bilateral cochlear implants 7.2.7 Future directions 7.3 Visual prostheses 7.3.1 The Visual system 7.3.2 Vision loss 7.3.3 Retinal prostheses 7.3.4 Central visual prostheses 7.3.5 Perception through a vision prosthesis 7.3.6 Future directions 7.4 Sensory prostheses and brain plasticity 7.5 Conclusions Acknowledgments References 8. Neurobionics: Treatments for Disorders of the Central Nervous System Hugh McDermott 8.1 Introduction 8.2 Psychiatric conditions 8.2.1 Obsessive-compulsive disorder 8.2.2 Major depression 8.3 Movement disorders 8.3.1 Essential Tremor 8.3.2 Parkinson’s disease 8.3.3 Dystonia 8.3.4 Tourette syndrome 8.4 Epilepsy 8.5 Pain 8.6 Future directions Acknowledgements References 9. Brain Computer Interfaces David M. Brandman and Leigh R. Hochberg 9.1 Introduction 9.2 Motor Physiology 9.2.1 Neurons are the fundamental unit of the Brain 9.2.2 Movement occurs through coordinated activity between multiple regions of the nervous system 9.2.3 Motor Cortex: a first source for iBCI signals 9.2.4 The Parietal Cortex is implicated in spatial coordination 9.2.5 The premotor and supplementary motor cortices are engaged in movement goals 9.2.6 Functional brain organization is constantly changing 9.2.7 Section Summary 9.3 The Clinical Population for Brain Machine Interfaces 9.3.1 Paralysis may result from damage to the motor system 9.3.2 Individuals with spinal cord injuries develop motor impairments that may impact hand function 9.3.3 Individuals with LIS develop motor impairment that impacts communication 9.4 BCI Modalities 9.4.1 BCI Modalities 9.4.2 Electrodes placed in the cortex record action potentials from neurons 9.4.3 Raw voltage signals are processed into spikes 9.5 BCI Decoding and applications 9.5.1 BCI decoders convert neural information into control of devices 9.5.2 BCI decoders allow for the control of prosthetic devices 9.6 Future directions 9.6.1 Scientific and engineering directions for developing BMI technology 9.6.2 Clinical directions for development of BCI technology 9.7 Conclusion References 10. Taking a Device to Market: Regulatory and Commercial Issues John L. Parker 10.1 Introduction 10.2 Basic Research 10.3 Preclinical Development 10.4 Clinical trials and approval to sell 10.5 Building a Business not a product 10.6 Conclusions References 11. Ethical Considerations in the Development of Neural Prostheses Frank J. Lane, Kristian P. Nitsch, and Marcia Scherer 11.1 Introduction 11.2 Individuals with Disabilities & Technology Development 11.3 Ethical Principles of Biomedical Research 11.4 Conclusions References Appendix: Companies Developing and/or Marketing Bionic Devices

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Book SynopsisIn vivo magnetic resonance imaging (MRI) has evolved into a versatile and critical, if not gold standard', imaging tool with applications ranging from the physical sciences to the clinical -ology'. In addition, there is a vast amount of accumulated but unpublished inside knowledge on what is needed to perform a safe, in vivo MRI. The goal of this comprehensive text, written by an outstanding group of world experts, is to present information about the effect of the MRI environment on the human body, and tools and methods to quantify such effects. By presenting such information all in one place, the expectation is that this book will help everyone interested in the Safety and Biological Effects in MRI find relevant information relatively quickly and know where we stand as a community. The information is expected to improve patient safety in the MR scanners of today, and facilitate developing faster, more powerful, yet safer MR scanners of tomorrow. This book is arranged in three sections. The first, named Static and Gradient Fields' (Chapters 1-9), presents the effects of static magnetic field and the gradients of magnetic field, in time and space, on the human body. The second section, named Radiofrequency Fields' (Chapters 10-30), presents ways to quantify radiofrequency (RF) field induced heating in patients undergoing MRI. The effect of the three fields of MRI environment (i.e. Static Magnetic Field, Time-varying Gradient Magnetic Field, and RF Field) on medical devices, that may be carried into the environment with patients, is also included. Finally, the third section, named Engineering' (chapters 31-35), presents the basic background engineering information regarding the equipment (i.e. superconducting magnets, gradient coils, and RF coils) that produce the Static Magnetic Field, Time-varying Gradient Magnetic Field, and RF Field. The book is intended for undergraduate and post-graduate students, engineers, physicists, biologists, clinicians, MR technologists, other healthcare professionals, and everyone else who might be interested in looking into the role of MRI environment on patient safety, as well as those just wishing to update their knowledge of the state of MRI safety. Those, who are learning about MRI or training in magnetic resonance in medicine, will find the book a useful compendium of the current state of the art of the field. Table of ContentsContributors Series Preface Preface Acknowledgments Part A: Static and Gradient Fields 1 Static and Low Frequency Electromagnetic Fields and Their Effects in MRIs 3Zhenyu Zhang and Stuart Feltham 2 Magnetic-field-induced Vertigo in the MR Environment 23Paul Glover 3 Effects of Magnetic Fields and Field Gradients on Living Cells 33Jarek Wosik, Martha Villagran, Ahmed Uosef, Rafik M. Ghobrial, John H. Miller Jr., and Malgorzata Kloc 4 Effect of Strong Time-varying Magnetic Field Gradients on Humans 53John Nyenhuis and David Gross 5 Peripheral Nerve Stimulation Modeling for MRI 67Mathias Davids, Bastien Guérin, Lothar R. Schad, and Lawrence L. Wald 6 Magnetically Induced Force and Torque on Medical Devices 87Terry O. Woods 7 A Review of MRI Acoustic Noise and its Potential Impact on Patient and Worker Health 95Michael C. Steckner 8 Modeling Blood Flow 119Michael Keith Sharp 9 Effect of Magnetic Field on Blood Flow 133G.C. Shit and Sreeparna Majee Part B: Radiofrequency Fields 10 Safety Standards for MRI 161Michael C. Steckner 11 On the Choice of RF Safety Metric in MRI: Temperature, SAR, or Thermal Dose 173Devashish Shrivastava 12 RF Coil and MR Safety 181J. Thomas Vaughan 13 Local SAR Assessment for Multitransmit Systems: A Study on the Peak Local SAR Value as a Function of Magnetic Field Strength 195Alexander J.E. Raaijmakers and Bart R. Steensma 14 Radio Frequency Safety Assessment for Open Source Pulse Sequence Programming 207Sairam Geethanath, Julie Kabil, and J. Thomas Vaughan 15 RF Heating Due to a 3T Birdcage Whole-body Transmit Coil in Anesthetized Sheep 219Samat Turdumamatov, Ça˘gda¸s Oto, Oktay Algın, Hamza Ergüder, and Tahir Malas 16 In Vivo Radiofrequency Heating due to 1.5, 3, and 7 T Whole-body Volume Coils 227Shuo Song, Ji Chen, Rongxing Zhang, Qiang He, J. Thomas Vaughan, and Devashish Shrivastava 17 Temperature Management and Radiofrequency Heating During Pediatric MRI Scans 239Stanley Thomas Fricke, Marjean H. Cefaratti, and Andrew Matisoff 18 Failure to Monitor and Maintain Thermal Comfort During an MRI Scan: A Perspective from a Thermal Physiologist Turned Patient 245Christopher J. Gordon 19 MR Thermometry to Assess Heating Induced by RF Coils Used in MRI 251Henrik Odéen, John Rock Hadley, Dylan Palomino, Katelynn Stroth, and Dennis L. Parker 20 Heating of RF coil 273Joseph Murphy-Boesch 21 RF-Induced Heating in Bare and Covered Stainless Steel Rods: Effect of Length, Covering, and Diameter 289Sunder Rajan, Peter Serano, Joshua Guag, Tayeb Zaidi, Kyoko Fujimoto, Maria Ida Iacono, and Leonardo M. Angelone 22 On the Development of a Novel Leg Phantom for RF Safety Assessment for Circular Ring External Fixation Devices in 1.5 T 295Xing Huang and Ji Chen 23 RF Safety of Active Implantable Medical Devices 311Berk Silemek, Volkan Açıkel, and Ergin Atalar 24 An Analysis of Factors Influencing MRI RF Safety for Patients with AIMDs 333Jingshen Liu, Jianfeng Zheng, Qingyan Wang, and Ji Chen 25 On Using Fluoroptic Thermometry to Measure Time-varying Temperatures in MRI 345Devashish Shrivastava, Mykhaylo Nosovskyy, and Charles A. Lemaire 26 On Using Magnetic Resonance Thermometry to Measure ‘Strong’ Spatio-temporal Tissue Temperature Variations and Compute Thermal Dose 351Devashish Shrivastava 27 The Use and Safety of Iron-Oxide Nanoparticles in MRI and MFH 361Hattie L. Ring, John C. Bischof, and Michael Garwood 28 Numerical Simulation for MRI RF Coils and Safety 379Julie M. Kabil and Anand Gopinath 29 Integral Equation Approach to Modeling RF Fields in Human Body in MRI Systems for Safety 399Anand Gopinath 30 Safety Practices and Protocols in the MR Research Center of the Columbia University in the City of New York 407Kathleen Durkin, Dania Elder, and David H. Gultekin Part C: Engineering 31 History, Physics, and Design of Superconducting Magnets for MRI 423Bruce Breneman 32 Fabrication of Superconducting Magnets for MRI 447Bruce Breneman 33 Magnet Field Shimming and External Ferromagnetic Influences on the Homogeneity and Site Shielding of Superconducting MRI Magnets 469Bruce Breneman 34 Gradient Coils 489Maxim Zaitsev, Philipp Amrein, Feng Jia, and Sebastian Littin 35 RF Coil Construction for MRI 504J. Thomas Vaughan and Russell Lagore Index 521

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Book SynopsisPlant polyphenols are secondary metabolites that constitute one of the most common and widespread groups of natural products. They express a large and diverse panel of biological activities including beneficial effects on both plants and humans. Many polyphenols, from their structurally simplest representatives to their oligo/polymeric versions (also referred to as vegetable tannins), are notably known as phytoestrogens, plant pigments, potent antioxidants, and protein interacting agents.Sponsored by the scholarly society Groupe Polyphénols, this publication, which is the fifth volume in this highly regarded Recent Advances in Polyphenol Research series, is edited by Kumi Yoshida, Véronique Cheynier and Stéphane Quideau. They have once again, like their predecessors, put together an impressive collection of cutting-edge chapters written by expert scientists, internationally respected in their respective field of polyphenol sciences. This Volume 5 highlights some of tTable of ContentsContributors xv Preface xix 1 The Physical Chemistry of Polyphenols: Insights into the Activity of Polyphenols in Humans at the Molecular Level 1Olivier Dangles, Claire Dufour, Claire Tonnelé and Patrick Trouillas 1.1 Introduction 1 1.2 Molecular complexation of polyphenols 4 1.3 Polyphenols as electron donors 11 1.4 Polyphenols as ligands for metal ions 21 1.5 Conclusions 27 References 28 2 Polyphenols in Bryophytes: Structures, Biological Activities, and Bio- and Total Syntheses 36Yoshinori Asakawa 2.1 Introduction 36 2.1 Distribution of cyclic and acyclic bis-bibenzyls in Marchantiophyta (liverworts) 37 2.3 Biosynthesis of bis-bibenzyls 39 2.4 The structures of bis-bibenzyls and their total synthesis 50 2.5 Biological activity of bis-bibenzyls 58 2.6 Conclusions 60 Acknowledgments 61 References 61 3 Oxidation Mechanism of Polyphenols and Chemistry of Black Tea 67Yosuke Matsuo and Takashi Tanaka 3.1 Introduction 67 3.2 Catechin oxidation and production of theaflavins 71 3.3 Theasinensins 73 3.4 Coupled oxidation mechanism 75 3.5 Bicyclo[3.2.1]octane intermediates 77 3.6 Structures of catechin oxidation products 78 3.7 Oligomeric oxidation products 82 3.8 Conclusions 84 Acknowledgments 85 References 85 4 A Proteomic-Based Quantitative Analysis of the Relationship Between Monolignol Biosynthetic Protein Abundance and Lignin Content Using Transgenic Populus trichocarpa 89Jack P. Wang, Sermsawat Tunlaya-Anukit, Rui Shi, Ting-Feng Yeh, Ling Chuang, Fikret Isik, Chenmin Yang, Jie Liu, Quanzi Li, Philip L. Loziuk, Punith P. Naik, David C. Muddiman, Joel J. Ducoste, Cranos M. Williams, Ronald R. Sederoff and Vincent L. Chiang 4.1 Introduction 90 4.2 Results 94 4.3 Discussion 101 4.4 Materials and methods 102 References 104 5 Monolignol Biosynthesis and Regulation in Grasses 108Peng Xu and Laigeng Li 5.1 Introduction 108 5.2 Unique cell walls in grasses 109 5.3 Lignin deposition in grasses 110 5.4 Monolignol biosynthesis in grasses 111 5.5 Regulation of monolignol biosynthesis in grasses 114 5.6 Remarks 119 Acknowledgments 119 References 120 6 Creation of Flower Color Mutants Using Ion Beams and a Comprehensive Analysis of Anthocyanin Composition and Genetic Background 127Yoshihiro Hase 6.1 Introduction 127 6.2 Induction of flower color mutants by ion beams 129 6.3 Mutagenic effects and the molecular nature of the mutations 131 6.4 Comprehensive analyses of flower color, pigments, and associated genes in fragrant cyclamen 131 6.5 Mutagenesis and screening 133 6.6 Genetic background and the obtained mutants 136 6.7 Carnations with peculiar glittering colors 137 6.8 Conclusion 139 Acknowledgments 140 References 140 7 Flavonols Regulate Plant Growth and Development through Regulation of Auxin Transport and Cellular Redox Status 143Sheena R. Gayomba, Justin M. Watkins and Gloria K. Muday 7.1 Introduction 143 7.2 The flavonoids and their biosynthetic pathway 144 7.3 Flavonoids affect root elongation and gravitropism through alteration of auxin transport 146 7.4 Mechanisms by which flavonols regulate IAA transport 149 7.5 Lateral root formation 151 7.6 Cotyledon, trichome, and root hair development 152 7.7 Inflorescence architecture 154 7.8 Fertility and pollen development 154 7.9 Flavonols modulate ROS signaling in guard cells to regulate stomatal aperture 155 7.10 Transcriptional machinery that controls synthesis of flavonoids 157 7.11 Hormonal controls of flavonoid synthesis 160 7.12 Flavonoid synthesis is regulated by light 161 7.13 Conclusions 162 Acknowledgments 163 References 163 8 Structure of Polyacylated Anthocyanins and Their UV Protective Effect 171Kumi Yoshida, Kin-ichi Oyama and Tadao Kondo 8.1 Introduction 171 8.2 Occurrence and structure of polyacylated anthocyanins in blue flowers 173 8.3 Molecular associations of polyacylated anthocyanins in blue flower petals 178 8.4 UV protection of polyacylated anthocyanins from solar radiation 183 8.5 Conclusion 187 References 188 9 The Involvement of Anthocyanin-Rich Foods in Retinal Damage 193Kenjirou Ogawa and Hideaki Hara 9.1 Introduction 193 9.2 Anthocyanin-rich foods for eye health 195 9.3 Experimental models to mimic eye diseases and the effect of anthocyanin-rich foods 196 9.4 Conclusions 201 References 203 10 Prevention and Treatment of Diabetes Using Polyphenols via Activation of AMP-Activated Protein Kinase and Stimulation of Glucagon-like Peptide-1 Secretion 206Takanori Tsuda 10.1 Introduction 206 10.2 Activation of AMPK and metabolic change 207 10.3 GLP-1 action and diabetes prevention/suppression 212 10.4 Future issues and prospects 220 References 222 11 Beneficial Vascular Responses to Proanthocyanidins: Critical Assessment of Plant-Based Test Materials and Insight into the Signaling Pathways 226Herbert Kolodziej 11.1 Introduction 227 11.2 Appraisal of test materials 228 11.3 Endothelial dysfunction 233 11.4 In vitro test systems 234 11.5 Vasorelaxant mechanisms 235 11.6 Bioavailability and metabolic transformation: the missing link in the evidence to action in the body 249 11.7 Conclusions 250 References 251 12 Polyphenols for Brain and Cognitive Health 259Katherine H. M. Cox and Andrew Scholey 12.1 Introduction 259 12.2 Studies of total polyphenols and cognition 260 12.3 Pine bark 272 12.4 Discussion and conclusions 283 References 283 13 Curcumin and Cancer Metastasis 289Ikuo Saiki 13.1 Introduction 290 13.2 Effects of curcumin on intra-hepatic metastasis of liver cancer 293 13.3 Effects of curcumin on lymp node metastasis of lung cancer 298 13.4 Effects of curcumin on tumor angiogenesis 303 13.5 Conclusions 307 References 307 14 Phytochemical and Pharmacological Overview of Cistanche Species 313Hai-Ning Lv, Ke-Wu Zeng, Yue-Lin Song, Yong Jiang and Peng-Fei Tu 14.1 Introduction 313 14.2 Chemical constituents of Cistanche species 314 14.3 Bioactivities of the extracts and pure compounds from Cistanche species 322 14.4 Conclusions 334 References 334 Index 342

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Book SynopsisAdvanced, recent developments in biochips and medical imaging Biochips and Medical Imaging is designed as a professional resource, covering recent biochip and medical imaging developments. Within the text, the authors encourage uniting aspects of engineering, biology, and medicine to facilitate advancements in the field of molecular diagnostics and imaging. Biochips are microchips for efficiently screening biological analytes. This book aims at presenting information on the state-of-the-art and emerging biosensors, biochips, and imaging devices of the body's systems, including the endocrine, circulatory, and immune systems. Medical diagnostics includes biochips (in-vitro diagnostics) and medical and molecular imaging (in-vivo imaging). Biochips and Medical Imaging explores the role of in-vitro and in-vivo diagnostics. It enables an instructor to share in-depth examples of the use of biochips in diagnosing cancer and cardiovascular diseases. Provides real-life knowledge on biochipTable of ContentsForeword xvii Preface xix Acknowledgments xxi 1 Cell Biology 1 1.1 Cell Biology Introduction 1 1.2 Cell Structure 1 1.3 Cell Membrane 2 1.4 Proteins 2 1.5 Cytoplasm and Organelles 3 1.6 Nucleus 6 1.7 Nucleic Acids (DNA and RNA) 8 1.8 Central Dogma and Recent Revisions 10 1.9 Mutations 14 1.10 Cell Cycle 14 1.11 Additional Information 17 2 Biological Lab Techniques 27 2.1 Overview 27 2.2 Beer Lambert's Law 27 2.3 DNA Lab Techniques 28 2.4 Additional Information 38 3 Human Physiology 47 3.1 Overview 47 3.2 Nervous System 47 3.3 Circulatory System 68 3.4 Endocrine System 74 3.5 Lymphatic System 83 3.6 Immune System 85 4 Cancer 103 4.1 Epidemiology (Statistics) 103 4.2 What Causes Cancer 104 4.3 Oncogenesis (Cancer Development) 106 4.4 The Six Hallmarks of Cancer 109 4.5 Conclusion 118 5 Cardiovascular Diseases (CVDs) 123 5.1 Epidemiology and Introduction 123 5.2 Types of CVD 125 5.3 Diagnosis of CVDs 130 5.4 Treatment of CVDs 135 5.5 Conclusion 138 6 DNA Chips and Sequencing 143 6.1 Introduction to DNA Chips and PCR 143 6.2 Polymerase Chain Reaction (PCR) 143 6.3 DNA and RNA Chip Technology 147 6.4 DNA Sequencing 155 6.5 Conclusion 156 6.6 Additional Information 156 7 Next-Generation Sequencing and FET-Based Biochips 161 7.1 Introduction to Next-Generation Sequencing 161 7.2 Optical-Based Methods 162 7.3 Electronic-Based Methods 165 7.4 Conclusion 172 8 Protein Assays and Chips 179 8.1 Introduction 179 8.2 ELISA 179 8.3 Protein Arrays 183 8.4 Conclusion 190 8.5 Additional Information 190 9 Label-Free Affinity-Based Biosensors 197 9.1 Introduction 197 9.2 Surface Plasmon Resonance (SPR) Sensor 197 9.3 Nanowire Field-Effect (FET) Sensors 203 9.4 Cantilever Sensors 204 9.5 Electrochemical Sensors 205 9.6 Multiplex Detection of Polymicrobial UTI (Urinary Tract Infection) 207 9.7 Conclusion 211 10 Magneto-Nanosensor Biochips 215 10.1 Magnetism Overview 215 10.2 GMR Magneto-Nanosensor Biochips 216 10.3 Point-of-Care Testing 223 10.4 Non-GMR Magnetic Nanobiosensors 228 10.5 Conclusion 231 11 Microfluidic Chips for Capturing Circulating Tumor Cells 235 11.1 Circulating Tumor Cells 235 11.2 Identifying CTC and WBC by 3-Color Staining 235 11.3 Fluorescence-Activated Cell Sorting (FACS) 236 11.4 Magnetically Activated Cell Sorting (MACS) 237 11.5 Magnetic Separation Devices 238 11.6 CTC Enrichment By Size Filtering 243 11.7 CTC-CHIP (HARVARD UNIVERSITY) 243 11.8 Clinical Utility From CTCs 245 11.9 Conclusion 247 12 Molecular Diagnostics 251 12.1 Molecular Diagnostics (Dx) 251 12.2 Molecular Diagnostics for Cancer 251 12.3 Important Concepts in Diagnostics 254 12.4 Conclusion 261 12.5 Additional Information 261 13 Magnetic Resonance Imaging 271 13.1 Medical Imaging -- Categorization 271 13.2 Overview For Imaging Section 271 13.3 MRI: Past, Present, and Future 273 13.4 Physics of MRI Overview 274 13.5 Physics of MRI 274 13.6 Image Acquisition in MRI 279 13.7 MRI Contrast Agents 282 13.8 Conclusion 287 14 Radionuclide Imaging 295 14.1 Radioactivity 295 14.2 Basics of Positron Emission Tomography (PET) 299 14.3 Single-Photon Emission Computer Tomography (SPECT) 303 14.4 Contrast and Imaging Agents 306 14.5 Conclusion 312 15 Fluorescence and Raman Imaging 317 15.1 Introduction to Optical Imaging 317 15.2 Photon/Tissue Interaction 317 15.3 Fluorescence Imaging 320 15.4 Raman Imaging 328 15.5 Fluorescence Imaging vs. Raman Imaging 331 15.6 Conclusion 332 16 Optical Coherence Tomography 337 16.1 Introduction 337 16.2 Applications of OCT 346 16.3 Contrast Enhancement 351 16.4 Conclusion 359 17 Photoacoustic Imaging 363 17.1 Photoacoustic Effect 363 17.2 The Thermal and Stress Confinements 364 17.3 Photoacoustic Imaging 365 17.4 Contrast Agents 367 17.5 Conclusion 373 18 Imaging Controls and Concepts 377 18.1 Controls 377 18.2 Imaging Concepts 382 18.3 Clinical Translation 386 18.4 Conclusion 390 Problems 390 References 394 Further Reading 394 Index 395

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Book SynopsisAn emerging field at the interface of biology and engineering, mechanobiology explores the mechanisms by which cells sense and respond to mechanical signalsand holds great promise in one day unravelling the mysteries of cellular and extracellular matrix mechanics to cure a broad range of diseases. Mechanobiology: Exploitation for Medical Benefit presents a comprehensive overview of principles of mechanobiology, highlighting the extent to which biological tissues are exposed to the mechanical environment, demonstrating the importance of the mechanical environment in living systems, and critically reviewing the latest experimental procedures in this emerging field. Featuring contributions from several top experts in the field, chapters begin with an introduction to fundamental mechanobiological principles; and then proceed to explore the relationship of this extensive force in nature to tissues of musculoskeletal systems, heart and lung vasculature, the kidney glomerulusTable of Contents List of Contributors xiii Preface xvii 1 Extracellular Matrix Structure and Stem Cell Mechanosensing 1Nicholas D. Evans and Camelia G. Tusan 1.1 Mechanobiology 1 1.2 Stem Cells 3 1.3 Substrate Stiffness in Cell Behavior 5 1.3.1 A Historical Perspective on Stiffness Sensing 5 1.4 Stem Cells and Substrate Stiffness 7 1.4.1 ESCs and Substrate Stiffness 8 1.4.2 Collective Cell Behavior in Substrate Stiffness Sensing 11 1.5 Material Structure and Future Perspectives in Stem Cell Mechanobiology 14 1.6 Conclusion 15 References 16 2 Molecular Pathways of Mechanotransduction: From Extracellular Matrix to Nucleus 23Hamish T. J. Gilbert and Joe Swift 2.1 Introduction: Mechanically Influenced Cellular Behavior 23 2.2 Mechanosensitive Molecular Mechanisms 24 2.3 Methods Enabling the Study of Mechanobiology 29 2.4 Conclusion 34 Acknowledgements 34 References 34 3 Sugar-Coating the Cell: The Role of the Glycocalyx in Mechanobiology 43Stefania Marcotti and Gwendolen C. Reilly 3.1 What is the Glycocalyx? 43 3.2 Composition of the Glycocalyx 44 3.3 Morphology of the Glycocalyx 45 3.4 Mechanical Properties of the Glycocalyx 46 3.5 Mechanobiology of the Endothelial Glycocalyx 49 3.6 Does the Glycocalyx Play a Mechanobiological Role in Bone? 50 3.7 Glycocalyx in Muscle 52 3.8 How Can the Glycocalyx be Exploited for Medical Benefit? 53 3.9 Conclusion 53 References 54 4 The Role of the Primary Cilium in Cellular Mechanotransduction: An Emerging Therapeutic Target 61Kian F. Eichholz and David A. Hoey 4.1 Introduction 61 4.2 The Primary Cilium 63 4.3 Cilia-Targeted Therapeutic Strategies 68 4.4 Conclusion 70 Acknowledgements 70 References 70 5 Mechanosensory and Chemosensory Primary Cilia in Ciliopathy and Ciliotherapy 75Surya M. Nauli, Rinzhin T. Sherpa, Caretta J. Reese, and Andromeda M. Nauli 5.1 Introduction 75 5.2 Mechanobiology and Diseases 76 5.3 Primary Cilia as Biomechanics 78 5.4 Modulating Mechanobiology Pathways 83 5.5 Conclusion 85 References 86 6 Mechanobiology of Embryonic Skeletal Development: Lessons for Osteoarthritis 101Andrea S. Pollard and Andrew A. Pitsillides 6.1 Introduction 101 6.2 An Overview of Embryonic Skeletal Development 102 6.3 Regulation of Joint Formation 103 6.4 Regulation of Endochondral Ossification 105 6.5 An Overview of Relevant Osteoarthritic Joint Changes 106 6.6 Lessons for Osteoarthritis from Joint Formation 108 6.7 Lessons for Osteoarthritis from Endochondral Ossification 109 6.8 Conclusion 110 Acknowledgements 111 References 111 7 Modulating Skeletal Responses to Mechanical Loading by Targeting Estrogen Receptor Signaling 115Gabriel L. Galea and Lee B. Meakin 7.1 Introduction 115 7.2 Biomechanical Activation of Estrogen Receptor Signaling: In Vitro Studies 116 7.3 Skeletal Consequences of Altered Estrogen Receptor Signaling: In Vivo Mouse Studies 120 7.4 Skeletal Consequences of Human Estrogen Receptor Polymorphisms: Human Genetic and Exercise-Intervention Studies 125 7.5 Conclusion 126 References 126 8 Mechanical Responsiveness of Distinct Skeletal Elements: Possible Exploitation of Low Weight-Bearing Bone 131Simon C. F. Rawlinson 8.1 Introduction 131 8.2 Anatomy and Loading-Related Stimuli 132 8.3 Preosteogenic Responses In Vitro 135 8.4 Site-Specific, Animal-Strain Differences 136 8.5 Exploitation of Regional Information 137 8.6 Conclusion 138 References 138 9 Pulmonary Vascular Mechanics in Pulmonary Hypertension 143Zhijie Wang, Lian Tian, and Naomi C. Chesler 9.1 Introduction 143 9.2 Pulmonary Vascular Mechanics 143 9.3 Measurements of Pulmonary Arterial Mechanics 147 9.4 Mechanobiology in Pulmonary Hypertension 150 9.5 Computational Modeling in Pulmonary Circulation 151 9.6 Impact of Pulmonary Arterial Biomechanics on the Right Heart 152 9.7 Conclusion 153 References 153 10 Mechanobiology and the Kidney Glomerulus 161Franziska Lausecker, Christoph Ballestrem, and Rachel Lennon 10.1 Introduction 161 10.2 Glomerular Filtration Barrier 161 10.3 Podocyte Adhesion 163 10.4 Glomerular Disease 165 10.5 Forces in the Glomerulus 166 10.6 Mechanosensitive Components and Prospects for Therapy 167 10.7 Conclusion 169 References 169 11 Dynamic Remodeling of the Heart and Blood Vessels: Implications of Health and Disease 175Ken Takahashi, Hulin Piao, and Keiji Naruse 11.1 Introduction 175 11.2 Causes of Remodeling 176 11.3 Mechanical Transduction in Cardiac Remodeling 177 11.4 The Remodeling Process 178 11.5 Conclusion 183 References 183 12 Aortic Valve Mechanobiology: From Organ to Cells 191K. Jane Grande-Allen, Daniel Puperi, Prashanth Ravishankar, and Kartik Balachandran 12.1 Introduction 191 12.2 Mechanobiology at the Organ Level 192 12.3 Mechanobiology at the Cellular Level 197 12.4 Conclusion 201 Acknowledgments 201 References 201 13 Testing the Perimenopause Ageprint using Skin Visoelasticity under Progressive Suction 207Gérald E. Piérard, Claudine Piérard-Franchimont, Ulysse Gaspard, Philippe Humbert, and Sébastien L. Piérard 13.1 Introduction 207 13.2 Gender-Linked Skin Aging 208 13.3 Dermal Aging, Thinning, and Wrinkling 209 13.4 Skin Viscoelasticity under Progressive Suction 209 13.5 Skin Tensile Strength during the Perimenopause 211 13.6 Conclusion 214 Acknowledgements 215 References 216 14 Mechanobiology and Mechanotherapy for Skin Disorders 221Chao-Kai Hsu and Rei Ogawa 14.1 Introduction 221 14.2 Skin Disorders Associated with Mechanobiological Dysfunction 223 14.3 Mechanotherapy 231 14.4 Conclusion 232 Acknowledgement 232 References 233 15 Mechanobiology and Mechanotherapy for Cutaneous Wound-Healing 239Chenyu Huang, Yanan Du, and Rei Ogawa 15.1 Introduction 239 15.2 The Mechanobiology of Cutaneous Wound-Healing 240 15.3 Mechanotherapy to Improve Cutaneous Wound-Healing 242 15.4 Future Considerations 246 References 246 16 Mechanobiology and Mechanotherapy for Cutaneous Scarring 255Rei Ogawa and Chenyu Huang 16.1 Introduction 255 16.2 Cutaneous Wound-Healing and Mechanobiology 255 16.3 Cutaneous Scarring and Mechanobiology 256 16.4 Cellular and Tissue Responses to Mechanical Forces 257 16.5 Keloids and Hypertrophic Scars and Mechanobiology 258 16.6 Relationship Between Scar Growth and Tension 260 16.7 A Hypertrophic Scar Animal Model Based on Mechanotransduction 261 16.8 Mechanotherapy for Scar Prevention and Treatment 262 16.9 Conclusion 263 References 264 17 Mechanobiology and Mechanotherapy for the Nail 267Hitomi Sano and Rei Ogawa 17.1 Introduction 267 17.2 Nail Anatomy 267 17.3 Role of Mechanobiology in Nail Morphology 268 17.4 Nail Diseases and Mechanical Forces 269 17.5 Current Nail Treatment Strategies 270 17.6 Mechanotherapy for Nail Deformities 270 17.7 Conclusion 271 References 271 18 Bioreactors: Recreating the Biomechanical Environment In Vitro 275James R. Henstock and Alicia J. El Haj 18.1 The Mechanical Environment: Forces in the Body 275 18.2 Bioreactors: A Short History 276 18.3 Bioreactor Types 278 18.4 Commercial versus Homemade Bioreactors 288 18.5 Automated Cell-Culture Systems 289 18.6 The Future of Bioreactors in Research and Translational Medicine 290 References 291 19 Cell Sensing of the Physical Properties of the Microenvironment at Multiple Scales 297Julien E. Gautrot 19.1 Introduction 297 19.2 Cells Sense their Mechanical Microenvironment at the Nanoscale Level 298 19.3 Cell Sensing of the Nanoscale Physicochemical Landscape of the Environment 306 19.4 Cell Sensing of the Microscale Geometry and Topography of the Environment 312 19.5 Conclusion 319 References 319 20 Predictive Modeling in Musculoskeletal Mechanobiology 331Hanifeh Khayyeri, Hanna Isaksson, and Patrick J. Prendergast 20.1 What is Mechanobiology? Background and Concepts 331 20.2 Examples of Mechanobiological Experiments 333 20.3 Modeling Mechanobiological Tissue Regeneration 337 20.4 Mechanoregulation Theories for Bone Regeneration 338 20.5 Use of Computational Modeling Techniques to Corroborate Theories and Predict Experimental Outcomes 340 20.6 Horizons of Computational Mechanobiology 341 References 343 21 Porous Bone Graft Substitutes: When Less is More 347Charlie Campion and Karin A. Hing 21.1 Introduction 347 21.2 Bone: The Ultimate Smart Material 350 21.3 Bone-Grafting Classifications 353 21.4 Synthetic Bone Graft Structures 356 21.5 Conclusion 361 References 362 22 Exploitation of Mechanobiology for Cardiovascular Therapy 373Winston Elliott, Amir Keshmiri, and Wei Tan 22.1 Introduction 373 22.2 Arterial Wall Mechanics and Mechanobiology 374 22.3 Mechanical Signal and Mechanotransduction on the Arterial Wall 375 22.4 Physiological and Pathological Responses to Mechanical Signals 377 22.5 The Role of Vascular Mechanics in Modulating Mechanical Signals 378 22.6 Therapeutic Strategies Exploiting Mechanobiology 380 22.7 The Role of Hemodynamics in Mechanobiology 381 22.8 Conclusion 390 References 391 Index 401

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Book SynopsisHighlighting dynamic developments in polymer synthesis, this book focuses on the chemical techniques to synthesize and characterize biomedically relevant polymers and macromolecules. Aids researchers developing polymers and materials for biomedical applications Describes biopolymers from a synthetic perspective, which other similar books do not do Covers areas that include: cationically-charged macromolecules, pseudo-peptides, polydrugs and prodrugs, controlled radical polymerization, self-assembly, polycondensates, and polymers for surface modificationTable of ContentsList of Contributors ix Part I. Pseudo-Peptides, Polyamino acids and Polyoxazolines 1 Chapter 1 - Characterization of Polypeptides and Polypeptoides­ –Methods and Challenges 3David Huesmann and Matthias Barz Chapter 2- Poly(2-Oxazoline): The structurally Diverse Biocompatibilizing Polymer 31Rodolphe Obeid Chapter 3- Poly(2-oxazoline) Polymers – synthesis, characterization and Applications in Development of Therapeutics 51Randall W. Moreadith and Tacey X. Viegas Chapter 4- Polypeptoid Polymers: Synthesis, Characterization and Properties 77Brandon A. Chan, Sunting Xuan, Ang Li, Jessica M. Simpson and Donghui Zhang Part II - Advanced Polycondensates 121 Chapter 5 - Polyanhydrides: Synthesis and Characterization 123Rohan Ghadi, Eameema Muntimadugu Wahid Khan and Abraham J. Domb Chapter 6 - New Routes to Tailor-Made Polyesters 149Kazuki Fukushima and Tomoko Fujiwara Chapter 7 - Polyphosphoesters: An old biopolymer in a new light 191Kristin N. Bauer, Hisaschi T.C. Tee, Evandro M. Alexandrino and Frederik R. Wurm Part III. Cationically Charged Macromolecules 243 Chapter 8 - Design and Synthesis of Amphiphilic Vinyl Copolymers with Antimicrobial Activity 245Leanna L. Foster, Masato Mizutani, Yukari Oda, Edmund F. Palermo and Kenichi Kuroda Chapter 9 - Enhanced Polyethylenimine-Based Delivery of Nucleic Acids 273Jeff Sparks, Tooba Anwer and Khursheed Anwer Chapter 10 - Cationic graft copolymers for DNA engineering 297Atsushi Maruyama and Naohiko Shimada Part IV. Biorelated polymers by Controlled Radical Polymerization 313 Chapter 11 - Synthesis of (Bio)degradable Polymers by Controlled/“Living” Radical Polymerization 315Shannon R. Woodruff and Nicolay V. Tsarevsky Part V. Polydrugs and Polyprodrugs 355 Chapter 12 - Polymerized drugs – a novel approach to controlled release systems 357B. Demirdirek, J. J. Faig, R. Guliyev and K.E.Uhrich Chapter 13 - Structural design and synthesis of polymer prodrugs 391Petr Chytil, Libor Kostka and Tomáš Etrych Part VI. Biocompatibilization of Surfaces 421 Chapter 14 - Polymeric ultrathin films for surface modifications 423Henning Menzel Chapter 15 - Surface Functionalization of Biomaterials by Poly(2-oxazoline)s 457Giulia Morgese and Edmondo M. Benetti Chapter 16 - Biorelated polymer brushes by surface initiated reversible deactivation radical polymerization 487Rueben Pfukwa, Lebohang Hlalele and Bert Klumperman Part VII. Self-assembled Structures and Formulations 525 Chapter 17 - Synthesis of amphiphilic invertible polymers for biomedical applications 527A.M. Kohut, I.O. Hevus, S.A. Voronov and A.S. Voronov Chapter 18 - Bioadhesive Polymers for Drug Delivery 559Eenko Larrañeta and Ryan F. Donnelly INDEX

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Book SynopsisRheology and Processing of Polymer Nanocomposites examines the current state of the art and new challenges in the characterization of nanofiller/polymer interactions, nanofiller dispersion, distribution, filler-filler interactions and interfaces in polymer nanocomposites.Table of ContentsList of Contributors xiii 1 Materials for Polymer Nanocomposites 1Jiji Abraham, Soney C. George, Rene Muller, Nandakumar Kalarikkal, and Sabu Thomas 1.1 Introduction, 1 1.3 Recent Developments and Opportunities in the Area of Polymer Nanocomposites, 16 1.4 Challenges in the Area of Polymer Nanocomposites, 17 1.5 Relationships of Macroscopic Rheological Properties to Nanoscale Structural Variables, 18 1.6 Conclusion, 19 Acknowledgments, 20 References, 20 2 Manufacturing Polymer Nanocomposites 29Yuvaraj Haldorai and Jae-Jin Shim 2.1 Introduction, 29 2.2 Nanofillers, 30 2.3 Polymer Matrices, 36 2.4 Preparation of Nanocomposites, 37 2.5 Characterization, 58 2.6 Conclusions, 60 References, 61 3 Rheology and Processing of Polymer Nanocomposites: Theory, Practice, and New Challenges 69Jean-Charles Majesté 3.1 Introduction, 69 3.2 Viscoelasticity of Nanocomposites, 72 3.3 Flow Properties of Nanocomposites, 92 3.4 Theory and Modeling of Nanocomposites Rheology, 103 3.5 Processing of Nanocomposites, 119 3.6 Conclusion and Futures Challenges, 125 Acknowledgments, 127 References, 127 4 Mixing of Polymers Using the Elongational Flow Mixer (RMX®) 135Rigoberto Ibarra-Gómez and René Muller 4.1 Introduction, 135 4.2 Polymer Blends, 136 4.3 Polymer Nanocomposites, 147 4.4 Elongational Flow Mixer (RMX®), 151 4.5 RMX® Mixing of Polymer Blends, 158 4.6 Mixing of Polymer Nanocomposites, 173 4.7 Concluding Remarks, 182 References, 182 5 Rheology and Processing of Polymer/Layered Silicate Nanocomposites 187Masami Okamoto 5.1 Introduction, 187 5.2 Nanostructure Development, 189 5.3 Novel Compounding Methods for Delamination of OMLFs, 199 5.4 Nanostructure and Rheological Properties, 202 5.5 Nanocomposite Foams, 222 5.6 Future Prospects, 230 References, 230 6 Processing and Rheological Behaviors of CNT/Polymer Nanocomposites 235Mohan Raja, Modigunta Jeevan Kumar Reddy, Kwang Ho Won, Jae Ik Kim, Sang Hun Cha, Han Na Bae, Dae Hyeon Song, Sung Hun Ryu, and Andikkadu Masilamani Shanmugharaj 6.1 Introduction, 235 6.2 Processing Techniques of Polymer/CNT Nanocomposites, 237 6.3 Rheological Properties of Polymer/Carbon Nanotube Composites, 254 6.4 Summary, 274 Acknowledgment, 274 References, 274 7 Unusual Phase Separation in PS Rich Blends with PVME in Presence of MWNTs 279Priti Xavier and Suryasarathi Bose 7.1 Introduction, 279 7.2 Experimental Methods, 280 7.3 Theory Background, 281 7.4 Results and Discussion, 284 7.5 Conclusions, 291 Acknowledgements, 291 References, 291 8 Rheology and Processing of Polymer/POSS Nanocomposites 293Krzysztof Pielichowski, Tomasz M. Majka, and Konstantinos N. Raftopoulos 8.1 Introduction, 293 8.2 Polyhedral Oligomeric Silsesquioxanes, 296 8.3 Processing of Polymer/POSS Nanocomposites, 299 8.4 Rheological Behavior of POSS-Based Polymer Nanocomposites, 314 8.5 Conclusions, 318 Acknowledgments, 320 References, 320 9 Polymer and Composite Nanofiber: Electrospinning Parameters and Rheology Properties 329Palaniswamy Suresh Kumar, Sundaramurthy Jayaraman, and Gurdev Singh 9.1 Introduction, 329 9.2 Electrospinning, 331 9.3 Electrospinning Process Parameters, 333 9.4 Polymer-Based Nanofiber and its Rheology, 337 9.5 Nanofiber and its Polymer Composites, 348 9.6 Conclusion, 351 References, 351 10 Rheology and Processing of Inorganic Nanomaterials and Quantum Dots/Polymer Nanocomposites 355Sneha Mohan, Jiji Abraham, Oluwatobi S. Oluwafemi, Nandakumar Kalarikkal, and Sabu Thomas 10.1 Inorganic Nanoparticle Filled Polymer Nanocomposites, 356 10.2 Fabrication of Inorganic Nanoparticle Filled Polymer Nanocomposites, 356 10.3 Why Rheological Study is Important for Polymer Nanocomposites, 357 10.4 Rheology of Quantum Dot Based Polymer Nanocomposites, 359 10.5 Metal Oxide Nanoparticle-Based Polymer Nanocomposites, 366 10.6 Conclusion, 379 References, 379 11 Rheology and Processing of Laponite/Polymer Nanocomposites 383Huili Li, Wenchen Ren, Jinlong Zhu, Shimei Xu, and Jide Wang 11.1 Introduction, 383 11.2 Rheology, 384 11.3 Processing, 388 11.4 Conclusions and Outlook, 399 Acknowledgement, 400 References, 400 12 Graphene-Based Nanocomposites: Mechanical, Thermal, Electrical, and Rheological Properties 405Rachid Bouhfid, Hamid Essabir, and Abou el kacem Qaiss 12.1 Introduction, 405 12.2 Graphene, 407 12.3 The Use of Graphene in Nanocomposite Materials, 408 12.4 Nanocomposite Characterization, 412 12.5 Conclusion, 425 12.6 Future Perspective, 425 References, 426 13 Processing, Rheology, and Electrical Properties of Polymer/Nanocarbon Black Composites 431Luís C. Costa and Manuel P. Graça 13.1 Introduction, 431 13.2 Experimental, 435 13.3 Electrical Properties of Carbon Black Composites and Applications, 437 13.4 Conclusion, 447 References, 447 14 Rheology and Processing of Nanocellulose, Nanochitin, and Nanostarch/Polymer Bionanocomposites 453Carmen-Alice Teaca and Ruxanda Bodirlau14.1 Introduction, 453 14.2 Biopolymers as Nanofillers for Polymer/Nanocomposites, 455 14.3 Potential Applications of Polysaccharide Nanofillers/Polymer Nanocomposites, 478 14.4 Conclusions and Future Perspectives, 481 References, 482 15 Rheology and Processing of Nanoparticle Filled Polymer Blend Nanocomposites 491Chongwen Huang and Wei Yu 15.1 Rheology of Polymer Blends, 491 15.2 Effect of Nanoparticles on the Morphology of Polymer Blend, 509 15.3 Rheology of Nanoparticles Filled Polymer Blend, 531 15.4 Summary, 540 References, 541 16 Rheology as a Tool for Studying In Situ Polymerized Carbon Nanotube Nanocomposites 551Guo-Hua Hu, Philippe Marchal, Sandrine Hoppe, and Christian Penu 16.1 Introduction, 551 16.2 Basic Principles of Rheokinetics, 552 16.3 Rheokinetics of In Situ Polymerization of Carbon Nanotube/Monomer Systems, 560 16.4 Rheological Percolation Threshold of Carbon Nanotube-Based Nanocomposites, 567 16.5 Concluding Remarks, 581 References, 581 Index 587

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Book SynopsisThe present book is covers the recent advances in the development on the regulation of such theragnosis system and their biomedical perspectives to act as a future nanomedicine. Advanced Theranostics Materialsis written by a distinguished group of contributors and provides comprehensive coverage of the current literature, up-to-date overview of all aspects of advanced theranostics materials ranging from system biology, diagnostics, imaging, image-guided therapy, therapeutics, biosensors, and translational medicine and personalized medicine, as well as the much broader task of covering most topics of biomedical research. The books focusses on the following topics: Part 1: System biology and translational medicine Aberrant Signaling Pathways: Hallmark of Cancer Cells and Target for Nanotherapeutics Application of Nanoparticles in Cancer Treatment Biomacromolecule-Gated Mesoporous Silica Drug Delivery Systems Construction of Table of ContentsPreface xiii Part 1: System Biology and Translational Medicine 1 Aberrant Signaling Pathways 3Gulnaz T. Javan, Sheree J. Finley, Ismail Can, Amandeep Salhotra, Ashinm Malhotra, and Shivani Soni 1.1 Cancer 4 1.2 Pathways Deregulated in Cancer: Introduction 4 1.3 Introduction to Nanotechnology 6 1.3.1 Overview of Clinical Nanotechnology 9 1.3.2 Current Usage in Cancer Treatment 13 1.4 Current Uses in Cancer Diagnostic 14 1.4.1 The Phosphatidylinositol 3-Kinase-AKT Pathway 15 1.4.2 The MAPK Pathway 18 1.4.3 mTOR Pathway 20 1.4.4 Receptor Tyrosine Kinase 23 Acknowledgment 26 References 27 2 Application of Nanoparticles in Cancer Treatment 37Behnoud Hormozi 2.1 Introduction 38 2.1.1 Nanotechnology 38 2.1.2 Nanobiotechnology 38 2.1.3 Nanotechnology in Medicine 39 2.1.4 Cancer and Nano in Medicine 41 2.2 Nanoparticles in Cancer Treatment 41 2.3 Nanoparticle Platforms as Drug Delivery Systems for Cancer Therapy 43 2.3.1 Lipid-based Nanoparticle Platforms 44 2.3.2 Polymer-based Nanoparticle Platforms 45 2.3.3 Protein-based Nanoparticle Platforms 47 2.3.4 Inorganic Nanoparticle Platforms 47 2.4 Theranostic Nanomedicine 50 2.4.1 Theranostic Nanomedicine for Cancer Therapy 54 2.5 Selective Drug Delivery and Encapsulation for Chemotherapy 54 2.6 Stimuli-Sensitive Nanopreparations 55 2.7 Multifunctional Nanopreparations 56 2.8 Cancer Nanotechnology: Future and Challenges 58 References 59 3 Biomacromolecule-Gated Mesoporous Silica Drug Delivery Systems for Stimuli-Responsive Controlled Release 67Xuezhong Du 3.1 Introduction 68 3.2 Protein-Gated MSN Drug Delivery Systems 69 3.2.1 Ligand-Binding Protein-Gated MSN Systems 70 3.2.2 Metal-Chelating Protein-Gated MSN Systems 74 3.3 DNA-Gated MSN Drug Delivery Systems 75 3.3.1 Single-Stranded DNA-Gated MSN Systems 76 3.3.2 Double-Stranded DNA-Gated MSN Systems 77 3.3.3 Hairpin or Quadruplex DNA-Gated MSN Systems 80 3.3.4 Native DNA-Gated MSN Systems 83 3.3.5 Near-Infrared Light-Triggered DNA-Gated MSN Systems 87 3.4 Conclusions and Perspectives 89 Acknowledgments 90 References 90 4 Construction of Functional DNA Nanostructures for Theranostic Applications 93Jiang Li, Fan Li, Hao Pei, Lihua Wang, Qing Huang, and Chunhai Fan 4.1 The Progress of Structural DNA Nanotechnology 94 4.2 DNA Nanostructures for Diagnostics 96 4.3 DNA Nanostructures for Diagnostics on the Interface 96 4.4 Diagnostic in Homogeneous Solution 99 4.4.1 Spherical Nucleic Acids (SNA) Probes for Detections in Solution 99 4.4.2 Nanochips in Solution 100 4.4.3 Intracellular/In Vivo Diagnosis 103 4.5 DNA Nanostructures for Therapeutics 106 4.5.1 Delivery of Small-Molecular Drugs 107 4.5.2 Delivery of CpG DNAs 109 4.5.3 RNA Interference (RNAi) 111 4.5.4 Delivery of Proteins 114 4.6 Integration of Diagnosis and Therapy: Smart DNA Theranostic Nanodevices 115 4.7 Targeted Delivery 115 4.8 Controlled/Triggered Release 117 4.9 Summary and Perspectives 119 4.9.1 The Bioeffects of DNA Nanostructures 119 4.9.2 Purity and Yield 120 4.9.3 Dynamic Structures for Theranostic 120 References 121 Part 2: Imaging and Therapeutics 5 Dimercaptosuccinic Acid-Coated Magnetic Nanoparticles as a Localized Delivery System in Cancer Immunotherapy 133Raquel Mejías, Lucía Gutiérrez, María P. Morales, and Domingo F. Barber 5.1 Introduction 134 5.1.1 Nanoparticle-based Drug Delivery Systems 134 5.1.2 Nanoparticles for Drug Delivery in Cancer Treatment 135 5.1.3 Magnetic Nanoparticles (MNP) 135 5.1.4 Nanoparticle Biodistribution and Degradation 136 5.2 Nanoparticle Detection and Quantification: In Vitro and In Vivo Techniques 137 5.2.1 Optical Microscopy 137 5.2.2 Colorimetric Assays 137 5.2.3 Transmission Electron Microscopy 138 5.2.4 Magnetic Methods 140 5.2.5 Elemental Analysis 142 5.2.6 Nuclear Magnetic Resonance (NMR) 143 5.3 Evaluation of Nanoparticle-Induced Toxicity 143 5.3.1 In Vitro Toxicity 143 5.4 Magnetic Targeting of Nanoparticles 147 5.5 A Specific Example: DMSA-Coated Magnetic Nanoparticles 1485.5.1 In Vitro DMSA-MNP Uptake and Intracellular Localization 148 5.5.2 In Vitro DMSA-MNP Toxicity 149 5.5.3 In Vitro DMSA-MNP-Induced Cell Stress and Apoptosis 150 5.5.4 In Vivo DMSA-MNP Distribution 150 5.5.5 In Vivo DMSA-MNP-Induced Toxicity 152 5.5.6 In Vivo DMSA-MNP Biotransformation 152 5.6 Conclusions 153 Acknowledgments 154 References 154 6 Cardiovascular Nanomedicine 159Suryyani Deb and Hirak Kumar Patra 6.1 Introduction 160 6.2 Nanoscale Cardiovascular Diagnostics 160 6.2.1 Cardiac Molecular Biomarker Detection from Peripheral Blood 161 6.2.2 Diagnosis through Nano-based Molecular Imaging 163 6.2.3 Determination of Stem Cell Delivery 165 6.3 Nanotechnology in Cardiovascular Therapeutics 167 6.3.1 Drug Delivery 167 6.3.2 Gene Delivery 169 6.3.3 Tissue Engineering 169 6.4 Nanotechnology in the Surgery of Cardiovascular Disease 170 6.5 Conclusion 172 References 173 7 Chitosan-based Interpenetrating Polymeric Network Systems for Sustained Drug Release 183Amit Kumar Nayak and Dilipkumar Pal 7.1 Introduction 184 7.2 IPNs and Their Uses in Drug Delivery 185 7.3 Chitosan 187 7.4 Chitosan-Tamarind Seed Polysaccharide IPN Microparticles and Matrix Tablets for Sustained Release of Aceclofenac 189 7.5 Chitosan-Hydroxyethyl Cellulose IPN Microspheres of Isoniazid 193 7.6 Chitosan-Methyl Cellulose IPN Microspheres of Theophylline 194 7.7 Chitosan-Acrylamide-Grafted-Poly(Vinyl Alcohol) and Hydrolyzed Acrylamide-Grafted-Poly(Vinyl Alcohol) IPN Microgels of Cefadroxil 198 7.8 Chitosan-Poly(N-Isopropylacrylamide) IPN Discs of Diclofenac Sodium 199 7.9 Chitosan-Poly(Ethylene Oxide-Grafted-Acrylamide) Semi-IPN Hydrogel Microspheres of Capecitabine 200 7.10 Acrylamide-Grafted Dextran-Chitosan Semi-IPN Microspheres of Acyclovir 201 7.11 Chitosan-Acrylamide-Grafted Hydroxyethylcellulose Semi-IPN Microspheres of Diclofenac Sodium 202 7.12 Poly [N-Acryloylglycine-Chitosan] IPN Hydrogel of 5-Fluorouracil 202 7.13 Chitosan-N,N′-Dimethylacrylamide Semi-IPN Microspheres of Chlorothiazide 203 7.14 Conclusion 203 References 204 8 Nanocapsules in Biomedicine 209Frank J. Hernandez, Murat Kavruk, Luiza I. Hernandez, and Veli C. Ozalp 8.1 Nanocapsules: A Novel Nano-Drug Delivery System 210 8.2 Magic Bullets: Nanocapsules in Future Medicine 211 8.3 In Vitro Applications of Nanocapsules 212 8.3.1 Functionalized Mesoporous Silica Materials for Controlled Drug Delivery 212 8.3.2 Cationic Polymer Nanocapsules for Controlled Multi-drug Delivery 220 8.3.3 Lipid Nanocapsules 221 8.4 In Vivo Applications of Nanocapsules 224 8.4.1 In Vivo Diagnostic Imaging 225 8.4.2 In Vivo Therapeutics 226 8.5 Conclusions 228 References 228 9 Chitosan-based Polyelectrolyte Complexes 235Bojan Èalija, Nebojša Cekiæ, and Jela Miliæ 9.1 Introduction 236 9.2 Chitosans: Chemical Structure, Physicochemical Properties, and Toxicological and Regulatory Aspects 237 9.2.1 Chemical Structure and Source 237 9.2.2 Physicochemical Properties 238 9.2.3 Toxicological and Regulatory Aspects 239 9.3 Polyelectrolyte Complexes: Theoretical Background, Structure, and Basic Properties 240 9.4 Chitosan-based Polyelectrolyte Complexes in Particulate Drug Carriers 242 9.4.1 PECs Comprised of Chitosans and Natural or Semisynthetic Polyanions 243 9.4.2 PECs Comprised of Chitosans and Synthetic Polyanions 249 9.4.3 Influence of Chitosans Functional Properties and Experimental Conditions on Polyelectrolyte Complexation 254 9.5 Characterization of Chitosan-Based PECs and Chitosan-based PEC Particulate Drug Carriers 258 9.5.1 Size and Morphology 258 9.5.2 Zeta Potential 259 9.5.3 Structural Analysis 259 9.5.4 Encapsulation Efficiency and Drug Loading Capacity 261 9.5.5 In Vitro Swelling Studies 262 9.5.6 In Vitro Drug Release Studies 263 9.6 Conclusion 263 Acknowledgment 264 References 264 Part 3: Diagnostics and Featured Prognostics 10. Non-invasive Glucose Biosensors Based on Nanomaterials 273Farnoush Faridbod, Mohammad Reza Ganjali, Bagher Larijani and Parviz Norouzi 10.1 Diabetes and Its Prevalence 274 10.2 Importance of Glucose Monitoring 274 10.3 Glucose Measurement Methods 275 10.4 Non-invasive Glucose Determination 275 10.4.1 Non-invasive Glucose Determination Using Tissues 276 10.4.2 Non-invasive Glucose Determination Method Using Fluids 277 10.5 Glucose Biosensors 279 10.6 New Generation of Non-invasive Glucose Biosensors-Based Nanomaterials 281 10.7 Future Perspective in Glucose Monitoring 290 10.8 Conclusion 292 References 292 11 Self-Directed Assembly of Nanoparticles 297Arun Prakash Upadhyay, Dilip Kumar Behara, Gyan Prakash Sharma, Raj Ganesh S. Pala, and Sri Sivakumar 11.1 Introduction 297 11.2 Self-Assembly through Molecular Interactions/Forces 298 11.2.1 Van der Waals Interactions 298 11.2.2 Electrostatic Interaction 301 11.3 Hydrogen-Bonding Interactions 304 11.3.1 Covalent Interactions 306 11.3.2 DNA-Based Cross-Linking Interactions 311 11.4 Directed Self-Assembly by External Forces 315 11.4.1 Magnetic Field-Driven Directed Self-Assembly 315 11.4.2 Electric Field-Driven Directed Self-Assembly 319 11.4.3 Flow Field-Driven Directed Self-Assembly 321 11.5 Conclusion 325 Acknowledgment 326 References 326 Index 337

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Book SynopsisThis book is the first of its kind to discuss error estimation with a model-based approach. From the basics of classifiers and error estimators to distributional and Bayesian theory, it covers important topics and essential issues pertaining to the scientific validity of pattern classification.Table of ContentsPreface xiii Acknowledgments xix List of Symbols xxi 1 Classification 1 1.1 Classifiers 1 1.2 Population-Based Discriminants 3 1.3 Classification Rules 8 1.4 Sample-Based Discriminants 13 1.4.1 Quadratic Discriminants 14 1.4.2 Linear Discriminants 15 1.4.3 Kernel Discriminants 16 1.5 Histogram Rule 16 1.6 Other Classification Rules 20 1.6.1 k-Nearest-Neighbor Rules 20 1.6.2 Support Vector Machines 21 1.6.3 Neural Networks 22 1.6.4 Classification Trees 23 1.6.5 Rank-Based Rules 24 1.7 Feature Selection 25 Exercises 28 2 Error Estimation 35 2.1 Error Estimation Rules 35 2.2 Performance Metrics 38 2.2.1 Deviation Distribution 39 2.2.2 Consistency 41 2.2.3 Conditional Expectation 41 2.2.4 Linear Regression 42 2.2.5 Confidence Intervals 42 2.3 Test-Set Error Estimation 43 2.4 Resubstitution 46 2.5 Cross-Validation 48 2.6 Bootstrap 55 2.7 Convex Error Estimation 57 2.8 Smoothed Error Estimation 61 2.9 Bolstered Error Estimation 63 2.9.1 Gaussian-Bolstered Error Estimation 67 2.9.2 Choosing the Amount of Bolstering 68 2.9.3 Calibrating the Amount of Bolstering 71 Exercises 73 3 Performance Analysis 77 3.1 Empirical Deviation Distribution 77 3.2 Regression 79 3.3 Impact on Feature Selection 82 3.4 Multiple-Data-Set Reporting Bias 84 3.5 Multiple-Rule Bias 86 3.6 Performance Reproducibility 92 Exercises 94 4 Error Estimation for Discrete Classification 97 4.1 Error Estimators 98 4.1.1 Resubstitution Error 98 4.1.2 Leave-One-Out Error 98 4.1.3 Cross-Validation Error 99 4.1.4 Bootstrap Error 99 4.2 Small-Sample Performance 101 4.2.1 Bias 101 4.2.2 Variance 103 4.2.3 Deviation Variance, RMS, and Correlation 105 4.2.4 Numerical Example 106 4.2.5 Complete Enumeration Approach 108 4.3 Large-Sample Performance 110 Exercises 114 5 Distribution Theory 115 5.1 Mixture Sampling Versus Separate Sampling 115 5.2 Sample-Based Discriminants Revisited 119 5.3 True Error 120 5.4 Error Estimators 121 5.4.1 Resubstitution Error 121 5.4.2 Leave-One-Out Error 122 5.4.3 Cross-Validation Error 122 5.4.4 Bootstrap Error 124 5.5 Expected Error Rates 125 5.5.1 True Error 125 5.5.2 Resubstitution Error 128 5.5.3 Leave-One-Out Error 130 5.5.4 Cross-Validation Error 132 5.5.5 Bootstrap Error 133 5.6 Higher-Order Moments of Error Rates 136 5.6.1 True Error 136 5.6.2 Resubstitution Error 137 5.6.3 Leave-One-Out Error 139 5.7 Sampling Distribution of Error Rates 140 5.7.1 Resubstitution Error 140 5.7.2 Leave-One-Out Error 141 Exercises 142 6 Gaussian Distribution Theory: Univariate Case 145 6.1 Historical Remarks 146 6.2 Univariate Discriminant 147 6.3 Expected Error Rates 148 6.3.1 True Error 148 6.3.2 Resubstitution Error 151 6.3.3 Leave-One-Out Error 152 6.3.4 Bootstrap Error 152 6.4 Higher-Order Moments of Error Rates 154 6.4.1 True Error 154 6.4.2 Resubstitution Error 157 6.4.3 Leave-One-Out Error 160 6.4.4 Numerical Example 165 6.5 Sampling Distributions of Error Rates 166 6.5.1 Marginal Distribution of Resubstitution Error 166 6.5.2 Marginal Distribution of Leave-One-Out Error 169 6.5.3 Joint Distribution of Estimated and True Errors 174 Exercises 176 7 Gaussian Distribution Theory: Multivariate Case 179 7.1 Multivariate Discriminants 179 7.2 Small-Sample Methods 180 7.2.1 Statistical Representations 181 7.2.2 Computational Methods 194 7.3 Large-Sample Methods 199 7.3.1 Expected Error Rates 200 7.3.2 Second-Order Moments of Error Rates 207 Exercises 218 8 Bayesian MMSE Error Estimation 221 8.1 The Bayesian MMSE Error Estimator 222 8.2 Sample-Conditioned MSE 226 8.3 Discrete Classification 227 8.4 Linear Classification of Gaussian Distributions 238 8.5 Consistency 246 8.6 Calibration 253 8.7 Concluding Remarks 255 Exercises 257 A Basic Probability Review 259 A.1 Sample Spaces and Events 259 A.2 Definition of Probability 260 A.3 Borel-Cantelli Lemmas 261 A.4 Conditional Probability 262 A.5 Random Variables 263 A.6 Discrete Random Variables 265 A.7 Expectation 266 A.8 Conditional Expectation 268 A.9 Variance 269 A.10 Vector Random Variables 270 A.11 The Multivariate Gaussian 271 A.12 Convergence of Random Sequences 273 A.13 Limiting Theorems 275 B Vapnik–Chervonenkis Theory 277 B.1 Shatter Coefficients 277 B.2 The VC Dimension 278 B.3 VC Theory of Classification 279 B.3.1 Linear Classification Rules 279 B.3.2 kNN Classification Rule 280 B.3.3 Classification Trees 280 B.3.4 Nonlinear SVMs 281 B.3.5 Neural Networks 281 B.3.6 Histogram Rules 281 B.4 Vapnik–Chervonenkis Theorem 282 C Double Asymptotics 285 Bibliography 291 Author index 301 Subject index 305

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Book SynopsisOver 170 contributions (invited talks, oral presentations, and posters) were presented by participants from universities, research institutions, and industry, which offered interdisciplinary discussions indicating strong scientific and technological interest in the field of nanostructured systems. This issue contains 23 peer-reviewed papers that cover various aspects and the latest developments related to nanoscaled materials and functional ceramics.Table of ContentsPreface ix Introduction xi MULTIFUNCTIONAL MATERIALS Oxynitride Glasses as Grain Boundary Phases in Silicon Nitride: Correlations of Chemistry and Properties 3Stuart Hampshire Preparation and Properties of Aluminosilicate Glasses Containing N and F 15Michael J. Pomeroy Comparison of Conventional and Microwave Sintering of Bioceramics 23Anne Leriche, Etienne Savary, Anthony Thuault, Jean-Christophe Hornez, Michel Descamps, and Sylvain Marinel A Novel Additive Manufacturing Technology for High-Performance Ceramics 33Johannes Homa and Martin Schwentenwein Characterization of Matrix Materials for Additive Manufacturing of Silicon Carbide-Based Composites 41Mrityunjay Singh, Michael C. Halbig, and Shirley X. Zhu An Industrial Microwave (Hybrid) System for In-Line Processing of High Temperature Ceramics 49Ramesh D. Peelamedu and Donald A. Seccombe Jr. Comparison of Properties of YSZ Prepared by Microwave and Conventional Processing 61Kanchan L. Singh, Anirudh P. Singh, Ajay Kumar, and S.S. Sekhon Diffusion Bonding and Interfacial Characterization of Sintered Fiber Bonded Silicon Carbide Ceramics using Boron–Molybdenum Interlayers 73H. Tsuda, S. Mori, M. C. Halbig, M. Singh, and R. Asthana Mechanical Behavior of Green Ceramic Tapes used in a Viscoelastic Shaping Process 81Ming-Jen Pan, Stephanie Wimmer, and Virginia DeGiorgi Mechanical Behavior of Foamed Insulating Ceramics 89Vania R. Salvini, Dirceu Spinelli, and Victor C. Pandolfelli Stress Estimation for Multiphase Ceramics Laminates during Sintering 101Kouichi Yasuda,Tadachika Nakayama, and Satoshi Tanaka Advanced Measurements of Indentation Fracture Resistance of Alumina by the Powerful Optical Microscopy for Small Ceramic Products 107Hiroyuki Miyazaki and Yu-ichi Yoshizawa The Microstructure and Dielectric Properties of Sm2O3 Doped Ba0.6Sr0.4TiO3-MgO Compound for Phase Shifters 115Xiaohong Wang, Mengjie Wang, and Wenzhong Lu Dielectric Properties of BaTiO3 Ceramics and Curie-Weiss and Modified Curie-Weiss Affected by Fractal Morphology 123 NANOSTRUCTURED MATERIALS Understanding Diamond Nanoparticle Evolution during Zirconia Spark Plasma Sintering 137Kathy Lu, Wenle Li, and George Li Influence of Ti4+ on the Energetics and Microstructure of SnO2 Nanoparticles 145Joice Miagava, Douglas Gouvêa, Ricardo H. R. Castro, and Alexandra NavrotskyAnnealing Effect on the Structural, Morphological, and Photovoltaic Properties of ZnO-CNTs Nanocomposite Thin Films 153Huda Abdullah, Azimah Omar, Izamarlina Asshaari, Mohd Ambar Yarmo, Mohd Zikri Razali, Sahbudin Shaari, Savisha Mahalingam, and Aisyah Bolhan Investigation of Multilayer Superhard Ti-Hf-Si-N/NbN/Al2O3 Coatings for High Performance Protection 163A. D. Pogrebnjak, A. S. Kaverina, V. M. Beresnev, Y. Takeda, K. Oyoshi, H. Murakami, A. P. Shypylenko, M. G. Kovaleva, M.S. Prozorova, O. V. Kolisnichenko, B. Zholybekov, and D. A. Kolesnikov Influence of the Structure and Elemental Composition on the Physical and Mechanical Properties of (TiZrHfVNb)N Nanostructured Coatings 173A. D. Pogrebnjak, I. V. Yakushchenko, O. V. Bondar, A. A. Bagdasaryan, V. M. Beresnev, D.A. Kolesnikov, G. Abadias, P. Chartier, Y. Takeda, and M. O. Bilokur Effects of Mg Contents on ZnAl2O4 Thin Films by Sol Gel Method and Its Application 185Huda Abdullah, Wan Nasarudin Wan Jalal, Mohd Syafiq Zulfakar, Badariah Bais, Sahbudin Shaari, Mohammad Tariqul Islam, and Sarada Idris Synthesis and Characterization of Si-Doped Carbon Nanotubes 197Qi Zhen, Shaoming Dong, Yanmei Kan, Yue Leng, Jianbao Hu Structural and Morphology of Zn1-xCuxS Films as Anti-Reflecting Coating (ARC) Affected the Cell Performance 205Huda Abdullah, Ili Salwani, and Sahbudin Saari Nanoceramics Processing: Revolutionizing Medicine 213Qi Wang and Thomas J. Webster Author Index 219

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Book SynopsisA collection of 15 papers from The American Ceramic Society's 38th International Conference on Advanced Ceramics and Composites, held in Daytona Beach, Florida, January 26-31, 2014. This issue includes papers presented in Symposium 5 - Next Generation Bioceramics and Biocomposites and Symposium 9 - Porous Ceramics: Novel Developments and Applications.Table of ContentsPreface vii Introduction ix BIOCERAMICS Influence of the Hydroxyapatite Powder Properties on Its Properties Rheology Behavior 3Y.M.Z. Ahmed, S.M. El-Sheikh, and Z.I. Zaki Nanostructural Ca-Aluminate Based Biomaterials—An Overview 13Leif Hermansson and Jesper Lööf Antimicrobial Effects of Formable Gelatinous Hydroxyapatite-Calcium Silicate Nanocomposites for Biomedical Applications 25Hsin Chen, Dong-Joon Lee, He Zhang, Roland Arnold, and Ching-Chang Ko Use of Inter-Fibril Spaces among Electrospun Fibrils as Ion-Fixation and Nano-Crystallization 33Yuki Shirosaki, Satoshi Hayakawa, Yuri Nakamura, Hiroki Yoshihara, Akiyoshi Osaka, and Artemis Stamboulis Fractographic Analysis of Broken Ceramic Dental Restorations 39G. D. Quinn In Vivo Evaluation of Scaffolds with a Grid-Like Microstructure Composed of a Mixture of Silicate (13-93) and Borate (13-93B3) Bioactive Glasses 53Yifei Gu, Wenhai Huang, and Mohamed N. Rahaman Osteoconductive and Osteoinductive Implants Composed of Hollow Hydroxyapatite Microspheres 65Mohamed N. Rahaman, Wei Xiao, Yongxing Liu, and B. Sonny Bal Deposition of Amorphous CaP on Pure Titanium in DMEM at 37°C 81A. Cuneyt Tas One-Pot Synthesis of Monodisperse Nanospheres of Amorphous Calcium Phosphate (ACP) in a Simple Biomineralization Medium 93A. Cuneyt Tas POROUS CERAMICS Determination of Elastic Moduli for Porous SOFC Cathode Films using Nanoindentation and FEM 111Zhangwei Chen, Finn Giuliani, and Alan Atkinson Mechanical Modeling of Microcracked Porous Ceramics 129Ray S. Fertig III and Seth Nickerson Synthesis and Characterization of Aerogel Glass Materials for Window Glazing Applications 141Tao Gao, Bjørn Petter Jelle, Arild Gustavsen, and Jianying He Reticulated Ceramics under Bending: The Non-Linear Regime before Their Catastrophic Failure 151Ehsan Rezaei, Giovanni Bianchi, Alberto Ortona, and Sandro Gianella Novel Low Temperature Ceramics for CO2 Capture 165Hutha Sarma and Steven Ogunwumi Effects of SiC Particle Size and Sintering Temperature on Microstructure of Porous SiC Ceramics Based on In-Situ Grain Growth 173Katsumi Yoshida, Chin-Chet See, Satoshi Yokoyama, and Toyohiko Yano Author Index 185

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Book SynopsisPolymers are one of the most fascinating materials of the present era finding their applications in almost every aspects of life. Polymers are either directly available in nature or are chemically synthesized and used depending upon the targeted applications.Advances in polymer science and the introduction of new polymers have resulted in the significant development of polymers with unique properties. Different kinds of polymers have been and will be one of the key in several applications in many of the advanced pharmaceutical research being carried out over the globe. This 4-partset of books contains precisely referenced chapters, emphasizing different kinds of polymers with basic fundamentals and practicality for application in diverse pharmaceutical technologies. The volumes aim at explaining basics of polymers based materials from different resources and their chemistry along with practical applications which present a future direction in the pharmaceutical industry. EachTable of ContentsPreface xix 1 Bioactive Polysaccharides of Vegetable and Microbial Origins: An Overview 1 Giuseppina Tommonaro, Annarita Poli, Paola Di Donato, Roberto Abbamondi Gennaro, Ilaria Finore and Barbara Nicolaus 1.1 Introduction 1 1.2 Anticarcinogenic Polysaccharides 3 1.3 Anti-inflammatory/Immunostimulating Polysaccharides 8 1.4 Antiviral Polysaccharides 13 1.5 Antioxidant Polysaccharides 17 1.6 Other Biotechnological Applications 21 1.7 Conclusions and Future Perspectives 23 Acknowledgments 23 Reference 24 2 Chitosan: An Emanating Polymeric Carrier for Drug Delivery 33 Priti Girotra and Shailendra Kumar Singh 2.1 Introduction 33 2.2 Preparation of Chitosan 34 2.3 Physicochemical Properties of Chitosan 35 2.4 Biological Activities of Chitosan 36 2.5 Pharmaceutical Applications of Chitosan 39 2.6 Functionalization of Chitosan 49 2.7 Conclusion and Future Perspectives 49 Reference 51 3 Fungi as Sources of Polysaccharides for Pharmaceutical and Biomedical Applications 61 Filomena Freitas, Christophe Roca and Maria A. M. Reis 3.1 Introduction 61 3.2 The Fungal Cell 62 3.3 Polysaccharides Produced by Fungi 69 3.4 Production and Extraction of Polysaccharides from Fungi 77 3.5 Fungal Polysaccharides in Biomedical and Pharmaceutical Applications 81 3.6 Commercial Exploitation of Fungal Polysaccharides in Biomedical and Pharmaceutical Applications 89 3.7 Conclusion and Future Perspective 91 Reference 91 4 Environmentally Responsive Chitosan-based Nanocarriers (CBNs) 105 Ankit Jain and Sanjay K. Jain 4.1 Introduction 105 4.2 Graft Copolymerized CBNs 107 4.3 pH-Sensitive CBNs 109 4.4 Thermosensitive CBNs 111 4.5 pH-Sensitive and Thermosensitive CBNs 112 4.6 pH- and Ionic-Sensitive CBNs 113 4.7 Photosensitive CBNs 114 4.8 Electrical-Sensitive CBNs 115 4.9 Magneto-Responsive CBNs 115 4.10 Chemo-Sensitive CBNs 115 4.11 Biodegradation of Chitosan and Its Derivatives 116 4.12 Toxicity of CBNs 120 4.13 Conclusions and Future Perspectives 120 References 120 5 Biomass Derived and Biomass Inspired Polymers in Pharmaceutical Applications 127 Elisavet D. Bartzoka, Claudia Crestini and Heiko Lange 5.1 Introduction 127 5.2 Biodegradable Polymers in Biomedical Applications – Relevant Aspects 129 5.3 Biodegradable Natural Polymers in Pharmaceutical Applications 133 5.4 Micro- and Nanocrystalline Natural Polymers and Fibrils – General Regulative Considerations 175 5.5 Concluding Remarks and Outlook 176 Reference 177 6 Modification of Cyclodextrin for Improvement of Complexation and Formulation Properties 205 Tapan K. Dash and V. Badireenath Konkimalla Abbreviations 205 6.1 Introduction 206 6.2 Cyclodextrin and Its Degradation 206 6.3 Complexation by CDs and Release 207 6.4 Modifications and Scope with Respect to Pharmaceutical Application 208 6.5 Concluding Remarks 218 Acknowledgements 218 Reference 218 7 Cellulose-, Ethylene Oxide- and Acrylic-Based Polymers in Assembled Module Technology (Dome Matrix®) 225 Camillo Benetti, Paolo Colombo and Tin Wui Wong 7.1 Dome MatrixR Technology 225 7.2 Polymers for Controlled Drug Release 228 7.3 Cellulose Derivatives 230 7.4 Acrylic Acid Polymers 232 7.5 Polymethacrylates 234 7.6 Polyethylene Oxide 236 7.7 Conclusions 237 Acknowledgments 237 Reference 237 8 Structured Biodegradable Polymers for Drug Delivery 243 Nishi Mody, Udita Agrawal, Rajeev Sharma and S. P. Vyas 8.1 Introduction 243 8.2 Classification 249 8.3 Degradation Processes in Biodegradable Polymers 254 8.4 Responsive Stimuli-Sensitive Polymers 260 8.5 Conclusion and Future Prospects 271 References 271 9 Current State of the Potential Use of Chitosan as Pharmaceutical Excipient 275 A. Raquel Madureira, Bruno Sarmento and Manuela Pintado 9.1 The World of Pharmaceutical Excipients 275 9.2 Chitosan 276 9.3 Activities Found for Chitosan 277 9.4 Properties of Chitosan 280 9.5 Applications as a Pharmaceutical Excipient 282 9.6 Conclusion 289 References 290 10 Modification of Gums: Synthesis Techniques and Pharmaceutical Benefits 299 Vikas Rana, Sunil Kamboj, Radhika Sharma and Kuldeep Singh 10.1 Introduction 299 10.2 Synthesis of Modified Gums 302 10.3 Characterization 320 10.4 Pharmaceutical Applications of Modified Gums 332 10.5 Conclusion and Future Prospective 354 Reference 355 11 Biomaterials for Functional Applications in the Oral Cavity via Contemporary Multidimensional Science 365 V. Tamara Perchyonok, Vanessa Reher, Nicolaas Basson and Sias Grobler 11.1 Introduction 365 11.2 Free Radical Formation, Antioxidants and Relevance in Health 366 11.3 Oral Diseases: Oxidative Stress and the Role of Antioxidant Defenses in the Oral Cavity 369 11.4 Biomaterials and Intelligent Design of Functional Biomaterials 371 11.5 In-Vitro Developments of Free Radical Defense Mechanisms and Drug-Delivery Systems 372 11.6 Practical In-Vitro Applications of Chitosan-Based Functional Biomaterial Prototypes in Dentistry 375 11.7 Conclusion 398 References 399 12 Role of Polymers in Ternary Drug Cyclodextrin Complexes 413 Renu Chadha, Madhu Bala, Parnika, Kunal Chadha and Maninder Karan 12.1 Introduction 413 12.2 Cyclodextrins (Cycloamyloses, Cyclomaltoses, Schardinger Dextrins) 414 12.3 Role of Biodegradable/Water-Soluble Polymers in Efficacy of Inclusion Complexes 416 12.4 Solubility, Dissolution and Bioavailability Enhancement: Case Studies 423 12.5 Conclusion 433 References 433 13 Collagen-Based Materials for Pharmaceutical Applications 439 Daniela Pamfil, Manuela Tatiana Nistor and Cornelia Vasile 13.1 Introduction 439 13.2 Collagen Structure and Its Properties 440 13.3 Preparation Methods of Collagen-Based Biomaterials 443 13.4 Pharmaceutical Applications of Collagen-Based Products 450 13.5 Concluding Remarks and Future Perspectives 462 Acknowledgments 468 References 468 14 Natural Polysaccharides as Pharmaceutical Excipients 483 Nazire Deniz Yılmaz, Gülbanu Koyundereli Çılgı and Kenan Yılmaz 14.1 Introduction 483 14.2 Natural Polysaccharides 485 14.3 Conclusion 510 Reference 510 15 Structure, Chemistry and Pharmaceutical Applications of Biodegradable Polymers 517 Mazhar Ul-Islam, Shaukat Khan, Muhammad Wajid Ullah and Joong Kon Park 15.1 Introduction 517 15.2 History of Polymers 518 15.3 Concept of Biodegradability 522 15.4 Biodegradable Polymers and Their Classification 522 15.5 Biocompatibility of Biodegradable Polymers 528 15.6 Biodegradable Polymers in Pharmaceutical Applications 530 15.7 Development of Various Biodegradable Polymer Systems for Drug Delivery 532 15.8 Future Prospects 535 Acknowledgment 536 Reference 536 16 Preparation and Properties of Biopolymers: A Critical Review 541 Selvaraj Mohana Roopan, T. V. Surendra and G. Madhumitha 16.1 Introduction 541 16.2 Nature of Biopolymers 543 16.3 Common Biopolymers 544 16.4 Biopolymers in Drug Development 545 16.5 Biobased Polymers Production 548 16.6 Properties of Biopolymers 551 Acknowledgement 553 Reference 553 17 Engineering Biodegradable Polymers to Control Their Degradation and Optimize Their Use as Delivery and Theranostic Systems 557 Ilaria Armentano, Loredana Latterini, Nicoletta Rescignano, Luigi Tarpani, Elena Fortunati and Josè Maria Kenny 17.1 Introduction 557 17.2 Nanotechnology 559 17.3 Nanostructured Biodegradable Polymers 560 17.4 Design Strategies for Fluorescent Biodegradable Polymeric Systems 566 17.5 Conclusions and Perspectives 570 Reference 570 Index 577

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Book SynopsisProvides comprehensive coverage of the research into and clinical uses of bioceramics and biocomposites Developments related to bioceramics and biocomposites appear to be one the most dynamic areas in the field of biomaterials, with multiple applications in tissue engineering and medical devices. This book covers the basic science and engineering of bioceramics and biocomposites for applications in dentistry and orthopedics, as well as the state-of-the-art aspects of biofabrication techniques, tissue engineering, remodeling, and regeneration of bone tissue. It also provides insight into the use of bionanomaterials to create new functionalities when interfaced with biological molecules or structures. Featuring contributions from leading experts in the field, Bioceramics and Biocomposites: From Research to Use in Clinical Practice offers complete coverage of everything from extending the concept of hemopoietic and stromal niches, to the evolution of bioceraTable of ContentsChapter 1. Multi-functionalized ferri-liposomes for hyperthermia induced glioma targeting and brain drug deliveryDi Shi, Gujie Mi, and Thomas J Webste Chapter 2. Biofabrication techniques for ceramics and composite bone scaffoldsFengyuan Liu, Boyang Huang, Sri Hinduja, Paulo Jorge da Silva Bartolo Chapter 3. Developments in hydrogel-based scaffolds and bioceramics for bone regenerationIzabela-Cristina Stancu, Daniel Chappard Chapter 4. Zirconia-based composites for biomedical applicationsPaula Palmero Chapter 5. Bioceramics derived from marble and sea shells as potential bone substitution materialsMiculescu Florin, Mocanu Aura Cătălina, Stan GE, Maidaniuc Andreea, Miculescu Marian, Voicu Stefan Ioan, Antoniac Iulian Chapter 6. Bioglasses and glass-ceramics in the Na2O-CaO-MgO-SiO2-P2O5-CaF2 systemS. Agathopoulos and D.U. Tulyaganov Chapter 7. Electrical functionalization and fabrication of nanostructured hydroxyapatite coatingsVladimir Bystrov, Anna Bystrova, Yuri Dekhtyar, Igor Khlusov, Vladimir Pichugin, Konstantin Prosolov, Yurii Sharkeev Chapter 8. Bioactive microarc calcium phosphate coatings on nanostructured and ultrafine-grained bioinert metals and alloysYurii Sharkeev, Ekaterina Komarova, Maria Sedelnikova, Igor Khlusov, Anna Eroshenko, Larisa Litvinova, Valeria Shupletsova Chapter 9. Engineering of bioceramics- based scaffold and its clinical applications in dentistryIka Dewi Ana Chapter 10. Bioceramics in endodonticsAlexandru Andrei Iliescu, Paula Perlea, Gabriel Tulus, Mihaela Georgiana Iliescu, Irina Maria Gheorghiu, Horia Octavian Manolea Chapter 11. Extending the concept of hemopoietic and stromal niches as an approach to regenerative medicineIgor A. Khlusov and Marina Yu. Khlusova Chapter 12. Experimental and pilot clinical study of different tissue-engineered bone grafts based on calcium phosphate, mesenchymal stem cells and adipose-derived stromal vascular fractionI.Y. Bozo, G.A. Volozhin, V.L. Zorin, R.V. Deev, S.I. Rozhkov, P.S. Eremin, E.N. Toropov, A.A. Pulin, B.I. Grachev, I.I. Eremin, V.S. Komlev Chapter 13. Bone substitutes in orthopedic and trauma surgeryLupescu Olivera, Antoniac Iulian

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Book SynopsisA guide to common control principles and how they are used to characterize a variety of physiological mechanisms The second edition of Physiological Control Systems offers an updated and comprehensive resource that reviews the fundamental concepts of classical control theory and how engineering methodology can be applied to obtain a quantitative understanding of physiological systems. The revised text also contains more advanced topics that feature applications to physiology of nonlinear dynamics, parameter estimation methods, and adaptive estimation and control. The authora noted expert in the fieldincludes a wealth of worked examples that illustrate key concepts and methodology and offers in-depth analyses of selected physiological control models that highlight the topics presented. The author discusses the most noteworthy developments in system identification, optimal control, and nonlinear dynamical analysis and targets recent bioengineering advances.Table of ContentsPreface xiii About the Companion Website xvii 1 Introduction 1 1.1 Preliminary Considerations, 1 1.2 Historical Background, 2 1.3 Systems Analysis: Fundamental Concepts, 4 1.4 Physiological Control Systems Analysis: A Simple Example, 6 1.5 Differences Between Engineering and Physiological Control Systems, 8 1.6 The Science (and Art) of Modeling, 11 1.7 “Systems Physiology” Versus “Systems Biology”, 12 Problems, 13 Bibliography, 15 2 Mathematical Modeling 17 2.1 Generalized System Properties, 17 2.2 Models with Combinations of System Elements, 21 2.3 Linear Models of Physiological Systems: Two Examples, 24 2.4 Conversions Between Electrical and Mechanical Analogs, 27 2.5 Distributed-Parameter Versus Lumped-Parameter Models, 29 2.6 Linear Systems and the Superposition Principle, 31 2.7 Zero-Input and Zero-State Solutions of ODEs, 33 2.8 Laplace Transforms and Transfer Functions, 34 2.8.1 Solving ODEs with Laplace Transforms, 36 2.9 The Impulse Response and Linear Convolution, 38 2.10 State-Space Analysis, 40 2.11 Computer Analysis and Simulation: MATLAB and SIMULINK, 43 Problems, 49 Bibliography, 53 3 Static Analysis of Physiological Systems 55 3.1 Introduction, 55 3.2 Open-Loop Versus Closed-Loop Systems, 56 3.3 Determination of the Steady-State Operating Point, 59 3.4 Steady-State Analysis Using SIMULINK, 63 3.5 Regulation of Cardiac Output, 66 3.5.1 The Cardiac Output Curve, 67 3.5.2 The Venous Return Curve, 69 3.5.3 Closed-Loop Analysis: Heart and Systemic Circulation Combined, 73 3.6 Regulation of Glucose Insulin, 74 3.7 Chemical Regulation of Ventilation, 78 3.7.1 The Gas Exchanger, 80 3.7.2 The Respiratory Controller, 82 3.7.3 Closed-Loop Analysis: Lungs and Controller Combined, 82 Problems, 86 Bibliography, 91 4 Time-Domain Analysis of Linear Control Systems 93 4.1 Linearized Respiratory Mechanics: Open-Loop Versus Closed-Loop, 93 4.2 Open-Loop Versus Closed-Loop Transient Responses: First-Order Model, 96 4.2.1 Impulse Response, 96 4.2.2 Step Response, 97 4.3 Open-Loop Versus Closed-Loop Transient Responses: Second-Order Model, 98 4.3.1 Impulse Responses, 98 4.3.2 Step Responses, 103 4.4 Descriptors of Impulse and Step Responses, 107 4.4.1 Generalized Second-Order Dynamics, 107 4.4.2 Transient Response Descriptors, 111 4.5 Open-Loop Versus Closed-Loop Dynamics: Other Considerations, 114 4.5.1 Reduction of the Effects of External Disturbances, 114 4.5.2 Reduction of the Effects of Parameter Variations, 115 4.5.3 Integral Control, 116 4.5.4 Derivative Feedback, 118 4.5.5 Minimizing Effect of External Disturbances by Feedforward Gain, 119 4.6 Transient Response Analysis Using MATLAB, 121 4.7 SIMULINK Application 1: Dynamics of Neuromuscular Reflex Motion, 122 4.7.1 A Model of Neuromuscular Reflex Motion, 122 4.7.2 SIMULINK Implementation, 126 4.8 SIMULINK Application 2: Dynamics of Glucose–Insulin Regulation, 127 4.8.1 The Model, 127 4.8.2 Simulations with the Model, 131 Problems, 131 Bibliography, 135 5 Frequency-Domain Analysis of Linear Control Systems 137 5.1 Steady-State Responses to Sinusoidal Inputs, 137 5.1.1 Open-Loop Frequency Response, 137 5.1.2 Closed-Loop Frequency Response, 141 5.1.3 Relationship between Transient and Frequency Responses, 143 5.2 Graphical Representations of Frequency Response, 145 5.2.1 Bode Plot Representation, 145 5.2.2 Nichols Charts, 147 5.2.3 Nyquist Plots, 148 5.3 Frequency-Domain Analysis Using MATLAB and SIMULINK, 152 5.3.1 Using MATLAB, 152 5.3.2 Using SIMULINK, 154 5.4 Estimation of Frequency Response from Input–Output Data, 156 5.4.1 Underlying Principles, 156 5.4.2 Physiological Application: Forced Oscillation Technique in Respiratory Mechanics, 157 5.5 Frequency Response of a Model of Circulatory Control, 159 5.5.1 The Model, 159 5.5.2 Simulations with the Model, 160 5.5.3 Frequency Response of the Model, 162 Problems, 164 Bibliography, 165 6 Stability Analysis: Linear Approaches 167 6.1 Stability and Transient Response, 167 6.2 Root Locus Plots, 170 6.3 Routh–Hurwitz Stability Criterion, 174 6.4 Nyquist Criterion for Stability, 176 6.5 Relative Stability, 181 6.6 Stability Analysis of the Pupillary Light Reflex, 184 6.6.1 Routh–Hurwitz Analysis, 186 6.6.2 Nyquist Analysis, 187 6.7 Model of Cheyne–Stokes Breathing, 190 6.7.1 CO2 Exchange in the Lungs, 190 6.7.2 Transport Delays, 192 6.7.3 Controller Responses, 193 6.7.4 Loop Transfer Functions, 193 6.7.5 Nyquist Stability Analysis Using MATLAB, 194 Problems, 196 Bibliography, 198 7 Digital Simulation of Continuous-Time Systems 199 7.1 Preliminary Considerations: Sampling and the Z-Transform, 199 7.2 Methods for Continuous-Time to Discrete-Time Conversion, 202 7.2.1 Impulse Invariance, 202 7.2.2 Forward Difference, 203 7.2.3 Backward Difference, 204 7.2.4 Bilinear Transformation, 205 7.3 Sampling, 207 7.4 Digital Simulation: Stability and Performance Considerations, 211 7.5 Physiological Application: The Integral Pulse Frequency Modulation Model, 216 Problems, 221 Bibliography, 224 8 Model Identification and Parameter Estimation 225 8.1 Basic Problems in Physiological System Analysis, 225 8.2 Nonparametric and Parametric Identification Methods, 228 8.2.1 Numerical Deconvolution, 228 8.2.2 Least-Squares Estimation, 230 8.2.3 Estimation Using Correlation Functions, 233 8.2.4 Estimation in the Frequency Domain, 235 8.2.5 Optimization Techniques, 237 8.3 Problems in Parameter Estimation: Identifiability and Input Design, 243 8.3.1 Structural Identifiability, 243 8.3.2 Sensitivity Analysis, 244 8.3.3 Input Design, 248 8.4 Identification of Closed-Loop Systems: “Opening the Loop”, 252 8.4.1 The Starling Heart–Lung Preparation, 253 8.4.2 Kao’s Cross-Circulation Experiments, 253 8.4.3 Artificial Brain Perfusion for Partitioning Central and Peripheral Chemoreflexes, 255 8.4.4 The Voltage Clamp, 256 8.4.5 Opening the Pupillary Reflex Loop, 257 8.4.6 Read Rebreathing Technique, 259 8.5 Identification Under Closed-Loop Conditions: Case Studies, 260 8.5.1 Minimal Model of Blood Glucose Regulation, 262 8.5.2 Closed-Loop Identification of the Respiratory Control System, 267 8.5.3 Closed-Loop Identification of Autonomic Control Using Multivariate ARX Models, 273 8.6 Identification of Physiological Systems Using Basis Functions, 276 8.6.1 Reducing Variance in the Parameter Estimates, 276 8.6.2 Use of Basis Functions, 277 8.6.3 Baroreflex and Respiratory Modulation of Heart Rate Variability, 279 Problems, 283 Bibliography, 285 9 Estimation and Control of Time-Varying Systems 289 9.1 Modeling Time-Varying Systems: Key Concepts, 289 9.2 Estimation of Models with Time-Varying Parameters, 293 9.2.1 Optimal Estimation: The Wiener Filter, 293 9.2.2 Adaptive Estimation: The LMS Algorithm, 294 9.2.3 Adaptive Estimation: The RLS Algorithm, 296 9.3 Estimation of Time-Varying Physiological Models, 300 9.3.1 Extending Adaptive Estimation Algorithms to Other Model Structures, 300 9.3.2 Adaptive Estimation of Pulmonary Gas Exchange, 300 9.3.3 Quantifying Transient Changes in Autonomic Cardiovascular Control, 304 9.4 Adaptive Control of Physiological Systems, 307 9.4.1 General Considerations, 307 9.4.2 Adaptive Buffering of Fluctuations in Arterial PCO2, 308 Problems, 313 Bibliography, 314 10 Nonlinear Analysis of Physiological Control Systems 317 10.1 Nonlinear Versus Linear Closed-Loop Systems, 317 10.2 Phase-Plane Analysis, 320 10.2.1 Local Stability: Singular Points, 322 10.2.2 Method of Isoclines, 325 10.3 Nonlinear Oscillators, 329 10.3.1 Limit Cycles, 329 10.3.2 The van der Pol Oscillator, 329 10.3.3 Modeling Cardiac Dysrhythmias, 336 10.4 The Describing Function Method, 342 10.4.1 Methodology, 342 10.4.2 Application: Periodic Breathing with Apnea, 345 10.5 Models of Neuronal Dynamics, 348 10.5.1 The Hodgkin–Huxley Model, 349 10.5.2 The Bonhoeffer–van der Pol Model, 352 10.6 Nonparametric Identification of Nonlinear Systems, 359 10.6.1 Volterra–Wiener Kernel Approach, 360 10.6.2 Nonlinear Model of Baroreflex and Respiratory Modulated Heart Rate, 364 10.6.3 Interpretations of Kernels, 367 10.6.4 Higher Order Nonlinearities and Block-Structured Models, 369 Problems, 370 Bibliography, 374 11 Complex Dynamics in Physiological Control Systems 377 11.1 Spontaneous Variability, 377 11.2 Nonlinear Control Systems with Delayed Feedback, 380 11.2.1 The Logistic Equation, 380 11.2.2 Regulation of Neutrophil Density, 384 11.2.3 Model of Cardiovascular Variability, 387 11.3 Coupled Nonlinear Oscillators: Model of Circadian Rhythms, 397 11.4 Time-Varying Physiological Closed-Loop Systems: Sleep Apnea Model, 401 11.5 Propagation of System Noise in Feedback Loops, 409 Problems, 415 Bibliography, 416 Appendix A Commonly Used Laplace Transform Pairs 419 Appendix B List of MATLAB and SIMULINK Programs 421 Index 425

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Book SynopsisThis volume incorporates 13 contributions from renowned experts from the relevant research fields that are related biodegradable and biobased polymers and their environmental and biomedical applications. Specifically, the book highlights: Developments in polyhydroxyalkanoates applications in agriculture, biodegradable packaging material and biomedical field like drug delivery systems, implants, tissue engineering and scaffolds The synthesis and elaboration of cellulose microfibrils from sisal fibres for high performance engineering applications in various sectors such as the automotive and aerospace industries, or for building and construction The different classes and chemical modifications of tannins Electro-activity and applications of Jatropha latex and seed The synthesis, properties and applications of poly(lactic acid) The synthesis, processing and properties of poly(butylene succinate), its copolymers, coTable of ContentsPreface xvii 1 Biomedical Applications for Thermoplastic Starch 1 Antonio José Felix de Carvalho and Eliane Trovatti 1.1 Starch as Source of Material in the Polymer Industry 1 1.2 Starch in Plastic Material and Thermoplastic Starch 2 1.3 Uses of Starch and TPS in Biomedical and Pharmaceutical Fields 5 1.3.1 Native Starch (Granule) as Pharmaceutical Excipient 6 1.3.2 Gelatinized and Thermoplastic Starch in Biomedical Application 6 1.3.3 Starch-based Scaffolds 10 1.3.4 Starch-based Biosorbable Materials - Degradation Inside Human Body 12 1.3.5 Cell Response to Starch and Its Degradation Products 15 1.4 Conclusion and Future Perspectives for Starch-based Polymers 16 Acknowledgment 16 References 16 2 Polyhydroxyalkanoates: The Application of Eco-Friendly Materials 25 G.V.N. Rathna, Bhagyashri S. Thorat Gadgil and Naresh Killi 2.1 Introduction 25 2.2 Natural Occurrence 26 2.3 Bio-Synthetic/ Semi-Synthetic Approach 29 2.4 Environmental Aspects 31 2.5 Applications 33 2.6 Biomedical Applications 33 2.6.1 Drug Delivery 34 2.6.2 Implants and Scaffolds 36 2.7 Biodegradable Packaging Material 38 2.8 Agriculture 44 2.9 Other Applications 45 2.10 Scope of PHAs 46 2.11 Conclusions 46 References 47 3 Cellulose Microfibrils from Natural Fiber Reinforced Biocomposites and its Applications 55 Atul P Johari, Smita Mohanty and Sanjay K Nayak 3.1 Introduction 55 3.1.1 Industrial Applications 57 3.2 Natural Fibers: Applications and Limitations 58 3.3 Plant-based Fibers 59 3.4 Chemical Composition, structure and Properties of Sisal Fiber 60 3.4.1 Cellulose Fibers 61 3.4.2 Hemicellulose 61 3.4.3 Lignin 62 3.4.4 Pectin 63 3.4.5 Bio-based and Biodegradable Polymers 63 3.5 Biocomposites 64 3.6 Classification of Biocomposites 65 3.6.1 Green Composites 65 3.6.2 Hybrid Composites 66 3.7 Biocomposites of CMF Reinforced of Poly (lactic acid) 67 3.7.1 Extraction of Cellulose Microfibrils from Sisal Fiber 67 3.7.2 CMF Extraction Process 69 3.7.3 Fabrication of PLA/CMF Biocomposite 72 3.8 Effect of CMF Reinforcement on the Mechanical Properties of PLA 72 3.9 FT-IR Analysis of Untreated Sisal Fiber (UTS), Mercerized Sisal Fiber (MSF) and Cellulose Microfibrils (CMF) 73 3.10 Crystalline Structure of UTS, MSF and CMF 75 3.11 Particle Size Determination: Transmission Electron Microscopy (TEM) 76 3.12 Thermal Properties 77 3.12.1 Differential Scanning Calorimetry of CMF Reinforced PLA biocomposites 77 3.12.2 Thermo Gravimetric Analysis of CMF Reinforced PLA Biocomposites 79 3.12.3 Dynamic Mechanical Analysis (DMA) of CMF Reinforced PLA Biocomposites 82 3.13 Scanning Electron Microscopy 85 3.13.1 Surface Morphology of Sisal Fiber (USF, MSF and CMF) 85 3.13.2 Surface Morphology of CMF Reinforced PLA References 91 4 Tannins: A Resource to Elaborate Aromatic and Biobased Polymers 97 Alice Arbenz and Luc Avérous 4.1 Introduction 97 4.2 Tannin Chemistry 98 4.2.1 Historical Outline 98 4.2.2 Classification and Chemical Structure of Vascular Plant Tannins 99 4.2.3 Hydrolysable Tannins 99 4.3 Complex Tannins 101 4.4 Condensed Tannins 101 4.5 Non-vascular Plant Tannins 103 4.5.1 Phlorotannins with Ether Bonds 104 4.5.2 Phlorotannins with Phenyl bonds 104 4.5.3 Phlorotannins with Ether and Phenyl bonds 105 4.5.4 Phlorotannins with Ibenzo-p-dioxin Links 106 4.6 Extraction of Tannins 106 4.7 Chemical Modification 108 4.7.1 General Background 108 4.7.2 Heterocycle Reactivity 108 4.8 Heterocyclic Ring Opening with Acid 110 4.9 Sulfonation 112 4.9.1 Reactivity of Nucleophilic Sites 113 4.9.2 Bromination 114 4.9.3 Reactions with Aldehydes 116 4.9.4 Reaction with the Hexamine 117 4.10 Mannich Reaction 119 4.11 Coupling Reaction 119 4.11.1 Michael Reaction 119 4.11.2 Oxa-Pictet-Spengler Reaction 120 4.11.3 Functionalization of the Hydroxyl Groups 121 4.11.4 Acylation 121 4.12 Etherification 124 4.12.1 Substitution by Ammonia 127 4.12.2 Reactions Between Tannin and Epoxy Groups 128 4.13 Alkoxylation 129 4.13.1 Reaction with Isocyanates 130 4.14 Toward Biobased Polymers and Materials 130 4.14.1 Adhesives 130 4.14.2 Phenol-formaldehyde Foam Type 132 4.15 Materials Based on Polyurethane 133 4.15.1 Polyurethanes Foams 133 4.15.2 Non-porous Polyurethane Materials 133 4.16 Materials Based on Polyesters 134 4.16.1 Materials Based on Epoxy Resins 134 4.17 Conclusion 135 Acknowledgments 136 References 136 5 Electroactivity and Applications of Jatropha Latex and Seed 149 S. S. Pradhan and A. Sarkar 5.1 Introduction 149 5.2 Plant Latex 150 5.3 Jatropha Latex 151 5.3.1 Chemistry 151 5.4 Jatropha Seed 151 5.5 Material Preparation 151 5.6 Microscopic Observations 153 5.6.1 X-ray Diffraction 153 5.6.2 Electronic or Vibrational Properties 154 5.7 Electroactivity in Jatropha Latex 157 5.7.1 Ionic Liquid Property 157 5.8 Electroactivity in Jatropha Latex 158 5.8.1 DC Volt-ampere Characteristics 162 5.8.2 Temperature Variation of AC Conductivity 164 5.9 Applications 165 5.10 Conclusion 167 Acknowledgements 168 References 168 6 Characteristics and Applications of PLA 171 Sandra Domenek and Violette Ducruet 6.1 Introduction 171 6.2 Production of PLA 172 6.2.1 Production of Lactic Acid 172 6.2.2 Synthesis of PLA 174 6.3 Physical PLA properties 179 6.4 Microstructure and Thermal properties 181 6.4.1 Amorphous Phase of PLA 181 6.4.2 Crystalline Structure of PLA 183 6.4.3 Crystallization Kinetics of PLA 185 6.4.4 Melting of PLA 187 6.5 Mechanical Properties of PLA 188 6.6 Barrier Properties of PLA 190 6.6.1 Gas Barrier Properties of PLA 190 6.6.2 Water Vapour Permeability of PLA 193 6.6.3 Permeability of Organic Vapours through PLA 194 6.7 Degradation Behaviour of PLA 195 6.7.1 Thermal Degradation 195 6.7.2 Hydrolysis 196 6.7.3 Biodegradation 198 6.8 Processing 200 6.9 Nanocomposites 202 6.10 Applications 204 6.10.1 Biomedical Applications of PLA 204 6.10.2 Packaging Applications Commodity of PLA 205 6.10.3 Textile Applications 208 6.10.4 Automotive Applications of PLA 209 6.10.5 Building Applications 210 6.10.6 Other Applications of PLA 210 6.11 Conclusion 211 References 211 7 PBS Makes Its Entrance into the Family of Biobased Plastics 225 Laura Sisti, Grazia Totaro and Paola Marchese 7.1 Introduction 225 7.2 PBS Market 227 7.3 PBS Production 229 7.3.1 Succinic Acid Production 230 7.3.2 1,4-Butanediol Production 233 7.3.3 Synthesis of PBS 234 7.4 Properties of PBS 237 7.5 Copolymers of PBS 240 7.5.1 Random Copolymers 240 7.5.2 Block Copolymers 247 7.5.3 Chain Branching 250 7.6 PBS Composites and Nanocomposites 253 7.6.1 Inorganic Fillers 253 7.6.2 Natural Fibers 258 7.7 Degradation and Recycling 262 7.7.1 Enzymatic Degradation 262 7.7.2 Non Enzymatic Degradation 266 7.7.3 Natural Weathering Degradation 266 7.7.4 Thermal Degradation 267 7.7.5 Recycling 267 7.8 Processing and Applications of PBS and its Copolymers 269 7.9 Conclusions 273 Abbreviations 273 References 274 8 Development of Biobased Polymers and Their Composites from Vegetable Oils 289 Patit P. Kundu and Rakesh Das 8.1 Introduction 289 8.2 Source and Functional Groups of Vegetable Oil 290 8.3 Direct Cross-Linking of Vegetable Oil for Polymer Synthesis 292 8.3.1 Cationic Polymerization 292 8.4 Free Radical Polymerization 295 8.5 Chemical Modification of Vegetable Oils for Polymer Synthesis 297 8.5.1 Synthesis of Polymers after Epoxidation of Vegetable Oils 297 8.6 Polymer Synthesis after Esterification of Vegetable Oils 299 8.7 Polyol and Polyurethanes from Vegetable Oils 302 8.8 Polymer Composites and Nanocomposites from Vegetable Oils 306 8.9 Conclusions 311 References 312 9 Polymers as Drug Delivery Systems 323 Magdy W. Sabaa 9.1 Introduction 323 9.2 Types of Modified Drug Delivery Systems 324 9.3 Concept of Drug Delivery Matrix 325 9.4 Polymeric Materials as Carriers for Drug Delivery Systems 326 9.4.1 Polysaccharides and Modified Polysaccharides as Matrices for Drug Delivery Systems 326 9.4.2 pH-sensitive as Drug Delivery Systems 331 9.4.3 Thermo-sensitive as Drug Delivery Systems 335 9.4.4 Light-sensitive as Drug Delivery Systems 338 9.5 Conclusions 340 References 341 10 Nanocellulose as a Millennium Material with Enhancing Adsorption Capacities 351 Norhene Mahfoudhi and Sami Boufi 10.1 Introduction 351 10.2 From Cellulose to Nanocellulose 353 10.3 General Remarks about Adsorption Phenomena 355 10.4 Nanobibrillated Cellulose as a Novel Adsorbent 359 10.5 NFC in Heavy Metal Adsorption 363 10.6 NFC as an Adsorbent for Organic Pollutants 372 10.7 NFC in Oil Adsorption 373 10.8 NFC in Adsorption of Dyes 376 10.9 Nanofibrillar Cellulose as a Flocculent for Waste Water 379 10.10 NFC in CO2 Adsorption 380 10.11 Conclusion 381 References 381 11 Towards Biobased Aromatic Polymers from Lignins 387 Stephanie Laurichesse and Luc Avérous 387 11.1 Introduction 388 11.2 Lignin Chemistry 389 11.2.1 Historical Outline 389 11.2.2 Chemical Structure 390 11.2.3 Physical Properties 391 11.3 Isolation of Lignin from Wood 393 11.3.1 The Biorefinery Concept 393 11.3.2 Extraction Processes and their Resulting Technical Lignins 394 11.4 Chemical Modification 398 11.4.1 General Background 398 11.4.2 Fragmentation of Lignin 399 11.4.3 Pyrolysis 401 11.4.4 Gasification 403 11.4.5 Oxidation 403 11.4.6 Liquefaction 404 11.4.7 Enzymatic Oxidation 406 11.4.8 Outlook 407 11.5 Synthesis of New Chemical Active Sites 407 11.5.1 Alkylation/Dealkylation 407 11.5.2 Hydroxalkylation 409 11.5.3 Amination 410 11.5.4 Nitration 411 11.6 Functionalization of Hydroxyl Groups 412 11.6.1 Esterification 412 11.6.2 Phenolation 415 11.6.3 Etherification and Ring Opening Polymerisations 416 11.6.4 Urethanisation 418 11.7 Toward Lignin Based Polymers and Materials 420 11.7.1 Lignin as a Viable Route for Polymers Syntheses 420 11.7.2 ATRP - A Useful Method to Develop Lignin-Based Functional Material 422 11.7.3 High Performance Material Made with Lignin: Carbon Fibers 423 11.7.4 Toward Commercialized Lignin-based Polymers 424 11.8 Conclusion 424 Acknowledgments 425 References 425 12 Biopolymers – Proteins (Polypeptides) and Nucleic Acids 439 S. Georgiev, Z. Angelova and T. Dekova 12.1 Structure of Protein Molecules 440 12.1.1 Peptide Bonds 441 12.1.2 Secondary Structure of Protein Molecule 441 12.1.3 Tertiary Structure of Proteins 442 12.1.4 Quaternary Structure of Proteins 443 12.2 Abnormal Haemoglobin 444 12.3 Methods for Proteome Analysis 446 12.4 Advantages of the Method 446 12.5 Study of Proteins with Post-Translational Modifications 447 12.6 Biodegradable Polymers 448 12.6.1 DNA The Molecule of Heredity 451 12.6.2 Experiments Designate DNA as the Genetic Material 452 12.6.3 Bacterial Transformation Implicates DNA as the Substance of Genes 452 12.6.4 Identification of RNA as the Genetic Material 454 12.6.5 The Structures of DNA and RNA 455 12.6.6 Left Handed DNA Helices 456 12.6.7 Some DNA Molecules are Circular instead of Linear 456 12.6.8 RNA as the Genetic Material (Structure) 457 12.6.9 Hammerhead Ribozymes HHRs 458 12.7 Regulation Gene Function Through RNA Interfering and MicroRNA Pathways 460 12.7.1 How dsRNA can Switch off Expression of a Gene? 461 12.7.2 MicroRNAs Also Control the Expression of Some Genes 463 12.8 DNA Vaccines 464 12.9 Conclusion 467 References 467 13 Tamarind Seed Polysaccharide-based Multiple-unit Systems for Sustained Drug Release 471 Amit Kumar Nayak 471 13.1 Introduction 471 13.2 Tamarind Seed Polysaccharide 473 13.2.1 Sources and Extraction 473 13.3 Composition 474 13.4 Properties 474 13.5 Use of Tamarind Seed Polysaccharide in Drug Delivery 475 13.6 Tamarind Seed Polysaccharide-based Microparticle/Beads for Sustained Drug Delivery 476 13.7 Extrusion-Spheronization Method 476 13.7.1 Tamarind Seed Polysaccharide Spheroids Containing Diclofenac Sodium 476 13.8 Ionotropic-Gelation Method 478 13.8.1 Tamarind Seed Polysaccharide-alginate Beads Containing Diclofenac Sodium 478 13.8.2 Tamarind Seed Polysaccharide-alginate Mucoadhesive Microspheres Containing Gliclazide 480 13.8.3 Tamarind Seed Polysaccharide-alginate Mucoadhesive Beads Containing Metformin HCl 481 13.7.4 Tamarind Seed Polysaccharide-pectinate Mucoadhesive Beads Containing Metformin HCl 481 13.8.5 Tamarind Seed Polysaccharide-gellan Mucoadhesive Beads Containing Metformin HCl 483 13.9 Covalent Crosslinking 485 13.9.1 Chitosan-Tamarind Seed Polysaccharide Interpenetrating Polymeric Network Microparticles Containing Aceclofenac 485 13.10 Combined Ionotropic-Gelation/Covalent Crosslinking 488 13.10.1 Interpenetrated Polymer Network Microbeads Containing Diltiazem-Indion 254® Complex made of Tamarind Seed Polysaccharide and Sodium Alginate 488 13.11 By Ionotropic Emulsion-gelation 489 13.11.1 Oil-entrapped Tamarind Seed Polysaccharide- Alginate Blend Floating Beads Containing Diclofenac Sodium 489 13.12 Conclusion 490 References 490 Index 493

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Book SynopsisThis unique, self-contained resource is the first volume on electron paramagnetic resonance (EPR) spectroscopy in the eMagRes Handbook series. The 27 chapters cover the theoretical principles, the common experimental techniques, and many important application areas of modern EPR spectroscopy. EPR Spectroscopy: Fundamentals and Methods is presented in four major parts: A: Fundamental Theory, B: Basic Techniques and Instrumentation, C: High-Resolution Pulse Techniques, and D: Special Techniques. The first part of the book gives the reader an introduction to basic continuous-wave (CW) EPR and an overview of the different magnetic interactions that can be determined by EPR spectroscopy, their associated theoretical description, and their information content. The second provides the basics of the various EPR techniques, including pulse EPR, and EPR imaging, along with the associated instrumentation. Parts C and D builds on parts A and B and offer introductory accounts of a Table of ContentsContributors xi Series Preface xv Preface xvii Part A: Fundamental Theory 1 1 Continuous-Wave EPR 3 Art van der Est 2 EPR Interactions – g-Anisotropy 17 Peter Gast and Edgar J.J. Groenen 3 EPR Interactions – Zero-field Splittings 29 Joshua Telser 4 EPR Interactions – Coupled Spins 63 Eric J.L. McInnes and David Collison 5 EPR Interactions – Hyperfine Couplings 81 Marina Bennati 6 EPR Interactions – Nuclear Quadrupole Couplings 95 Stefan Stoll and Daniella Goldfarb 7 Quantum Chemistry and EPR Parameters 115 Frank Neese 8 Spin Dynamics 143 Akiva Feintuch and Shimon Vega 9 Relaxation Mechanisms 175 Sandra S. Eaton and Gareth R. Eaton Part B: Basic Techniques and Instrumentation 193 10 Transient EPR 195 Stefan Weber 11 Pulse EPR 215 Stefan Stoll 12 EPR Instrumentation 235 Edward Reijerse and Anton Savitsky 13 EPR Imaging 261 Boris Epel and Howard J. Halpern 14 EPR Spectroscopy of Nitroxide Spin Probes 277 Enrica Bordignon Part C: High-Resolution Pulse Techniques 303 15 FT-EPR 305 Michael K. Bowman, Hanjiao Chen, and Alexander G. Maryasov 16 Hyperfine Spectroscopy – ENDOR 331 Jeffrey R. Harmer 17 Hyperfine Spectroscopy – ELDOR-detected NMR 359 Daniella Goldfarb 18 Hyperfine Spectroscopy – ESEEM 377 Sabine Van Doorslaer 19 Dipolar Spectroscopy – Double-resonance Methods 401 Gunnar Jeschke 20 Dipolar Spectroscopy – Single-resonance Methods 425 Peter P. Borbat and Jack H. Freed 21 Shaped Pulses in EPR 463 Philipp E. Spindler, Philipp Schöps, Alice M. Bowen, Burkhard Endeward, and Thomas F. Prisner Part D: Special Techniques 483 22 Pulse Techniques for Quantum Information Processing 485 Gary Wolfowicz and John J.L. Morton 23 Rapid-scan EPR 503 Gareth R. Eaton and Sandra S. Eaton 24 EPR Microscopy 521 Aharon Blank 25 Optically Detected Magnetic Resonance (ODMR) 537 Etienne Goovaerts 26 Electrically Detected Magnetic Resonance (EDMR) Spectroscopy 559 Christoph Boehme and Hans Malissa 27 Very-high-frequency EPR 581 Alexander Schnegg Index 603

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Book SynopsisThis book will have the recent information on the developments in the emerging field of environmental-friendly coatings. Crucial aspects associtaed with coating research will be presented in form of the indivudual chapters. Close attention will be paid to include essential aspects that are necessary to understand the porperties and applications of the novel materials. Different methods and techniques of synthesis and charcaterization will be detailed as individual chapters. It will also discuss the characterization techniques used in the area of such coatings. there will be chapters that descirbe the current status and future prospects. The topics will be selected so they are easy to understand and useful to new scholars as well as advanced learners. No book has been written on this subject so far.Table of ContentsPreface xi 1 Novel Bio-based Polymers for Coating Applications 1 Harjoyti Kalita, Deep Kalita, Samim Alam, Andrey Chernykh, Ihor Tarnavchyk, James Bahr, Satyabrata Samanta, Anurad Jayasooriyama, Shashi Fernando, Sermadurai Selvakumar, Dona Suranga Wickramaratne, Mukund Sibi, and Bret J. Chisholm 1.1 Introduction 1 1.2 Polymers Based on Plant Oils 3 1.2.1 Properties of Homopolymers and Their Surface Coatings 5 1.2.2 Properties of Copolymers and Their Surface Coatings 7 1.3 Polymers Based on Cardanol 9 1.4 Polymers Based on Eugenol 10 1.5 Conclusion 14 Acknowledgments 14 Disclaimer 14 References 15 2 Deposition of Environmentally Compliant Cerium-Containing Coatings and Primers on Copper-Containing Aluminium Aircraft Alloys 17 Stephan V. Kozhukharov 2.1 Importance and Indispensability of the Corrosion-Protective Coating Layers 17 2.1.1 Employment of Reliable Materials for the Aircraft Industry 17 2.1.2 Corrosion Phenomena, Basic Definitions and Concepts 20 2.1.3 Brief Summary 22 2.2 Introduction to the Cerium Conversion Primer Layers 23 2.2.1 Background and Basic Definitions 23 2.2.2 Deposition Methods 23 2.2.3 Technical Stages of CeCC Deposition 25 2.2.3.1 Preliminary Treatment Procedures 25 2.2.3.2 Deposition Process, Mechanisms and Factors 28 2.2.3.3 Posterior Sealing Procedures 37 2.2.4 Brief Summary 37 2.3 Elaboration of Hybrid and Composite Upper and Finishing Coating Layers 38 2.3.1 Advantages of the Hybrid Coatings Systems 38 2.3.2 Technological Bases of the Sol–Gel Approach 43 2.3.3 Hybrid Nanocomposite Primer Coatings: Basic Concepts 46 2.3.4 Corrosion Inhibitors as Self-Healing Coating Ingredients 47 2.3.4.1 Rare Earth Salts as Corrosion Inhibitors 47 2.3.4.2 Organic Compounds as Corrosion Inhibitors 52 2.3.5 Technological Features of the Production of Hybrid Nanocomposite Primer Coatings 53 2.3.6 Alternatives for the Inhibitor Containing Self-Healing Coatings 54 2.3.6.1 Coatings with Recuperative Microcapsules 54 2.3.6.2 Exterior Ice-Phobic and UV Protective Finishes 55 2.3.7 Brief Summary 57 Acknowledgment 58 References 58 3 Ferrites as Non-toxic Pigments for Eco-friendly Corrosion Protection Coatings 71 D.O. Grigoriev, T. Vakhitov, and S.N. Stepin 3.1 Introduction 71 3.2 Crystalline Structure, Physicochemical Properties, and Inhibition Mechanism of Ferrites 72 3.3 Methods for the Preparation of Ferrites 76 3.3.1 Ceramic Method 76 3.3.2 Ceramic Method with Utilizing Industrial Wastes 78 3.3.3 Other Methods of Ferrites Preparation 79 3.4 Novel Types of Ferrite Pigments 81 3.5 Ferrite-Based Multifunctional Coatings 83 3.6 Conclusion 84 Acknowledgement 84 References 84 4 Application of Coatings and Films in Fruits and Vegetables 87 R.K. Dhall 4.1 Introduction 87 4.2 Coatings versus Films 88 4.3 Structural Matrix: Hydrocolloids and Lipids 88 4.4 Application of Hydrocolloids Coatings 89 4.5 Application of Lipid Coatings 91 4.6 Application of Composite Coatings 91 4.7 Addition of Active Compounds 93 4.7.1 Antimicrobial Coatings 93 4.7.2 Antioxidant Coatings 95 4.7.3 Texture Enhances 96 4.7.4 Nutraceutical Coatings 97 4.8 Nanotechnology 97 4.9 Commercial Application of Edible Coatings 98 4.10 Problems Associated with Edible Coatings 98 4.11 Regulatory Status and Food Safety Issues 104 4.12 Conclusions 105 References 106 5 Development of Novel Biobased Epoxy Films with Aliphatic and Aromatic Amine Hardeners for the Partial Replacement of Bisphenol A in Primer Coatings 121 Rafael S. Peres, Carlos A. Ferreira, Carlos Alemán, and Elaine Armelin 5.1 Introduction 121 5.2 Recent Advances on Vegetable Oils Chemistry 123 5.3 Control of the Epoxidation Reaction of Vegetable Oils 125 5.4 Spectroscopy Characterization of Epoxidized Linseed Oil Cured with Amine Hardeners 128 5.5 Thermal Properties of Epoxidized Linseed Oil Cured with Amine Hardeners 134 5.6 Swelling, Wettability and Morphology of New Epoxy Films 136 5.7 Mechanical Properties of Epoxidized Linseed Oil Cured with Amine Hardeners 139 5.8 Applications of Vegetable Oils in Coatings 140 5.9 Conclusions 142 Acknowledgments 142 References 143 6 Silica-Based Sol–Gel Coatings: A Critical Perspective from a Practical Viewpoint 149 Rosaria Ciriminna, Alexandra Fidalgo, Giovanni Palmisano, Laura M. Ilharco, and Mario Pagliaro 6.1 Introduction: Need of Practical Perspective 149 6.2 A Green, Simple Technology 151 6.3 The Market 152 6.4 Conclusions 157 Acknowledgements 157 References 158 7 Fatty Acid-Based Waterborne Coatings 161 Mónica Moreno, Monika Goikoetxea, and María J. Barandiaran 7.1 Introduction 161 7.2 Fatty Acids as Raw Materials 163 7.2.1 Chemical Modification of Fatty Acids for Free Radical Polymerization 164 7.3 Polymerization of Fatty Acid-Based Monomers in Aqueous Media 167 7.3.1 Emulsion Polymerization 167 7.3.2 Miniemulsion Polymerization 170 7.3.3 Effect of Preserving Alkyl Double Bonds 172 7.3.3.1 Kinetics and Microstructural Properties 172 7.3.3.2 Auto-Oxidative Curing and Mechanical Properties 174 7.3.3.3 Effect of Incorporating α-MBL as Comonomer 175 7.4 Incorporation of Fatty Acid Derivatives in Waterborne Coatings 176 7.5 Conclusion 178 References 179 8 Environmentally Friendly Coatings 183 Xiaofeng Ren, Lei Meng, and Mark Soucek 8.1 Waterborne Coatings 183 8.1.1 Introduction of Waterborne Coatings 183 8.1.2 History of Waterborne Coatings 184 8.1.3 Category of Waterborne Coatings 186 8.1.3.1 Water-Reducible Coatings 187 8.1.3.2 Latex Coatings 187 8.1.3.3 Emulsion Coatings 188 8.1.4 Development and Prospect of Waterborne Coatings 192 8.1.4.1 Development of Resins Used in Waterborne Systems 192 8.1.4.2 Combination of Waterborne with Other Techniques 194 8.2 Seed Oil-Based Coatings 195 8.2.1 Seed Oils 195 8.2.2 Seed Oil-Based Coatings from Copolymerization with Vinyl Monomers 198 8.2.2.1 Seed Oil-Based Reactive Diluents for Coating Applications 198 8.2.3 Seed Oil-Based Epoxy for UV-Curable Coatings 201 8.2.4 Seed Oil-Based Polyurethanes 205 8.2.5 Seed Oil-Based Thiol-ene Chemistry in UV-Curable Coatings 206 8.2.6 Seed Oil-Based Organic–Inorganic Coatings 209 8.2.7 Seed Oil-Based Alkyd Coatings 211 8.2.7.1 Introduction of Alkyds 211 8.2.7.2 Modified Alkyds for Coatings 213 8.3 Conclusion 219 References 219 9 Low-Temperature Aqueous Coatings for Solar Thermal Absorber Applications 225 Saleh Khamlich and Malik Maaza 9.1 Introduction 225 9.2 Samples Preparation 228 9.3 Structural and Morphological Investigations of α-Cr2O3 Monodispersed Meso-Spherical Particles 228 9.3.1 Raman Spectroscopic Study 228 9.3.2 Attenuated Total Reflection Study 229 9.3.3 Field-Emission Scanning Electron Microscopy (FESEM) and Energy-Dispersive X-Ray Analysis (EDX) 230 9.4 Growth Mechanism 231 9.4.1 Development of a Mathematical Model [Lifshitz–Slyozov–Wagner (LSW) Model] 232 9.4.1.1 Basic Assumptions 232 9.4.1.2 Mathematical Formulation 233 9.5 Potential Applications in Solar Absorbers 238 9.5.1 Diffuse Reflectance and the Infrared Emissivity (ε) Study of α-Cr2O3 Meso-spherical Particles 239 9.6 Conclusions 240 Acknowledgements 240 References 241 10 Eco-Friendly Recycled Pharmaceutical Inhibitor/Waste Particle Containing Hybrid Coatings for Corrosion Protection 245 Victoria Bustos, Liseth Concha, Carmina Menchaca-Campos, Jorge Uruchurtu, Mario A. Romero, Marcos Esparza, Alba Covelo, Miguel Hernandez, and Estela Sarmiento 10.1 Introduction 245 10.1.1 Recycled Pharmaceutical Inhibitors 246 10.1.2 Hybrid Coatings 247 10.2 Hybrid Coating Preparation 247 10.2.1 Recycled Pharmaceutical Inhibitors 247 10.2.2 Mesoporous Particles 248 10.2.3 Hybrid Coating 248 10.2.3.1 Characterization 248 10.3 Hybrid Coatings Performance 249 10.3.1 Materials Characterization 249 10.3.2 Electrochemical Inhibitor Evaluation 249 10.3.2.1 Potentiodynamic Polarization 250 10.3.2.2 Electrochemical Impedance 251 10.3.3 Electrochemical Hybrid Coating Evaluation 253 10.4 Conclusions 254 Acknowledgment 255 References 255 11 Chemical Interaction of Modified Zinc–Phosphate Green Pigment on Waterborne Coatings in Steel 257 Miguel Hernandez, Alba Covelo, and Jorge Uruchurtu 11.1 Introduction 257 11.2 Cathodic Delamination of Coatings 258 11.3 Modified Zinc–Phosphate Pigment 260 11.4 Conclusions 263 Acknowledgement 263 References 263 12 Development of Soybean Oil-Based Polyols and Their Applications in Urethane and Melamine-Cured Thermoset Coatings 265 Senthilkumar Rengasamy and Vijay Mannari 12.1 Introduction 265 12.2 Experimental 266 12.2.1 Raw Materials 266 12.2.2 Standard Testing Methods 267 12.2.3 Coating Composition and Sample Preparation 267 12.2.4 Synthesis of ESO-Based Phosphate Ester Polyol (ESO–Polyol) 267 12.2.5 Synthesis of Epoxidized Soybean Oil Monoglyceride (EMG) 267 12.2.6 Synthesis of EMG-Based Phosphate Ester Polyol (EMG Polyol) 268 12.2.7 Synthesis of EMG-Based Phthalic Acid Ester Polyol (EMG–PEP) 269 12.3 Results and Discussion 270 12.3.1 Characterization of Polyols 270 12.3.2 Proton NMR Characterization 271 12.3.3 FTIR Characterization 271 12.3.4 Urethane and Melamine-Cured Film Properties 273 12.4 Conclusion 275 Acknowledgements 276 References 276 13 Powder Coatings from Recycled Polymers and Renewable Resources 279 Martino Colonna, Claudio Gioia, Annamaria Celli, and Alessandro Minesso 13.1 Introduction 279 13.2 Powder Coating as a Green Approach to Coatings 280 13.3 The Use of Materials from Renewable Resources in Powder Coating Applications 283 13.4 The Use of Recycled Polymers for the Preparation of Coatings 286 13.5 Powder Coatings from the Combined Chemical Recycle of Polymers and the Use of Renewable Resources 289 13.5.1 Depolymerization of PET with Isosorbide 292 13.5.1.1 Catalysts Used for the Depolymerization of PET with Isosorbide 292 13.5.1.2 Depolymerization Process 292 13.5.1.3 Polycondensation after Glycolysis with Isosorbide 293 13.5.2 Coatings Application Tests 293 13.5.2.1 Blooming Resistance 294 13.5.2.2 Effect of Overbaking 295 13.5.2.3 Effect of Ageing 296 13.5.2.4 Solvent Resistance 296 13.5.3.5 Boiling Water Resistance Tests 297 13.6 Conclusions 297 References 29814 Th e Synthesis and Applications of Non-isocyanate Based Polyurethanes as Environmentally Friendly “Green” Coatings 301 Peter Zarras, Paul A. Goodman, Alfred J. Baca, Joshua E. Baca, and Shelley Vang 14.1 Introduction to Isocyanate-based Polyurethane Chemistry 301 14.2 Synthesis of Isocyanates 302 14.3 Toxicological Properties of Isocyanates 303 14.4 Synthesis of Phosgene-free Precursors 304 14.5 Non-isocyanate-based Polyurethanes (NIPU) 305 14.5.1 Polycondensation Reaction 306 14.5.2 Polyaddition Reaction 308 14.5.3 Additional Polymerization Reactions Leading to Non-isocyanate Polyurethanes (NIPU) 309 14.6 Applications of Non-isocyanate Polyurethanes (NIPU) 310 14.7 Conclusions 311 Acknowledgements 311 References 311

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Book SynopsisAntennas and Wireless Power Transfer Methods for Biomedical Applications Join the cutting edge of biomedical technology with this essential reference The role of wireless communications in biomedical technology is a significant one. Wireless and antenna-driven communication between telemetry components now forms the basis of cardiac pacemakers and defibrillators, cochlear implants, glucose readers, and more. As wireless technology continues to advance and miniaturization progresses, it's more essential than ever that biomedical research and development incorporate the latest technology. Antennas and Wireless Power Transfer Methods for Biomedical Applications provides a comprehensive introduction to wireless technology and its incorporation into the biomedical field. Beginning with an introduction to recent developments in antenna and wireless technology, it analyzes the major wireless systems currently available and their biomedical applications, actual and potential. The result is

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Book SynopsisTaking place at the David L. Lawrence Convention Center, Pittsburgh, Pennsylvania, this CT Volume contains 17 papers from the following 2014 Materials Science and Technology (MS&T''14) symposia: Next Generation Biomaterials Surface Properties of Biomaterials Table of ContentsPreface NEXT GENERATION BIOCERAMICS Evaluation of Long-Term Mechanical and Biological Biocompatibility of Low-Cost -Type Ti-Mn Alloys for Biomedical Applications 3Ken Cho, Mitsuo Niinomi, Masaaki Nakai, Pedro Fernandes Santos, Alethea Morgane Liens, Masahiko Ikeda, and Tomokazu Hattori Control of Ag Release from Ag-Containing Calcium Phosphates in Simulated Body Fluid 13Ozkan Gokcekaya, Kyosuke Ueda, and Takayuki Narushima Gallium-Containing Ferrites for Hyperthermia Treatment 21J. Sánchez, Dora Alicia Cortés-Hernández, José C. Escobedo-Bocardo, Rosario A. Jasso-Terán, Pamela Y. Reyes-Rodríguez, and Gilberto F. Hurtado-López Exploration of Amorphous and Crystalline Tri-Magnesium Phosphates for Bone Cements 33Nicole Ostrowski, Vidisha Sharma, Abhijit Roy, and Prashant N. Kumta Micro-X-Ray Diffraction Study of New Nickel-Titanium Rotary Endodontic Instruments 47William A. Brantley, Masahiro Iijima, William A.T. Clark, Scott R. Schricker, John M. Nusstein, and Itaru Mizoguchi Torsional Properties of Nanostructured Titanium Cortical Bone Screws 55J.A.Disegi, B. Shultzabarger, and Michael Roach Strengthening Behaviors of Low-Precious Ag-Pd-Au-Zn Alloys for Dental Applications 63Mitsuo Niinomi, Masaaki Nakai, Junko Hieda, Ken-Cho, Yonghwan Kim, and Hisao Fukui Effect of Immersion Medium on the Degradation and Conversion of Silicate (13-93) Bioactive Glass Scaffolds 73Yifei Gu, Wenhai Huang, and Mohamed N. Rahaman Evaluation of Long-Term Bone Regeneration in Rat Calvarial Defects Implanted with Strong Porous Bioactive Glass (13-93) Scaffolds 85Mohamed N. Rahaman, Yinan Lin, Wei Xiao, X. Liu, and B. Sonny Bal Magnesium Single Crystal as a Biodegradable Implant Material 97Madhura Joshi, Pravahan Salunke, Guangqi Zhang, Vibhor Chaswal, Zhongyun Dong, and Vesselin Shanov SURFACE PROPERTIES OF BIOMATERIALS Damage Evaluation of TiO2 Nanotubes on Titanium 117Anish Shivaram, Susmita Bose, and Amit Bandyopadhyay Drug Delivery from Surface Modified Titanium Alloy for Load-Bearing Implants 129Susmita Bose, Dishary Banerjee, Sam Robertson, Solaiman Tarafder, and Amit Bandyopadhyay A Family of Novel Biostable Reticulated Elastomeric and Resilient Biointregative Crosslinked Polyurethane-Urea Scaffolds 137Arindam Datta and Larry Lavelle In Situ Nitridation of Titanium Using LENS™ 149Himanshu Sahasrabudhe, Julie Soderlind, and Amit Bandyopadhyay Magnesium Doped Hydroxyapatite: Synthesis, Characterization and Bioactivity Evaluation 161Jaswinder Singh, Harpal Singh, and Uma Batra Novel PLA- and PCL-HA Porous 3D Scaffolds Prepared by Robocasting Facilitate MC3T3-E1 Subclone 4 Cellular Attachment and Growth 175V. G. Varanasi, J. Russias, E. Saiz, P. M. Loomer, and A. P. Tomsia Dextran Coated Cerium Oxide Nanoparticles for Inhibiting Bone Cancer Cell Functions 187Ece Alpaslan, Hilal Yazici, Negar Golshan, Katherine S. Ziemer, and Thomas J. Webster Author Index 197

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Book SynopsisThe Ceramic Engineering and Science Proceeding has been published by The American Ceramic Society since 1980. This series contains a collection of papers dealing with issues in both traditional ceramics (i.e., glass, whitewares, refractories, and porcelain enamel) and advanced ceramics. Topics covered in the area of advanced ceramic include bioceramics, nanomaterials, composites, solid oxide fuel cells, mechanical properties and structural design, advanced ceramic coatings, ceramic armor, porous ceramics, and more.Table of ContentsPreface vii Introduction ix BIOCERAMICS Potential of Bioactive Glass Scaffolds as Implants for Structural Bone Repair 3Mohamed N. Rahaman, B. Sonny Bal, and Lynda F. Bonewald In Vitro Degradation and Conversion of Melt-Derived Bioactive Glass Microfibers in Simulated Body Fluid 17Mohamed N. Rahaman, Xin Liu, and Delbert E. Day On the Formation of Apatites in the Chemically Bonded CaO-Al2O3-SiO2-H2O Bioceramic System 29Leif Hermansson, Gunilla Gomez-Ortega, Emil Abrahamsson, and Jesper Lööf Fabrication and Characterization of Nano Bioglass-Ceramic Scaffold for Bone Tissue Engineering 37Sampath Kumar Arepalli, Himanshu Tripathi, M. Vyshali Nanda, V.Sri Sravya, Ram Pyare, and S. P. Singh Synthesis and Characterization of Co-Cu Ferrite and Bioglass Composites for Hyperthermia Treatment of Cancer 51V. Chalisgaonkar, K. Pandey, A. S. Kumar, H. Tripathi, S. P. Singh, and R. Pyare Alpha–Beta Phase Transformation in Tricalcium Phosphate (TCP) Ceramics: Effect of Mg2+ Doping 63Matteo Frasnelli and Vincenzo M. Sglavo Experimental Approach to Study the Thermal Induced State of Stress in a Medical Ceramic Bilayer 71V. Mercurio Effect of Grain Boundary Segregation on the Hydrothermal Degradation of Dental 3Y-TZP Ceramics 81F. Zhang, M. Inokoshi, K. Vanmeensel, B. Van Meerbeek, I. Naert, and J. Vleugels POROUS CERAMICS Treatment of Produced Water using Silicon Carbide Membrane Filters 91Abhaya K. Bakshi, Rajendra Ghimire, Eric Sheridan, and Melanie Kuhn Microcapsules from Pickering Emulsions Stabilized by Clay Particles 107Gisèle L. Lecomte-Nana, Volga Niknam, Anne Aimable, Marguerite Bienia, David Kpogbemabou, Jean-Charles Robert-Arnouil, and Asma Lajmi Author Index 125

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Book SynopsisAn essential guide to healthcare data problems, sources, and solutions Strategies in Biomedical Data Science provides medical professionals with much-needed guidance toward managing the increasing deluge of healthcare data.Table of ContentsForeword xi Acknowledgments xv Introduction 1 Who Should Read This Book? 3 What’s in This Book? 4 How to Contact Us 6 Chapter 1 Healthcare, History, and Heartbreak 7 Top Issues in Healthcare 9 Data Management 16 Biosimilars, Drug Pricing, and Pharmaceutical Compounding 18 Promising Areas of Innovation 19 Conclusion 25 Notes 25 Chapter 2 Genome Sequencing: Know Thyself, One Base Pair at a Time 27 Content contributed by Sheetal Shetty and Jacob Brill Challenges of Genomic Analysis 29 The Language of Life 30 A Brief History of DNA Sequencing 31 DNA Sequencing and the Human Genome Project 35 Select Tools for Genomic Analysis 38 Conclusion 47 Notes 48 Chapter 3 Data Management 53 Content contributed by Joe Arnold Bits about Data 54 Data Types 56 Data Security and Compliance 59 Data Storage 66 SwiftStack 70 OpenStack Swift Architecture 78 Conclusion 94 Notes 94 Chapter 4 Designing a Data-Ready Network Infrastructure 105 Research Networks: A Primer 108 ESnet at 30: Evolving toward Exascale and Raising Expectations 109 Internet2 Innovation Platform 111 Advances in Networking 113 InfiniBand and Microsecond Latency 114 The Future of High-Performance Fabrics 117 Network Function Virtualization 119 Software-Defined Networking 121 OpenDaylight 122 Conclusion 157 Notes 157 Chapter 5 Data-Intensive Compute Infrastructures 163 Content contributed by Dijiang Huang, Yuli Deng, Jay Etchings, Zhiyuan Ma, and Guangchun Luo Big Data Applications in Health Informatics 166 Sources of Big Data in Health Informatics 168 Infrastructure for Big Data Analytics 171 Fundamental System Properties 186 GPU-Accelerated Computing and Biomedical Informatics 187 Conclusion 190 Notes 191 Chapter 6 Cloud Computing and Emerging Architectures 211 Cloud Basics 213 Challenges Facing Cloud Computing Applications in Biomedicine 215 Hybrid Campus Clouds 216 Research as a Service 217 Federated Access Web Portals 219 Cluster Homogeneity 220 Emerging Architectures (Zeta Architecture) 221 Conclusion 229 Notes 229 Chapter 7 Data Science 235 NoSQL Approaches to Biomedical Data Science 237 Using Splunk for Data Analytics 244 Statistical Analysis of Genomic Data with Hadoop 250 Extracting and Transforming Genomic Data 253 Processing eQTL Data 256 Generating Master SNP Files for Cases and Controls 259 Generating Gene Expression Files for Cases and Controls 260 Cleaning Raw Data Using MapReduce 261 Transpose Data Using Python 263 Statistical Analysis Using Spark 264 Hive Tables with Partitions 268 Conclusion 270 Notes 270 Appendix: A Brief Statistics Primer 290 Content Contributed by Daniel Peñaherrera Chapter 8 Next-Generation Cyberinfrastructures 307 Next-Generation Cyber Capability 308 NGCC Design and Infrastructure 310 Conclusion 327 Note 330 Conclusion 335 Appendix A The Research Data Management Survey: From Concepts to Practice 337 Brandon Mikkelsen and Jay Etchings Appendix B Central IT and Research Support 353 Gregory D. Palmer Appendix C HPC Working Example: Using Parallelization Programs Such as GNU Parallel and OpenMP with Serial Tools 377 Appendix D HPC and Hadoop: Bridging HPC to Hadoop 385 Appendix E Bioinformatics + Docker: Simplifying Bioinformatics Tools Delivery with Docker Containers 391 Glossary 399 About the Author 419 About the Contributors 421 Index 427

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Book SynopsisOverall, this book presents a detailed and comprehensive overview of the state-of-the-art development of different nanoscale intelligent materials for advanced applications. Apart from fundamental aspects of fabrication and characterization of nanomaterials, it also covers key advanced principles involved in utilization of functionalities of these nanomaterials in appropriate forms. It is very important to develop and understand the cutting-edge principles of how to utilize nanoscale intelligent features in the desired fashion. These unique nanoscopic properties can either be accessed when the nanomaterials are prepared in the appropriate form, e.g., composites, or in integrated nanodevice form for direct use as electronic sensing devices. In both cases, the nanostructure has to be appropriately prepared, carefully handled, and properly integrated into the desired application in order to efficiently access its intelligent features. These aspects are reviewed in detail in three themed sTable of ContentsPreface xvii Part 1 Nanomaterials, Fabrication and Biomedical Applications 1 Electrospinning Materials for Skin Tissue Engineering 3 Beste Kinikoglu 1.1 Skin Tissue Engineering Scaffolds 4 1.2 Conclusions 14 References 15 2 Electrospinning: A Versatile Technique to Synthesize Drug Delivery Systems 21 Xueping Zhang, Dong Liu and Tianyan You 2.1 Introduction 21 2.2 The Types of Delivered Drugs 22 2.3 Polymers Used in Electrospinning 29 2.4 The Development of Electrospinning Process for Drug Delivery 36 2.5 Conclusions 41 Acknowledgment 42 References 42 3 Electrospray Jet Emission: An Alternative Interpretation Invoking Dielectrophoretic Forces 51 Francesco Aliotta, Oleg Gerasymov and Pietro Calandra 3.1 Introduction 52 3.2 Electrospray: How It Works? 54 3.3 Historical Background 63 3.4 How the Current (and Wrong) Description of the Electrospray Process Has Been Generated? 65 3.5 What Is Wrong in the Current Description? 68 3.6 Some Results Shedding More Light 70 3.7 Discriminating between Electrophoretic and Dielectrophoretic Forces 72 3.8 Some Theoretical Aspects of Dielectrophoresis 76 3.9 Conclusions 83 References 86 4 Advanced Silver and Oxide Hybrids of Catalysts During Formaldehyde Production 91 Anita Kovač Kralj 4.1 Introduction 92 4.2 The Catalysis 93 4.3 Case Study 95 4.4 Limited Hybrid Catalyst Method for Formaldehyde Production 97 4.5 Conclusion 104 4.6 Nomenclatures 105 References 105 5 Physico-chemical Characterization and Basic Research Principles of Advanced Drug Delivery Nanosystems 107 Natassa Pippa, Stergios Pispas and Costas Demetzos 5.1 Introduction 108 5.2 Basic Research Principles and Techniques for the Physicochemical Characterization of Advanced Drug Delivery Nanosystems 108 5.3 Conclusions 122 References 122 6 Nanoporous Alumina as an Intelligent Nanomaterial for Biomedical Applications 127 Moom Sinn Aw and Dusan Losic 6.1 Introduction 127 6.2 Nanoporous Anodized Alumina as a Drug Nano-carrier 129 6.3 Biocompatibility of NAA and NNAA Materials 138 6.4 NAA for Diabetic and Pancreatic Applications 143 6.5 NAA Applications in Orthopedics 144 6.6 NAA Applications for Heart, Coronary, and Vasculature Treatment 148 6.7 NAA in Dentistry 150 6.8 Conclusions and Future Prospects 152 Acknowledgment 153 References 154 7 Nanomaterials: Structural Peculiarities, Biological Effects, and Some Aspects of Applications 161 N.F. Starodub, M.V. Taran, A.M. Katsev, C. Bisio and M. Guidotti 7.1 Introduction 162 7.2 Physicochemical Properties Determining the Bioavailability and Toxicity of NPS 164 7.3 Current Nanoecotoxicological Knowledge 168 7.4 Modern Direction of the Application of Nanocomposites as Basis for Detoxication Process 187 7.5 Conclusions 189 Acknowledgments 190 References 190 8 Biomedical Applications of Intelligent Nanomaterials 199 M. D. Fahmy, H. E. Jazayeri, M. Razavi, M. Hashemi, M. Omidi, M. Farahani, E. Salahinejad, A. Yadegari, S. Pitcher and Lobat Tayebi 8.1 Introduction 200 8.2 Polymeric Nanoparticles 202 8.3 Lipid-based Nanoparticles 206 8.4 Carbon Nanostructures 213 8.5 Nanostructured Metals 219 8.6 Hybrid Nanostructures 223 8.7 Concluding Remarks 228 References 229 Part 2 Nanomaterials for Energy, Electronics, and Biosensing 9 Phase Change Materials as Smart Nanomaterials for Thermal Energy Storage in Buildings 249 M. Kheradmand, M. Abdollahzadeh, M. Azenha and J.L.B. de Aguiar 9.1 Introduction 250 9.2 Phase Change Materials: Definition, Principle of Operation, and Classifications 252 9.3 PCM-enhanced Cement-based Materials 254 9.4 Hybrid PCM for Thermal Storage 255 9.5 Numerical Simulations 267 9.6 Thermal Modeling of Phase Change 269 9.7 Nanoparticle-enhanced Phase Change Material 280 9.8 Conclusions (General Remarks) 288 References 289 10 Nanofluids with Enhanced Heat Transfer Properties for Thermal Energy Storage 295 Manila Chieruzzi, Adio Miliozzi, Luigi Torre and José Maria Kenny 10.1 Introduction 296 10.2 Thermal Energy Storage 298 10.3 Nanofluids for Thermal Energy Storage 313 10.4 Nanofluids Based on Molten Salts: Enhancement of Thermal Properties 330 10.5 Conclusions 349 References 351 11 Resistive Switching of Vertically Aligned Carbon Nanotubes for Advanced Nanoelectronics Devices 361 O.A. Ageev, Yu. F. Blinov, M.V. Il’ina, B.G. Konoplev and V.A. Smirnov 11.1 Introduction 362 11.2 Theoretical Description of Resistive Switching Mechanism of Structures Based on VACNT 363 11.3 Techniques for Measuring the Electrical Resistivity and Young’s Modulus of VACNT Based on Scanning Probe Microscopy 377 11.4 Experimental Studies of Resistive Switching in Structures Based on VACNT Using Scanning Tunnel Microscopy 384 References 391 12 Multi-objective Design of Nanoscale Double Gate MOSFET Devices Using Surrogate Modeling and Global Optimization 395 T. Bentrcia, F. Djeffal and E. Chebaki 12.1 Introduction 396 12.2 Downscaling Parasitic Effects 400 12.3 Modeling Framework 405 12.4 Simulation and Results 412 12.5 Concluding Remarks 422 References 422 13 Graphene-based Electrochemical Biosensors: New Trends and Applications 427 Georgia-Paraskevi Nikoleli, Stephanos Karapetis, Spyridoula Bratakou, Dimitrios P. Nikolelis, Nikolaos Tzamtzis and Vasillios N. Psychoyios 13.1 Introduction 428 13.2 Scope of This Review 429 13.3 Graphene and Sensors 430 13.4 Graphene Nanomaterials Used in Electrochemical (Bio)sensors Fabrication 430 13.5 Graphene-based Enzymatic Electrodes 432 13.6 Graphene-based Electrochemical DNA Sensors 437 13.7 Graphene-based Electrochemical Immunosensors 439 13.8 Commercial Activities in the Field of Graphene Sensors 442 13.9 Recent Developments in the Field of Graphene Sensors 442 13.10 Conclusions and Future Prospects 443 Acknowledgments 445 References 445 Part 3 Smart Nanocomposites, Fabrication, and Applications 14 Carbon Fibers-based Silica Aerogel Nanocomposites 451 Agnieszka Ślosarczyk 14.1 Introduction to Nanotechnology 451 14.2 Chemistry of Sol–gel Process 454 14.3 Types of Silica Aerogel Nanocomposites 462 14.4 Carbon Fiber-based Silica Aerogel Nanocomposites 476 14.5 Conclusions 493 References 494 15 Hydrogel–carbon Nanotubes Composites for Protection of Egg Yolk Antibodies 501 Bellingeri Romina, Alustiza Fabrisio, Picco Natalia, Motta Carlos, Grosso Maria C, Barbero Cesar, Acevedo Diego and Vivas Adriana 15.1 Introduction 502 15.2 Polymeric Hydrogels 504 15.3 Carbon Nanotubes 507 15.4 Polymer–CNT Composites 511 15.5 Egg Yolk Antibodies Protection 515 15.6 In Vitro Evaluation of Nanocomposite Performance 517 15.7 In Vivo Evaluation of Nanocomposite Performance 518 15.8 Concluding Remarks and Future Trends 521 References 522 16 Green Fabrication of Metal Nanoparticles 533 Anamika Mubayi, Sanjukta Chatterji and Geeta Watal 16.1 Introduction 533 16.2 Development of Herbal Medicines 535 16.3 Green Synthesis of Nanoparticles 536 16.4 Characterization of Phytofabricated Nanoparticles 539 16.5 Impact of Plant-mediated Nanoparticles on Therapeutic Efficacy of Medicinal Plants 540 16.6 Conclusions 550 References 551

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Book SynopsisThis book contains material contributed by forward-looking scientists who work at the interface of stem cell research and applied science with the aim to improve human fetal safety and the understanding of human developmental and degenerative disorders. Provides important platforms and contemporary accounts of the state of stem cell research in the fields of toxicology and teratologyConsiders both in vitro uses of stem cells as platforms for teratology and also stem cellopathies, which are in vivo developmental and degenerative disordersHelps the pharmaceutical industry and safety and environmental authorities validate the status quo of in vitro toxicity test systems based on human pluripotent stem cells and their derivativesTable of ContentsList of Contributors xiii Preface xix Part I Introduction and Overview 1 1 The Basics of Stem Cells and Their Utility as Platforms to Model Teratogen Action and Human Developmental and Degenerative Disorders 3Bindu Prabhakar, Soowan Lee, and Theodore P. Rasmussen 1.1 Stem Cell Types and Basic Function 3 1.2 Pluripotency 6 1.2.1 Poised Chromatin of the Pluripotent Epigenome 6 1.2.2 Undirected Differentiation of Pluripotent Cells to Embryoid Bodies 7 1.2.3 Directed Differentiation of Pluripotent Cells 8 1.3 In vitro Uses of Pluripotent Cells 9 1.3.1 Pluripotent Cells for Toxicology 9 1.3.2 Pluripotent Cells for Teratology 11 1.3.3 Limitations of Pluripotent Stem Cells 12 1.4 Adult Stem Cells in vivo 13 1.5 Emerging Trends in Stem Cell Culture 14 1.5.1 Use of Coculture 15 1.5.2 Organoids 16 1.5.3 Microfluidics 17 1.5.4 Other Cell Types with Stem-Cell-like Properties 18 1.6 Future Directions 18 1.6.1 iPSCs, Pharmacogenomics, and Predictive Teratology 18 1.6.2 Stem Cell Systems for Environmental Toxicology 19 References 20 Part II Using Pluripotent Cells for the Detection and Analysis of Teratogens 25 2 Stem Cells and Tissue Engineering Technologies for Advancing Human Teratogen Screening 27Jiangwa Xing, Geetika Sahni, and Yi-Chin Toh Abbreviations 27 2.1 Introduction 28 2.2 Current DART Regulatory Guidelines and Methods 29 2.2.1 Governing Bodies 29 2.2.2 Terminologies and Definitions 29 2.2.3 Testing Methodologies 30 2.2.4 Limitations of Animal-Based DART Testing 32 2.3 In vitro Animal-Based Models for Developmental Toxicity Testing 33 2.3.1 Current In vitro Animal-Based Models for Developmental Toxicity Testing 33 2.3.2 The MM Assay 35 2.3.3 The WEC Assay 35 2.3.4 The ZEDT Assay 36 2.3.5 New Engineering and Microfabrication Technologies for Model Improvement 38 2.4 In vitro Stem-Cell-Based Developmental Toxicity Models 42 2.4.1 Embryonic Stem Cell Test (EST) 42 2.4.2 ReproGlo Reporter Assay 45 2.4.3 Metabolite Biomarker Assay Using hESCs 46 2.4.4 Mesoendoderm Biomarker-Based Human Pluripotent Stem Cell Test (hPST) 47 2.4.5 The Micropatterned Human Pluripotent Stem Cell Test(μP-hPST) 48 2.5 Conclusion and Future Directions 50 References 51 3 Use of Embryoid Bodies for the Detection of Teratogens and Analysis of Teratogenic Mechanisms 59Anthony Flamier 3.1 Embryoid Body Assays: Background 59 3.1.1 Teratogens and Teratogenesis 59 3.1.2 Classic Protocols for Teratogen Assays 60 3.1.3 Pluripotent Stem Cell Technology and its Applications for Teratogen Detection 62 3.2 Detection of Teratogens Using EBs 63 3.2.1 Formation of Embryoid Bodies for Teratogen Assays 63 3.2.2 Cytotoxicity versus Teratogenicity 65 3.2.3 EB Treatments 65 3.3 Teratogenic Mechanisms 65 3.3.1 EB Growth and Morphogenesis 65 3.3.2 Molecular Analysis 66 3.3.3 Alternative Analyses 67 Acknowledgments 67 References 67 4 Stem-Cell-Based In vitro Morphogenesis Models to Investigate Developmental Toxicity of Chemical Exposures 71Yusuke Marikawa 4.1 Introduction 71 4.2 Stem-Cell-Based In vitro Morphogenesis Model 73 4.2.1 Mouse P19C5 EB as an In vitro Gastrulation Model 73 4.2.2 Quantitative Evaluation of Morphogenetic Impact 77 4.2.3 Detection of Developmentally Toxic Exposures Using Morphometric Analyses 78 4.2.4 Investigations into the Molecular Mechanisms of Teratogen Actions Using P19C5 EBs 81 4.3 Future Directions: Enhancing Morphogenesis-Based Assays 83 4.3.1 Analyses of Changes in Gene Expression Relevant for Teratogenesis 83 4.3.2 Detection of Proteratogens Using Metabolic Systems 84 4.3.3 Representation of Additional Developmental Regulator Signals 84 4.3.4 Recapitulation of Human Embryogenesis Using Human Embryonic Stem Cells 85 4.4 Concluding Remarks 85 Acknowledgment 86 References 86 5 Risk Assessment Using Human Pluripotent Stem Cells: Recent Advances in Developmental Toxicity Screens 91Kristen Buck and Nicole I. zur Nieden 5.1 Introduction 91 5.2 Animal Embryo Studies to Evaluate Developmental Toxicity 91 5.3 Usage of Mouse Embryonic Stem Cells in Developmental Toxicity 94 5.4 Alternative Endpoint Read-Out Approaches in the EST 96 5.4.1 Simple and Complex Methods – Trends Are Ever Changing 96 5.4.2 Genomics, Transcriptomics, Proteomics, and Metabolomics 98 5.5 Novel Methods and Protocols to Replicate Human Development 99 5.5.1 Human Embryonic Stem Cells 100 5.5.2 Multipotent Stem Cells and Beyond 103 5.6 Future Applications 105 Acknowledgments 105 References 106 Part III Human Developmental Pathologies Mediatedby Adult Stem Cells 119 6 Modeling the Brain in the Culture Dish: Advancements and Applications of Induced Pluripotent Stem-Cell-Derived Neurons 121Sandhya Chandrasekaran, Prashanth Rajarajan, Schahram Akbarian, and Kristen Brennand 6.1 Introduction 121 6.2 Methods to Generate Patient-Derived Neurons 122 6.2.1 Directed Differentiation of Neurons from Pluripotent Stem Cells 122 6.2.2 Dopaminergic Neurons 123 6.2.3 Glutamatergic Neurons 123 6.2.4 GABAergic Interneurons 124 6.2.5 Striatal Neurons 125 6.2.6 Other Neurons (Serotonergic and Motor) 126 6.2.7 Limitations of Directed Differentiation 127 6.3 Neuronal Induction from Fibroblasts and hiPSCs 127 6.3.1 Induced Neurons (iNeurons) 128 6.3.2 Dopaminergic iNeurons 129 6.3.3 Glutamatergic iNeurons 130 6.3.4 Induced GABAergic Interneurons 130 6.3.5 Induced Medium Spiny Neurons 131 6.3.6 Serotonergic iNeurons 131 6.3.7 Induced Motor Neurons 131 6.3.8 Limitations of Neuronal Induction 132 6.4 Cerebral Organoids: Neural Modeling in Three Dimensions 132 6.4.1 Current Methods for Deriving Cerebral Organoids 132 6.4.2 Applications of Cerebral Organoids: Disease Modeling 134 6.4.3 Limitations in the Use of Cerebral Organoids 135 6.5 Epigenetic Considerations in hiPSC Donor Cell Choice 136 6.6 Aging Neurons 137 6.6.1 Techniques to Age hiPSCs 137 6.6.2 Aging and Dedifferentiation 138 6.6.3 Future Directions 139 6.7 Drug Testing Using hiPSCs 140 6.7.1 Facilitating Clinical Trials 140 6.7.2 Titrating Drug Dosage 140 6.7.3 Evaluating Chemotherapies 141 6.7.4 Steering Personalized Medicine 141 6.7.5 Forging Neural Networks 142 6.8 Promises in the Field 142 6.8.1 High-Throughput Automation 142 6.8.2 Neural Tissue Engineering Using hiPSCs 142 6.8.3 hiPSC-Based Transplantation Therapies 143 6.8.4 Advances Using Gene-Editing Technologies 144 6.9 Concluding Remarks 145 References 146 7 Modeling Genetic and Environment Interactions Relevant to Huntington’s and Parkinson’s Disease in Human Induced Pluripotent Stem Cells (hiPSCs)-Derived Neurons 159Piyush Joshi, M. Diana Neely, and Aaron B. Bowman 7.1 Gene–Environment Interactions Assessed in hiPSC-Derived Neurons 159 7.2 Modeling of Neurological Diseases with hiPSCs 160 7.3 Cell Viability Assays 162 7.4 Mitochondria 163 7.5 Oxidative Stress 164 7.6 Neurite Length by Immunocytochemistry (ICC) 164 7.7 Conclusions 166 References 167 8 Alcohol Effects on Adult Neural Stem Cells – A Novel Mechanism of Neurotoxicity and Recovery in Alcohol Use Disorders 173Rachael A. Olsufka, Hui Peng, Jessica S. Newton, and Kimberly Nixon 8.1 Introduction 173 8.2 The “Birth” of the Study of “Neuronal Cell Birth” 175 8.3 Components of Adult Stem-Cell-Driven Neurogenesis 180 8.3.1 Permissive Sites of Adult Neurogenesis in Brain 180 8.3.2 Stem Cells Versus Progenitors 182 8.3.3 Proliferation 184 8.3.4 Differentiation and Migration 187 8.3.5 Cell Survival and Integration 188 8.4 Alcohol Effects on Adult Neural Stem Cells and Neurogenesis 189 8.4.1 Proliferation 189 8.4.2 Differentiation and Migration 193 8.4.3 Survival and Integration 194 8.5 Extrinsic Factors Influence the Neurogenic Niche 196 8.6 Alcohol and the Niche 198 8.7 Conclusions 200 References 201 9 Fetal Alcohol Spectrum Disorders: A Stem-Cellopathy? 223Amanda H. Mahnke, Nihal A. Salem, Alexander M. Tseng, Annette S. Fincher, Andrew Klopfer, and Rajesh C. Miranda 9.1 Fetal Alcohol Spectrum Disorders 223 9.2 Stem Cells 225 9.2.1 Totipotent Stem Cells 227 9.2.2 Placental Stem Cells – Trophoblast 230 9.2.3 Embryonic Stem Cells and Induced Pluripotent Stem Cells 231 9.3 Endoderm 234 9.3.1 Liver 234 9.4 Mesoderm 235 9.4.1 Cardiac Development 235 9.4.2 Kidney 237 9.5 Ectoderm 238 9.5.1 Neuroectoderm Development 238 9.5.2 Neural Crest 239 9.5.3 Neural Tube Development 240 9.6 Future Directions 243 9.6.1 Fetal Origin of Adult Stem Cells 243 9.6.2 Sex Differences 244 9.6.3 Stem Cell Therapy 245 9.7 Conclusion 245 References 246 10 Toxicological Responses in Keratinocyte Interfollicular Stem Cells 261Rambon Shamilov and Brian J. Aneskievich 10.1 Epidermal Keratinocyte Stem Cells 261 10.2 Arsenic 267 10.3 Dioxin 269 10.4 Bacterial Toxins 273 10.5 Conclusions and Prospective Considerations 274 References 275 Part IV Recent Innovations in Stem Cell Bioassay and Platform Development 285 11 Stem-Cell Microscale Platforms for Toxicology Screening 287Tiago G. Fernandes and Joaquim M. S. Cabral 11.1 Introduction 287 11.2 Stem Cell Models for Toxicology Assessment 288 11.3 Biomimetic Microscale Systems for Drug Screening 290 11.3.1 Design and Microfabrication: Soft Lithography and Replica Molding 290 11.3.2 Microcontact Printing and Surface Patterning 292 11.3.3 Robotic Spotting and Printing 292 11.4 Microtechnologies for Drug Discovery 293 11.5 Devices for High-Throughput Toxicology Studies 294 11.6 Cellular Microarray Platforms 295 11.7 Microfluidic Platforms 298 11.8 Conclusions and Future Perspectives 301 Acknowledgments 301 References 302 12 HepaRG Cells as a Model for Hepatotoxicity Studies 309André Guillouzo and Christiane Guguen-Guillouzo 12.1 Introduction 309 12.2 Characteristics of HepaRG Cells 310 12.2.1 A Bipotent Human Liver Cell Line 310 12.2.2 HepaRG Hepatocytes Express Liver-Specific Functions 314 12.2.1 Long-Term Functional Stability of HepaRG Hepatocytes 315 12.3 Biotransformation and Detoxification Activities 316 12.3.1 Drug Metabolism Capacity 316 12.3.2 Biokinetics and Intrinsic Clearances 318 12.3.3 Applications 319 12.4 Toxicity Studies 320 12.4.1 Hepatotoxicity Screening 320 12.4.2 Cellular Cytotoxicity 322 12.4.3 Genotoxicity and Carcinogenicity Screening 324 12.4.1 Identification of Target Genes 325 12.4.2 Cholestasis 326 12.4.3 Steatosis 327 12.4.4 Phospholipidosis 328 12.5 Conclusions and Perspectives 328 Acknowledgments 329 References 330 Index 341

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Book SynopsisMost composites, particularly those made using thermoset resins, cannot be recycled or reused. As a result, most of them end up in landfills at the end of their useful life which is neither sustainable nor environment-friendly. Various laws enacted by Governments around the world and heightened global awareness about sustainability and global warming is changing this situation. Significant research is being conducted in developing and utilizing sustainable fibers and resins, mostly derived from plant, to fabricate 'Green' composites. The significant progress in the past 20 or so years in this field has led to the development of green composites with high strength or so called Advanced Green Composites. More interestingly, green composites have also acquired various different properties such as fire resistance, transparency, barrier to gases and others. The term 'advanced' which only included high strength and stiffness now includes all these special properties. The world is on the cuspTable of ContentsPreface xiii 1 Introduction 1Anil N. Netravali 1.1 Introduction 2 2 Green Resins from Plant Sources and Strengthening Mechanisms 11Muhammad M. Rahman and Anil N. Netravali 2.1 Introduction 12 2.2 Green Resins from Agro-Resources 14 2.2.1 Plant Protein-Based Resins 14 2.2.2 Plant Starch-Based Resins 21 2.3 Green Resins from Microbial Fermentation 25 2.3.1 Polyhydroxyalkanoates 25 2.3.2 Pullulan 27 2.4 Green Resins Using Monomers from Agricultural Resources 29 2.4.1 Polylactic Acid 29 2.5 Strengthening of Green Resins using Nano-Fillers 32 2.5.1 Inorganic Nano-Fillers 33 2.5.2 Organic Nano-Fillers 38 2.6 Conclusions 43 References 44 3 High Strength Cellulosic Fibers from Liquid Crystalline Solutions 57Yuxiang Huang and Jonathan Y. Chen 3.1 Introduction 57 3.2 Fibers from Liquid Crystalline Solutions of Cellulose Derivatives 59 3.3 Fibers from Liquid Crystalline Solution of Nonderivatized Cellulose 60 3.4 Regenerated-Cellulose/CNT Composite Fibers with Ionic Liquids 61 3.5 Future Prospects 63 Summary 64 References 65 4 Cellulose Nanofibers: Electrospinning and Nanocellulose Self-Assemblies 67You-Lo Hsieh 4.1 Introduction 68 4.2 Electrospinning of Cellulose Solutions 70 4.3 Cellulose Nanofibers via Electrospinning and Hydrolysis of Cellulose Acetate 70 4.4 Bicomponent Hybrid and Porous Cellulose Nanofibers 72 4.5 Wholly Polysaccharide Cellulose/Chitin/Chitosan Hybrid Nanofibers 74 4.6 Surface-Active Cellulose Nanofibers 76 4.7 Nanocelluloses 77 4.8 Nanocelluloses from Agricultural By-Products 79 4.9 Source Effects – CNCs from Grape Skin, Tomato Peel, Rice Straw, Cotton Linter 80 4.10 Process Effect – Nanocelluloses from Single Source (Corn Cob, Rice Straw) 82 4.11 Ultra-Fine Cellulose Fibers from Electrospinning and Self-Assembled Nanocellulose 85 4.12 Further Notes on Nanocellulose Applications and Nanocomposites 87 Acknowledgement 88 References 88 5 Advanced Green Composites with High Strength and Toughness 97Anil N. Netravali 5.1 Introduction 98 5.2 ‘Greener’ Composites 99 5.3 Fully ‘Green’ Composites 101 5.4 ‘Advanced Green Composites’ 102 5.5 Conclusions 106 References 108 6 All-Cellulose (Cellulose–Cellulose) Green Composites 111Shuji Fujisawa, Tsuguyuki Saito and Akira Isogai 6.1 Introduction 111 6.1.1 Cellulose 111 6.1.2 Nanocelluloses for Polymer Composite Materials 112 6.1.3 All-Cellulose Composites 114 6.2 Preparation of ACCs 114 6.2.1 Dissolution of Cellulose 114 6.2.1.1 Aqueous Solvents 114 6.2.1.2 Organic Solvents 115 6.2.1.3 Ionic Liquids 115 6.2.2 Preparation of ACCs 116 6.2.2.1 One-Phase Preparation 116 6.2.2.2 Two-Phase Preparation 116 6.3 Structures and Properties of ACCs 120 6.3.1 Optical Properties 120 6.3.2 Mechanical Properties 120 6.3.3 Thermal Expansion Behavior 124 6.3.4 Gas Barrier Properties 124 6.3.5 Biodegradability 125 6.4 Future Prospects 125 6.5 Summary 126 6.6 Acknowledgements 127 References 127 7 Self-Healing Green Polymers and Composites 135Joo Ran Kim and Anil N. Netravali 7.1 Introduction 136 7.1.1 Self-Healing Property in Materials: What is it and Why it is Needed? 136 7.2 Types of Self-Healing Approaches Used in Thermoset Polymers 137 7.2.1 Microcapsule-Based Self-Healing System 138 7.2.1.1 Microencapsulation Techniques 139 7.2.1.2 Microcapsule Systems for Self-Healing 148 7.2.2 Vascular Self-Healing System 158 7.2.2.1 One-, Two-, or Three-Dimensional Microvascular Systems 159 7.2.3 Intrinsic Self-Healing System 161 7.2.3.1 Test Methods to Characterize Self-Healing 162 7.2.3.2 Quasi-Static Fracture Methods 163 7.2.3.3 Fatigue Fracture Methods 165 7.2.3.4 Impact Fracture Methods 166 7.2.3.5 Other Techniques 166 7.3 Self-Healing Polymers from Green Sources 167 7.3.1 Self-Healing Polymers in Biomaterials 168 7.3.2 Self-Healing Green Resins and Green Composites 170 7.4 Summary and Prospects 173 Acknowledgements 175 References 175 8 Transparent Green Composites 187Antonio Norio Nakagaito, Yukiko Ishikura and Hitoshi Takagi 8.1 Introduction 187 8.2 Cellulose Nanofiber-Based Composites and Papers 189 8.2.1 Bacterial Cellulose-Based Composites 189 8.2.2 CNF-Based Composites 191 8.2.3 Transparent Nanopapers 194 8.2.4 All Cellulose Transparent Composites 195 8.3 Chitin-Based Transparent Composites 197 8.3.1 Chitin Nanofiber-Based Composites 197 8.3.2 Micro-Sized Chitin Composites 199 8.3.3 Chitin-Chitosan Transparent Green Composites 200 8.3.4 All Chitin Nanofiber Transparent Films 202 8.4 Electronic Devices Based on CNF Films and Composites 202 8.5 Future Prospects 205 8.6 Summary 206 References 206 9 Toughened Green Composites: Improving Impact Properties 211Koichi Goda 9.1 Introduction 211 9.2 Significance of Fiber Length in Toughened Fibrous Composites 212 9.3 Impact Properties of Green Composites 217 9.3.1 Relation Between Interfacial and Mechanical Properties in Green Composites 217 9.3.2 A Pattern of Increase in Tensile Strength and Decrease in Impact Strength 221 9.3.3 Effect of Toughened Resin 227 9.3.4 Approaches to Increase Both TS and IS 228 9.4 Role of Large Elongation at Break in Regenerated Cellulose Fibers 229 9.5 Toughened Cellulose Fibers and Green Composites 231 9.5.1 Toughening Mechanism of Regenerated Cellulose Fibers 231 9.5.2 Mercerization Effect 234 9.5.3 Other Beneficial Chemical Treatments 238 9.6 Conclusions 240 Appendix 241 References 243 10 Cellulose Reinforced Green Foams 247Jasmina Obradovic, Carl Lange, Jan Gustafsson and Pedro Fardim 10.1 Introduction 248 10.2 Bio-Based Foams 249 10.2.1 Starch-Based Foams 250 10.2.2 Foams Based on Vegetable Oils 253 10.2.3 Foams Based on Poly(Lactic Acid) 255 10.3 Surface Engineering of Cellulose Fibres Used in Foams 256 10.3.1 Chemical Modifications of Cellulose Fibres 257 10.3.2 In Situ Synthesis of Hybrid Fibres 258 10.3.2.1 Topology and Particle Content on Hybrid Fibres 260 10.3.2.2 Foam Formation 262 10.3.2.3 Combustion Behavior of Foams 262 10.4 Prospects 265 10.5 Summary 266 Acknowledgements 267 References 267 11 Fire Retardants from Renewable Resources 275Zhiyu Xia, Weeradech Kiratitanavit, Shiran Yu, Jayant Kumar, Ravi Mosurkal and Ramaswamy Nagarajan 11.1 Introduction 276 11.2 Fire Retardant Additives Based on Phosphorus and Nitrogen from Renewable Resources 278 11.2.1 Nucleic Acids 279 11.2.2 Proteins Containing Phosphorus and Sulfur 286 11.2.3 Phosphorus/Nitrogen-Rich Carbohydrates 289 11.2.4 Carbohydrates 291 11.3 Natural Phenolic Compounds as Flame Retardant Additives 295 11.3.1 Lignin 296 11.3.2 Tannins 300 11.3.3 Cardanol and Polymers of Cardanol 306 11.3.4 Polydopamines 307 11.4 Other FR Materials from Renewable Sources 308 11.4.1 Chicken Eggshell 308 11.4.2 Banana Pseudostem Sap 308 11.5 Prospects 310 11.6 Summary 311 11.7 Acknowledgements 312 References 312 12 Green Composites with Excellent Barrier Properties 321Arvind Gupta, Akhilesh Kumar Pal, Rahul Patwa, Prodyut Dhar and Vimal Katiyar 12.1 Introduction 321 12.2 Biodegradable Polymers: Classifications and Challenges 323 12.2.1 Poly (lactic acid): Properties Evaluation, Modifications and its Applications 328 12.2.2 Cellulose Based Composites: Chemical Modifications, Property Evaluation, and Applications. 333 12.2.3 Chitosan Based Composites: Chemical Modifications, Properties Evaluation, and Applications 338 12.2.4 Natural Gum Based Composites: Chemical Modification, Property Evaluation and Applications 343 12.2.5 Silk Based Composites: Property Evaluation, Chemical Modifications and Applications 348 12.3 Summary 355 Acknowledgements 355 References 356 13 Nanocellulose-Based Composites in Biomedical Applications 369M. Osorio, A. Cañas, R. Zuluaga, P. Gañán, I. Ortiz and C. Castro 13.1 Introduction 370 13.2 Nanocellulose Sources and Properties 370 13.2.1 Nanocellulose Sources 370 13.2.2 Nanocellulose Characteristics as Green Material 373 13.2.3 Nanocellulose Properties for Biomedical Composites 374 13.2.3.1 Mechanical Properties 374 13.2.3.2 Morphology 375 13.2.3.3 Surface Charge 375 13.2.3.4 Conformability 378 13.2.3.5 Thermal Properties 378 13.2.3.6 Non-Toxic 379 13.2.3.7 Biocompatibility 379 13.3 Biomedical Applications of Nanocellulose-Based Composites 379 13.3.1 Nanocellulose-Based Composites with Various Polymers 380 13.3.1.1 Polyvinyl Alcohol 380 13.3.1.2 Chitosan (Ch) 381 13.3.1.3 Acrylic Acid (AA) 382 13.3.1.4 Polyhydroxyalkanoates (PHAs) 382 13.3.1.5 Silk Fibroin 383 13.3.1.6 Polyaniline and Polypyrrole 383 13.3.1.7 Alginate 384 13.3.1.8 Collagen 384 13.3.2 Nanocellulose-Based Composites with Bioactive Ceramics 385 13.3.2.1 Hydroxyapatite (HA) 385 13.3.2.2 Iron Oxide Nanoparticles 385 13.3.2.3 Calcium Peroxide (CaO2) 386 13.3.2.4 Carbon Nanotubes 386 13.3.3 Nanocellulose-Based Composites with Metals 386 13.3.3.1 Silver Nanoparticles (Ag) 386 13.3.3.2 Gold Nanoparticles (Au) 387 13.4 Summary 387 13.5 Prospects 390 Acknowledgments 390 References 390 Index 403

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Book SynopsisMolecularly imprinted polymers (MIPs) are an important functional material because of their potential implications in diverse research fields. The materials have been developed for a range of uses including separation, environmental, biomedical and sensor applications.Table of ContentsPreface xiii Part 1 Strategies of Affinity Materials 1 Recent Molecularly Imprinted Polymer-based Methods for Sample Preparation 3 Antonio Martín-Esteban 1.1 Introduction 3 1.2 Molecularly Imprinted Solid-phase Extraction 6 1.3 Molecularly Imprinted Solid-phase Microextraction 14 1.4 Molecularly Imprinted Stir Bar Sorptive Extraction 17 1.5 Other Formats 18 1.6 Conclusions 20 References 21 2 A Genuine Combination of Solvent-free Sample Preparation Technique and Molecularly Imprinted Nanomaterials 29 Santanu Patra, Ekta Roy, Rashmi Madhuri and Prashant K. Sharma 2.1 Introduction 30 2.2 Molecularly Imprinted Polymer Modified Fiber for Solid-phase Microextraction 40 2.3 In-tube Solid-phase Microextraction Technique 55 2.4 Monolithic Fiber 58 2.5 Micro-solid-phase Extraction 70 2.6 Stir-bar Sorptive Extraction 73 2.7 Conclusion and Future Scope 76 Acknowledgments 76 Abbreviations 77 References 78 3 Fluorescent Molecularly Imprinted Polymers 89 Kornelia Gawlitza, Wei Wan, Sabine Wagner and Knut Rurack 3.1 Introduction 89 3.2 Classes of Emitters to Endow MIPs with Fluorescence 91 3.3 Fluorescent Molecularly Imprinted Silica 108 3.4 Post-imprinting of MIPs 111 3.5 fMIPs as Labels 113 3.6 Formats for fMIPs 115 3.7 Conclusion 119 References 120 4 Molecularly Imprinted Polymer-based Micro- and Nanotraps for Solid-phase Extraction 129 Rıdvan Say, Rüstem Keçili and Arzu Ersöz 4.1 Introduction 130 4.2 MIPs as SPE Materials 130 4.3 Conclusions 149 References 153 5 Imprinted Carbonaceous Nanomaterials: A Tiny Looking Big Thing in the Field of Selective and Secific Analysis 165 Ekta Roy, Santanu Patra, Rashmi Madhuri and Prashant K. Sharma 5.1 Introduction 166 5.2 Graphene-modified Imprinted Polymer 179 5.3 Carbon Nanotubes-modified Imprinted Polymer 190 5.4 Combination of graphene, CNTs, and MIPs 197 5.5 Graphene Quantum Dots and/or Carbon Dots 198 5.6 Fullerene 201 5.7 Activated carbon 202 5.8 Conclusions 203 Acknowledgments 204 List of abbreviations 204 References 205 6 Molecularly Imprinted Materials for Fiber-optic Sensor Platforms 217 Yavuz Orhan Yaman, Necdet Başaran, Kübra Karayagiz, Zafer Vatansever, Cengiz Yegin, Önder Haluk Tekbaş and Müfrettin Murat Sari 6.1 Introduction 218 6.2 Material Aspect: Morphology and Physical Forms of MIPs in FO Sensors 223 6.3 Molecularly Imprinting Technology for Fiber-optic Sensors 231 6.4 State-of-the-art Fiber-optic Sensors Applications Using Molecularly Imprinted Materials 268 6.5 Conclusion 273 References 274 Part 2 Rational Design of MIP for Advanced Applications 7 Molecularly Imprinted Polymer-based Sensors for Biomedical and Environmental Applications 285 Anca Florea, Oana Hosu, Bianca Ciui and Cecilia Cristea 7.1 Introduction 285 7.2 Molecularly Imprinted Polymers for Analytes of Biomedical Interest 296 7.3 Molecularly Imprinted Polymers for Analytes of Environmental Interest 306 7.4 Conclusion 314 Acknowledgments 316 References 316 8 Molecularly Imprinted Polymers: The Affinity Adsorbents for Environmental Biotechnology 327 Bo Mattiasson and Gizem Ertürk 8.1 Introduction 327 8.2 Molecularly Imprinted Polymers 329 8.3 Monomers 329 8.4 Cross-linking Agents 331 8.5 Mode of Polymerization 332 8.6 Cryogels 334 8.7 Process Technology 336 8.8 Applications 338 References 345 9 Molecular Imprinting Technology for Sensing and Separation in Food Safety 353 Baran Önal Ulusoy, Mehmet Odabaşi and Neşe Hayat Aksoy 9.1 Food Safety 354 9.2 Food Analysis 355 9.3 Current Separation Methods Used for Food Safety Purposes 356 9.4 What Is MIP? 357 9.5 MIP Applications Used for Food Safety Purposes 359 References 377 10 Advanced Imprinted Materials for Virus Monitoring 389 Zeynep Altintas 10.1 Introduction 390 10.2 Virus Imprinting 393 10.3 Artificial MIP Receptors for Viruses 398 10.4 Virus Monitoring and Detection Using Biomimetic Sensors 399 10.5 Virus Imprinting for Separation Technologies 401 10.6 Conclusions 405 References 406 11 Design and Evaluation of Molecularly Imprinted Polymers as Drug Delivery Systems 413 André Luís Morais Ruela and Gislaine Ribeiro Pereira 11.1 Introduction 414 11.2 Synthesis and Characterization of MIPs Intended for Drug Release Using Non-covalent Approaches 418 11.3 Design and Evaluation of Drug Delivery Systems Based on MIPs 436 11.4 Conclusions 445 References 446 12 Molecularly Imprinted Materials for Controlled Release Systems 455 Yagmur Yegin, Gökhan Yilmaz, Ömer Karakoç, Cengiz Yegin, Servet Çete, Mustafa Akbulut and Müfrettin Murat Sari 12.1 Introduction 456 12.2 Selectivity, Release Mechanism and Functionality of MIPs-based CR Systems 459 12.3 Molecularly Imprinted Polymers Production for Controlled Release 482 12.4 Controlled Release Applications Using Molecularly Imprinted Materials-based Controlled Release 491 12.5 Conclusion 506 References 507 13 Molecular Imprinting: The Creation of Biorecognition Imprints on the Biosensor Surfaces 523 Gizem Ertürk and Bo Mattiasson 13.1 Introduction 523 13.2 Molecular Imprinting 524 13.3 Microcontact Imprinting 525 13.4 Capacitive Biosensors 529 13.5 Surface Plasmon Resonance Biosensors 541 13.6 Concluding Remarks 549 References 550 14 Molecular Imprinted Polymers for Sensing of Volatile Organic Compounds in Human Body Odor 561 Sunil Kr. Jha 14.1 Introduction 562 14.2 MIP-QCM Sensor Array Preparation 573 14.3 Chemical Vapor Sensing 576 14.4 Analysis Outcomes 603 14.5 Conclusion 624 Acknowledgments 624 References 624 15 Development of Molecularly Imprinted Polymer-based Microcantilever Sensor System 637 Meltem Okan and Memed Duman 15.1 Introduction to Mass Sensors 637 15.2 Principles of Mass Sensors 640 15.4 Molecularly Imprinted Polymer Technology 655 15.5 Molecularly Imprinted Polymer-based QCM Sensors 658 15.6 Ongoing Studies on Molecularly Imprinted Polymers-based Microcantilevers 661 Acknowledgments 669 References 669

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Book SynopsisAn important guide that reviews the basics of magnetic biosensor modeling and simulation Magnetic Sensors for Biomedical Applicationsoffers a comprehensive review of magnetic biosensor modelling and simulation. The authorsnoted experts on the topicexplore the model's strengths and weaknesses and discuss the competencies of different modelling software, including homemade and commercial (for example Multi-physics modelling software). The section on sensor materials examines promising materials whose properties have been used for sensing action and predicts future smart-materials that have the potential for sensing application. Next, the authors present classifications of sensors that are divided into different sub-types. They describe their working and highlight important applications that reveal the benefits and drawbacks of relevant designs. The book also contains information on the most recent developments in the field of each sensor type. This important book: Provides an even treTable of ContentsPreface xiii 1 Introduction 1 1.1 Overview 1 1.2 History of Magnetism Studies and of Its Use in Magnetic Sensors 2 1.3 Natural and Technical Magnetic Fields and Their Order of Magnitude 3 1.3.1 Natural Magnetic Fields 3 1.3.1.1 The Earth’s Magnetic Field 3 1.3.1.2 Magnetic Fields in Outer Space 3 1.3.1.3 Biomagnetic Fields 3 1.3.2 Technical Magnetic Fields 5 1.3.2.1 Magnetic Fields in the Vicinity of Transformers and Electric Motors 5 1.3.2.2 Fields of Permanent Magnets 5 1.4 Magnetic Terms and Units 6 1.5 Magnetic (Micro) Sensors 7 1.5.1 Definition of Magnetic Sensors 7 1.5.2 Soft and Hard Magnetic Materials for Sensors 8 1.5.2.1 Shape of the Hysteresis Loop 8 1.5.2.2 Saturation Polarization Js and Coercivity Hc 10 1.5.2.3 Initial Permeability μi 10 1.5.2.4 Specific Electrical Resistivity ρ 11 1.5.3 Mechanical Properties of Magnetic Materials 12 1.5.4 Relations Between Sensing Techniques and Sensor Applications 12 1.5.5 Classification of Magnetic Sensors 14 1.6 Characteristics of Magnetic Sensors 15 1.6.1 Characteristics Related to OUT(B)C 15 1.6.1.1 Magnetosensitivity 15 1.6.1.2 Nonlinearity 16 1.6.1.3 Calibration 17 1.6.1.4 Sensor Excitation 17 1.6.1.5 Frequency Response 17 1.6.1.6 Resolution 17 1.6.1.7 Error 17 1.6.1.8 Accuracy 18 1.6.1.9 Hysteresis 18 1.6.1.10 Repeatability 18 1.6.2 Characteristics Related to OUT(C)B 18 1.6.2.1 Noise 18 1.6.2.2 Offset 18 1.6.2.3 Cross-Sensitivity and Temperature Error 19 1.6.2.4 Drift and Creep 19 1.6.2.5 Response Time 19 1.6.3 Characteristics Related to the System Description 19 1.6.3.1 Electrical Excitation 19 1.6.3.2 Input and Output Impedance 20 1.6.3.3 Environmental Conditions 20 1.7 Magnetic Noise 20 1.7.1 Noise Formalism 20 1.7.1.1 Fluctuations, Average and Distribution 20 1.7.1.2 Correlations 22 1.7.1.3 Frequency Space and Spectral Density 22 1.7.2 Sensitivity, Signal-to-Noise Ratio, and Detectivity 24 1.7.3 Different Sources of Noise 25 1.7.3.1 Separation of Magnetic and Nonmagnetic Noise 25 1.7.3.2 Frequency-Independent Noise (Thermal or Johnson–Nyquist Noise), Shot Noise 25 1.7.4 Low Frequency Noise 26 1.7.4.1 1/f Noise 26 1.7.4.2 Random Telegraph Noise 28 1.7.5 High Frequency Noise and Ferromagnetic Resonance 28 1.7.6 External Noise 29 1.7.7 Electronics and Noise Measurements 29 1.7.7.1 Electronics Design 29 1.7.7.2 Connections Noise 30 1.7.7.3 Correlation for Preamplification Noise Suppression 30 References 30 2 Magnetic Sensors Based on Hall Effect 33 2.1 Overview 33 2.2 Devices Based on Hall Effect 34 2.2.1 Geometry 34 2.2.2 Material 35 2.3 Horizontal Versus Vertical CMOS Hall Devices 36 2.4 Current-Mode Versus Voltage-Mode Technique 37 2.5 Magnetic Sensor Characteristics 39 2.5.1 Sensitivity 39 2.5.2 Offset 43 2.5.2.1 Current Spinning Technique 44 2.5.3 Noise 46 2.5.4 Nonlinearity 46 2.6 State-of-the-art in CMOS Hall Magnetic Sensors 47 2.6.1 Sensitivity Improvement 47 2.6.2 Offset Reduction 48 2.7 Applications of Hall Magnetic Sensors 49 2.7.1 Biosensors 49 2.7.2 Contactless Current Sensors 50 2.7.3 Contactless Angular, Linear, and Joystick Position Sensors 50 2.7.4 Electronic Compass 51 2.7.5 Speed and Timing Sensors 52 2.7.6 Specific Sensors 52 References 53 3 Magnetoresistive Sensors 57 3.1 Introduction 57 3.2 Materials and Principles of AMR, GMR, and TMR 58 3.2.1 Anisotropic Magnetoresistance 58 3.2.1.1 Anisotropic Magnetoresistance Effect and Principles 58 3.2.1.2 AMR Device Material 61 3.2.2 Giant Magnetoresistance 62 3.2.2.1 Giant Magnetoresistance Effect and Principles 62 3.2.2.2 Mechanism of GMR Effect 64 3.2.2.3 GMR Effect in Multilayers 66 3.2.3 Magnetic Tunnel Junctions 67 3.2.3.1 TMR Structures 69 3.3 Classes of Magnetoresistive Sensors 71 3.3.1 General Purpose Magnetometers 71 3.3.2 MR Sensors in Harsh Environments 73 3.3.3 Electrical Current Sensing 74 3.3.3.1 Industrial Electronics Applications (Large to Medium Currents) 75 3.3.3.2 Differential Currents 76 3.3.3.3 Switching Regulators 76 3.3.3.4 Wattmeter 77 3.3.3.5 IC Current Monitoring 78 3.3.4 Automotive Applications 78 3.3.4.1 BLDC Rotor Position Measurement 78 3.3.4.2 Steering Angle Application 79 3.3.4.3 Crankshaft Speed and Position Measurement 79 3.3.4.4 Wheel Speed Measurement for ABS and ESC Systems 80 3.3.5 Magnetoresistive Elements in Data Storage Applications 80 3.3.6 Space 81 3.4 Modeling and Simulations 81 3.4.1 Finite Element Modeling and Methodology 81 3.4.2 Finite Element Method 82 3.4.3 Finite Difference Method 82 3.4.4 The Boundary Element Method 82 3.4.5 MR Sensors Simulation and Modeling 83 3.5 Design and Fabrication Technologies 87 3.5.1 GMR Devices 87 3.5.1.1 Deposition Techniques 87 3.5.1.2 Patterning 90 3.6 Biomedical Magnetoresistive Sensing Applications 94 3.6.1 Detection of Bioanalytes 95 3.6.2 Monitoring of Magnetic Fluids 95 3.6.3 Biomolecular Recognition Experiments 95 3.6.4 Ultrasensitive Magnetic Array for Recording of Neuronal Activity (UMANA) 98 References 100 4 Resonance Magnetometers 113 4.1 Introduction 113 4.2 Nuclear Magnetic Resonance 115 4.2.1 Classical Model 116 4.2.1.1 Rotating Frame of Reference 117 4.2.1.2 Strength of RF Pulses 117 4.2.2 Basic Design of a NMR Spectrometer 118 4.2.3 Nuclear Magnetic Resonance in Molecular and Atomic Beams 120 4.2.4 The Sources of Magnetic Fields 123 4.2.5 NMR Spins Used in Life Science 124 4.2.6 NMR Relaxation 125 4.2.6.1 Relaxation Rates 125 4.2.6.2 Molecular Mechanisms Leading to Relaxation 126 4.2.7 NMR and Biological Structures 127 4.2.8 Difficulties in Studying Biological System by NMR 128 4.2.8.1 Sensitivity 128 4.2.8.2 Resolution 129 4.2.8.3 Water Signal 129 4.2.8.4 Line Widths 130 4.2.8.5 Quantification 130 4.3 Magnetic Resonance Imaging 130 4.3.1 Introduction 130 4.3.2 The Obtaining of Spin Images from NMR Induction Signals in Inhomogeneous Field 131 4.3.3 MRI Instrumentation 132 4.3.3.1 Magnets and Designs 135 4.3.3.2 Resistive Electromagnets 135 4.3.3.3 Permanent Magnets 136 4.3.3.4 Superconducting 136 4.3.3.5 Stability, Homogeneity, and Fringe Field 137 4.3.3.6 Gradient Coils 137 4.3.3.7 RF Coils 138 4.3.3.8 RF Decoupling 138 4.3.4 MRI of Flow 139 4.3.4.1 Time-of-Flight Techniques 139 4.4 Electron Spin Resonance 143 4.4.1 The ESR Experiment 145 4.4.1.1 Sensitivity 146 4.4.1.2 Saturation 147 4.4.2 Operation of an ESR Spectrometer 147 4.4.3 Optimization of Operating Parameters 150 4.4.3.1 Microwave Frequency 150 4.4.3.2 Center Field, Sweep Width, and Field Offset 151 4.4.3.3 Sweep Time 151 4.4.3.4 Modulation Frequency 151 4.4.3.5 Second Harmonic Detection 151 4.4.3.6 Modulation Amplitude 152 4.4.3.7 Modulation Phase 152 4.4.3.8 Signal Gain 152 4.4.4 Biological Application of the ESR 152 4.4.4.1 ESR Oximetry 153 4.4.4.2 Direct Detection of Paramagnetic Species 154 4.4.4.3 EPR Revealed the Nitrite Reductase Activity of Myoglobin 155 4.4.4.4 Mitochondrial Dysfunction in Severe Sepsis 155 4.4.4.5 Spin Trapping ESR 155 References 157 5 SQUID Sensors 163 5.1 Introduction 163 5.1.1 History 163 5.2 SQUID Fundamentals 164 5.2.1 Josephson Junctions 164 5.2.2 DC SQUIDs 166 5.2.2.1 Practical Devices 171 5.2.3 rf SQUID 174 5.2.4 Cryogenics and Systems 177 5.2.5 SQUID Electronics 178 5.2.5.1 Flux Locked Loop 178 5.3 SQUID Fabrication 180 5.4 Lithography and Thin-Film Techniques 180 5.4.1 Junction Fabrication 182 5.5 SQUID Applications in Biomagnetism 183 5.5.1 Biomagnetism 183 5.5.2 History of SQUID Applications in Biomagnetism 184 5.5.3 Biomagnetic Fields 185 5.5.3.1 Gradiometers 186 5.5.4 Magnetoencephalography 188 5.5.4.1 MEG Signals 189 5.5.4.2 Sensor Types for MEG 191 5.5.5 Magnetocardiography 195 5.5.5.1 Cardiomagnetic Instrumentation 196 5.5.6 Magnetoneurography 197 5.5.6.1 History of Measuring Signal Propagation in Nerves 197 5.5.6.2 Measurement Technique and Signal Processing 199 5.5.6.3 Source Modeling for Magnetoneurography 200 5.5.6.4 Clinical Perspective 200 References 201 6 Conclusion 213 6.1 Outlook 213 6.2 A Conclusion on Galvanomagnetic Sensors 214 6.2.1 Hall Elements: Hall Voltage Mode Versus Hall Current Mode and Magnetoresistance Mode of Operation 215 6.2.2 Hall Sensors Versus Ferromagnetic Magnetoresistors 215 6.2.3 Performance of Integrated Hall Magnetic Sensors 216 6.2.4 Performance of Ferromagnetic Magnetoresistors 216 6.2.5 Integrated Hall Sensors Versus AMRs and GMRs 218 6.3 A Conclusion on NMR and ESR Spectroscopy 218 6.3.1 Differences Between NMR and ESR 219 6.3.1.1 Resonant Frequency 219 6.3.1.2 Relaxation Times 219 6.3.1.3 Differences Between ESR and NMR Imaging 220 6.3.1.4 ESR Applications 220 6.4 Superconductive Quantum Interference Devices 221 6.4.1 SQUID Fabrication Trend 221 6.4.2 Trends in SQUID Electronics 222 6.4.3 Trends in SQUIDs for Nondestructive Evaluation of Materials 222 References 223 Index 225

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Book SynopsisNANOMATERIALS AND NANOTECHNOLOGY IN MEDICINE A comprehensive introduction to nanomaterials and their application in the field of medicine The use of nanotechnology and nanomaterials more generally is an emerging field that has generated a lot of interest in the last few years. To this point, there have been few books that deal with the recent advances in nanomaterials or nanocomposites in the medical discipline. Intended as a one-stop reference, Nanomaterials and Nanotechnology in Medicine provides the reader with the most-up-to-date and comprehensive exploration of the field of nanomedicine. The scope of the topic is huge, with nano applications in every medical specializationfrom diagnostics to pharmaceuticals, from biological therapies to surgical devices, and from regenerative therapies to gene therapy. As such, this volume provides the most comprehensive coverage of this intriguing field of study. Nanomaterials and Nanotechnology in Medicine readers will also find: An applicatTable of ContentsList of Contributors xi Preface xvii 1 Nanomaterials and Nanotechnology in Medicine 1 P. M. Visakh 1.1 Nanoneurology 1 1.2 Nanomolecular Diagnostics 3 1.3 Nanopharmaceuticals 4 1.4 Role of Nanotechnology in Biological Therapies 6 1.5 Nanomaterials for Gene Therapy 8 1.6 Nanotools for the Treatment of Ocular Diseases 10 1.7 Nanotechnology Applications in Food and Nutrition Science 11 1.8 Rubber Nanocomposites for Biomedical Applications 13 References 15 2 Nanoneurology 27 LironL. Israel and Eggehard Holler 2.1 Introduction and Recent Advances 27 2.2 Types of Nanomaterials 30 2.3 Nanomaterial Applications for Neurodegenerative Diseases 32 2.4 Nanomaterial Applications for Strokes 38 2.5 Nanomaterial Applications for Spinal Cord Injuries 41 2.6 Nanomaterial Applications for Brain Tumors 44 2.7 Adverse Effects of Nanomaterials 50 2.8 Regulatory Issues 53 2.9 Conclusions 54 References 54 3 Nanomolecular Diagnostics 65 Anila Fariq, Ayesha Selhaba, Anum Zulfiqar, and Azra Yasmin 3.1 Introduction 65 3.2 Nanodiagnostics 67 3.3 Nanoparticles for Molecular Diagnostics 68 ftoc.indd 5 04/25/2022 14:43:47 vi  Contents 3.4 Applications of Nanoparticles for Molecular Diagnostics 75 3.5 Comparison Between Nanomaterials and Other Materials in Molecular Diagnostics 79 3.6 Prospects of Nanodiagnostics 79 3.7 Regulatory Issues 80 3.8 Conclusion 81 References 82 4 Nanopharmaceuticals 87 David Quintanar-Guerrero, Gerardo Leyva-Gómez, Nancy Evelyn Magaña Vergara, and Néstor Mendoza Muñoz 4.1 Introduction 87 4.2 Liposomes in Nanopharmaceuticals 89 4.3 Polymeric Nanoparticles in Nanopharmaceuticals 93 4.4 Solid Lipid Nanoparticles in Nanopharmaceuticals 99 4.5 Dendrimers in Nanopharmaceuticals 101 4.6 Quantum Dots in Nanopharmaceuticals 104 4.7 Regulatory Issues 106 4.8 Conclusion 109 References 109 5 Role of Nanotechnology in Biological Therapies 115 Blanca Ocampo-García, Liliana Aranda Lara, Guillermina Ferro-Flores, Enrique Morales-Avila, and Keila Isaac-Olivé 5.1 Introduction 115 5.2 Biological Therapies 116 5.3 Nanoparticles in Biological Therapies 118 5.4 Application of Nanotechnology in Biological Therapies 131 5.5 Advantages and Disadvantages of Nanoparticles in Biological Therapies 136 5.6 Conclusion 137 References 137 6 Nanomaterials for Gene Therapy 153 V. Karthik, A. Vigneshwaran, D. Dharun Daniel Raj, T.G.N. Nagrajun, S. Poornima, R. Subbaiya, and M. Saravanan 6.1 Introduction and Recent Advances 153 6.2 Nanomaterials and their Physicochemical Properties 153 6.3 Methods of Characterizing the Physicochemical Properties of Nanomaterials 154 6.4 Target Organ Biocompatibility/Toxicity 155 6.5 Gene Delivery 158 6.6 Regulatory Issues 163 References 163 7 Nanotools for the Treatment of Ocular Diseases 169 Elisa J. Campos, António Campos, João Martins, and António F. Ambrósio 7.1 Introduction 169 ftoc.indd 6 04/25/2022 14:43:47 Contents vii 7.2 Ocular Anatomy 170 7.3 Physiological Barriers in the Eye 171 7.4 Methods of Ocular Disease Treatment 173 7.5 Nanomedicine in Ocular Therapy 174 7.6 Closing Remarks 180 Conflict of Interest 181 References 181 8 Nanotechnology Applications in Food and Nutrition Science 185 Kobra S. Rizi, Majid Rezayi, Ehsan Aryan, Zahra Meshkat, and Majid G. Mobarhan 8.1 Introduction 185 8.2 Nanostructured Delivery Systems 186 8.3 Nanoparticles Based on Inorganic Materials 202 8.4 Metal Nanoparticles 204 8.5 Conclusion 205 References 206 9 Rubber Nanocomposites for Biomedical Applications 225 Jayalatha Gopalakrishnan 9.1 Introduction 225 9.2 Rubbers for Biomedical Applications 226 9.3 Rubber- based Nanocomposites 229 9.4 Conclusions 246 References 246 10 Nanomaterials and Nanotechnology in Medicine 251 P. M Visakh 10.1 Nanomaterials and Scaffolds for Tissue Engineering and Regenerative Medicine 251 10.2 Nanorobotics in Nanomedicine 253 10.3 Nanosensors 255 10.4 Inorganic Nanoparticles for Drug-delivery Applications 257 10.5 Intelligent Nanomaterials for Medicine 259 10.6 Polymer- based Nanocomposites for Biomedical Applications 261 10.7 Toxicity of Nanomaterials 263 10.8 Multifunctional Nanomaterials for Medical Applications 264 10.9 Antimicrobial Applications of Nanoparticles 265 References 266 11 Nanomaterials and Scaffolds for Tissue Engineering and Regenerative Medicine 279 Saeid Kargozar, Simin Nazarnezhad, Farzad Kermani, and Francesco Baino 11.1 Introduction and Recent Advances 279 11.2 Tissue Engineering and Regenerative Medicine: General Concepts 280 11.3 Implantable Nanomaterials to Regenerate Living Tissues 282 11.4 Nanomaterials as Carriers for Therapeutic Agents 283 ftoc.indd 7 04/25/2022 14:43:47 viii  Contents 11.5 Nanofibrous Scaffolds 285 11.6 Nano- topography Techniques for Tissue-engineered Scaffolds 288 11.7 Regulatory Issues 290 11.8 Conclusion 290 References 291 12 Nanorobotics in Nanomedicine 303 Vaishali Y. Londhe and Rupali S. Bhadale 12.1 Introduction 303 12.2 What is Nanorobotics? 304 12.3 Nanorobotics in Nanomedicines 306 12.4 Nanorobots for Medical Imaging 307 12.5 Nanorobots for Targeted Drug Delivery 309 12.6 Enzymatic Nanolithography 313 12.7 Biomimetic Approach 314 12.8 Cell Biochips 315 12.9 Nanorobots for Precision Surgery 315 12.10 Nanorobots for Detoxification 317 12.11 Fabrication of Nanorobots 318 12.12 Toxicity 321 12.13 Administration and Retrieval 321 12.14 Clinical Presence of Nanorobots 322 12.15 Reproducibility and Standardization 322 12.16 Regulatory Issues 323 12.17 Conclusion 324 References 325 13 Nanosensors 333 Asit Behera, A.K. Sahoo and S.S. Mohapatra 13.1 Introduction and Recent Advances 333 13.2 Classification of Nanosensors 336 13.3 Nanosensor Fabrication 339 13.4 Inorganic Nanosensors 343 13.5 Biopolymer- derived Nanosensors 346 13.6 Applications 348 13.7 Regulatory Issues 358 13.8 Conclusions 359 References 360 14 Inorganic Nanoparticles for Drug-delivery Applications 367 Chinnu Sabu, V.K. Ameena Shirin, Renu Sankar and K. Pramod 14.1 Introduction 367 14.2 Synthesis of Inorganic Nanoparticles 368 14.3 Properties of Inorganic Nanoparticles 371 ftoc.indd 8 04/25/2022 14:43:47 Contents ix 14.4 Functionalization of Inorganic Nanoparticles 372 14.5 Quantum Dots for Drug Delivery 374 14.6 Drug Delivery by Mesoporous Silica Nanoparticles 376 14.7 Silver Nanoparticles for Drug Delivery 379 14.8 Gold Nanoparticles for Drug Delivery 383 14.9 Superparamagnetic Iron Oxide Nanoparticles for Drug Delivery 385 14.10 Hybrid Systems of Inorganic Nanoparticles 386 14.11 Prospects of Inorganic Nanoparticles 388 14.12 Conclusion 388 References 388 15 Intelligent Nanomaterials for Medicine 401 Ajit Behera and Ranjan K. Mohapatra 15.1 Introduction to Intelligent Nanomaterials 401 15.2 Design and Function of Intelligent Nanoparticles 403 15.3 Various Intelligent Materials for Medicines 405 15.4 Type of Stimuli in Intelligent Nanomaterials in Medicine 415 15.5 Clinical Applications of Intelligent Nanomaterials 416 15.6 Potential Risk Factors in Nanomaterial Application 419 15.7 Summary and Future Prospects 420 References 420 16 Polymer-based Nanocomposites for Biomedical Applications 427 Chander Amgoth, Kaxi Yu, Shuai Chen, Hongzhen Bai and Guping Tang 16.1 Introduction and Recent Advances 427 16.2 Polymers for Biomedical Fields 428 16.3 Synthesis of Nanocomposites 432 16.4 Characterization Tools for Nanocomposites 432 16.5 Size, Shape, and Morphology of Nanocomposites 433 16.6 Polymer Nanocomposites for Various Applications 436 16.7 Nanocomposites for Molecular Diagnosis and Biopharmaceutics 437 16.8 Perspectives of Nanocomposites 441 16.9 Conclusion 442 References 442 17 Toxicity of Nanomaterials 447 Elham Abohamzeh, M. Sheikholeslami and Ahmad Shafee 17.1 Introduction and Recent Advances 447 17.2 Biomedical Applications of Nanomaterials 449 17.3 Biodistribution, Mechanism, and Excretion of Nanomaterials 453 17.4 Toxicity of Nanomaterials 457 17.5 Physicochemical Properties and Toxicity of Nanomaterials 461 17.6 Regulatory Issues 464 17.7 Conclusion 466 ftoc.indd 9 04/25/2022 14:43:47 x  Contents References 466 18 Multifunctional Nanomaterials for Medical Applications 479 Jitha S Jayan, Ramya Rajan, Saritha Appukuttan, and Kuruvilla Joseph 18.1 Introduction and Recent Advances 479 18.2 Multifunctional Nanomaterials 481 18.3 Diagnostic Application 483 18.4 Therapeutic Application 485 18.5 External Stimuli-responsive Nanoparticles for Medicinal Applications 487 18.6 Regulatory Issues 498 18.7 Conclusion and Future Perspectives 498 References 499 19 Antimicrobial Applications of Nanoparticles 517 19.1 Introduction 517 19.2 Antimicrobial Properties of Nanoparticles 518 19.3 Antimicrobial Applications of Nanoparticles 525 19.4 Conclusions 539 References 540 Index 000

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Book SynopsisSince the launch of Telemedicine Technologies (Wiley, 2010), the technologies surrounding telemedicine have changed immeasurably, particularly with the emerging trends of Internet-of-Things (IoT), digital/e-Health, and wearable, smart and assistive technologies. This second edition overhauls and expands on the original text to reflect the technical advances of the last decade. It covers applications from traditional healthcare services to remote patient monitoring and recovery, to alternative medicine and general health assessment for maintaining optimal health. This welcome update brings together a broad range of topics demonstrating how information and wireless technologies can be used in healthcare.Table of ContentsForeword xi Preface xiii Acknowledgments xv About the Book xvii Book Overview xix 1 Introduction 1 1.1 Information Technology and Healthcare Professionals 1 1.2 Providing Healthcare to Patients 2 1.2.1 Technical Perspectives 4 1.2.2 Healthcare Providers 5 1.2.3 End Users 5 1.2.4 Authorities 6 1.3 Healthcare Informatics Developments 6 1.4 Different Definitions of Telemedicine 8 1.5 The Growth of E-health to M-health 11 1.5.1 Evolving from the Internet 11 1.5.2 Digital Health on the Move 12 1.5.3 Data is Sent as a Sequence of “Packets” 13 1.6 The Connected World Between Human and Devices 14 References 14 2 Communication Networks and Services 17 2.1 The Basics of Wireless Communications 17 2.1.1 Wired vs. Wireless 19 2.1.2 Conducting vs. Optical Cables 20 2.1.3 Data Transmission Speed 22 2.1.4 Electromagnetic Interference 23 2.1.5 Modulation 23 2.2 Types of Wireless Networks 24 2.2.1 Bluetooth 24 2.2.2 Infrared (IR) 25 2.2.3 Wireless Local Area Network (WLAN) and Wi-Fi 25 2.2.4 ZigBee 26 2.2.5 Li-Fi 26 2.2.6 Cellular Networks 26 2.2.7 Broadband Wireless Access (BWA) 28 2.2.8 Satellite Networks 29 2.2.9 Licensed and Unlicensed Frequency Bands 29 2.3 M-health and Telemedicine Applications 29 2.4 The Outdoor Operating Environment 30 2.5 RFID in Telemedicine 35 References 38 3 Information and Communications Technology in Health Monitoring 41 3.1 Body Area Networks 42 3.2 Emergency Rescue 44 3.2.1 At the Scene 45 3.2.2 Smart Ambulance 47 3.2.3 Network Backbone 49 3.2.4 At the Hospital 50 3.2.5 The Authority 50 3.3 Remote Recovery 51 3.3.1 At Sea 51 3.3.2 Forests and Mountains 52 3.3.3 Buildings on Fire 53 3.4 Smart Hospital 55 3.4.1 Radiology Detects Cancer and Abnormality 56 3.4.2 Robot Assisted Telesurgery 58 3.4.3 Ward Management Using RFID 59 3.4.4 Electromagnetic Interference on Medical Instrument 61 3.4.5 Smart Wearable Integration 61 3.5 General Health Assessments 61 3.5.1 Case Study I: Fitness Monitoring for a Morning Jog 62 3.5.2 Case Study II: Gym Workout 63 3.5.3 Case Study III: Swimming 64 3.6 Multisensory Stimulation for Aging Care 66 References 68 4 Data Analytics and Medical Information Processing 71 4.1 Noninvasive Health Data Collection 72 4.1.1 Body Temperature 73 4.1.2 Heart Rate 75 4.1.3 Blood Pressure 78 4.1.4 Respiration Rate 80 4.1.5 Blood Oxygen Saturation 81 4.1.6 Blood Glucose Concentration 83 4.2 Biosignal Transmission and Processing 83 4.2.1 Medical Imaging 84 4.2.1.1 Magnetic Resonance Imaging 85 4.2.1.2 X-ray 85 4.2.1.3 Ultrasound 89 4.2.2 Medical Image Transmission and Analysis 90 4.2.3 Image Compression 93 4.2.4 Biopotential Electrode Sensing 94 4.3 Patient Records and Data Mining Applications 98 4.4 Knowledge Management for Clinical Applications 101 4.5 Artificial Intelligence (AI) in Digital Health 104 4.5.1 Deep Learning 106 4.5.2 AI in Mobile Health 107 4.5.3 Virtual Reality (VR) and Augmented Reality (AR) 109 4.5.4 Electronic Drug Store 110 References 111 5 Wireless Telemedicine System Deployment 115 5.1 Planning and Deployment Considerations 116 5.1.1 The OSI Model 117 5.1.2 Site Survey 119 5.1.3 Standalone Ad Hoc Versus Centrally Coordinated Networks 120 5.1.4 Link Budget Evaluation 121 5.1.5 Antenna Placement 122 5.2 Scalability to Support Future Growth 123 5.2.1 Modulation 124 5.2.2 Cellular Configuration 125 5.2.3 Multiple Access 127 5.2.4 Orthogonal Polarization 130 5.3 Integration with Existing IT Infrastructure 132 5.3.1 Middleware 133 5.3.2 Database 133 5.3.3 Involving Different People 134 5.4 Evaluating an IT Service and Solution Provider 135 5.4.1 Outsourcing 135 5.4.2 Preparing for the Future 136 5.4.3 Reliability and Liability 136 5.5 Quality Assurance 138 5.6 IoT and Cloud Integration 140 5.6.1 IoT in Telemedicine 140 5.6.2 Patient Location Tracking 142 5.6.3 Cloud for Patients and Practitioners 144 References 145 6 Safeguarding Medical Data and Privacy 147 6.1 Information Security Overview 147 6.1.1 What are the Risks? 148 6.1.2 Computer Viruses 151 6.1.3 Security Devices 152 6.1.4 Security Management 152 6.2 Cryptography 154 6.2.1 Certificate 155 6.2.2 Symmetric Cryptography 156 6.2.3 Asymmetric Cryptography 156 6.2.4 Digital Signature 158 6.3 Safeguarding Patient Medical History 159 6.3.1 National Electronic Patient Record 159 6.3.2 Personal Controlled Health Record (PCHR) 160 6.3.3 Patients’ Concerns 161 6.4 Anonymous Data Collection and Processing 161 6.4.1 Information Sharing Between Different Authorities and Agencies 162 6.4.2 Disease Control 164 6.4.3 Policy Planning 166 6.5 Biometric Security and Identification 169 6.5.1 Fingerprint Recognition 170 6.5.2 Palmprint Recognition 172 6.5.3 Iris and Retina Recognition 174 6.5.4 Facial Recognition 176 6.5.5 Voice Recognition 177 6.6 Conclusion 178 References 179 7 Information Technology in Alternative Medicine 183 7.1 Technology for Natural Healing and Preventive Care 184 7.1.1 Acupuncture and Acupressure 184 7.1.2 Body Contour and Acupoints 186 7.1.3 Temporary On-scene Relief Treatment Support 188 7.1.4 Herbal Medicine 190 7.2 Interactive Gaming for Healthcare 191 7.2.1 Games and Physical Exercise: eSport 191 7.2.2 Monitoring and Optimizing Children’s Health 191 7.2.3 Wireless Control Technology 193 7.3 Consumer Electronics in Healthcare 194 7.3.1 Assortment of Consumer Appliances 195 7.3.2 Safety and Design Considerations 196 7.3.3 Marketing Myths, What Something Claims to Achieve 197 7.4 Telehealth in General Healthcare and Fitness 197 7.4.1 Technology Assisted Exercise 198 7.4.2 In the Gym 199 7.4.3 Continual Health Assessment 200 References 201 8 Digital Health for Community Care 205 8.1 Telecare 205 8.1.1 Telehealth 206 8.1.2 Equipment 207 8.1.3 Sensory Therapy 209 8.1.4 Are we Ready? 209 8.1.5 Liability 210 8.2 Safeguarding Senior Citizens and the Aging Population 210 8.2.1 Telecare for Senior Citizens 212 8.2.2 The User Interface 217 8.2.3 Active Versus Responsive 219 8.2.4 Supporting Independent Living 220 8.3 Telemedicine in Physiotherapy 221 8.3.1 Movement Detection 221 8.3.2 Physical Medicine and Rehabilitation 224 8.3.3 Active Prevention 224 8.4 Healthcare Access for Rural Areas 226 8.5 Healthcare Technology and the Environment 228 8.5.1 A Long History 229 8.5.2 Energy Conservation and Safety 231 8.5.3 Medical Radiation: Risks, Myths, and Misperceptions 232 References 235 9 Wearable Healthcare 239 9.1 From Mobile to Wearable 239 9.1.1 Size Matters 239 9.1.2 Continuous Versus Continual Monitoring 242 9.1.3 Wearable Monitoring for Everyone 243 9.2 Medical Devices Versus Consumer Electronics Gadgets 245 9.2.1 Definition of Medical Devices 245 9.2.2 Device Classification 246 9.3 Connectivity 248 9.3.1 Deployment Options 248 9.3.2 Connectivity for Quality Monitoring 249 9.4 Enhancing Caring Efficiency 249 9.4.1 Mobility Assistance 250 9.4.2 Preparation for an Emergency Situation: A Case Study of a Nursing Home 251 9.5 Wearable Physiotherapy 252 References 253 10 Smart and Assistive Technologies 257 10.1 Affordability in Assistive Technologies 257 10.1.1 Assistive Technology Becomes Affordable 257 10.1.2 Connecting People and Machines 258 10.1.3 Emotional Intelligence: Remaining Happy and Healthy 258 10.2 Smart Home Integration 259 10.2.1 Consumer Electronics in the Home Setting 259 10.2.2 Integrating Healthcare and Lifestyle into the Home 260 10.3 Digital Health in Improving Treatment 261 10.3.1 Treatment Innovations 261 10.3.2 Smart Pills 263 10.4 Prognostics in Telemedicine 265 10.4.1 Smart Network Management in Telemedicine 265 10.4.2 Self-calibration 269 10.5 Clothing Technology in Telehealth 270 10.5.1 Self-powered Devices 271 10.5.2 Noninvasive Glucose Monitoring Wristband: A Case Study 272 References 273 11 Future Trends in Healthcare Technology 277 11.1 Haptic Sensing for Practitioners 277 11.2 Business Intelligence in Healthcare Prevention 278 11.2.1 Medical Tourism 279 11.2.2 Cyber Physical Systems 279 11.3 Cross-border Care: A Case Study of Syndromic Surveillance 282 11.4 5G-basedWireless Telemedicine 283 11.4.1 5G and IoT to Tackle DCD: A Case Study 285 11.4.2 Faster Wireless Communications for Supporting Virtual Reality (VR) in Telemedicine 285 11.5 The Future of Telemedicine and Information Technology for Everyone: From Newborn to Becoming a Medical Professional all the Way Through to Retirement 286 References 290 Index 293

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Book SynopsisA guide to a holistic approach to healthcare measurement aimed at improving access and outcomes Healthcare System Access is an important resource that bridges two areas of researchaccess modeling and healthcare system engineering. The book's mathematical modeling approach highlights fundamental approaches on measurement of and inference on healthcare access. This mathematical modeling facilitates translating data into knowledge in order to make data-driven estimates and projections about parameters, patterns, and trends in the system. The complementary engineering approach uses estimates and projections about the system to better inform efforts to design systems that will yield better outcomes. The authora noted expert on the topicoffers an in-depth exploration of the concepts of systematic disparities, reviews measures for systematic disparities, and presents a statistical framework for making inference on disparities with application to disparities in aTable of ContentsPreface vii 1 Introduction 1 2 A Multidimensional Framework for Measuring Access 13 3 Disparities in Healthcare Access 61 4 Linking Access to Health Outcomes 99 5 Healthcare Interventions for Improving Access 137 6 Data Analytics 195 Index 249

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Book SynopsisMusculoskeletal Disorders Hands-on guidance and tools for the prevention of musculoskeletal injuries in the workplace In Musculoskeletal Disorders: The Fatigue Failure Mechanism, a team of accomplished occupational health experts delivers an essential and incisive discussion of how musculoskeletal disorders (MSDs) develop and progress, as well as how they can be prevented and controlled. Offering a novel, evidence-based approach to this costly problem, the book has broad implications for employers, insurers, and other stakeholders in workplace health and safety. The authors identify new risk assessment approaches based on the cumulative effects of exposure to highly variable loading conditions. These new approaches can also be applied to evaluate the efficacy of job rotation scenarios and to quantify exoskeleton efficacy. The complexities associated with fatigue failure in biological environments are also explored in addition to suggested models for underTable of ContentsPreface Acknowledgements Author the Editors 1. Introduction 2. Common Musculoskeletal Disorders 3. Structure and Function of The Musculoskeletal System 4. Structure and Function of the Nervous System, and Its Relation to Pain 5. Fundamental Biomechanics Concepts 6. Material Properties of Musculoskeletal and Peripheral Nerve Tissues 7. Fatigue Failure of Musculoskeletal Tissues 8. MSDs as a fatigue failure process 9. Fundamentals of Fatigue Failure Analysis 10. Fatigue failure in a biological environment 11. Injury and Self-Repair of Musculoskeletal Tissues 12. Personal Characteristics and MSD Risk 13. Using Fatigue Failure Principles to Assess MSD Risk 14. Implications for MSD Prevention 15. Optimizing Musculoskeletal Health 16. Status of knowledge and unanswered questions Index

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Book SynopsisThis book is organized into 12 important chapters that focus on the progress made by metal-based drugs as anticancer, antibacterial, antiviral, anti-inflammatory, and anti-neurodegenerative agents, as well as highlights the application areas of newly discovered metallodrugs. It can prove beneficial for researchers, investigators and scientists whose work involves inorganic and coordination chemistry, medical science, pharmacy, biotechnology and biomedical engineering.Table of ContentsPreface xiii 1 Metallodrugs in Medicine: Present, Past, and Future Prospects 1Imtiyaz Yousuf and Masrat Bashir 1.1 Introduction 2 1.2 Therapeutic Metallodrugs 6 1.2.1 Anticancer Metallodrugs 6 1.2.1.1 Mechanism of Anticancer Action 7 1.2.2 Antimicrobial and Antiviral Metallodrugs 15 1.2.2.1 Antimicrobial Metallodrugs 15 1.2.2.2 Antiviral Metallodrugs 16 1.2.3 Radiopharmaceuticals and Radiodiagnostic Metallodrugs 17 1.2.4 Anti-Diabetic Metallodrugs 19 1.2.5 Catalytic Metallodrugs 22 1.3 Future Prospects 23 1.4 Conclusion 25 References 26 2 Chemotherapeutic Potential of Ruthenium Metal Complexes Incorporating Schiff Bases 41Manzoor Ahmad Malik, Parveez Gull, Ovas Ahmad Dar, Mohmmad Younus Wani, Md Ikbal Ahmed Talukdar and Athar Adil Hashmi 2.1 Introduction 42 2.2 Schiff Base Complexes of Ruthenium as Anticancer Agents 43 2.3 Conclusion 63 References 64 3 Role of Metallodrugs in Medicinal Inorganic Chemistry 71Manish Kumar, Gyanendra Kumar, Arun Kant and Dhanraj T. Masram 3.1 Introduction 72 3.2 Platinum Anticancer Drugs 74 3.2.1 Nucleophilic Displacement Reactions in Complexes of Platinum 80 3.2.2 Mode of the Interaction of Cisplatin Species With Nitrogen Donors of DNA Strand 80 3.2.3 Systemic Toxicity of Cisplatin 82 3.3 Copper-Based Anticancer Complexes 82 3.3.1 Copper is Essential for Health and Nutrition 82 3.3.2 Healthcare Applications of Copper 83 3.3.3 Copper and Human Health Disorders 83 3.3.3.1 Wilson’s Disease (WD) 84 3.3.3.2 Menkes’ Disease 85 3.3.4 Role of Copper Complexes as Potential Therapeutic Agents 85 3.3.4.1 Thiosemicarbazones-Based Complexes 86 3.3.4.2 Quinolones-Based Copper Complexes 88 3.3.4.3 Naphthoquinones 88 3.4 Zinc Anticancer Complexes 89 3.4.1 Biologically Importance of Zinc 90 3.4.2 Schiff Base Chemistry 92 3.4.2.1 Schiff Base and Their Metal Complexes 92 3.4.3 Zinc-Based Complexes 93 3.4.4 Top Food Sources of Zinc 94 3.4.5 Role of Zinc in Human Body 97 3.4.6 Zinc as a Health Benefit 98 3.4.7 Zinc in Alloy and Composites 100 3.4.8 Zinc Supplementation as a Treatment 100 3.4.8.1 Zinc Deficiency 101 3.4.8.2 Zinc Toxicity 102 3.4.8.3 Zinc and Viral Infections 102 3.4.9 Gastrointestinal Effects 103 3.5 Future Prospects of Metallodrugs 103 References 104 4 Ferrocene-Based Metallodrugs 115Hamza Shoukat, Ataf Ali Altaf and Amin Badshah 4.1 Introduction 115 4.2 Ferrocene-Based Antimalarial Agents 117 4.2.1 Mechanism of Action 118 4.3 Ferrocene-Based Antibacterial and Antifungal Drugs 118 4.3.1 Schiff Base Derived Ferrocene Conjugates as Antibacterial Agents 119 4.3.2 Ferrocenyl Guanidines as Antibacterial and Antifungal Agents 121 4.3.3 Sedaxicene as Antifungal Agents 122 4.4 Ferrocene-Based Anti-Tumor and Anti-Cancerous Drugs 123 4.4.1 Ferricenium Salts as Anti-Tumor Agents 124 4.4.2 Ferrocenylalkylazoles Active Anti-Tumor Drugs 124 4.4.3 Ferrocene Conjugated to Peptides for Lung Cancer 125 4.4.4 Ferrocenylalkyl Nucleobases Potential Anti-Cancerous Drugs 126 4.4.5 Ferrocenyl Sub-Ordinates of Illudin-M 126 4.4.6 Ferrocenyl Derivatives of Retinoids Potential Anti-Tumor Drug 127 4.4.7 Targeting Breast Cancer With Selective Ferrocene-Based Estrogen Receptor Modulators (SERM) 128 4.5 Conclusion 131 4.6 Future of Ferrocene-Based Drugs 131 References 132 5 Recent Advances in Cobalt Derived Complexes as Potential Therapeutic Agents 137Manzoor Ahmad Malik, Ovas Ahmad Dar and Athar Adil Hashmi 5.1 Introduction 137 5.2 Cobalt Complexes as Potential Therapeutic Agents 138 5.3 Conclusion 153 References 154 6 NO-, CO-, and H2S-Based Metallopharmaceuticals 157R. C. Maurya and J. M. Mir 6.1 Introduction 158 6.2 Signaling Molecules: Concept of “Gasotransmitter” 160 6.2.1 Therapeutic Applications of NO, CO, and H2S 162 6.2.1.1 Exogenous NO Donating Molecules 163 6.3 NO Donors Incorporated in Polymeric Matrices 167 6.3.1 Metal Nitrosyl Complexes 168 6.3.1.1 Sodium Nitroprusside (SNP) 168 6.4 Dinitrosyl Iron Thiol Complexes (DNICs) 170 6.5 Photoactive Transition Metal Nitrosyls as NO Donors 170 6.6 Exogenous CO Donating Molecules 173 6.7 H2S Donating Compounds 176 6.7.1 H2S Gas: A Fast Delivering Compound 176 6.7.2 Sulfide Salts: Fast Delivering H2S Compounds 177 6.7.3 Synthetic Moieties 178 6.7.3.1 Slow-Delivering H2S Compounds 178 6.7.3.2 H2S-Releasing Composite Compounds 179 6.7.4 Naturally Occurring Plant Derived Compounds 182 6.7.4.1 Garlic 182 6.7.4.2 Broccoli and Other Cruciferous Vegetables 184 6.8 Concluding Remarks and Future Outlook 185 References 186 7 Platinum Complexes in Medicine and in the Treatment of Cancer 203Rakesh Kumar Ameta and Parth Malik 7.1 What is Cancer? 203 7.1.1 Characteristic Features of Cancer Cells 205 7.1.2 Definition of Anticancer Compound 206 7.1.3 Anticancer Attributes of Pt Complexes 207 7.1.4 Native State Behavior of Pt Complexes 208 7.2 Compatibility of Pt Compounds in Cancer Treatment 209 7.2.1 Significance of DNA as Primary Target 209 7.2.2 Kinetics of DNA Binding Activities 210 7.2.3 Structural and Regioselectivity of DNA Adducts 210 7.2.4 Studies on Action Mechanism 211 7.3 Pt Complexes as Anticancer Drugs 214 7.3.1 DNA-Coordinating Pt(II) Complexes 214 7.3.2 DNA-Covalently Binding Pt(II) Complexes 219 7.3.3 Targeted Pt(II) Complexes 222 7.3.4 Pt(IV) Prodrugs 224 7.3.5 Multiple Action of Pt(IV) Prodrugs 225 7.3.6 Targeted Pt(IV) Prodrugs 228 7.3.7 Photodynamic Killing of Cancer Cell by Pt Complexes 231 7.4 Conclusion 231 Acknowledgments 232 References 232 8 Recent Advances in Gold Complexes as Anticancer Agents 247Mohammad Nadeem Lone, Zubaid-ul-khazir, Ghulam Nabi Yatoo, Javid A. Banday and Irshad A. Wani 8.1 Introduction 248 8.2 Evolution of Metal Complexes as Anticancer Agents 250 8.3 Gold Complexes 251 8.3.1 Complexes with Nitrogen Donar Ligands 252 8.3.2 Complexes with Sulphur Donar Ligands 254 8.3.3 Complexes with Phosphorus Donar Ligands 255 8.3.4 Complexes with Sulphur-Phosphorus Donar Ligands 256 8.3.5 Organometallic Gold Complexes 259 8.3.6 Miscellaneous 260 8.4 Nano-Formulations of Gold Complexes 262 8.5 Future Challenges and Perspectives 263 8.6 Conclusion 265 Acknowledgements 266 References 266 9 Recent Developments in Small Molecular HIV-1 and Hepatitis B Virus RNase H Inhibitors 273Fenju Wei, Dongwei Kang, Luis Menéndez-Arias, Xinyong Liu and Peng Zhan 9.1 Introduction 273 9.1.1 Activity and Function of HIV and HBV RNases H 274 9.1.2 The Metal-Chelating RNase H Active Site 274 9.2 RNase H Inhibitors and Strategies in the Discovery of Active Compounds 276 9.2.1 High-Throughput Screening 276 9.2.2 Design Based on Pharmacophore Models 278 9.2.3 Novel Inhibitors Obtained by Using “Click Chemistry” 279 9.2.4 Dual-Target Inhibitors Against HIV-1 Integrase (IN) and RNase H 280 9.2.5 Inhibitors Obtained by Using Privileged Fragment-Based Libraries 282 9.2.6 RNase H Inhibitors in Natural Products 283 9.2.7 Drug Repurposing Based on Privileged Structures 284 9.3 Conclusion 286 References 287 10 The Role of Metals and Metallodrugs in the Modulation of Angiogenesis 293Mehmet Varol and Tuğba Ören Varol 10.1 Introduction 294 10.2 Metallodrugs in Anticancer Therapy 297 10.3 Angiogenesis as a Substantial Target of Tumorigenesis 300 10.4 Metals and Metallodrugs in Angiogenesis 302 10.5 Concluding Remarks and Future Prospects 306 References 306 11 Metal-Based Cellulose: An Attractive Approach Towards Biomedicine Applications 319Kulsoom Koser and Athar Adil Hashmi 11.1 Introduction 320 11.2 History of Cellulose 320 11.3 The Properties and Structure of Cellulose 321 11.4 Modification of Cellulose 322 11.4.1 Acid Hydrolysis 322 11.4.2 Oxidation 324 11.4.3 Esterification 326 11.4.4 Amidation 331 11.4.5 Carbamiation 333 11.4.6 Etherification 336 11.4.7 Nucleophilic Substitution 339 11.4.8 Further Modification 341 11.5 Present and Future Medical Applications of Cellulose as Well as Its Components 344 11.5.1 Cellulose Used as Wound Dressing 344 11.5.2 Dental Applications 345 11.5.3 Engineering 346 11.5.4 Controllable Drug Delivery System 348 11.5.5 Blood Purification 348 11.5.6 Wrapping Purpose 350 11.5.7 Renal Failure 351 11.6 Conclusion 351 References 352 12 Multifunctional Nanomedicine 363Nobel Tomar, Maroof A. Hashmi and Athar Adil Hashmi 12.1 Introduction 364 12.2 Diagnostics and Imaging 366 12.3 Drug Delivery and Therapy 369 12.3.1 Drug Delivery by Organic Nanomaterials 369 12.3.1.1 Liposomal Drug Delivery 369 12.3.1.2 Polymeric Drug Delivery 371 12.3.1.3 Proteins and Peptides for Drug Delivery 373 2.3.2 Drug Delivery by Inorganic Nanomaterials 374 12.3.2.1 Metal and Metal Oxides 374 12.3.2.2 Au NPs 375 12.3.2.3 Carbon-Based NPs 375 12.3.2.4 Silicon-Based Nanostructures for Drug Delivery 378 12.3.3 Photo Therapy 379 12.3.3.1 Photodynamic Therapy 380 12.3.3.2 Photothermal Therapy 381 12.3.4 Radiation Therapy 383 12.3.5 Neutron Capture Therapy 384 12.4 Regenerative Medicine 385 12.5 Future Prospects and Conclusion 386 References 387 Index 403

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Book SynopsisThefirstvolume of the ultimate reference on the science and applications of aggregation-induced emission TheHandbook of Aggregation-Induced Emissionexplores foundational and advanced topics in aggregation-induced emission, as well as cutting-edge developments in the field,celebratingtwenty years of progress and achievement in this important and interdisciplinary field.The three volumes combine to offer readers a comprehensive and insightful interpretation accessible to both new and experiencedresearchersworking onaggregation-induced emission. In thisfirst volume of three, theeditorssurveythe subjectofaggregation-induced emissionwith afocus on the fundamentals of various branches of the discipline, such ascrystallization-induced emission,room temperature phosphorescence,aggregation-induced delayed fluorescence, and more.Thisbook coversthe new properties of materials endowed by molecular aggregates. It also includes: A thorough introduction totTable of ContentsList of Contributors xv Preface to Handbook of Aggregation-Induced Emission xxi Preface to Volume 1: Fundamentals xxiii 1 The Mechanistic Understanding of the Importance of Molecular Motions to Aggregation-induced Emission 1Junkai Liu and Ben Zhong Tang 1.1 Introduction 1 1.2 Restriction of Intramolecular Motion 2 1.2.1 Restriction of Intramolecular Rotation 3 1.2.2 Restriction of Intramolecular Vibration 4 1.2.3 Ultrafast Insights into Tetraphenylethylene Derivatives 6 1.2.4 Theoretical Insights into Restriction of Intramolecular Motion 8 1.3 Restricted Access to Conical Intersection 12 1.4 Restriction of Access to the Dark State 14 1.5 Suppression of Kasha’s Rule 15 1.6 Through Space Conjugation 17 1.6.1 Clusterization-Triggered Emission 18 1.6.2 Polymerization-induced Emission 19 1.6.3 Excited-state Through-space Conjugation 19 1.7 Perspective 21 References 23 2 Understanding the AIE Mechanism at the Molecular Level 27Xiaoyan Zheng and Qian Peng 2.1 Introduction 27 2.2 Theoretical Methods 28 2.2.1 Radiative and Nonradiative Rate Constants 28 2.2.2 Computational Details 29 2.3 Revealed AIE Mechanism 31 2.3.1 Rotating Vibrations of Intramolecular Aromatic Ring 31 2.3.2 Stretching Vibrations of Bonds 33 2.3.3 Bending Vibration of Bonds 34 2.3.4 Flipping Vibrations of Molecular Skeletons 35 2.3.5 Twisting Vibration of Molecular Skeletons 36 2.4 Visualize Calculated Parameters in Experiments 37 2.4.1 Stokes Shift vs Reorganization Energy 37 2.4.2 Resonance Raman Spectroscopy (RSS) vs Reorganization Energy 38 2.4.3 Isotope Effect vs DRE 40 2.4.4 Linear Relationship between Fluorescence Intensity and Amorphous Aggregate Size 42 2.4.5 Pressure-induced Enhanced Emission (PIEE) 44 2.5 Molecular Design Based on AIE Mechanism 45 2.6 Summary and Outlook 46 Acknowledgments 48 References 48 3 Aggregation-induced Emission from the Restriction of Double Bond Rotation at the Excited State 55Ming Hu and Yan-Song Zheng 3.1 Introduction 55 3.2 AIE Phenomena and Applications from RDBR Mechanism 58 3.2.1 Evolvement and Development of AIE Mechanisms 58 3.2.2 Investigation of RDBR AIE Mechanism by E/Z isomerization 64 3.2.3 Investigating of RDBR AIE Mechanism by Immobilization of TPE Propeller-like Conformation 69 3.2.4 Research of Theoretical Calculation on RDBR 78 3.2.5 Other AIEgens Involving RBDR Process 84 3.3 Conclusions 93 References 94 4 The Expansion of AIE Thought: From Single Molecule to Molecular Uniting 99Qiuyan Liao, Qianqian Li, and Zhen Li 4.1 Aggregation-Induced Emission 99 4.2 Photoluminescence Materials Based on Molecular Set 101 4.3 Mechanoluminescence Materials Based on Molecular Set 106 4.3.1 Mechanoluminescence Materials with Fluorescence Emission 106 4.3.2 Mechanoluminescence Materials with Mechanical Induced Dual-or Tri-color Emission 115 4.3.3 Quantitative Research of Mechanoluminescence Property 121 4.4 Mechanochromism Materials 122 4.4.1 Mechanochromism Materials Based on Polymorphs 122 4.4.2 Mechanochromism Materials Based on Excimer Emission 125 4.4.3 Other Kinds of Mechanochromism Materials 128 4.5 Room Temperature Phosphorescence Materials Based on Molecular Uniting 131 4.5.1 Room Temperature Phosphorescence Materials with Aromatics 131 4.5.2 Room Temperature Phosphorescence Materials with Simple or Nonaromatic Structure 140 4.5.3 Room Temperature Phosphorescence Materials with Multiple Emission 142 4.5.4 Photoinduced Room Temperature Phosphorescence Materials 144 4.6 Conclusion and Perspectives 147 References 147 5 Clusterization-Triggered Emission 153Haoke Zhang and Ben Zhong Tang 5.1 Introduction 153 5.2 Pure n-Electron Systems 156 5.3 Pure π-Electron Systems 160 5.4 (n, π)-Electrons Systems 164 5.5 Other Systems 166 5.6 Summary 167 References 168 6 Crystallization-induced Emission Enhancement 177Yong Qiang Dong, Yingying Liu, Mengyang Liu, Qian Wang, and Kang Wang 6.1 Introduction 177 6.2 Tetraphenylethylene Derivatives 178 6.3 CIEE Active Luminogens with Bulky Conjugation Core 183 6.3.1 Dibenzofulvene (DBF) Derivatives (Chart 6.2) 183 6.3.2 9-([1,1′-Biphenyl]-4-ylphenylmethylene)-9H-xanthene 185 6.3.3 Dicyanomethylenated Acridones 186 6.3.4 Bis(diarylmethylene)dihydroanthracene [31] 187 6.4 Other High-contrast CIEE Luminogens 190 6.4.1 4-Dimethylamino-2-Benzylidene Malonic Acid Dimethyl Ester 190 6.4.2 Diphenyl Maleimide Derivatives [33] 191 6.4.3 3,4-Bisthienylmaleic Anhydride [34] 192 6.4.4 Boron-containing CIEE Luminogens 193 6.5 Potential Applications 196 6.5.1 Volatile Organic Compounds (VOCs) Sensor 196 6.5.2 OLED 196 6.5.3 High-density Data Storage 197 6.5.4 Mechanochromic (MC) Luminescent Sensor 198 6.6 Summary and Perspective 198 References 198 7 Surface-fixation Induced Emission 203Yohei Ishida and Shinsuke Takagi 7.1 Introduction 203 7.2 What Happened to the Characteristics of Molecules on the Clay Mineral Nanosheets 205 7.3 Clay–Molecular Complexes 206 7.4 Absorption Spectra of Clay–Molecular Complexes 207 7.5 Emission Enhancement Phenomenon in Clay–Molecular Complexes: S-FIE 208 7.6 Mechanism of Surface-Fixation Induced Emission 211 7.7 Summary and Outlook 214 Acknowledgment 215 References 215 8 Aggregation-induced Delayed Fluorescence 221Yan Fu, Hao Chen, Zujin Zhao, and Ben Zhong Tang 8.1 Introduction 221 8.2 Novel Aggregation-induced Delayed Fluorescence Luminogens 222 8.3 Conclusion and Outlook 247 References 247 9 Homogeneous Systems to Induce Emission of AIEgens 251Kenta Kokado and Kazuki Sada 9.1 Introduction 251 9.2 Homogeneous Solution 252 9.2.1 Complexation with Anions 253 9.2.2 Complexation with Cations 254 9.2.3 Inclusion Complexes 256 9.2.4 Adhesion on Macromolecules 257 9.2.5 Steric Hindrance 258 9.2.6 Covalent Linkage 259 9.3 Liquid 260 9.4 Gels and Network Polymers 261 9.4.1 Chemically Crosslinked Gels 261 9.4.2 Physically Crosslinked Gels 262 9.5 Crystalline Materials 264 9.6 Outlook and Future Perspectives 266 References 266 10 Hetero-aggregation-induced Tunable Emission (HAITE) Through Cocrystal Strategy 273Yinjuan Huang and Qichun Zhang 10.1 Introduction 273 10.2 Interactions Within Organic Cocrystals 274 10.3 Preparation of Organic Cocrystals 275 10.4 Molecular Stacking Modes Within Organic Cocrystals 276 10.5 Characterization of Organic Cocrystals 277 10.6 HAITE Through Cocrystal Strategy 277 10.6.1 HAITE with Tunable Color and Enhanced Emission 278 10.6.1.1 Insignificant Changed Intensity but Tuned Color 278 10.6.1.2 Enhanced Emission and Tuned Color 287 10.6.2 HAITE with Increased PLQY but Intrinsic Color 291 10.6.3 HAITE: Thermally Activated Delayed Fluorescence 297 10.6.4 HAITE-phosphorescence 300 10.7 Summary and Outlook 302 References 304 11 Anti-Kasha Emission from Organic Aggregates 311Wenbin Huang and Zikai He 11.1 Introduction 311 11.2 Anti-Kasha Emission from Aromatic Carbonyl Compounds in Aggregates 312 11.3 Anti-Kasha Emission from Azulene Compounds in Aggregate 322 11.4 Anti-Kasha Emission from Other Unconventional Aromatic Compounds in Aggregates 324 11.5 Conclusions 327 References 327 12 Aggregation-enhanced Emission: From Flexible to Rigid Cores 333Harnimarta Deol, Gurpreet Singh, Vandana Bhalla, and Manoj Kumar 12.1 Introduction 333 12.2 Freely Moving Rotors-induced Emission Enhancement 334 12.3 Guest-induced Emission Enhancement 344 12.4 Conclusion 366 Acknowledgment 367 References 367 13 Room-temperature Phosphorescence of Pure Organics 371Tianwen Zhu, Zihao Zhao, Tianjia Yang, and Wang Zhang Yuan 13.1 Introduction 371 13.2 Fundamental Mechanism in Organic Phosphorescence 372 13.2.1 Photophysical Process for Phosphorescence 372 13.2.2 Theoretical Study on Phosphorescent Process 373 13.3 Recent Progress in Organic RTP Materials 375 13.3.1 Crystallization-induced RTP 375 13.3.1.1 Heavy Atom Effect 376 13.3.1.2 Molecular Interaction 380 13.3.1.3 H-aggregation 380 13.3.2 Doping in Rigid Matrix-induced RTP 382 13.3.2.1 Host–Guest System 385 13.3.2.2 Doping in Polymer Matrix 387 13.3.3 Clustering-triggered RTP 389 13.3.3.1 Natural Products 389 13.3.3.2 Synthetic Compounds 394 13.3.4 Other Systems 399 13.3.4.1 Amorphous Organics 399 13.3.4.2 Organic Framework 399 13.3.4.3 Supramolecular Organics 402 13.3.4.4 Hybrid Perovskites 403 13.3.5 Applications 405 13.4 Conclusions and Perspectives 405 References 407 14 A Global Potential Energy Surface Approach to the Photophysics of AIEgens: The Role of Conical Intersections 411Rachel Crespo-Otero and Lluís Blancafort 14.1 Introduction 411 14.2 Methodological Aspects 412 14.2.1 Intramolecular Restriction Models and the FGR-based Approach 412 14.2.2 A PES-based Description of Photochemical Mechanisms 412 14.2.3 Computational Approaches for Excited States 416 14.2.3.1 Electronic Structure Methods for Excited States 416 14.2.3.2 Dynamics Simulations in the Context of AIE 420 14.2.4 Methods for Large Systems 420 14.3 CI-centered Global PES for AIEgens 424 14.3.1 Double-bond Torsion 424 14.3.2 Double-bond Torsion vs Cyclization in TPE Derivatives 428 14.3.3 Excited-state Intramolecular Proton Transfer (ESIPT) Compounds 431 14.3.4 Ring Puckering 432 14.3.5 Bond Stretching 435 14.3.6 A View of AIE Based on the RACI Model and the Global PES 436 14.4 Crystallization-induced Phosphorescence 436 14.5 Effect of Intermolecular and Intramolecular Interactions on the Photophysics of AIEgens 437 14.5.1 Excitonic Effects in AIE 437 14.5.2 Effect of Intramolecular and Intermolecular Interactions on Emission Color 439 14.6 New Challenges 439 14.6.1 The Role of Dark States in AIE 439 14.6.2 Pressure-induced Emission Enhancement 440 14.6.3 AIE in Transition Metal (TM) Compounds 442 14.7 Conclusions and Outlook 443 References 444 15 Multicomponent Reactions as Synthetic Design Tools of AIE and Emission Solvatochromic Quinoxalines 455Lukas Biesen and Thomas J. J. Müller 15.1 Introduction 455 15.2 Synthetic Approaches to Quinoxalines via Multicomponent Reactions and One-Pot Processes 456 15.3 Photophysical Properties and Emission Solvatochromicity of Quinoxalines 462 15.4 AIE Characteristics and Effects of Quinoxalines 468 15.5 Conclusion 476 Acknowledgments 476 References 476 16 Aggregation-induced Emission Luminogens with Both High-luminescence Efficiency and Charge Mobility 485Ying Yu, Zheng Zhao, and Ben Zhong Tang 16.1 Introduction 485 16.2 p-Type OSCs 487 16.3 n-Type OSCs 495 16.4 Ambipolar OSCs 500 16.5 Conclusion and Perspective 505 References 505 17 Morphology Modulation of Aggregation-induced Emission: From Thermodynamic Self-assembly to Kinetic Controlling 509Kaizhi Gu, Chenxu Yan, Zhiqian Guo, and Wei-Hong Zhu 17.1 Introduction 509 17.2 Aggregation Modulation of AIE Bioprobes via Hydrophilicity Improvement 511 17.2.1 Molecular Modification 511 17.2.2 Polymerization with Hydrophilic Matrix 515 17.3 Thermodynamic Self-assembly of AIE Materials 519 17.4 Morphology Tuning of AIE Nanoaggregates 519 17.5 Kinetic-driven Preparation of AIE NPs 523 17.6 Conclusion and Outlook 527 References 527 18 AIE-active Polymer 531Rong Hu, Anjun Qin, and Ben Zhong Tang 18.1 Introduction 531 18.2 Photophysical Properties 532 18.2.1 Quantum Yield 532 18.2.2 Photosensitization 536 18.2.3 Two-photon Absorption and Emission 538 18.2.4 Circularly Polarized Luminescence 540 18.3 Applications 541 18.3.1 Chem-sensor 541 18.3.2 Bioimaging 543 18.3.3 Therapy Applications 546 18.4 Conclusion and Perspective 549 Acknowledgments 550 References 550 19 Liquid-crystalline AIEgens: Materials and Applications 555Kyohei Hisano, Supattra Panthai, and Osamu Tsutsumi 19.1 Introduction 555 19.2 Materials: Molecular Design 556 19.2.1 Discotic LC AIEgen 556 19.2.2 Calamitic LC AIEgens 561 19.2.3 Polymeric LC AIEgens 566 19.3 Applications of LC AIEgens 567 19.3.1 Linearly Polarized Luminescence 567 19.3.2 Circularly Polarized Luminescence 568 19.4 Conclusion 571 References 571 20 Push–Pull AIEgens 575Andrea Nitti and Dario Pasini 20.1 Introduction 575 20.2 Basic Concept of Molecular Design 576 20.2.1 Photophysical Excited States in Aggregates 576 20.2.2 Fundamental Molecular Design to Achieve Push–Pull AIEgens 579 20.3 Push–Pull AIEgens from Rotor Structure 581 20.3.1 Double Bond Stator 582 20.3.2 Point-restricted Rotors from Atoms or Functional Groups 584 20.3.3 Aromatic Rotors 587 20.4 Push–Pull AIEgens from ACQ Chromophores 589 20.4.1 BT-based AIEgens 589 20.4.2 Cyanine and DCM-based AIEgens 594 20.4.3 QM-based AIEgens 595 20.4.4 DPP-based AIEgens 597 20.4.5 Rylene-based AIEgens 599 20.5 Concluding Remarks 602 References 602 Index 609

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Book SynopsisThesecond volume of theultimate reference on the science and applications of aggregation-induced emission TheHandbook of Aggregation-Induced Emissionexplores foundational and advanced topics in aggregation-induced emission, as well as cutting-edge developments in the field,celebratingtwenty years of progress and achievement in this important and interdisciplinary field.The three volumes combine to offer readers a comprehensive and insightful interpretation accessible to both new and experiencedresearchersworking on aggregation-induced emission. InVolume 2: TypicalAIEgensDesign,the editorsaddress the design and synthesis of typicalAIEgensthat have made significant contributions toaggregation-induced emissionresearch.Recent advances in the development ofaggregation-induced emissionsystems are discussedand the bookcoversnovelaggregation-induced emissionsystems in small moleculeorganogels,polymersomes,metal-organic coordination complexes and metal nanoTable of ContentsList of Contributors xvii Preface to Handbook of Aggregation-Induced Emission xxiii Preface to Volume 2: Typical AIEgens Design xxv 1 Tetraphenylpyrazine-based AIEgens: Synthesis and Applications 1Ming Chen, Anjun Qin, and Ben Zhong Tang 1.1 Introduction 1 1.2 Synthesis of TPP-based AIEgens 3 1.2.1 Cyclization Reaction 3 1.2.2 Suzuki–Miyaura Reaction 7 1.3 Functionalities of TPP-based AIEgens 8 1.3.1 Organic Light-emitting Diodes 8 1.3.2 Fluorescent Sensors 9 1.3.3 Chiral Cage for Self-assembly to Achieve White-light Emission 13 1.3.4 Metal–organic Framework 15 1.4 Conclusion 17 References 18 2 AIEgens Based on 9,10-Distyrylanthracene (DSA): From Small Molecules to Macromolecules 23Leijing Liu, Bin Xu, and Wenjing Tian 2.1 Introduction 23 2.2 Application of AIE Luminogens Based on 9,10-Distyrylanthracene 24 2.2.1 Smart Materials with Stimulus Response 24 2.2.1.1 Piezofluorochromic Materials 24 2.2.1.2 Photochromic Materials 27 2.2.1.3 Thermochromic Materials 27 2.2.1.4 Acidichromic Materials 27 2.2.1.5 Multistimuli-responsive Materials 30 2.2.2 High Solid-state Luminescent Materials 30 2.2.3 Fluorescent Materials for Bioimaging 35 2.2.4 Fluorescent Probes for Chemical and Biological Sensing 41 2.2.4.1 Fluorescent Probes for Chemical Sensing 41 2.2.4.2 Fluorescent Probes for Biological Sensing 44 2.3 Conclusions and Outlook 46 Acknowledgments 47 References 47 3 Typical AIEgens Design: Salicylaldehyde Schiff Base 53Yue Zheng and Aijun Tong 3.1 Introduction 53 3.1.1 AIE and ESIPT of Salicylaldehyde Schiff Base 53 3.1.2 Universal Design of SSB-based AIEgens 55 3.2 Fluorescent Probes 55 3.2.1 Metal Ion Detection and Imaging 55 3.2.2 Biologically and Environmentally Related Molecular Detection and Imaging 63 3.2.3 Ratiometric pH Probes 76 3.2.4 Bioimaging 76 3.3 Fluorescent Materials 81 3.3.1 Solid Fluorescence Emitting and Stimuli-Responsive Materials 81 3.3.2 Nanoparticles 88 3.4 Summary and Perspectives 91 References 92 4 Diaminodicyanoquinodimethanes: Fluorescence Emission Enhancement in Aggregates and Solids 97N. Senthilnathan and T. P. Radhakrishnan 4.1 Introduction 97 4.1.1 Molecular Materials 97 4.1.2 ‘Push–Pull’ Molecules 97 4.1.3 Diaminodicyanoquinodimethanes 98 4.2 Nonlinear Optical Materials based on DADQs 100 4.2.1 Molecular Hyperpolarizability 100 4.2.2 SHG Materials 100 4.2.3 Structure–Property Correlations 101 4.3 Enhanced Fluorescence in Aggregates and Solids Based on DADQs 102 4.3.1 Remote Functionalized Systems 102 4.3.2 Color Tuning, Nanocrystals, and Colloids 103 4.3.3 Ultrathin Films 105 4.3.4 New Directions 105 4.4 Mechanistic Insights into the Enhanced Fluorescence 106 4.4.1 Relevance of Intramolecular Effects 106 4.4.2 Role of Intermolecular Effects 106 4.5 Impact of Crystallinity on the Fluorescence Response 108 4.5.1 Amorphous-to-Crystalline Transformation: Fluorescence Switching and Tuning 108 4.5.2 Reversible Amorphous–Crystalline Transformations: Phase Change Materials 108 4.5.3 Impact of External Stimuli 110 4.6 Emergent and Potential Applications of DADQs 110 4.6.1 Electroluminescence and Nonlinear Optics 110 4.6.2 Bioimaging 110 4.6.3 Photoelectrochemical and Photobioelectrochemical Applications 112 4.6.4 Memory Devices 112 4.7 Concluding Remarks 113 Acknowledgements 114 References 114 5 Aggregation-induced Emission from the Sixth Main Group 119Jan Balszuweit, Bibhisan Roy, and Jens Voskuhl 5.1 Introduction 119 5.2 Oxygen 119 5.2.1 Oxygen-Containing Heterocycles 120 5.2.2 Oxo-ether Containing AIE-Active Luminogens 122 5.3 Sulfur 126 5.3.1 Luminogens Based on Thiophenes 126 5.3.2 Thioethers with Aggregation-Induced Emission Properties 129 5.3.3 Emissive Sulfones 131 5.4 Selenium and Tellurium 132 5.4.1 Selenium-Containing Luminophores 132 5.4.2 Tellurium-Containing Luminophores 134 5.5 Conclusion 138 Acknowledgment 138 References 138 6 Fluorescence Detection of Dynamic Aggregation Processes Using AIEgens: Hexaphenylsilole and Cyanostilbene 143Fuyuki Ito 6.1 Introduction 143 6.2 Selective Detection of Phase Transformation During Evaporative Crystallization of Hexaphenylsilole 145 6.3 Observation of the Initial Stage of Organic Crystal Formation During Solvent Evaporation Using a Cyanostilbene Derivative 149 6.4 Chemometrix Analysis of the Aggregated Structure of Cyanostilbene in a Reprecipitation Solution Using Fluorescence Excitation Spectroscopy 152 6.5 UV-triggered Fluorescence Enhancement of a Dicyanostilbene Derivative Film Cast from an Ethanol Solution 158 6.6 Concluding Remarks 162 Acknowledgments 162 References 162 7 Cyclic Triimidazole Derivatives: An Intriguing Family of Multifaceted Emitters 165Elena Cariati, Elena Lucenti, Andrea Previtali, and Alessandra Forni 7.1 Introduction 165 7.2 The Protoype: Cyclic Triimidazole 166 7.3 Halogenated Derivatives of Cyclic Triimidazole 175 7.3.1 Bromine Derivatives 176 7.3.2 Iodine Derivatives 179 7.4 Organic Derivatives 184 7.4.1 2-Fluoropyridine Derivative 185 7.4.2 Tribenzoimidazole Derivative 186 7.5 Hybrid Inorganic/Organic Derivatives 188 7.6 Conclusions 191 Acknowledgments 191 References 191 8 Synthesis of Multi-phenyl-substituted Pyrrole (MPP)-based AIE Materials and Their Applications 195Zhengxu Cai, Yunxiang Lei, and Yuping Dong 8.1 Introduction 195 8.2 Modular Approach: Systematic Synthesis of MPPs 196 8.3 Structures and Photophysical Properties 198 8.4 Applications of MPP-based Materials 204 8.4.1 Chemical/Biological Sensing 204 8.4.2 Multi-stimulus Response Materials 208 8.4.3 Optoelectronic Systems 210 8.4.4 Biological Application 213 8.5 Conclusion and Outlook 216 References 216 9 Development of a New Class of AIEgens: Tetraarylpyrrolo [3,2-b] Pyrroles (TAPPs) 221Vishal G. More, Ratan W. Jadhav, Mohammad Al Kobaisi, Lathe A. Jones, and Sheshanath V. Bhosale 9.1 Introduction 221 9.2 The Accidental Discovery of TAPP 223 9.3 Synthesis of TAPP 223 9.4 Possible Mechanism of TAPP Synthesis 227 9.5 Reactivity of TAPP 228 9.6 π-Expansion of TAPP 229 9.7 π-Expanded 1,4-dihydropyrrolo[3,2-b] pyrrole 231 9.8 Photophysical Optical Properties of TAPP 239 9.9 Conclusion and Outlook 245 Acknowledgments 247 References 247 10 Small Molecule Organogels from AIE Active α-Cyanostilbenes 255Jagadish Katla, Beena Kumari, and Sriram Kanvah 10.1 Introduction 255 10.2 Organogels with Trifluoromethyl Substitution 256 10.3 Organogels with Chiral Units/Chiral Hosts 260 10.4 Stimuli–Responsive Organogels 262 10.5 Organogels with Sensing Applications 266 10.6 Concluding Remarks 271 Acknowledgments 271 References 271 11 Stimuli-responsive Pure Organic Luminescent Supramolecules 277Siyu Sun and Xiang Ma 11.1 Introduction 277 11.2 Pure Organic Fluorescent Supramolecules 280 11.2.1 Pure Organic Fluorescent Supramolecules Containing Macrocycles 280 11.2.1.1 Pure Organic Fluorescent Supramolecules Containing Cyclodextrins 280 11.2.1.2 Pure Organic Fluorescent Supramolecules Containing Calixarenes 284 11.2.1.3 Pure Organic Fluorescent Supramolecules Containing Cucurbiturils 284 11.2.1.4 Pure Organic Fluorescent Supramolecules Containing Pillararene 288 11.2.1.5 Pure Organic Fluorescent Supramolecules Containing Crown Ether 290 11.2.2 Pure Organic Fluorescent Supramolecules Without Macrocycles 291 11.3 Pure Organic Phosphorescent Supramolecules 293 11.3.1 Pure Organic Phosphorescent Supramolecules Based on Macrocyclic Molecules 293 11.3.1.1 Pure Organic Phosphorescent Supramolecules Containing Cyclodextrin 293 11.3.1.2 Pure Organic Phosphorescent Supramolecules Containing Cucurbiturils 297 11.3.1.3 Pure Organic Phosphorescent Supramolecules Containing Calixarenes 297 11.3.1.4 Pure Organic Phosphorescent Supramolecules Containing Crown Ether 297 11.3.2 Pure Organic Phosphorescent Supramolecules Without Macrocyclic Molecules 299 11.3.2.1 Pure Organic Supramolecular Phosphorescence System With Doping-Based Host–Guest Interaction 299 11.3.2.2 Other Pure Organic Phosphorescent Supramolecules 301 11.4 Conclusions 306 Acknowledgments 306 References 307 12 AIE Fluorescent Polymersomes 311Hui Chen and Min-Hui Li 12.1 Introduction 311 12.2 Structural Consideration of Block Copolymers for Polymersome Formation 314 12.3 Methods of Polymersome Preparation 315 12.4 Techniques of Polymersome Characterization 317 12.5 AIE Polymersomes Based on PEG-b-POSS 317 12.6 AIE Polymersomes Based on Amphiphilic Polypeptoids 319 12.7 AIE Polymersomes Based on PEG-b-Polycarbonate 321 12.8 AIE Polymersomes Based on Amphiphilic Polynorbornene 323 12.9 AIE Polymersomes Based on Amphiphilic Block Copolymers by RAFT Polymerization 326 12.10 Summary and Perspectives 330 References 334 13 Designs for AIE Molecules and Functional Luminescent Materials Based on Boron-containing Element-blocks 341Kazuo Tanaka, Masayuki Gon, Shunichiro Ito, and Yoshiki Chujo 13.1 Introduction 341 13.1.1 Generals of Commodity Luminescent Boron Complexes 341 13.1.2 Trends in the Development of Advanced Organic Electronic Devices 342 13.1.3 Strategies for Obtaining Solid-state Luminescence and Stimuli-responsiveness 343 13.1.4 New Ideas for Material Design Based on “Element-blocks” 343 13.2 Solid-state Luminescence and Luminochromism of o-Carboranes 344 13.2.1 Emission Mechanism of Aryl-modified o-Carboranes 344 13.2.2 AIE Behavior of o-Carborane Materials 344 13.2.3 Formation of Twisted Intramolecular Charge Transfer (TICT) State in the Crystalline State of o-Carboranes 346 13.2.4 Thermochromic Luminescence of o-Carboranes 346 13.2.5 Intense Solid-state Luminescent Molecules 347 13.2.6 Solid-state Excimer Emission 348 13.3 Boron Complexes with β-Ketimine and β-Diketimine Ligands 349 13.3.1 Generals of Boron Ketiminates and Diketiminates 349 13.3.2 Unique Solid-state Luminescent Properties of Conjugated Boron Complexes 350 13.3.3 Thermally Stable Mechanochromic Luminescent Hybrid with the Siloxane Unit 350 13.3.4 Luminescent Properties of β-Diketiminate Complexes 352 13.3.5 AIE-active Conjugated Polymers 352 13.3.6 Design for Film-type Sensors 353 13.3.7 Sensitive Luminochromic Sensors with Gallium Complexes 354 13.4 Rational Design for AIE-active Molecules Based on “Flexible” Boron Complexes 355 13.4.1 Concept for Rational Design 355 13.4.2 Ring-fused or Nonring-fused Molecules 355 13.4.3 Thermosalient-active Molecules 357 13.4.4 Solid-state Luminescent π-Conjugated Polymer 358 13.5 Conclusion 359 References 359 14 Aggregation-induced Emission (AIE) Active Metal–Organic Coordination Complexes 367Xueliang Shi, Xuzhou Yan, and Hai-Bo Yang 14.1 Introduction 367 14.2 Conception and Design Strategy 368 14.3 AIE Active Metallacycles 371 14.3.1 AIE Active Simple Metallacycles 371 14.3.2 AIE Active Fused Metallacycles 378 14.3.3 AIE Active Metallacycle Polymers 382 14.4 AIE Active Metallacages 389 14.5 AIE Active Metal–organic Frameworks (MOFs) 397 14.6 Summary and Outlook 405 Acknowledgments 406 References 406 15 AIE-type Luminescent Metal Nanoclusters 411Zhennan Wu, Qiaofeng Yao, and Jianping Xie 15.1 Introduction 411 15.2 In the “Single-cluster” Scenario 412 15.2.1 AIE-type Luminescent Metal NCs 412 15.2.2 Atomically Precise AIE-type Luminescent Metal NCs 416 15.2.3 Approaches to Luminescence Enhancement of Metal NCs in the Scheme of AIE 418 15.2.3.1 Surface Engineering 418 15.2.3.2 Roles of the Core 422 15.3 Beyond the “Single-cluster” Scenario 423 15.3.1 Poor-solvent-induced AIE of Metal NCs 423 15.3.2 Ion-induced AIE of Metal NCs 423 15.3.3 Supramolecular Interactions Induced AIE of Metal NCs 426 15.3.4 Spatial Confinement-induced AIE of Metal NCs 429 15.4 Application of the AIE-type Luminescent Metal NCs 433 15.4.1 Chemical Sensing 433 15.4.2 Biological Applications 434 15.4.3 Photosensitizer 434 15.4.4 Light-emitting Diodes (LEDs) 434 15.5 Conclusion and Outlook 436 References 437 16 Aggregation-induced Emission in Coinage Metal Clusters 443Shuang-Quan Zang and Kai Li 16.1 Introduction 443 16.2 AIE-active Gold Cluster 444 16.3 AIE-active Silver Cluster 450 16.4 AIE-active Copper Cluster 454 16.5 AIE-active Bimetallic Cluster 462 16.6 Conclusions 465 References 466 17 Activated Alkynes in Metal-free Bioconjugation 471Xianglong Hu and Ben Zhong Tang 17.1 Introduction 471 17.2 Alkyne–Azide-based Bioconjugation 472 17.3 Activated Alkyne–Amine-based Bioconjugation 473 17.4 Activated Alkyne–Thiol-based Bioconjugation 480 17.5 Activated Alkyne–Hydroxyl-based Bioconjugation 483 17.6 Activated Alkyne-based Bioconjugation and Polymerization in Living Cells and Pathogens 484 17.7 Conclusion 488 References 488 18 AIE-active BODIPY Derivatives 493Yali Liu, Yuzhang Huang, Rongrong Hu, and Ben Zhong Tang 18.1 Introduction 493 18.2 Structures of BODIPY Derivatives 495 18.2.1 BODIPY Derivatives Without Other Chromophore 495 18.2.2 TPE-containing BODIPYs 496 18.2.3 TPA-containing BODIPYs 498 18.2.4 Benzodithiophene-containing BODIPYs 499 18.2.5 Chiral BODIPYs 500 18.2.6 Metal-containing BODIPYs 502 18.2.7 BODIPY-containing Polymers 503 18.2.8 Other BODIPY Derivatives 504 18.3 Structural–property Relationship 508 18.3.1 Conjugation Effect 508 18.3.2 Number and Position of Substitutes 508 18.3.3 Substitution Group 513 18.3.4 Alkyl Substitutes on BODIPY Core 516 18.3.5 AIEgens Attached Through Nonconjugated Spacers 518 18.3.6 Other Substitution Structures 519 18.4 Application 522 18.4.1 Chemosensor 522 18.4.2 Bioimaging 526 18.5 Conclusion 532 References 532 19 Photochemistry-regulated AIEgens and Their Applications 537Xia Ling and Meng Gao 19.1 Introduction 537 19.2 Photocleavage Reaction 537 19.3 Photoreduction Reaction 539 19.4 Photocyclodehydrogenation Reaction 540 19.5 Photooxidative Dehydrogenation Reaction 543 19.6 Spiropyran-merocyanine Reversible Conversion 544 19.7 Dithienylethene-based Ring-open/-closing Reaction 545 19.8 Enol–Keto Isomerization Reaction 550 19.9 E/Z Isomerization Reaction 552 19.10 Photo-induced [2 + 2] Cycloaddition 554 19.11 Combinational Photoreactions 554 19.12 Conclusion and Outlook 556 References 556 20 Design and Development of Naphthalimide Luminogens 559Niranjan Meher and Parameswar Krishnan Iyer 20.1 Introduction 559 20.2 Naphthalimides with N-Functionalization (I) 564 20.3 Naphthalimides Substituted at the 4th Position with Oxygen Atom (II) 567 20.4 Naphthalimides Substituted at the 4th Position with Nitrogen Atom (III) 570 20.5 Naphthalimides with C−C Aromatic Substitution (IV) 571 20.6 Naphthalimides with C−C Double-and Triple-Bond Substitutions (V and VI) 574 20.7 Naphthalimides with the Significant Role of Multifunctionalization (VII) 576 20.8 Conclusion and Outlooks 580 References 581 Index 587

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Book SynopsisThethirdvolume of the ultimate reference on the science and applications of aggregation-induced emission TheHandbook of Aggregation-Induced Emissionexplores foundational and advanced topics in aggregation-induced emission, as well as cutting-edge developments in the field,celebratingtwenty years of progress and achievement in this important and interdisciplinary field.The three volumes combine to offer readers a comprehensive and insightful interpretation accessible to both new and experiencedresearchersworking on aggregation-induced emission. InVolume3:Emerging Applications, the editorsaddress theapplications ofAIEgensin several fields, including bio-imaging, fluorescent molecular switches, electrochromic materials, regenerative medicine, detection of organic volatile contaminants,hydrogels, andorganogels.Topics covered include: AIE-active emitters and their applications in OLEDs,and circularly polarized luminescence of aggregation-inTable of ContentsList of Contributors xv Preface xxi Preface to Volume 3: Applications xxiii 1 AIE-active Emitters and Their Applications in OLEDs 1Qiang Wei, Jiasen Zhang, and Ziyi Ge 1.1 Introduction 1 1.2 Conventional Aggregation-induced Emissive Emitters 4 1.2.1 Blue Aggregation-induced Emissive Emitters 4 1.2.2 Green Aggregation-induced Emissive Emitters 7 1.2.3 Red Aggregation-induced Emissive Emitters 8 1.2.4 Aggregation-induced Emission-active Emitters-Based White OLED 9 1.3 High Exciton Utilizing Efficient Aggregation-induced Emissive Materials 13 1.3.1 Aggregation-induced Phosphorescent Emissive Emitters 13 1.3.2 Aggregation-induced Delayed Fluorescent Emitters 14 1.3.3 Hybridized Local and Charge Transfer Materials Aggregation-induced Emissive Emitters 15 1.4 Conclusion and Outlook 16 References 18 2 Circularly Polarized Luminescence of Aggregation-induced Emission Materials 27Fuwei Gan, Chengshuo Shen, and Huibin Qiu 2.1 Introduction of Circularly Polarized Luminescence 27 2.2 Small Organic Molecules 28 2.3 Macrocycles and Cages 33 2.4 Metal Complexes and Clusters 35 2.5 Supramolecular Systems 37 2.6 Polymers 46 2.7 Liquid Crystals 50 2.8 Conclusions and Outlook 51 References 53 3 AIE Polymer Films for Optical Sensing and Energy Harvesting 57Andrea Pucci 3.1 Introduction 57 3.2 Working Mechanism of AIEgens 59 3.3 AIE-doped Polymer Films for Optical Sensing 61 3.3.1 Mechanochromic AIE-doped Polymer Films 61 3.3.2 Thermochromic AIE-doped Polymer Films 65 3.3.3 Vapochromic AIE-doped Polymer Films 67 3.4 AIE-doped Polymer Films for Energy Harvesting 70 3.5 Conclusions 72 References 73 4 Aggregation-induced Electrochemiluminescence 79Serena Carrara 4.1 Introduction: From Electrochemiluminescence to AI-ECL 79 4.1.1 Mechanisms of AI-ECL 81 4.2 Classification and Properties of AI-ECL luminophores 85 4.2.1 Metal Transition Complexes 85 4.2.2 Polymers and Polymeric Nanoaggregates 87 4.2.3 Organic Molecules 90 4.2.4 Hybrid and Functional Materials 93 4.3 Applications and Outlooks 95 References 98 5 Mechanoluminescence Materials with Aggregation-induced Emission 105Zhiyong Yang, Juan Zhao, Eethamukkala Ubba, Zhan Yang, Yi Zhang, and Zhenguo Chi 5.1 Introduction 105 5.2 Mechanoluminescence of Organic Molecules Not Mentioned AIE 107 5.3 ML–AIE Materials 117 5.4 Summary and Outlook 132 References 133 6 Dynamic Super-resolution Fluorescence Imaging Based on Photo-switchable Fluorescent Spiropyran 139Cheng Fan, Chong Li, and Ming-Qiang Zhu 6.1 Introduction 139 6.2 Materials and Methods 141 6.2.1 Materials 141 6.2.2 The Preparation of PSt-b-PEO Block Copolymer Micelles 141 6.2.3 Super-resolution Microscope 141 6.2.4 Super-resolution Imaging 141 6.3 Super-resolution Imaging of Block Copolymer Self-assembly 141 6.4 Optimization of Spatial Resolution 144 6.5 Temporal Resolution 145 6.6 Dynamic Super-resolution Imaging 147 6.7 Conclusion and Prospection 147 References 149 7 Visualization of Polymer Microstructures 151Shunjie Liu, Yuanyuan Li, Ting Han, Jacky W. Y. Lam, and Ben Zhong Tang 7.1 Introduction 151 7.2 Synthetic Polymers 152 7.2.1 Polymer Self-assembly 152 7.2.2 Polymerization Reaction 154 7.2.3 Physical Process Visualization 155 7.2.3.1 Glass Transition Temperature 155 7.2.3.2 Solubility Parameter 157 7.2.3.3 Crystallization 158 7.2.3.4 Microphase Separation 158 7.2.4 Stimuli Response 161 7.2.4.1 Heat Response 161 7.2.4.2 Humidity Response 162 7.2.4.3 Other Response 164 7.3 Biological Polymers 164 7.3.1 DNA Synthesis 165 7.3.2 DNA Sequence 165 7.3.3 Protein Conformation 168 7.3.4 Protein Fibrillation 169 7.3.5 Other Process 171 7.4 Summary and Perspective 172 References 173 8 Self-assembly of Aggregation-induced Emission Molecules into Micelles and Vesicles with Advantageous Applications 179Jinwan Qi, Jianbin Huang, and Yun Yan 8.1 General Background of Micelles and Vesicles 179 8.2 AIE Micelles 180 8.2.1 General Strategies Leading to AIE Micelles 180 8.2.1.1 Incorporating Tetraphenylethylene (TPE) Unit into Single-Chained Surfactants 180 8.2.1.2 Incorporating Tetraphenylethylene (TPE) Unit into Gemini Surfactants 182 8.2.1.3 Incorporating Platinum Complex into Amphiphiles 182 8.2.1.4 Polymeric AIE Micelles 183 8.2.1.5 Coassembled AIE Micelles 188 8.2.2 Applications of AIE Micelles 190 8.2.2.1 Untargeted Bioimaging 191 8.2.2.2 Targeted Bioprobing 192 8.2.2.3 Micellar Theranostics 193 8.2.2.4 Sensing 197 8.2.2.5 Visualization of Physical Chemistry Process 199 8.3 AIE Vesicles 203 8.3.1 AIE Vesicles Based on Synthetic Amphiphiles 203 8.3.1.1 Synthetic Ionic Amphiphiles 203 8.3.1.2 Synthetic Nonionic AIE Amphiphiles 203 8.3.1.3 Synthetic Nonamphiphilic AIE Molecules 205 8.3.2 Supramolecular AIE Vesicles 206 8.3.2.1 AIE Vesicles Directed by Host–Guest Chemistry 208 8.3.2.2 AIE Vesicles Based on Electrostatic Interactions 209 8.3.2.3 AIE Vesicles Based on Coordination Interactions 209 8.3.3 Applications of AIE Vesicles 210 8.3.3.1 Cell Models 210 8.3.3.2 Bioimaging 211 8.3.3.3 Theranostics 212 8.3.3.4 Light-harvesting 214 8.3.3.5 Other Applications 216 8.4 Summary and Outlooks 217 References 217 9 Vortex Fluidics-mediated Fluorescent Hydrogels with Aggregation-induced Emission Characteristics 221Javad Tavakoli and Youhong Tang 9.1 Introduction 221 9.2 Tunning the Size and Property of AIEgens, a New Approach to Create FL Hydrogels with Superior Properties 222 9.3 AIEgens for Characterization of Hydrogels 231 9.4 Conclusion 238 References 238 10 Design and Preparation of Stimuli-responsive AIE Fluorescent Polymers-based Probes for Cells Imaging 243Juan Qiao and Li Qi 10.1 Introduction 243 10.2 Design and Preparation Strategies for AIE–SRP Probes 246 10.2.1 Mechanism of AIE–SRP Probes 246 10.2.2 Stimuli-Responsive Polymers 247 10.2.2.1 Thermal-Sensitive Polymers 247 10.2.2.2 pH-Sensitive Polymers 247 10.2.2.3 Photo-Sensitive polymers 247 10.2.2.4 Protein-Sensitive Polymers 248 10.2.3 AIE Dyes 249 10.2.4 Combination of Stimuli-Sensitive Polymer and AIE Dyes 251 10.2.4.1 Chemical Synthesis 251 10.2.4.2 Physical Blending 256 10.3 Application of AIE–SRP Probes 257 10.3.1 Thermal-Sensitive Application 257 10.3.2 pH-Sensitive Application 259 10.3.3 Photo-Sensitive Application 260 10.3.4 Protein-Sensitive Application 260 10.3.5 MultiSensitive Application 260 10.4 Summary and Prospect 262 References 263 11 AIE: New Strategies for Cell Imaging and Biosensing 269Tracey Luu, Bicheng Yao, and Yuning Hong 11.1 Introduction 269 11.2 Cellular Imaging 271 11.2.1 Cytoplasma Membrane Imaging 272 11.2.2 Mitochondria Imaging 273 11.2.3 Lysosome Imaging 275 11.2.4 Lipid Droplet Imaging 276 11.2.5 Nucleus Imaging 277 11.3 Biosensing 278 11.3.1 Ions 279 11.3.2 Lipids and Carbohydrates 281 11.3.3 Amino Acids, Proteins, and Enzymes 283 11.3.4 Nucleic Acids and Pathogens 286 11.4 Conclusion 289 References 289 12 AIE-based Systems for Imaging and Image-guided Killing of Pathogens 297Jiangman Sun, Fang Hu, Yongjie Ma, Yufeng Li, Guan Wang, and Xinggui Gu 12.1 Introduction 297 12.2 Bacteria Imaging Based on AIEgens 298 12.2.1 Broad-spectrum Bacterial Imaging and Identification 299 12.2.2 Gram Positive and Gram Negative Bacteria Distinguishing 299 12.2.3 Long-term Bacterial Tracking 303 12.2.4 Live and Dead Bacteria Discrimination Based on AIEgens 304 12.3 Bacteria-targeted Imaging and Ablation Based on AIEgens 305 12.3.1 Surfactant-structure Based AIEgens for Bacterial Elimination 305 12.3.2 Photodynamic Therapy for Bacterial Elimination 309 12.3.2.1 Vancomycin-bacteria Interaction Mediated Photodynamic Ablation 309 12.3.2.2 Positive-charged AIE PS for Bacteria Ablation 311 12.3.2.3 Metabolic Labeling-mediated Imaging and Photodynamic Ablation 313 12.3.3 AIEgen with Antimicrobial Agents for Bacteria Elimination 315 12.3.4 Biodegradable Biocides for Bacteria Elimination 315 12.4 Bacterial Susceptibility Evaluation and Antibiotics Screening 315 12.5 Sensors for Bacterial Detection Based on AIEgens 317 12.5.1 Fluorescent Sensor Arrays 317 12.5.2 Biosensors Constructed by Electrospun Fibers 319 12.5.3 Micromotors for Bacterial Detection 320 12.6 Conclusions and Perspectives 321 References 321 13 AIEgen-based Trackers for Cancer Research and Regenerative Medicine 329Chen Zhang and Kai Li 13.1 Introduction 329 13.2 AIEgens for Long-term Cancer Cell Tracking 330 13.2.1 AIEgen-based Long-term Cell Trackers with Emission in the Visible Range 330 13.2.2 AIEgen-based Long-term Cell Trackers with Near-infrared (NIR) Emission 334 13.2.3 AIEgen-based Long-term Cell Trackers with Multiphoton Absorption 335 13.2.4 AIEgen-based Hybrid or Multifunctional Systems for Cell Tracking 336 13.3 AIEgens for Stem Cell-based Regenerative Medicine and Regeneration-related Process 338 13.3.1 AIEgen-based Trackers for Adipose-derived Stem Cells 338 13.3.2 AIEgen-based Trackers for Bone Marrow Stem Cells 340 13.3.3 AIEgen-based Trackers for Embryo-related Cells 342 13.3.4 AIEgens for Monitoring Biological Process in Regenerative Medicine 345 13.3.5 AIEgen-based Nanocomplexes in Regenerative Medicine 346 13.4 Conclusion 347 References 350 14 AIE-active Fluorescence Probes for Enzymes and Their Applications in Disease Theranostics 355Jianguo Wang and Guoyu Jiang 14.1 Introduction 355 14.2 AIE-active Fluorescence Probes for Enzymes and Their Applications in Disease Theranostics 356 14.2.1 AIE-active Fluorescence Probes for Alkaline Phosphatase 356 14.2.2 AIE-active Fluorescence Probes for Caspases 358 14.2.3 AIE-active Fluorescence Probes for Cathepsin B 361 14.2.4 AIE-active Fluorescence Probes for β-Galactosidase 363 14.2.5 AIE-active Fluorescence Probes for γ-Glutamyltranspeptidase 365 14.2.6 AIE-active Fluorescence Probes for Reductases 366 14.2.6.1 AIE-active Fluorescence Probes for AzoR 366 14.2.6.2 AIE-active Fluorescence Probes for NQO1 369 14.2.6.3 AIE-active Fluorescence Probes for NTR 369 14.2.6.4 AIE-active Fluorescence Probes for CYP450 Reductase 371 14.2.7 AIE-active Fluorescence Probes for Chymase 371 14.2.8 AIE-active Fluorescence Probes for Esterase 372 14.2.8.1 AIE-active Fluorescence Probes for CaE 372 14.2.8.2 AIE-active Fluorescence Probes for Lipase 375 14.2.9 AIE-active Fluorescence Probes for Histone Deacetylase 376 14.2.10 AIE-active Fluorescence Probes for MMP-2 379 14.2.11 AIE-active Fluorescence Probes for Furin 380 14.2.12 AIE-active Fluorescence Probes for Trypsin 380 14.2.13 AIE-active Fluorescence Probes for Telomerase 385 14.2.14 AIE-active Fluorescence Probes for DPP-4 386 14.3 Summary and Outlook 387 References 388 15 AIE Nanoprobes for NIR-II Fluorescence In Vivo Functional Bioimaging 399Zhe Feng, Xiaoming Yu, and Jun Qian 15.1 Introduction 399 15.2 NIR-II Fluorescence Macroimaging In Vivo 400 15.3 NIR-II Fluorescence Wide-field Microscopic Imaging In Vivo 436 15.4 NIR-II Fluorescence Confocal Microscopic Imaging In Vivo 440 15.5 Summary and Perspectives 441 References 444 16 In Vivo Phototheranostics Application of AIEgen-based Probes 447Zhiyuan Gao, Heqi Gao, and Dan Ding 16.1 Introduction 447 16.2 AIE Fluorescent Probe with Photodynamic Therapy Function 448 16.3 AIE Photoacoustic Probe with Photothermal Therapy Function 451 16.4 Application of AIE Fluorescent Probe in Synergistic Therapy 454 16.5 AIE Fluorescent Probe with Immunotherapy Function 458 16.6 Conclusions and Perspectives 460 References 460 17 Red-emissive AIEgens Based on Tetraphenylethylene for Biological Applications 465Yanyan Huang, Fang Hu, and Deqing Zhang 17.1 Introduction 465 17.2 TPE-based AIEgens with Dicyanovinyl Group 466 17.2.1 Design of Red-emissive AIEgens with Dicyanovinyl Group 466 17.2.2 Red-emissive AIEgens as Photosensitizers 469 17.2.3 Photosensitization Enhancement of AIEgens with Dicyanovinyl Group 471 17.2.4 Self-assembly of AIEgens with Dicyanovinyl Groups 473 17.3 Pyridinium-based AIEgens 475 17.3.1 Photophysical Properties of Pyridinium-based AIEgens 475 17.3.2 Bio-sensing Applications of Pyridinium-substituted Tetraphenylethylenes 477 17.3.3 Bacterial Imaging and Ablation 479 17.3.4 Imaging and Interrupting Mitochondria and Related Biological Processes with Pyridinium-based AIEgens 480 17.4 Summary and Perspectives 485 References 485 18 Smart Luminogens for the Detection of Organic Volatile Contaminants 491Niranjan Meher and Parameswar Krishnan Iyer 18.1 Introduction 491 18.2 Smart AIE Nanomaterials and their Sensing Applications for OVCs 493 18.2.1 Organic Framework 493 18.2.2 Molecular Rotors 499 18.2.3 Other Small Molecule 502 18.3 Summary and Outlook 506 References 506 19 Bulky Hydrophobic Counterions for Suppressing Aggregation-caused Quenching of Ionic Dyes in Fluorescent Nanoparticles 511Ilya O. Aparin, Nagappanpillai Adarsh, Andreas Reisch, and Andrey S. Klymchenko 19.1 Introduction 511 19.2 Counterion Effect in Nanomaterials Based on Conventional Bright Fluorophores 513 19.3 Counterions and Aggregation-induced Emission 516 19.3.1 Counterion Effect in AIE Dyes 517 19.3.2 Ionic AIE: Lighting Up Environment-sensitive Ionic Dyes in Nanomaterials 519 19.4 Dye-loaded Polymeric NPs and the Crucial Role of Bulky Counterions 523 19.4.1 Principle 523 19.4.2 The Role of the Polymer 525 19.4.3 The Role of the Counterion 525 19.4.4 Dye Nature 528 19.4.5 Energy Transfer, Collective Behavior of Dyes and Biosensing 531 19.5 Conclusions 532 References 534 20 Fluorescent Silver Staining Based on a Fluorogenic Ag+ Probe with Aggregation-induced Emission Properties 541Chuen Kam, Sheng Xie, Alex Y. H. Wong, and Sijie Chen 20.1 Introduction 541 20.2 Historical Background of Silver Staining 541 20.2.1 Silver Staining for Neurological Studies 542 20.2.2 Silver Staining from Neuroscience to Proteomics 544 20.3 Conventional Silver Staining Methods 544 20.4 Fluorogenic Probes for Ag+ Detection 546 20.5 Fluorogenic Silver Staining in Polyacrylamide Gel 550 20.6 Concluding Remarks 554 References 554 Index 559

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Book SynopsisInnovation in healthcare is currently a hot topic. Innovation allows us to think differently, to take risks and to develop ideas that are far better than existing solutions. Currently, there is no single book that covers all topics related to microelectronics, sensors, data, system integration and healthcare technology assessment in one reference. This book aims to critically evaluate current state-of-the-art technologies and provide readers with insights into developing new solutions. With contributions from a fully international team of experts across electrical engineering and biomedical fields, the book discusses how advances in sensing technology, computer science, communications systems and proteomics/genomics are influencing healthcare technology today.Table of ContentsList of Contributors xiii Introduction xv 1 Maximizing the Value of Engineering and Technology Research in Healthcare: Development-Focused Health Technology Assessment 1Janet Boutell Hawkins and Eleanor Grieve 1.1 Introduction 1 1.2 What Is HTA? 3 1.3 What Is Development-Focused HTA? 4 1.4 Illustration of Features of Development-Focused HTA 5 1.4.1 Use-Focused HTA 6 1.4.2 Development-Focused HTA 6 1.5 Activities of Development-Focused HTA 7 1.6 Analytical Methods of Development-Focused HTA 9 1.6.1 Clinical Value Assessment 11 1.6.2 Economic Value Assessment 11 1.6.3 Evidence Generation 14 1.7 What Are the Challenges in the Development and Assessment of Medical Devices? 15 1.7.1 What Are Medical Devices? 15 1.7.2 Challenges Common to All medical Devices 16 1.7.2.1 Licensing and Regulation 16 1.7.2.2 Adoption 17 1.7.2.3 Evidence 18 1.7.3 Challenges Specific to Some Categories of Device 19 1.7.3.1 Learning Curve 19 1.7.3.2 Short Lifespan and Incremental Improvement 19 1.7.3.3 Workflow 19 1.7.3.4 Indirect Health Benefit 19 1.7.3.5 Behavioral and Other Contextual Factors 20 1.7.3.6 Budgetary Challenges 20 1.8 The Contribution of DF-HTA in the Development and Translation of Medical Devices 20 1.8.1 Case Study 1 - Identifying and Confirming Needs 21 1.8.2 Case Study 2 - What Difference Could This Device Make? 21 1.8.3 Case Study 3 - Which Research Project Has the Most Potential? 21 1.8.4 Case Study 4 - What Is the Required Performance to Deliver Clinical Utility? 21 1.8.5 Case Study 5 - What Are the Key Parameters for Evidence Generation? 22 1.9 Conclusion 22 References 23 2 Contactless Radar Sensing for Health Monitoring 29Francesco Fioranelli and Julien Le Kernec 2.1 Introduction: Healthcare Provision and Radar Technology 29 2.2 Radar and Radar Data Fundamentals 32 2.2.1 Principles of Radar Systems 32 2.2.2 Principles of Radar Signal Processing for Health Applications 35 2.2.3 Principles of Machine Learning Applied to Radar Data 38 2.2.4 Complementary Approaches: Passive Radar and Channel State Information Sensing 41 2.3 Radar Technology in Use for Health Care 42 2.3.1 Activities Recognition and Fall Detection 42 2.3.2 Gait Monitoring 46 2.3.3 Vital Signs and Sleep Monitoring 48 2.4 Conclusion and Outstanding Challenges 50 2.5 Future Trends 52 2.5.1 Paradigm Change in Radar Sensing 52 2.5.2 Multimodal Sensing 55 References 55 3 Pervasive Sensing: Macro to Nanoscale 61Qammer H. Abbasi, Hasan T. Abbas, Muhammad Ali Imran and Akram Alomainy 3.1 Introduction 61 3.2 The Anatomy of a Human Skin 64 3.3 Characterization of Human Tissue 65 3.4 Tissue Sample Preparation 70 3.5 Measurement Apparatus 70 3.6 Simulating the Human Skin 72 3.6.1 Human Body Channel Modelling 73 3.7 Networking and Communication Mechanisms for Body-Centric Wireless Nano-Networks 76 3.8 Concluding Remarks 78 References 78 4 Biointegrated Implantable Brain Devices 81Rupam Das and Hadi Heidari 4.1 Background 81 4.2 Neural Device Interfaces 83 4.3 Implant Tissue Biointegration 84 4.4 MRI Compatibility of the Neural Devices 87 4.5 Conclusion 90 References 90 5 Machine Learning for Decision Making in Healthcare 95Ali Rizwan, Metin Ozturk, Najah Abu Ali, Ahmed Zoha, Qammer H. Abbasi and M. Ali Imran 5.1 Introduction 95 5.2 Data Description 98 5.3 Proposed Methodology 99 5.3.1 Collection of the Data 99 5.3.2 Selection of the Window Size 100 5.3.3 Extraction of the Features 101 5.3.4 Selection of the Features 101 5.3.5 Deployment of the Machine Learning Models 102 5.3.6 Quantitative Assessment of the Models 103 5.3.7 Parallel Processing 104 5.4 Results 105 5.5 Analysis and Discussion 108 5.5.1 Postures 108 5.5.2 Window Sizes 109 5.5.3 Feature Combinations 109 5.5.4 Machine Learning Algorithms 111 5.6 Conclusions 113 References 113 6 Information Retrieval from Electronic Health Records 117Meshal Al-Qahtani, Stamos Katsigiannis and Naeem Ramzan 6.1 Introduction 117 6.2 Methodology 118 6.2.1 Parallel LSI (PLSI) 119 6.2.2 Distributed LSI (DLSI) 121 6.3 Results and Analysis 122 6.4 Conclusion 126 References 126 7 Energy Harvesting for Wearable and Portable Devices 129Rami Ghannam, You Hao, Yuchi Liu and Yidi Xiao 7.1 Introduction 129 7.2 Energy Harvesting Techniques 130 7.2.1 Photovoltaics 130 7.2.2 Piezoelectric Energy Harvesting 134 7.2.3 Thermal Energy Harvesting 137 7.2.3.1 Latest Trends 139 7.2.4 RF Energy Harvesting 141 7.3 Conclusions 145 References 146 8 Wireless Control for Life-Critical Actions 153Burak Kizilkaya, Bo Chang, Guodong Zhao and Muhammad Ali Imran 8.1 Introduction 153 8.2 Wireless Control for Healthcare 155 8.3 Technical Requirements 156 8.3.1 Ultra-Reliability 156 8.3.2 Low Latency 156 8.3.3 Security and Privacy 157 8.3.4 Edge Artificial Intelligence 157 8.4 Design Aspects 157 8.4.1 Independent Design 158 8.4.2 Co-Design 159 8.5 Co-Design System Model 159 8.5.1 Control Function 159 8.5.2 Performance Evaluation Criterion 161 8.5.2.1 Control Performance 161 8.5.2.2 Communication Performance 161 8.5.3 Effects of Different QoS 162 8.5.4 Numerical Results 163 8.6 Conclusions 165 References 165 9 Role of D2D Communications in Mobile Health Applications: Security Threats and Requirements 169Muhammad Usman, Marwa Qaraqe, Muhammad Rizwan Asghar and Imran Shafique Ansari 9.1 Introduction 169 9.2 D2D Scenarios for Mobile Health Applications 170 9.3 D2D Security Requirements and Standardization 171 9.3.1 Security Issues on Configuration 171 9.3.1.1 Configuration of the ProSe Enabled UE 171 9.3.2 Security Issues on Device Discovery 172 9.3.2.1 Direct Request and Response Discovery 172 9.3.2.2 Open Direct Discovery 173 9.3.2.3 Restricted Direct Discovery 173 9.3.2.4 Registration in Network-Based ProSe Discovery 173 9.3.3 Security Issues on One-to-Many Communications 174 9.3.3.1 One-to-many communications between UEs 174 9.3.3.2 Key Distribution for Group Communications 174 9.3.4 Security Issues on One-to-One Communication 175 9.3.4.1 One-to-One ProSe Direct Communication 175 9.3.4.2 One-to-One ProSe Direct Communication 175 9.3.5 Security Issues on ProSe Relays 175 9.3.5.1 Maintaining 3GPP Communication Security through Relay 175 9.3.5.2 UE-Network Relay 176 9.3.5.3 UE-to-UE Relay 176 9.4 Existing Solutions 176 9.4.1 Key Management 176 9.4.2 Routing 178 9.4.3 Social Trust and Social Ties 178 9.4.4 Access Control 180 9.4.5 Physical Layer Security 180 9.4.6 Network Coding 183 9.5 Conclusion 183 References 183 10 Automated Diagnosis of Skin Cancer for Healthcare: Highlights and Procedures 187Maram A. Wahba and Amira S. Ashour 10.1 Introduction 187 10.2 Framework of Computer-Aided Skin Cancer Classification Systems 188 10.2.1 Image Acquisition 188 10.2.2 Image Pre-Processing 189 10.2.2.1 Color Contrast Enhancement 189 10.2.2.2 Artifact Removal 190 10.2.3 Image Segmentation 191 10.2.3.1 Thresholding-Based Segmentation 192 10.2.3.2 Edge-Based Segmentation 192 10.2.3.3 Region-Based Segmentation 193 10.2.3.4 Active Contours-Based Segmentation 193 10.2.3.5 Artificial Intelligence-Based Segmentation 194 10.2.4 Feature Extraction 195 10.2.4.1 Color-based Features 196 10.2.4.2 Dimensional Features 196 10.2.4.3 Texture-Based Features 196 10.2.4.4 Dermoscopic Rules and Methods 197 10.2.5 Feature Selection 200 10.2.6 Classification 201 10.2.7 Classification Performance Evaluation 202 10.2.8 Computer-Aided Diagnosis Systems in Dermoscopic Images 203 10.3 Conclusion 205 Acknowledgment 205 References 205 Conclusions 213 Index 215

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Book SynopsisIn the fast-developing world of Industry 4.0, which combines Extended Reality (XR) technologies, such as Virtual Reality (VR) and Augmented Reality (AR), creating location aware applications to interact with smart objects and smart processes via Cloud Computing strategies enabled with Artificial Intelligence (AI) and the Internet of Things (IoT), factories and processes can be automated and machines can be enabled with self-monitoring capabilities. Smart objects are given the ability to analyze and communicate with each other and their human co-workers, delivering the opportunity for much smoother processes, and freeing up workers for other tasks. Industry 4.0 enabled smart objects can be monitored, designed, tested and controlled via their digital twins, and these processes and controls are visualized in VR/AR. The Industry 4.0 technologies provide powerful, largely unexplored application areas that will revolutionize the way we work, collaborate and live our lives. It is importantTable of ContentsList of Figures xi List of Tables xv Foreword xvii Introduction xix Preface xxiii Acknowledgments xxv Acronyms xxvii Part I Extended Reality Education 1 Mixed Reality Use in Higher Education: Results from an International Survey 3J. Riman, N. Winters, J. Zelenak, I. Yucel, J. G. Tromp 1.1 Introduction 4 1.2 Organizational Framework 4 1.3 Online Survey About MR Usage 5 1.4 Results 6 1.4.1 Use in Classrooms 8 1.4.2 Challenges 9 1.4.3 Examples of Research in Action 10 1.4.4 Hardware and Software for Use in Classrooms and Research 10 1.4.5 Challenges Described by Researcher Respondents 12 1.4.6 Anecdotal Responses about Challenges 12 1.5 Conclusion 13 References 15 2 Applying 3D VR Technology for Human Body Simulation to Teaching, Learning and Studying 17Le Van Chung, Gia Nhu Nguyen, Tung Sanh Nguyen, Tri Huu Nguyen, Dac-Nhuong Le 2.1 Introduction 18 2.2 Related Works 18 2.3 3D Human Body Simulation System 19 2.3.1 The Simulated Human Anatomy Systems 19 2.3.2 Simulated Activities and Movements 20 2.3.3 Evaluation of the System 23 2.4 Discussion of Future Work 25 2.5 Conclusion 26 References 26 Part II Internet of Things 3 A Safety Tracking and Sensor System for School Buses in Saudi Arabia 31Samah Abbas, Hajar Mohammed, Laila Almalki Maryam Hassan, Maram Meccawy 3.1 Introduction 32 3.2 Related Work 32 3.3 Data Gathering Phase 33 3.3.1 Questionnaire 34 3.3.2 Driver Interviews 35 3.4 The Proposed Safety Tracking and Sensor School Bus System 36 3.4.1 System Analysis and Design 37 3.4.2 User Interface Design 38 3.5 Testing and Results 41 3.6 Discussion and Limitation 42 3.7 Conclusions and Future Work 42 References 42 4 A Lightweight Encryption Algorithm Applied to a Quantized Speech Image for Secure IoT 45Mourad Talbi 4.1 Introduction 46 4.2 Applications of IoT 46 4.3 Security Challenges in IoT 47 4.4 Cryptographic Algorithms for IoT 47 4.5 The Proposed Algorithm 48 4.6 Experimental Setup 50 4.7 Results and Discussion 52 4.8 Conclusion 57 References 58 Part III Mobile Technology 5 The Impact of Social Media Adoption on Entrepreneurial Ecosystem 63Bodor Almotairy, Manal Abdullah, Rabeeh Abbasi 5.1 Introduction 64 5.2 Background 65 5.2.1 Small and Medium-Sized Enterprises (SMEs) 65 5.2.2 Social Media 65 5.2.3 Social Networks and Entrepreneurial Activities 66 5.3 Analysis Methodology 66 5.4 Understanding the Entrepreneurial Ecosystem 67 5.5 Social Media and Entrepreneurial Ecosystem 69 5.5.1 Social Media Platforms and Entrepreneurship 71 5.5.2 The Drivers of Social Media Adoption 71 5.5.3 The Motivations and Benefits for Entrepreneurs to Use Social Media 71 5.5.4 Entrepreneurship Activities Analysis Techniques in Social Media Networks 71 5.6 Research Gap and Recommended Solution 73 5.6.1 Research Gap 73 5.6.2 Recommended Solution 74 5.7 Conclusion 74 References 75 6 Human Factors for E-Health Training System: UX Testing for XR Anatomy Training App 81Zhushun Timothy Cai, Oliver Medonza, Kristen Ray, Chung Van Le, Damian Schofield, Jolanda Tromp 6.1 Introduction 82 6.2 Mobile Learning Applications 82 6.3 Ease of Use and Usability 82 6.3.1 Effectiveness 83 6.3.2 Efficiency 83 6.3.3 Satisfaction 83 6.4 Methods and Materials 86 6.5 Results 89 6.5.1 Task Completion Rate (TCR) 89 6.5.2 Time-on-Task (TOT) 90 6.5.3 After-Scenario Questionnaire (ASQ) 91 6.5.4 Post-Study System Usability Questionnaire (PSSUQ) 93 6.6 Conclusion 93 References 94 Part IV Towards Digital Twins and Robotics 7 Augmented Reality at Heritage Sites: Technological Advances and Embodied Spatially Minded Interactions 101Lesley Johnston, Romy Galloway, Jordan John Trench, Matthieu Poyade, Jolanda Tromp, Hoang Thi My 7.1 Introduction 102 7.2 Augmented Reality Devices 103 7.3 Detection and Tracking 105 7.4 Environmental Variation 106 7.5 Experiential and Embodied Interactions 109 7.6 User Experience and Presence in AR 114 7.7 Conclusion 115 References 116 8 TELECI Architecture for Machine Learning Algorithms Integration in an Existing LMS 121V. Zagorskis, A. Gorbunovs, A. Kapenieks 8.1 Introduction 122 8.2 TELECI Architecture 123 8.2.1 TELECI Interface to a Real LMS 123 8.2.2 First RS Steps in the TELECI System 124 8.2.3 Real Student Data for VS Model 125 8.2.4 TELECI Interface to VS Subsystem 126 8.2.5 TELECI Interface to AI Component 128 8.3 Implementing ML Technique 128 8.3.1 Organizational Activities 128 8.3.2 Data Processing 129 8.3.3 Computing and Networking Resources 130 8.3.4 Introduction to Algorithm 130 8.3.5 Calibration Experiment 132 8.4 Learners’ Activity Issues 133 8.5 Conclusion 136 References 137 Part V Big Data Analytics 9 Enterprise Innovation Management in Industry 4.0: Modeling Aspects 141V. Babenko 9.1 Introduction 142 9.2 Conceptual Model of Enterprise Innovation Process Management 144 9.3 Formation of Restrictions for Enterprise Innovation Management Processes 147 9.4 Formation of Quality Criteria for Assessing Implementation of Enterprise Innovation Management Processes 148 9.5 Statement of Optimization Task of Implementation of Enterprise Innovation Management Processes 148 9.6 Structural and Functional Model for Solving the Task of Dynamic 150 9.7 Formulation of the Task of Minimax Program Management of Innovation Processes at Enterprises 152 9.8 General Scheme for Solving the Task of Minimax Program Management of Innovation Processes at the Enterprises 154 9.9 Model of Multicriteria Optimization of Program Management of Innovation Processes 156 9.10 Conclusion 161 References 162 10 Using Simulation for Development of Automobile Gas Diesel Engine Systems and their Operational Control 165Mikhail G. Shatrov, Vladimir V. Sinyavski, Andrey Yu. Dunin, Ivan G. Shishlov, Sergei D. Skorodelov, Andrey L. Yakovenko 10.1 Introduction 166 10.2 Computer Modeling 167 10.3 Gas Diesel Engine Systems Developed 168 10.3.1 Electronic Engine Control System 168 10.3.2 Modular Gas Feed System 169 10.3.3 Common Rail Fuel System for Supply of the Ignition Portion of Diesel Fuel 169 10.4 Results and Discussion 172 10.4.1 Results of Diesel Fuel Supply System Simulation 172 10.4.2 Results of Engine Bed Tests 181 10.5 Conclusion 183 References 184 Part VI Towards Cognitive Computing 11 Classification of Concept Drift in Evolving Data Stream 189Mashail Althabiti and Manal Abdullah 11.1 Introduction 190 11.2 Data Mining 190 11.3 Data Stream Mining 191 11.3.1 Data Stream Challenges 191 11.3.2 Features of Data Stream Methods 193 11.4 Data Stream Sources 193 11.5 Data Stream Mining Components 193 11.5.1 Input 194 11.5.2 Estimators 194 11.6 Data Stream Classification and Concept Drift 194 11.6.1 Data Stream Classification 194 11.6.2 Concept Drift 194 11.6.3 Data Stream Classification Algorithms with Concept Drift 196 11.6.4 Single Classifier 196 11.6.5 Ensemble Classifiers 197 11.6.6 Output 200 11.7 Datasets 200 11.8 Evaluation Measures 200 11.9 Data Stream Mining Tools 201 11.10 Data Stream Mining Applications 202 11.11 Conclusion 202 References 202 12 Dynamical Mass Transfer Systems in Buslaev Contour Networks with Conflicts 207Marina Yashina, Alexander Tatashev, Ivan Kuteynikov 12.1 Introduction 208 12.2 Construction of Buslaev Contour Networks 210 12.3 Concept of Spectrum 211 12.4 One-Dimensional Contour Network Binary Chain of Contours 212 12.5 Two-Dimensional Contour Network-Chainmail 214 12.6 Random Process with Restrictions on the Contour with the Possibility of Particle Movement in Both Directions 218 12.7 Conclusion 218 References 219 13 Parallel Simulation and Visualization of Traffic Flows Using Cellular Automata Theory and QuasigasDynamic Approach 223Antonina Chechina, Natalia Churbanova, Pavel Sokolov, Marina Trapeznikova, Mikhail German, Alexey Ermakov, Obidzhon Bozorov 13.1 Introduction 224 13.2 The Original CA Model 224 13.3 The Slow-to-Start Version of the CA Model 225 13.4 Numerical Realization 225 13.5 Test Predictions for the CA Model 229 13.6 The QGD Approach to Traffic Flow Modeling 230 13.7 Parallel Implementation of the QGD Traffic Model 232 13.8 Test Predictions for the QGD Traffic Model 232 13.9 Conclusion 235 References 236

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Book SynopsisTable of ContentsIntroduction xvii Chapter 1 Healthcare IT and the Growing Need for AI Operations 1 A Brief History of AI and Healthcare 3 Healthcare IT Expansion and Growth 4 Data Overload 5 Digital Transformation of Healthcare 7 The Science of Healthcare Innovation 9 Artificial Intelligence in Healthcare 10 Healthcare IT Operations 14 AIOps Platform Strategy 18 Platform Types 19 Customer Experience and AIOps 20 AIOps Considerations and Goals 22 Summary 23 Chapter 2 AI Healthcare Operations (Clinical) 25 Clinical Impact of AIOps 26 Gaining a Competitive Edge with Intelligent Cloud, Data Analytics, and AI 27 Design and Innovation 29 AIOps for Healthcare Delivery 33 AIOps for Service Performance 38 Clinical AI, AIOps, and Future Platform Convergence 39 Security and Privacy 41 Why Security is Paramount in AIOps 41 HIPAA, PHI, and PII Protection 43 Summary 45 Chapter 3 AI Healthcare Operations (Operational Infrastructure) 47 Getting Started with AIOps 48 Strategy of AIOps Deployments 50 Creating a Scope 51 AIOps Platforms, Products, and Services Selection 54 AIOps Product Selection: General Topics 54 Product Review: AIOps Tool Splunk 57 Product Review: AIOps Tool ServiceNow 60 Product Review: AIOps Tool Dynatrace 64 Workflow and Event Management Design 67 Service Design with AIOps 67 Day-to-Day Operational Management 69 Summary 70 Chapter 4 Project Planning for AIOps 73 Project Planning Requirements 74 Assigning a Project Manager 75 Creating a Project Plan 77 Building the Project Plan 78 Planning a Healthcare System Project 83 Deploying AIOps 85 Deploying AIOps into the Environment 86 Configuring AIOps in the Environment 88 Summary 91 Chapter 5 Using AI for Metrics, Performance, and Reporting 93 System Performance Metrics 94 Information Technology Metrics 94 Using AI for Metrics, Performance, and Reporting 98 Strategy and Goals for AI Deployment 101 Benefits of Healthcare AIOps Service Performance Reporting 102 Developing Usable AIOps Metrics 104 Helpful Tools You Can Use 105 Gathering Usable Metrics 107 Using Dynatrace 108 Using Splunk 110 Using ServiceNow 117 Clinical and IT Metrics and Collective Actions 123 Usable Healthcare AIOps Dashboards 127 Summary 128 Chapter 6 AIOps and Automation in Healthcare Operations 131 Automation, Workflow, Process, and Intelligence Design 132 Designing the Framework for Automation 132 Understanding Automation 133 Improved User Experience 134 Designing Workflow and Process Engineering 135 Quality Control and Assurance 138 Foundational and Required Design Items 139 Configuring and Using AIOps Automation 146 Monitoring and Operating Event Management Services 148 Creating and Realizing Automation, ML, and AI 152 Automating Splunk and IT Service Analyzer 155 Splunk IT Service Intelligence 160 When Should You Use AI and ML? 162 Summary 163 Chapter 7 Cloud Operations and AIOps 165 Understanding the Cloud 166 Understanding Cloud Computing 166 Cloud as a Service 172 Hybrid Cloud Solutions 175 When You Should (and Shouldn’t) Consider the Cloud 178 Deploying to the Cloud 179 Conducting a Request for Proposal 182 Additional Deployment Options 184 Managing in the Cloud 186 Cloud Management and Monitoring Solutions 189 Summary 191 Chapter 8 The Future of Healthcare AI 193 The Dynamically Changing World of AI 194 The Future of AI 198 Artificial Intelligence and Healthcare Innovation 201 Big Data, DataOps, Analytics, and Informatics 201 Telehealth (Telemedicine) 204 Telehealth Innovations 206 Telehealth AI 209 Future Innovation Merging Clinical and IT Operations 212 The Future and Beyond 214 AIOps, the Cloud, and Security 218 Summary 218 Chapter 9 The Convergence of Healthcare AI Technology 221 Overview of Convergence 222 Systems Integration 225 Convergence of AI, HIT, and HIE 228 IoT and AI 230 IoT Management 237 AIOps Management and Security 239 Summary 245 Appendix Sample AIOps Use Cases and Examples 247 Index 259

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Book SynopsisBioactive Glasses and Glass-Ceramics Fundamentals and Applications A Comprehensive and Critical Overview of Bioactive Glasses and Glass-Ceramics Bioactive glasses and glass-ceramics are a versatile class of biocompatible materials that have an astonishing impact in biomedicine. Bioactive Glasses and Glass-Ceramics: Fundamentals and Applications presents topics on the functional properties, processing, and applications of bioactive glasses and glass-ceramics. The primary use of bioactive glasses and glass-ceramics is to repair bone and dental defects; however, their full potential is yet to be fulfilled. Many of today's achievements in regenerative medicine and soft tissue healing were unthinkable when research began. As a result, the research involving bioactive glasses and glass-ceramics is highly stimulating and continuously progresses across many different disciplines including chemistry, materials science, bioengineering, biology, and medicine. TopicsTable of ContentsPreface List of Contributors Chapter 1 Glass crystallisation and glass-ceramics – an overviewAraceli de Pablos Martín, Delia S. Brauer Chapter 2 Crystallisation of glasses and its impact on bioactivity and other propertiesAraceli de Pablos Martín, Delia S. Brauer Chapter 3 Bioactive glass S53P4 – from a statistically suggested composition to clinical successLeena Hupa and Nina C. Lindfors Chapter 4 Melt-Derived Bioactive Glasses: Beyond Silicate GlassesJonathan Massera Chapter 5 Borate bioactive glassSeiji Yamaguchi Chapter 6 Fabrication of bioactive structures from Sol-gel derived bioactive glass.D. Durgalakshmi and Anuj Kumar Chapter 7 Processing of Bioactive Glass Scaffolds for Bone Tissue EngineeringElisa Fiume, Carla Migneco, Saeid Kargozar, Enrica Verné, Francesco Baino Chapter 8 Strong, tough bioactive glasses and composite scaffoldsQiang Fu Chapter 9 Nano-Bioactive Glass: Advances and ApplicationsAhmed El-Fiqi Chapter 10 Tailoring the osteogenic properties of bioactive glasses by incorporation of therapeutic ions for orthopedic applicationsSebastian Wilkesmann, Fabian Westhauser Chapter 11 Bioactive glasses as carriers for the controlled release of therapeutic speciesMin Zhu, Yufang Zhu Chapter 12 Enhancing the biological performance of bioactive glasses by combination with phytotherapeutic compoundsKanwal Ilyas, Aldo R. Boccaccini Chapter 13 Bioactive Glass Based Coatings: Concepts for Improving the Biocompatibility of Implantable MaterialsJ. Fletcher, W. Alles, T.J. Keenan, A.W. Wren Chapter 14 Laser cladding and laser direct glass deposition of bioactive glass and glass-ceramicsR. Comesaña, J. del Val, F. Quintero, A. Riveiro, F. Arias-González, M. Boutinguiza, F. Lusquiños, J. Pou Chapter 15 Laser-assisted processing of CaSiO3‒Ca3(PO4)2 bioactive eutectic glasses and glass-ceramics for functional applicationsDaniel J. Sola Chapter 16 Molecular Dynamics (MD) Simulations of Bioactive Glasses and Glass-ceramicsMaziar Montazerian, Collin Wilkinson, John C. Mauro Chapter 17 In Vitro and In Vivo Studies of Bioactive GlassesSadaf Batool, Zakir Hussain, Usman Liaqat Chapter 18 Production of bioactive glass-ceramics for dental application through devitrification of glasses in the Na2O/K2O-CaO-MgO-SiO2-P2O5-CaF2 systemKonstantinos Dimitriadis, Dilshat U. Tulyaganov, Simeon Agathopoulos Chapter 19 Applications of bioactive glasses for implants in the earMario Milazzo, Glauco Cristofaro, Stefano Berrettini, and Serena Danti Chapter 20 Bioactive glass: soft tissue reparative and regenerative applicationsShreyasi Majumdar, Smriti Gupta, Sairam Krishnamurthy Chapter 21 Bioactive Glasses as Biologically Active Materials for Healing of Skin WoundsTina Mehrabi, Abdorreza S. Mesgar, Zahra Mohammadi Chapter 22 Biocompatible Glasses Applied in Cancer Treatment: Magnetic Hyperthermia and BrachytherapyRoger Borges, Ana Carolina S. Souza, Luis Antonio Genova, Joel Machado Jr., Giselle Zenker Justo, Juliana Marchi Chapter 23 Bioactive glasses with antibacterial properties: mechanisms, compositions, and applicationsMostafa Awaid and Ilaria Cacciotti Index

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Book SynopsisApplied Smart Health Care Informatics Explores how intelligent systems offer new opportunities for optimizing the acquisition, storage, retrieval, and use of information in healthcare Applied Smart Health Care Informatics explores how health information technology and intelligent systems can be integrated and deployed to enhance healthcare management. Edited and authored by leading experts in the field, this timely volume introduces modern approaches for managing existing data in the healthcare sector by utilizing artificial intelligence (AI), meta-heuristic algorithms, deep learning, the Internet of Things (IoT), and other smart technologies. Detailed chapters review advances in areas including machine learning, computer vision, and soft computing techniques, and discuss various applications of healthcare management systems such as medical imaging, electronic medical records (EMR), and drug development assistance. Throughout the text, the authors propose new reTable of ContentsPreface xiii About the Editors xix List of Contributors xxv 1 An Overview of Applied Smart Health Care Informatics in the Context of Computational Intelligence 1Sourav De and Rik Das 1.1 Introduction 1 1.2 Big Data Analytics in Healthcare 2 1.3 AI in Healthcare 3 1.4 Cloud Computing in Healthcare 4 1.5 IoT in Healthcare 4 1.6 Conclusion 5 References 5 2 A Review on Deep Learning Method for Lung Cancer Stage Classification Using PET-CT 9Kaushik Pratim Das, Chandra J, and Dr Nachamai M 2.1 Introduction 9 2.1.1 Scope of the Research 10 2.1.2 TNM Staging 11 2.1.2.1 TNM Descriptors for Staging per IASLC Guidelines 11 2.1.2.2 PET-CT Scan in Lung Cancer Imaging 12 2.2 Related Works 12 2.2.1 Artificial Intelligence in Medical Imaging 14 2.2.2 Classification for Medical Imaging 14 2.2.2.1 Deep Learning 15 2.2.2.2 Image Classification Using Deep-learning Techniques 15 2.3 Methods 15 2.3.1 Transfer Learning 15 2.3.2 AlexNet 16 2.3.3 AlexNet Architecture 16 2.3.4 Experimental Setup 17 2.3.4.1 Image Processing 18 2.3.4.2 Data Augmentation 19 2.3.4.3 Training and Validation 19 2.4 Results and Discussion 19 2.4.1 Primary Tumor (T) 19 2.4.2 Metastasis (M) 21 2.4.3 Lymph Node (N) 21 2.4.4 Classification Accuracy of AlexNet 24 2.4.5 Comparative Analysis 25 2.4.6 Limitations 26 2.5 Conclusion 26 References 27 3 Formal Methods for the Security of Medical Devices 31Srinivas Pinisetty, Nathan Allen, Hammond Pearce, Mark Trew, Manoj Singh Gaur, and Partha Roop 3.1 Introduction 31 3.1.1 Pacemaker Security 33 3.1.2 Overview 34 3.2 Background: Cardiac Pacemakers 34 3.2.1 Pacemakers 35 3.2.1.1 Operation of a DDD Mode Pacemaker 36 3.2.2 The Cardiac System 37 3.2.2.1 Electrograms and Electrocardiograms 38 3.3 State of the Art, Formal Verification Techniques 39 3.3.1 Formal Verification Techniques 40 3.3.1.1 Static Verification Techniques 41 3.3.1.2 Dynamic Verification Techniques 42 3.3.2 Runtime Verification 43 3.3.2.1 A Brief Overview of Some Runtime Verification Frameworks 44 3.3.3 Correcting Execution of a System at Runtime (Runtime Enforcement) 45 3.3.3.1 Runtime Enforcement of Untimed Properties 46 3.3.3.2 Runtime Enforcement Approaches for Timed Properties 46 3.4 Formal Runtime-Based Approaches for Medical Device Security 47 3.4.1 Overview of the Approach 47 3.4.2 Mapping EGM Properties to ECG Properties 48 3.4.3 Security of Pacemakers Using Runtime Verification 49 3.4.3.1 Timed Words, Timed Languages, and Defining Timed Properties 50 3.4.3.2 Runtime Verification Monitor 51 3.4.3.3 Architecture of the Monitoring System 53 3.4.3.4 Implementation of the ECG Processing and RV Monitor Modules 53 3.4.3.5 Summary of Experiments and Results 54 3.4.4 Securing Pacemakers with Runtime Enforcement Hardware 54 3.4.4.1 Preliminaries: Words, Languages, and Defining Properties as DTA 55 3.4.4.2 Runtime Enforcement Monitor 56 3.4.4.3 Verification of the Enforcer Hardware 58 3.4.4.4 How Does the Enforcer Prevent Security Attacks? 58 3.4.4.5 Summary of Experiments and Results 59 3.5 Summary 59 References 60 4 Integrating Two Deep Learning Models to Identify Gene Signatures in Head and Neck Cancer from Multi-Omics Data 67Suparna Saha, Sumanta Ray, and Sanghamitra Bandyopadhyay 4.1 Introduction 67 4.2 Related Work 68 4.3 Materials and Methods 70 4.3.1 A Brief Introduction of the Capsule Network 70 4.3.2 An Introduction to Autoencoders 71 4.4 Results 72 4.4.1 Data Set Details 72 4.4.1.1 Gene Expression Data (Illumina Hiseq) 72 4.4.1.2 Human Methylation 450K 73 4.4.2 Architecture of Autoencoder Model 73 4.4.3 Architecture of the Proposed Capsule Network Model 74 4.4.4 Validation of Two Deep Learning Models 75 4.4.5 Gene Signatures from Primary Capsules 76 4.5 Discussion 77 Acknowledgments 78 References 79 5 A Review of Computational Learning and IoT Applications to High-Throughput Array-Based Sequencing and Medical Imaging Data in Drug Discovery and Other Health Care Systems 83Soham Choudhuri, Saurav Mallik, Bhaswar Ghosh, Tapas Si, Tapas Bhadra, Ujjwal Maulik, and Aimin Li 5.1 Introduction 83 5.2 Biological Terms 84 5.3 Single-Cell Sequencing (scRNA-seq) Data 86 5.3.1 Computational Methods for Interpreting scRNA-seq Data 86 5.3.1.1 Visualizing and Clustering Cells 86 5.3.1.2 Inference and Branching Analysis of Cellular Trajectory 86 5.3.1.3 Identifying Highly Variable Genes 86 5.3.1.4 Identifying Marker and Differentially Expressed Genes 90 5.4 Methods of Multi-Omic Data Integration 90 5.4.1 Unsupervised Data Integration Methods 91 5.4.1.1 Matrix Factorization Methods 91 5.4.1.2 Bayesian Methods 91 5.4.1.3 Network-Based Methods 94 5.4.1.4 Multi-Step Analysis and Multiple Kernel Learning 94 5.4.2 Supervised Data Integration 95 5.4.2.1 Network-Based Methods 95 5.4.2.2 Multiple Kernel Learning 95 5.4.2.3 Multi-Step Analysis 95 5.4.3 Semi-Supervised Data Integration 95 5.4.3.1 GeneticInterPred 97 5.5 AI Drug Discovery 97 5.5.1 AI Primary Drug Screening 97 5.5.1.1 Cell Sorting and Classification with Image Analysis 97 5.5.2 AI Secondary Drug Screening 99 5.5.2.1 Physical Properties Predictions 99 5.5.2.2 Predictions of Bio-Activity 99 5.5.2.3 Prediction of Toxicity 99 5.5.3 AI in Drug Design 99 5.5.3.1 Prediction of Target Protein 3D Structures 99 5.5.3.2 Predicting Drug-Protein Interactions 100 5.5.4 Planning Chemical Synthesis with AI 100 5.5.4.1 Retro-Synthesis Pathway Prediction 100 5.5.4.2 Reaction Yield Predictions and Reaction Mechanism Insights 100 5.6 Medical Imaging Data Analysis 100 5.6.1 Analysis: Radio-Mic Quantification 101 5.6.2 Analysis: Bio-Marker Identification 101 5.7 Applying IoT (Internet of Things) to Biomedical Research 102 5.7.1 IoT and IoMT Applications for Healthcare and Well-Being 102 5.7.1.1 Wireless Medical Devices 102 5.8 Conclusions 102 Acknowledgments 102 References 102 6 Association Rule Mining Based on Ethnic Groups and Classification using Super Learning 111Md Faisal Kabir and Simone A. Ludwig 6.1 Introduction 111 6.2 Background 112 6.3 Motivation and Contribution 114 6.4 Data Analysis 115 6.4.1 Data Description 115 6.4.2 Data Preprocessing 115 6.4.3 Further Preprocessing for Ethnic Group Rule Discovery with Multiple Consequences 115 6.4.3.1 Transaction-Like Database for Association Rule 115 6.4.4 Classification Data Set 116 6.5 Methodology 117 6.5.1 Association Rule Mining 117 6.5.2 Super Learning 118 6.5.2.1 Ensemble or Super Learner Set-Up 118 6.6 Experiments and Results 119 6.6.1 Rules Discovery 120 6.6.1.1 Rules of Breast Cancer Patients Based on Ethnic Groups 120 6.6.1.2 Interpreting Rules 120 6.6.2 Evaluation Criteria of Classification Model 121 6.6.2.1 Super Learner Results 124 6.6.3 Discussion 125 6.7 Conclusion and Future Work 126 References 127 7 Neuro-Rough Hybridization for Recognition of Virus Particles from TEM Images 131Debamita Kumar and Pradipta Maji 7.1 Introduction 131 7.2 Existing Approaches for Virus Particle Classification 132 7.3 Proposed Algorithm 134 7.3.1 Extraction of Local Textural Features 135 7.3.2 Selection of Class-Pair Relevant Features 135 7.3.3 Extraction of Discriminating Features 138 7.3.4 Classification 139 7.4 Experimental Results and Discussion 140 7.4.1 Experimental Setup 140 7.4.2 Methods Compared 140 7.4.3 Database Considered 141 7.4.4 Effectiveness of Proposed Approach 141 7.4.5 Comparative Performance Analysis 143 7.4.5.1 Comparison with Deep Architectures 144 7.4.5.2 Comparison with Existing Approaches 145 7.5 Conclusion 146 References 147 8 Neural Network Optimizers for Brain Tumor Image Detection 151T. Kalaiselvi and S.T. Padmapriya 8.1 Introduction 151 8.2 Related Works 152 8.3 Background 153 8.3.1 Types of Neural Networks 153 8.3.2 Tunable Elements of Neural Networks 154 8.3.2.1 Basic Parameters 154 8.3.2.2 Hyperparameters 154 8.3.2.3 Regularization Techniques 155 8.3.2.4 Neural Network Optimizers 156 8.4 Case Study - Brain Tumor Detection 157 8.4.1 Methodology 157 8.4.2 Data Sets and Metrics 157 8.4.3 Results and Discussion 159 8.5 Conclusion 162 References 162 9 Abnormal Slice Classification from MRI Volumes using the Bilateral Symmetry of Human Head Scans 165N. Kalaichelvi, T. Kalaiselvi, and K. Somasundaram 9.1 Introduction 165 9.1.1 MRIs of the Human Brain 165 9.1.2 Normal and Abnormal Slices 166 9.1.3 Background 167 9.1.3.1 Decision Tree Classifiers 167 9.1.3.2 K-Nearest Neighbours (KNN) Classifiers 168 9.1.3.3 Support Vector Machine (SVM) 168 9.1.3.4 Naive Bayes 169 9.1.3.5 Artificial Neural Network (ANN) 169 9.1.3.6 Back-Propagation Neural Network (BPN) 170 9.1.3.7 Random Forest Classifiers 170 9.2 Literature Review 171 9.3 Methodology 172 9.3.1 Preprocessing 173 9.3.2 Feature Extraction 174 9.3.3 Feature Selection 175 9.3.4 Classification 177 9.3.5 Cross-Validation 177 9.3.6 Training Validation and Testing 178 9.4 Materials and Metrics 179 9.4.1 Confusion Matrix 179 9.5 Results and Discussion 180 9.6 Conclusion 182 References 183 10 Conclusion 187Siddhartha Bhattacharyya References 188 Index 191

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Book SynopsisMolecular Fluorescent Sensors for Cellular Studies Enables readers to fully understand the fundamentals and chemical principles of fluorescent sensing and the design of fluorescent sensors Fluorescent sensors are able to provide specific chemical information about cells and can be invaluable in understanding processes that underpin health and disease. Molecular Fluorescent Sensors for Cellular Studies provides an avenue into and overview of currently available fluorescent sensing technology and its application to biological imaging. This book aims to help the reader understand the principles of fluorescence and the mechanisms by which fluorescent sensors operate in order to ensure appropriate and optimal use of sensors. Key applications of fluorescent sensing are presented, with explanations not only of how new sensors can be designed, but also how existing sensors can be applied to various biological settings and conditions. Clear and engaging schematics throughout the book explainTable of ContentsList of Contributors ix 1 An Introduction to Small Molecule Fluorescent Sensors 1 Liam D. Adair, Kylie Yang, and Elizabeth J. New 1.1 What is Fluorescence? 1 1.2 Why Is Fluorescence Useful? 3 1.3 What Is a Fluorescent Sensor? 4 1.4 General Types of Fluorescent Sensors 5 1.5 Important Parameters 7 1.5.1 Excitation Maxima 7 1.5.2 Emission Maxima 8 1.5.3 Stokes Shift 8 1.5.4 Quantum Yield 9 1.5.5 Molar Extinction Coefficient 9 1.5.6 Brightness 10 1.5.7 Lifetime 10 1.5.8 Photobleaching 11 1.5.9 Anisotropy 12 1.5.10 Quenching 12 1.6 Fluorescence Mechanisms Used in Fluorescent Sensors 13 1.6.1 Photoinduced Electron Transfer 13 1.6.2 Internal Charge Transfer 14 1.6.3 Förster Resonance Energy Transfer 15 1.6.4 Through Bond Energy Transfer 17 1.6.5 Excited- State Intramolecular Proton Transfer 18 1.6.6 Aggregation- Induced Emission 19 1.6.7 Excimer Formation 21 1.7 Commonly Used Fluorophores 21 1.7.1 Fluorescein 22 1.7.2 Rhodamine 24 1.7.3 Coumarin 26 1.7.4 Naphthalimide 26 1.7.5 BODIPY (4,4- Difluoro4- bora- 3a,4a- diaza- s- indacene) 27 1.7.6 Cyanine 28 1.8 Summary 30 References 30 2 The Applications of Responsive Fluorescent Sensors to Biological Systems 37 Jia Hao Yeo and Elizabeth J. New 2.1 Criteria for Biologically Relevant Fluorescent Sensors 37 2.2 Microscopy for Visualising Fluorescent Sensors 39 2.2.1 Important Considerations in Microscopy 39 2.2.1.1 Resolution in Microscopy 39 2.2.1.2 Understanding the Competition Between True Signal and Noise 41 2.2.1.3 Phototoxicity in Cells 42 2.2.2 Common Microscopy Techniques 43 2.2.2.1 Fluorescence Microscopy 43 2.2.2.2 Confocal Microscopy 44 2.2.2.3 Multiphoton Microscopy 45 2.2.2.4 Fluorescence Lifetime Imaging Microscopy 45 2.2.2.5 Other Advanced Microscopy Techniques 47 2.3 Other Instrumental Techniques for Studying Cells Treated with Fluorescent Sensors 49 2.3.1 Flow Cytometry 49 2.3.1.1 Principles of Flow Cytometry 49 2.3.1.2 Understanding Flow Cytometry Data with Small- molecule Sensors 50 2.3.1.3 Recent Advances in Flow Cytometry 51 2.3.2 Fluorescence Plate- readers 51 2.3.2.1 Standard Plate- reader Assays 51 2.3.2.2 High- content Imaging (HCI) Plate- readers 52 2.4 Biological Samples to Which Fluorescent Sensors Can Be Applied 52 2.4.1 Cultured Mammalian Cells 52 2.4.1.1 Adherent Mammalian Cells 53 2.4.1.2 Non- adherent Cells 53 2.4.1.3 Multi- cellular Models 54 2.4.2 Bacteria 54 2.4.3 Plants 54 2.4.4 Multi- cellular Organisms 55 2.4.5 Towards In Vivo Imaging 55 2.5 Common Challenges and Misconceptions in the Applications of Fluorescent Sensors 56 2.5.1 Important Considerations in Applying Sensors 56 2.5.2 Common Misconceptions About the Use of Sensors – The Bridge Between Multiple Disciplines 57 2.6 Conclusions 60 References 60 3 Methods to Control the Subcellular Localisation of Fluorescent Sensors 63 Jiarun Lin, Kylie Yang, and Elizabeth J. New 3.1 Introduction 63 3.2 Targeting the Nucleus 64 3.3 Targeting Mitochondria 66 3.4 Targeting Lysosomes 67 3.5 Targeting Endosomes 69 3.6 Targeting Autophagic Compartments 70 3.7 Targeting Peroxisomes 70 3.8 Targeting the Endoplasmic Reticulum 71 3.9 Targeting the Golgi Apparatus 72 3.10 Targeting Lipid Droplets 73 3.11 Targeting the Plasma Membrane 74 3.12 Targeting the Cytoskeleton 75 3.13 Targeting the Cytosol 76 3.14 Trapping and Accumulation of Sensors 76 References 77 4 Recognition- based Sensors for Cellular Imaging 83 Amy A. Bowyer, Jianping Zhu, and Elizabeth J. New 4.1 Considerations for Recognition- based Sensing 83 4.1.1 Receptor–Analyte Recognition and Binding Affinity 84 4.1.1.1 Defining Binding Affinity 85 4.1.1.2 Measuring Binding Stoichiometries and Binding Affinity 85 4.1.2 Key Considerations to Enhance Selective Receptor to Analyte Recognition 87 4.1.2.1 Size 88 4.1.2.2 The Chelate Effect 88 4.1.2.3 Hard–Soft Acid–Base Theory 89 4.1.2.4 Crystal and Ligand Field Theory 89 4.2 Recognition- based Cation Sensing 91 4.2.1 Group I and II Metal Sensing 92 4.2.1.1 The Biological Significance of Group I and II Metals 92 4.2.1.2 Receptor Group Design for Group I and II Metals 93 4.2.2 Essential Transition Metal Sensing 98 4.2.2.1 The Biological Significance of Essential Transition Metals 98 4.2.2.2 Receptor Group Design for Essential Transition Metals 99 4.2.3 Toxic Metal Sensing 107 4.2.3.1 The Biological Significance of Toxic Metals 107 4.2.3.2 Receptor Group Design for Toxic Metals 108 4.3 Recognition- based Anion Sensing 110 4.3.1 Anion Sensing Approaches 110 4.3.1.1 Hydrogen Bonding 110 4.3.1.2 Displacement Approach 111 4.3.1.3 Metal Coordination 112 4.3.2 Halogen Ions Sensing 113 4.3.2.1 The Biological Role of Halogen Ions 113 4.3.2.2 Recognition- based Fluorescent Sensors for Halogen Ions 113 4.3.3 Inorganic Phosphates and Pyrophosphates 114 4.3.3.1 The Biological Role of Inorganic Phosphates and Pyrophosphates 114 4.3.3.2 Sensors for Inorganic Phosphates 115 4.3.3.3 Sensors for Inorganic Pyrophosphate 116 4.3.4 Bicarbonate, Hydrogen Sulfate, and Nitrate 120 4.3.4.1 The Biological Roles of Bicarbonate, Hydrogen Sulfate, and Nitrate 120 4.3.4.2 Sensors for Bicarbonate, Hydrogen Sulfate, and Nitrate 121 4.4 Conclusions 123 References 123 5 Activity- based Fluorescent Sensors and Their Applications in Biological Studies 129 Liam D. Adair, Nian Kee Tan, and Elizabeth J. New 5.1 Introduction 129 5.1.1 Design Principles 130 5.2 Oxidation Reactions for Sensing Oxidative Species 131 5.2.1 Fluorescent Sensors for Hydrogen Peroxide 131 5.2.2 Fluorescent Sensors for Peroxynitrite 134 5.2.3 Fluorescent Sensors for Hypochlorous Acid 136 5.2.4 Fluorescent Sensors for Nitric Oxide 137 5.2.5 Fluorescent Sensors for Singlet Oxygen 138 5.3 Reduction Reactions for Sensing Reductive Species 140 5.3.1 Fluorescent Sensors for Hydrogen Sulfides 140 5.3.2 Fluorescent Sensors for Glutathione, Cysteine, and Homocysteine 141 5.3.3 Fluorescent Sensors for Selenocysteine 144 5.4 Reactions for Sensing Carbonyl Species 145 5.4.1 Fluorescent Sensors for Formaldehyde 145 5.4.2 Fluorescent Sensors for Methylglyoxal 146 5.5 Metal- mediated Reactions 148 5.6 Metal- sensing Reactions 149 5.7 Enzymatic Reactions 155 5.8 Reversible Reactions 159 5.8.1 Nucleophilic Conjugate Additions 159 5.8.2 Nucleophilic Addition 162 5.8.3 Imine Formation 162 5.8.4 Oxidation–Reduction Reactions 163 5.9 Analyte Regeneration 164 5.10 Summary 166 References 166 6 Fluorescent Sensors of the Cellular Environment 173 Nian Kee Tan, Jianping Zhu, and Elizabeth J. New 6.1 Fluorescent Sensors for Polarity and Viscosity 173 6.1.1 The Biological Significance of Polarity and Viscosity 173 6.1.2 Twisted Intramolecular Charge Transfer as a Mechanism for Polarity and Viscosity Sensing 174 6.1.2.1 TICT- based Viscosity Sensors 176 6.1.2.2 TICT- based Polarity Sensors 178 6.1.3 Polarity Sensors Based on Other Mechanisms 178 6.1.3.1 Polarity Sensors Based on Intramolecular Charge Transfer Mechanism 178 6.1.3.2 Polarity Sensors Based on Excited- state Intramolecular Proton Transfer Mechanism 180 6.1.3.3 Polarity Sensors Based on Photoinduced Electron Transfer Mechanism 180 6.2 Fluorescent Sensors for pH 181 6.2.1 The Regulation of pH in Health and Disease 181 6.2.2 Considerations and Design Strategies for the Preparation of pH Sensors 182 6.2.2.1 Methods to Control pK a 183 6.2.3 Examples of pH Sensors 185 6.2.3.1 Photoinduced Electron Transfer as a Mechanism for Sensing 185 6.2.3.2 The Ring Opening of Rhodamines as a Mechanism for pH Sensing 187 6.2.3.3 Intramolecular Charge Transfer as a Mechanism for Ratiometric pH Sensing 188 6.2.3.4 pH Sensors Based on Addition Reactions 189 6.3 Fluorescent Redox Sensors for Biological Studies 190 6.3.1 The Regulation of Redox State in Health and Disease 190 6.3.2 Design Strategies of Fluorescent Redox Sensors and Key Examples 191 6.3.2.1 Redox Sensors Based on the Nitroxyl Radical/Hydroxylamine Redox Couple 191 6.3.2.2 Redox Sensors Based on the Quinone/Hydroquinone Redox Couple 192 6.3.2.3 Redox Sensors Based on Chalcogens 193 6.3.2.4 Redox Sensors Based on Flavins and Nicotinamides 194 6.4 Conclusions 196 References 197 7 Labelling Proteins and Biomolecules with Small Fluorescent Sensors 201 Joy Ghrayche, Marcus E. Graziotto, Paris I. Jeffcoat, and Elizabeth J. New 7.1 Labelling Biomolecules in Cells with Fluorescent Sensors 201 7.2 Small- molecule Modifications and Bioorthogonal Reactions 204 7.2.1 Polar Ketone and Aldehyde Condensations 204 7.2.2 Azide Bioorthogonal Chemistry 205 7.2.2.1 Staudinger Ligations 206 7.2.2.2 Copper Azide–Alkyne Cycloadditions 208 7.2.2.3 Strain- promoted Cycloadditions 208 7.2.2.4 Fluorogenic Dyes for Azide–Alkyne Labelling 209 7.2.3 Tetrazine Ligation 210 7.2.4 Commercial Fluorescent Labels 215 7.3 Short peptide Recognition Sequences 215 7.4 Fusion Protein Tagging Systems 218 7.4.1 FKBP Tag 219 7.4.2 eDHFR Tag 220 7.4.3 PYP Tag 223 7.4.4 SNAP- Tag and CLIP- Tag 225 7.4.5 HaloTag 229 7.5 Enzymatic Modifications for Labelling Proteins 230 7.5.1 The LAP- tag System 230 7.5.2 Protein Trans- splicing 233 7.6 Future Developments 235 References 235 8 Future Directions of Fluorescence Sensors for Cellular Studies 241 Jiarun Lin, Natalie Trinh, and Elizabeth New 8.1 Fluorescence Lifetime Imaging Microscopy 241 8.1.1 Introduction 241 8.1.2 Advantages of Fluorescence Lifetime Imaging Microscopy 242 8.1.3 Examples of Sensors for FLIM 242 8.1.3.1 Endogenous Sensors 242 8.1.3.2 Exogenous Sensors 243 8.1.4 Future Directions 245 8.2 Near- infrared Sensors 246 8.2.1 Strategies to Make NIR Sensors 247 8.2.2 NIR Fluorophore Scaffolds 247 8.2.2.1 Cyanine Dyes and Their Derivatives 247 8.2.2.2 BODIPY Dyes 250 8.2.2.3 Squaraine Dyes 250 8.2.2.4 Other Dye Scaffolds 251 8.2.3 Future Directions 252 8.3 Dual- analyte Sensing 252 8.3.1 Introduction 252 8.3.2 Reversible Dual- analyte Sensors 254 8.3.3 Reaction Dual- analyte Sensors 255 8.3.4 Mixed Dual- analyte Sensors 255 8.3.5 Sequence- specific Reactions 256 8.3.6 Conclusions and Future Directions 257 8.4 Super- resolution Microscopy 258 8.4.1 Introduction 258 8.4.2 Super- resolution Microscopy Techniques 258 8.4.3 Considerations for Use of Super Resolution Microscopy 262 8.4.4 Fluorescent Sensors for Super- resolution Microscopy 263 8.4.5 Future Directions 265 8.5 Multimodality 267 8.5.1 Introduction 267 8.5.2 Radioisotope Techniques 267 8.5.3 Computed Tomography 269 8.5.4 Magnetic Resonance Imaging 269 8.5.5 Photoacoustic Imaging 271 8.5.6 Vibrational Spectroscopy 271 8.5.7 Synchrotron X- ray Techniques 273 8.5.8 Mass Spectrometry 273 8.5.9 Electron Microscopy 274 8.5.10 Three or More Modalities 276 8.5.11 Future Directions 277 References 278 Index 285

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Book SynopsisA comprehensive guide to the current research, major challenges, and future prospects of controlled drug delivery systems Controlled drug delivery has the potential to significantly improve therapeutic outcomes, increase clinical benefits, and enhance the safety of drugs in a wide range of diseases and health conditions. Fundamentals of Drug Delivery provides comprehensive and up-to-date coverage of the essential principles and processes of modern controlled drug delivery systems. Featuring contributions by respected researchers, clinicians, and pharmaceutical industry professionals, this edited volume reviews the latest research in the field and addresses the many issues central to the development of effective, controlled drug delivery. Divided in three parts, the book begins by introducing the concept of drug delivery and discussing both challenges and opportunities within the rapidly evolving field. The second section presents an in-depth critique of the common administration routeTable of ContentsPreface xvii List of Contributors xix Part I Product Design, the Essence of Effective Therapeutics 1 1 Challenges and Innovations of Controlled Drug Delivery 3 Heather A.E. Benson and Michael S. Roberts 1.1 Background 3 1.2 Parenteral Dosage Forms 3 1.2.1 Intravenous Route (IV) 4 1.2.2 Intramuscular Route (IM) 5 1.2.3 Subcutaneous Route (SC) 5 1.2.4 Other Parenteral Routes 5 1.3 Oral Route and Delivery Systems 6 1.4 Nasal Drug Delivery 6 1.5 Pulmonary Drug Delivery 7 1.6 Transdermal Drug Delivery 7 1.7 Ocular Drug Delivery 9 1.8 Drug Delivery System Development Process 11 1.9 Conclusion 12 References 12 2 Challenges in Design of Drug Delivery Systems 15 S. Narasimha Murthy, Shivakumar H.N, and Sarasija Suresh 2.1 Drug Properties to be Considered in Design of Controlled Release Products 19 2.2 Physicochemical Factors that Need to be Considered in Design of CRDDS 19 2.2.1 Dose Size 19 2.2.2 MolecularWeight/Size 19 2.2.3 Aqueous Solubility 21 2.2.4 Lipid Solubility and Partition Coefficient 25 2.2.5 Physicochemical Stability 26 2.3 Biopharmaceutical Properties that Deserve Consideration in Design of Controlled Release Products 26 2.3.1 Biological Half-life 26 2.3.2 Absorption 27 2.3.3 Metabolism 30 2.3.4 Presystemic Clearance 32 2.3.5 Margin of Safety 32 2.3.6 Adverse Effects 33 2.3.7 Therapeutic Need 33 2.3.8 Role of Circadian Rhythm 34 2.4 Conclusion 35 References 35 3 Drug Delivery of the Future (?) 39 Adrian Williams 3.1 Introduction 39 3.2 Therapeutic Indicators 40 3.3 Drugs of the Future 43 3.4 Delivering the Drugs of the Future 45 3.5 A View to the Longer Term? 47 3.6 Conclusion 50 References 50 4 The Pharmaceutical Drug Development Process: Selecting a Suitable Drug Candidate 37 Lionel Trottet 4.1 The Oral Drug Candidate: How to Get There and Questions to Answer 53 4.2 Challenges for Selecting a Topical Drug Candidate 55 4.3 Percutaneous Flux as a Surrogate Measurement of Skin Tissue Concentration 57 4.4 Learnings from Past Topical Drug Development of Factors Affecting Efficacy 58 4.5 Dermal Pharmacokinetics/Pharmacodynamics 62 4.6 Assessment of Systemic Exposure 63 4.7 Screening Cascade Approach to Select a Dermal Drug Candidate 64 4.7.1 Efficacy (Lack of Target Engagement) 64 4.7.2 Developability 65 4.7.3 Local Safety 65 4.7.4 Systemic Safety 65 4.8 Opportunities for Repurposing Molecules into Dermally Active Treatments for Cosmeceutical or Pharmaceutical Approaches 66 4.9 Conclusion 66 References 67 5 Preformulation and Physicochemical Characterization Underpinning the Development of Controlled Drug Delivery Systems 73 Ronak Savla and Julien Meissonnier 5.1 When Is a Controlled Drug Delivery System Needed? 73 5.2 Optimizing Drug Characteristics 74 5.3 Defining the Product Profile 75 5.4 Preformulation and Physicochemical Characterization Underpinning Development of CDD 77 5.4.1 Feasibility and Risk Assessment 78 5.4.2 Solubility and Dissolution Rate 79 5.4.3 Permeability 82 5.4.4 Drug and Drug Product Particle Sizes 83 5.4.5 Solid-State Chemistry 84 5.4.6 Stability 85 5.4.7 Excipient Compatibility 86 5.4.8 Bulk Powder Properties 87 5.4.9 Drug Metabolism and Pharmacokinetic Modeling 88 5.5 Conclusion 89 References 89 6 Mathematical Models Describing Kinetics Associated with Controlled Drug Delivery Across Membranes 95 Annette L. Bunge 6.1 Introduction 95 6.1.1 General Description 95 6.1.2 Governing Equations 98 6.1.3 Other Derived Quantities 100 6.1.4 Dimensionless Variables and Groups 102 6.2 Model Solutions 104 6.2.1 Type A Models –Well-Stirred Vehicle on One Membrane 104 6.2.2 Type B Models – Unstirred Semi-infinite Vehicle on One Membrane 140 6.2.3 Type C –Well Stirred Vehicle on Two Membranes in Series 145 6.3 Solution Methods 149 6.3.1 Separation of Variables Solutions 150 6.3.2 Laplace Transform Solutions 159 6.3.3 Useful Identities 169 References 169 7 Understanding Drug Delivery Outcomes: Progress in Microscopic Modeling of Skin Barrier Property, Permeation Pathway, Dermatopharmacokinetics, and Bioavailability 171 Guoping Lian, Tao Chen, Panayiotis Kattou, Senpei Yang, Lingyi Li, and Lujia Han 7.1 Introduction 171 7.2 Governing Equation 172 7.2.1 Homogenized Model 172 7.2.2 Microscopic Model 174 7.2.3 Numerical Methods 175 7.3 Input Parameters 176 7.3.1 SC Microstructure 176 7.3.2 SC Lipid–Water Partition 177 7.3.3 Diffusivity in SC Lipids 177 7.3.4 Binding to Keratin 179 7.3.5 Diffusivity in Corneocytes 181 7.3.6 Solute Diffusivity and Partition in Sebum 181 7.4 Application 183 7.4.1 Steady-State 183 7.4.2 Dermatopharmacokinetics 184 7.4.3 Systemic Pharmacokinetics 184 7.4.4 Shunt Pathway 185 7.5 Perspective 186 References 188 8 Role of Membrane Transporters in Drug Disposition 193 Hong Yang and Yan Shu 8.1 Introduction 193 8.2 Distribution of Major Drug Transporters in Human Tissues 194 8.2.1 Major Drug Transporters in the Intestine 194 8.2.1.3 Expression of Drug Transporters in Different Intestinal Regions 197 8.2.2 Major Drug Transporters in the Liver 197 8.2.3 Major Drug Transporters in the Kidney 199 8.2.4 Major Drug Transporters in the Central Nervous System (CNS) 201 8.2.5 Major Drug Transporters in Other Tissues 202 8.3 Role of Drug Transporters in Drug Disposition 205 8.3.1 Role of P-gp in Drug Disposition 206 8.3.2 Role of BCRP in Drug Disposition 207 8.3.3 Role of BSEP in Drug-Induced Cholestatic Liver Injury 214 8.3.4 Role of MRPs (MRP2, MRP3, and MRP4) in Drug Disposition 214 8.3.5 Role of OATPs (OATP1B1, OATP1B3, and OATP2B1) in Drug Disposition 215 8.3.6 Role of OATs (OAT1 and OAT3) in Drug Disposition 216 8.3.7 Role of OCTs (OCT1 and OCT2)/MATEs (MATE1 and MATE2-K) in Drug Disposition 217 8.4 Closing Remarks 218 References 219 Part II Challenges in Controlled Drug Delivery and Advanced Delivery Technologies 231 9 Advanced Drug Delivery Systems for Biologics 233 May Wenche Jøraholmen, Selenia Ternullo, Ann Mari Holsæter, Gøril Eide Flaten, and Nataša Škalko-Basnet 9.1 Introduction 233 9.2 Considerations in Biologics Product Development 234 9.2.1 Challenges Specific to the Route of Administration 234 9.2.2 Challenges Related to Parenteral Administration 234 9.2.3 Optimization of Dosage Regimens 234 9.3 Administration Routes for Biologics Delivery 235 9.3.1 Parenteral Route 235 9.3.2 Oral Route 236 9.3.3 Buccal Route 237 9.3.4 Sublingual Route 238 9.3.5 Pulmonary Route 238 9.3.6 Intranasal Route 239 9.3.7 Trans(dermal) Delivery 240 9.3.8 Dermal Delivery of Growth Hormones 243 9.3.9 Vaginal Route 247 9.4 Conclusion 251 References 251 10 Recent Advances in Cell-Mediated Drug Delivery Systems for Nanomedicine and Imaging 263 Li Li and Zhi Qi 10.1 Introduction 263 10.2 Cell Types and Modification for Therapeutic Agent Delivery 264 10.2.1 Cell Types 264 10.2.2 Cargo Loading Methods 269 10.3 Imaging and Tracking of Cell-Based Delivery Systems 270 10.3.1 MRI 271 10.3.2 PET 272 10.3.3 X-Ray Imaging 272 10.3.4 Multimodal Imaging Techniques 272 10.4 Cell-Mediated Drug Delivery Systems for Disease Treatment 272 10.4.1 Cancer Therapy 272 10.4.2 Immunotherapy 272 10.4.3 Brain-Related Diseases 274 10.4.4 Inflammatory Diseases 274 10.4.5 Theranostic Application 275 10.4.6 Others 275 10.5 The Mechanism of Cell-Mediated Delivery Systems for the Cell Therapies 275 10.5.1 Detoxification 276 10.5.2 Adhesive Mechanism 277 10.5.3 Homing Mechanism 278 10.6 The Administration Approach of Cell-Assist Drug Delivery System 278 10.7 Clinical Application of Cell-Based Delivery Systems 279 10.8 Conclusion and Outlook 279 References 280 11 Overcoming the Translational Gap – Nanotechnology in Dermal Drug Delivery 285 Christian Zoschke and Monika Schäfer-Korting 11.1 Nanotechnology – Failure or Future in Drug Delivery? 285 11.2 Identification of the Clinical Need 286 11.3 Nanoparticle Design and Physicochemical Characterization 289 11.4 Biomedical Studies 294 11.4.1 Atopic Dermatitis 294 11.4.2 Psoriasis 295 11.4.3 Ichthyosis 296 11.4.4 Wound Healing 297 11.4.5 Infections 297 11.4.6 Skin Cancer 298 11.4.7 Alopecia Areata 299 11.5 Approaches to Fill the Translational Gaps in Nanotechnology 299 References 303 12 Theranostic Nanoparticles for Imaging and Targeted Drug Delivery to the Liver 311 Haolu Wang, Haotian Yang, Qi Ruan, Michael S. Roberts, and Xiaowen Liang 12.1 Introduction 311 12.2 The Types of Theranostic NPs 312 12.2.1 Lipid- and Polymer-Based NPs 312 12.2.2 Mesoporous Silica NPs 312 12.2.3 Bio-nanocapsules 313 12.2.4 Iron Oxide NPs 313 12.3 Mechanisms of NPs Targeting the Liver 313 12.3.1 Passive Targeting to the Liver 313 12.3.2 Active Targeting to the Liver 314 12.3.3 Strategies for Combining Passive and Active Targeting 315 12.4 NPs in Liver Target Imaging 315 12.4.1 NP-Based Contrast Agents in Liver MRI 315 12.4.2 NP-Based Contrast Agents in Liver CT Imaging 316 12.4.3 NPs for Near-Infrared Fluorescence Imaging in Liver 316 12.5 NPs for Therapeutic and Drug Delivery in Liver Disease 316 12.5.1 NP Delivery System in HCC 316 12.5.2 NP Delivery System in Non-tumoral Liver Disease 318 12.6 Theranostic NPs in Liver Diseases 318 12.7 Conclusions 322 References 323 13 Toxicology and Safety of Nanoparticles in Drug Delivery System 329 Klintean Wunnapuk 13.1 Introduction 329 13.2 Lipid-Based Nanocarrier: Liposomes 329 13.3 Cellular Uptake Mechanism of Liposomes 330 13.4 Biodistribution, Clearance and Toxicity of Liposomes 331 13.4.1 Effect of Lipid Compositions on Liposome Distribution and Blood Circulation 331 13.4.2 Effect of Surface Charge on Liposome Distribution and Blood Circulation 333 13.4.3 Effect of Size on Liposome Distribution and Blood Circulation 333 13.5 Application of Liposomes in Drug Delivery 334 13.6 Inorganic Nanocarrier: Carbon Nanotubes 336 13.7 Cellular Uptake Mechanism of Carbon Nanotubes 337 13.8 Biodistribution, Clearance, and Toxicity of Carbon Nanotubes 337 13.9 Application of Carbon Nanotubes in Drug Delivery 342 13.10 Conclusion 342 References 342 Part III Administrative Routes for Controlled Drug Delivery 349 14 Controlled Drug Delivery via the Ocular Route 351 Peter W.J. Morrison and Vitaliy V. Khutoryanskiy 14.1 Introduction 351 14.2 Physiology of the Eye 352 14.2.1 Ocular Membranes; Conjunctiva, Cornea, and Sclera 353 14.2.2 Internal Ocular Structures 354 14.2.3 Anterior Chamber, Lens, and Vitreous Body 355 14.3 Ocular Disorders 355 14.3.1 Periocular Disorders 355 14.3.2 Intraocular Disorders 356 14.4 Controlled Drug Delivery Systems 357 14.4.1 Formulation Strategies 358 14.4.2 Mucoadhesive Systems 358 14.4.3 Solution to Gel In Situ Gelling Systems 359 14.4.4 Penetration Enhancers 361 14.4.5 Contact Lenses and Ocular Inserts 364 14.4.6 Intraocular Systems (Implants, Injectables, and Degradable Microparticles) 366 14.4.7 Phonophoresis and Ionophoresis 367 14.4.8 Topical Prodrugs 368 14.4.9 Microneedle Systems 368 14.5 Conclusions 369 References 370 15 Controlled Drug Delivery via the Otic Route 377 Jinsong Hao and S. Kevin Li 15.1 Introduction 377 15.2 Anatomy and Physiology of the Otic Route 377 15.2.1 Anatomy of the Otic Route 377 15.2.2 Barriers Relevant to Inner Ear Drug Delivery 378 15.3 Controlled Drug Delivery Systems 381 15.3.1 Intratympanic Administration 381 15.3.2 Trans-OvalWindow Administration 384 15.3.3 Intracochlear Administration 385 15.4 Conclusions 388 References 388 16 Controlled Drug Delivery via the Nasal Route 393 Barbara R. Conway and Muhammad U. Ghori 16.1 Introduction 393 16.2 Anatomy and Physiology of the Nose 393 16.3 Absorption from the Nasal Cavity 395 16.3.1 The Epithelial Barrier 395 16.3.2 Absorption 395 16.4 Mucus and Mucociliary Clearance 398 16.5 Drug Delivery Systems 399 16.5.1 Solutions and Suspensions 400 16.5.2 Mucoadhesive Polymers 401 16.5.3 The Nasal Route and the Blood–Brain Barrier 415 16.5.4 The Nasal Route for Vaccinations 419 16.5.5 In Vitro/in Vivo Models for Nasal Absorption 421 16.6 Conclusion 423 References 423 17 Controlled Drug Delivery via the Buccal and Sublingual Routes 433 Javier O. Morales, Parameswara R. Vuddanda, and Sitaram Velaga 17.1 Introduction 433 17.2 Buccal and Sublingual Physiology and Barriers to Drug Delivery 434 17.2.1 Saliva and Mucus 434 17.2.2 Buccal and Sublingual Epithelium and Permeation Barrier 434 17.3 Controlled Drug Delivery Systems 436 17.3.1 Tablets 436 17.3.2 Films 437 17.3.3 Gels, Ointments, and Liquid Formulations 438 17.3.4 Spray 438 17.3.5 Wafers 439 17.3.6 Lozenges 439 17.3.7 Advanced and Novel Drug Delivery Systems 439 17.4 Functional Excipients Used in Controlled Release Systems to Enhance Buccal and Sublingual Drug Bioavailability 440 17.4.1 Permeation Enhancers 440 17.4.2 Mucoadhesive Polymers 441 17.5 Conclusions 442 Acknowledgments 443 References 443 18 Controlled Drug Delivery via the Lung 449 María V. Ramírez-Rigo, Nazareth E. Ceschan, and Hugh D. C. Smyth 18.1 Introduction 449 18.2 The Relevant Physiology of the Route Including the Barriers to Drug Delivery 449 18.3 Controlled Drug Delivery Systems 451 18.3.1 Formulations 451 18.3.2 Devices 459 18.4 Conclusions 464 Acknowledgments 464 References 464 19 Controlled Drug Delivery via the Vaginal and Rectal Routes 471 José das Neves and Bruno Sarmento 19.1 Introduction 471 19.2 Biological Features of the Vagina and Colorectum 472 19.2.1 Vagina 472 19.2.2 Colorectum 473 19.3 Controlled Drug Delivery Systems 474 19.3.1 Vaginal Route 476 19.3.2 Rectal Route 489 19.4 Conclusions 494 Acknowledgments 494 References 494 20 Controlled Drug Delivery into and Through Skin 507 Adrian Williams 20.1 Introduction 507 20.1.1 Human Skin Structure and Function 507 20.1.2 Drug Transport Through Skin 512 20.2 Controlled Drug Delivery into and Through Skin 513 20.2.1 Skin Barrier Modulation 513 20.2.2 Controlled Release Transdermal and Topical Systems 515 20.2.2.5 Particles 520 20.2.3 Device-Based Controlled Delivery 522 20.3 Combination Approaches 528 20.4 Conclusions 528 References 529 Index 535

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Book SynopsisINTELLIGENT SYSTEMS FOR REHABILITATION ENGINEERING Encapsulates different case studies where technology can be used as assistive technology for the physically challenged, visually and hearing impaired. Rehabilitation engineering includes the development of technological solutions and devices to assist individuals with disabilities, while also supporting the recovery of the disabled who have lost their physical and cognitive functions. These systems can be designed and built to meet a wide range of needs that can help individuals with mobility, communication, vision, hearing, and cognition. The growing technological developments in machine learning, deep learning, robotics, virtual intelligence, etc., play an important role in rehabilitation engineering. Intelligent Systems for Rehabilitation Engineering focuses on trending research of intelligent systems in rehabilitation engineering which involves the design and development of innovative technologies and techniques including rehabili

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Book SynopsisTable of ContentsAbout the Authors xvi Foreword by Prof. Willis J. Tompkins xviii Foreword by Prof. Alan V. Oppenheim xix Preface xxii Acknowledgments xxviii Symbols and Abbreviations xxxi About the Companion Website xxxix 1 Introduction to Biomedical Signals 1 1.1 The Nature of Biomedical Signals 1 1.2 Examples of Biomedical Signals 4 1.2.1 The action potential of a cardiac myocyte 5 1.2.2 The action potential of a neuron 9 1.2.3 The electroneurogram (ENG) 10 1.2.4 The electromyogram (EMG) 12 1.2.5 The electrocardiogram (ECG) 20 1.2.6 The electroencephalogram (EEG) 29 1.2.7 Event-related potentials (ERPs) 35 1.2.8 The electrogastrogram (EGG) 36 1.2.9 The phonocardiogram (PCG) 37 1.2.10 The carotid pulse 40 1.2.11 The photoplethysmogram (PPG) 41 1.2.12 Signals from catheter-tip sensors 43 1.2.13 The speech signal 44 1.2.14 The vibroarthrogram (VAG) 48 1.2.15 The vibromyogram (VMG) 52 1.2.16 Otoacoustic emission (OAE) signals 52 1.2.17 Bioacoustic signals 52 1.3 Objectives of Biomedical Signal Analysis 52 1.4 Challenges in Biomedical Signal Analysis 55 1.5 Why Use Computer-aided Monitoring and Diagnosis? 58 1.6 Remarks 60 1.7 Study Questions and Problems 60 1.8 Laboratory Exercises and Projects 62 References 63 2 Analysis of Concurrent, Coupled, and Correlated Processes 71 2.1 Problem Statement 71 2.2 Illustration of the Problem with Case Studies 72 2.2.1 The ECG and the PCG 72 2.2.2 The PCG and the carotid pulse 73 2.2.3 The ECG and the atrial electrogram 73 2.2.4 Cardiorespiratory interaction 75 2.2.5 Heart-rate variability 75 2.2.6 The EMG and VMG 77 2.2.7 The knee-joint and muscle-vibration signals 77 2.3 Application: Segmentation of the PCG 78 2.4 Application: Diagnosis and Monitoring of Sleep Apnea 79 2.4.1 Monitoring of sleep apnea by polysomnography 80 2.4.2 Home monitoring of sleep apnea 80 2.4.3 Multivariate and multiorgan analysis 82 2.5 Remarks 85 2.6 Study Questions and Problems 85 2.7 Laboratory Exercises and Projects 86 References 86 3 Filtering for Removal of Artifacts 91 3.1 Problem Statement 91 3.2 Random, Structured, and Physiological Noise 92 3.2.1 Random noise 92 3.2.2 Structured noise 98 3.2.3 Physiological interference 98 3.2.4 Stationary, nonstationary, and cyclostationary processes 99 3.3 Illustration of the Problem with Case Studies 101 3.3.1 Noise in event-related potentials 102 3.3.2 High-frequency noise in the ECG 102 3.3.3 Motion artifact in the ECG 102 3.3.4 Power-line interference in ECG signals 103 3.3.5 Maternal ECG interference in fetal ECG 105 3.3.6 Muscle-contraction interference in VAG signals 105 3.3.7 Potential solutions to the problem 106 3.4 Fundamental Concepts of Filtering 106 3.4.1 Linear shift-invariant filters and convolution 107 3.4.2 Transform-domain analysis of signals and systems 117 3.4.3 The pole–zero plot 123 3.4.4 The Fourier transform 125 3.4.5 The discrete Fourier transform 126 3.4.6 Convolution using the DFT 131 3.4.7 Properties of the Fourier transform 133 3.5 Synchronized Averaging 135 3.6 Time-domain Filters 139 3.6.1 Moving-average filters 139 3.6.2 Derivative-based operators to remove low-frequency artifacts 145 3.6.3 Various specifications of a filter 152 3.7 Frequency-domain Filters 153 3.7.1 Removal of high-frequency noise: Butterworth lowpass filters 154 3.7.2 Removal of low-frequency noise: Butterworth highpass filters 161 3.7.3 Removal of periodic artifacts: Notch and comb filters 162 3.8 Order-statistic Filters 169 3.9 The Wiener Filter 171 3.10 Adaptive Filters for Removal of Interference 180 3.10.1 The adaptive noise canceler 181 3.10.2 The least-mean-squares adaptive filter 184 3.10.3 The RLS adaptive filter 185 3.11 Selecting an Appropriate Filter 190 3.12 Application: Removal of Artifacts in ERP Signals 193 3.13 Application: Removal of Artifacts in the ECG 196 3.14 Application: Maternal–Fetal ECG 197 3.15 Application: Muscle-contraction Interference 199 3.16 Remarks 202 3.17 Study Questions and Problems 202 3.18 Laboratory Exercises and Projects 208 References 209 4 Detection of Events 213 4.1 Problem Statement 213 4.2 Illustration of the Problem with Case Studies 214 4.2.1 The P, QRS, and T waves in the ECG 214 4.2.2 The first and second heart sounds 215 4.2.3 The dicrotic notch in the carotid pulse 215 4.2.4 EEG rhythms, waves, and transients 215 4.3 Detection of Events and Waves 218 4.3.1 Derivative-based methods for QRS detection 218 4.3.2 The Pan–Tompkins algorithm for QRS detection 220 4.3.3 Detection of the P wave in the ECG 224 4.3.4 Detection of the T wave in the ECG 226 4.3.5 Detection of the dicrotic notch 228 4.4 Correlation Analysis of EEG Rhythms 228 4.4.1 Detection of EEG rhythms 228 4.4.2 Template matching for EEG spike-and-wave detection 231 4.4.3 Detection of EEG rhythms related to seizure 234 4.5 Cross-spectral Techniques 235 4.5.1 Coherence analysis of EEG channels 235 4.6 The Matched Filter 237 4.6.1 Derivation of the transfer function of the matched filter 237 4.6.2 Detection of EEG spike-and-wave complexes 241 4.7 Homomorphic Filtering 242 4.7.1 Generalized linear filtering 244 4.7.2 Homomorphic deconvolution 244 4.7.3 Extraction of the vocal-tract response 245 4.8 Application: ECG Rhythm Analysis 253 4.9 Application: Identification of Heart Sounds 254 4.10 Application: Detection of the Aortic Component of S 2 256 4.11 Remarks 259 4.12 Study Questions and Problems 259 4.13 Laboratory Exercises and Projects 261 References 262 5 Analysis of Waveshape and Waveform Complexity 267 5.1 Problem Statement 267 5.2 Illustration of the Problem with Case Studies 268 5.2.1 The QRS complex in the case of bundle-branch block 268 5.2.2 The effect of myocardial ischemia on QRS waveshape 268 5.2.3 Ectopic beats 268 5.2.4 Complexity of the EMG interference pattern 268 5.2.5 PCG intensity patterns 269 5.3 Analysis of ERPs 269 5.4 Morphological Analysis of ECG Waves 269 5.4.1 Correlation coefficient 270 5.4.2 The minimum-phase correspondent and signal length 270 5.4.3 ECG waveform analysis 274 5.5 Envelope Extraction and Analysis 277 5.5.1 Amplitude demodulation 278 5.5.2 Synchronized averaging of PCG envelopes 280 5.5.3 The envelogram 281 5.6 Analysis of Activity 283 5.6.1 The RMS value 283 5.6.2 Zero-crossing rate 285 5.6.3 Turns count 285 5.6.4 Form factor 286 5.7 Application: Normal and Ectopic ECG Beats 287 5.8 Application: Analysis of Exercise ECG 288 5.9 Application: Analysis of the EMG in Relation to Force 290 5.10 Application: Analysis of Respiration 292 5.11 Application: Correlates of Muscular Contraction 294 5.12 Application: Statistical Analysis of VAG Signals 295 5.12.1 Acquisition of knee-joint VAG signals 297 5.12.2 Estimation of the PDFs of VAG signals 297 5.12.3 Screening of VAG signals using statistical parameters 299 5.13 Application: Fractal Analysis of the EMG in Relation to Force 302 5.13.1 Fractals in nature 302 5.13.2 Fractal dimension 303 5.13.3 Fractal analysis of physiological signals 304 5.13.4 Fractal analysis of EMG signals 305 5.14 Remarks 306 5.15 Study Questions and Problems 307 5.16 Laboratory Exercises and Projects 309 References 310 6 Frequency-domain Characterization of Signals and Systems 317 6.1 Problem Statement 318 6.2 Illustration of the Problem with Case Studies 318 6.2.1 The effect of myocardial elasticity on heart sound spectra 318 6.2.2 Frequency analysis of murmurs to diagnose valvular defects 319 6.3 Estimation of the PSD 321 6.3.1 Considerations in the computation of the ACF 321 6.3.2 The periodogram 323 6.3.3 The need for averaging PSDs 325 6.3.4 The use of windows: spectral resolution and leakage 326 6.3.5 Estimation of the ACF from the PSD 330 6.3.6 Synchronized averaging of PCG spectra 331 6.4 Measures Derived from PSDs 333 6.4.1 Moments of PSD functions 334 6.4.2 Spectral power ratios 337 6.5 Application: Evaluation of Prosthetic Heart Valves 337 6.6 Application: Fractal Analysis of VAG Signals 339 6.6.1 Fractals and the 1/f model 339 6.6.2 F D via power spectral analysis 341 6.6.3 Examples of synthesized fractal signals 341 6.6.4 Fractal analysis of segments of VAG signals 342 6.7 Application: Spectral Analysis of EEG Signals 345 6.8 Remarks 349 6.9 Study Questions and Problems 350 6.10 Laboratory Exercises and Projects 351 References 353 7 Modeling of Biomedical Signal-generating Processes and Systems 357 7.1 Problem Statement 357 7.2 Illustration of the Problem 358 7.2.1 Motor-unit firing patterns 358 7.2.2 Cardiac rhythm 358 7.2.3 Formants and pitch in speech 359 7.2.4 Patellofemoral crepitus 360 7.3 Point Processes 360 7.4 Parametric System Modeling 365 7.5 Autoregressive or All-pole Modeling 369 7.5.1 Spectral matching and parameterization 374 7.5.2 Optimal model order 377 7.5.3 AR and cepstral coefficients 384 7.6 Pole–Zero Modeling 384 7.6.1 Sequential estimation of poles and zeros 387 7.6.2 Iterative system identification 389 7.6.3 Homomorphic prediction and modeling 393 7.7 Electromechanical Models of Signal Generation 395 7.7.1 Modeling of respiratory sounds 396 7.7.2 Modeling sound generation in coronary arteries 400 7.7.3 Modeling sound generation in knee joints 402 7.8 Electrophysiological Models of the Heart 404 7.8.1 Electrophysiological modeling at the cellular level 405 7.8.2 Electrophysiological modeling at the tissue and organ levels 410 7.8.3 Extensions to the models of the heart 412 7.8.4 Challenges and future considerations in modeling the heart 414 7.9 Application: Heart-rate Variability 416 7.10 Application: Spectral Modeling and Analysis of PCG Signals 418 7.11 Application: Coronary Artery Disease 421 7.12 Remarks 423 7.13 Study Questions and Problems 424 7.14 Laboratory Exercises and Projects 425 References 426 8 Adaptive Analysis of Nonstationary Signals 431 8.1 Problem Statement 432 8.2 Illustration of the Problem with Case Studies 432 8.2.1 Heart sounds and murmurs 432 8.2.2 EEG rhythms and waves 433 8.2.3 Articular cartilage damage and knee-joint vibration 433 8.3 Time-variant Systems 435 8.3.1 Characterization of nonstationary signals and dynamic systems 436 8.4 Fixed Segmentation 438 8.4.1 The short-time Fourier transform 438 8.4.2 Considerations in short-time analysis 441 8.5 Adaptive Segmentation 445 8.5.1 Spectral error measure 445 8.5.2 ACF distance 450 8.5.3 The generalized likelihood ratio 450 8.5.4 Comparative analysis of the ACF, SEM, and GLR methods 452 8.6 Use of Adaptive Filters for Segmentation 452 8.6.1 Monitoring the RLS filter 453 8.6.2 The RLS lattice filter 456 8.7 The Kalman Filter 463 8.8 Wavelet Analysis 474 8.8.1 Approximation of a signal using wavelets 474 8.9 Bilinear TFDs 479 8.10 Application: Adaptive Segmentation of EEG Signals 485 8.11 Application: Adaptive Segmentation of PCG Signals 489 8.12 Application: Time-varying Analysis of HRV 490 8.13 Application: Analysis of Crying Sounds of Infants 493 8.14 Application: Wavelet Denoising of PPG Signals 493 8.15 Application: Wavelet Analysis for CPR Studies 494 8.16 Application: Detection of Ventricular Fibrillation in ECG Signals 499 8.17 Application: Detection of Epileptic Seizures in EEG Signals 503 8.18 Application: Neural Decoding for Control of Prostheses 505 8.19 Remarks 506 8.20 Study Questions and Problems 507 8.21 Laboratory Exercises and Projects 507 References 508 9 Signal Analysis via Adaptive Decomposition 515 9.1 Problem Statement 517 9.2 Illustration of the Problem with Case Studies 517 9.2.1 Separation of the fetal ECG from a single-channel abdominal Ecg 517 9.2.2 Patient-specific EEG channel selection for BCI applications 518 9.2.3 Detection of microvolt T-wave alternans in long-term ECG recordings 518 9.3 Matching Pursuit 518 9.4 Empirical Mode Decomposition 520 9.4.1 Variants of empirical mode decomposition 521 9.5 Dictionary Learning 523 9.6 Decomposition-based Adaptive TFD 525 9.7 Separation of Mixtures of Signals 531 9.7.1 Principal component analysis 533 9.7.2 Independent component analysis 539 9.7.3 Nonnegative matrix factorization 542 9.7.4 Comparison of PCA, ICA, and NMF 546 9.8 Application: Detection of Epileptic Seizures Using Dictionary Learning Methods 553 9.9 Application: Adaptive Time–Frequency Analysis of VAG Signals 560 9.10 Application: Detection of T-wave Alternans in ECG Signals 568 9.11 Application: Extraction of the Fetal ECG from Single-channel Maternal ECG 572 9.12 Application: EEG Analysis for Brain–Computer Interfaces 577 9.12.1 NMF-based channel selection 579 9.12.2 Feature extraction 579 9.13 Remarks 586 9.14 Study Questions and Problems 586 9.15 Laboratory Exercises and Projects 586 References 587 10 Computer-aided Diagnosis and Healthcare 595 10.1 Problem Statement 596 10.2 Illustration of the Problem with Case Studies 596 10.2.1 Diagnosis of bundle-branch block 596 10.2.2 Normal or ectopic ECG beat? 597 10.2.3 Is there an alpha rhythm? 598 10.2.4 Is a murmur present? 598 10.2.5 Detection of sleep apnea using multimodal biomedical signals 598 10.3 Pattern Classification 599 10.4 Supervised Pattern Classification 600 10.4.1 Discriminant and decision functions 600 10.4.2 Fisher linear discriminant analysis 601 10.4.3 Distance functions 605 10.4.4 The nearest-neighbor rule 605 10.4.5 The support vector machine 606 10.5 Unsupervised Pattern Classification 607 10.5.1 Cluster-seeking methods 607 10.6 Probabilistic Models and Statistical Decision 611 10.6.1 Likelihood functions and statistical decision 611 10.6.2 Bayes classifier for normal patterns 613 10.7 Logistic Regression Analysis 614 10.8 Neural Networks 615 10.8.1 ANNs with radial basis functions 617 10.8.2 Deep learning 620 10.9 Measures of Diagnostic Accuracy and Cost 620 10.9.1 Receiver operating characteristics 623 10.9.2 McNemar’s test of symmetry 625 10.10 Reliability of Features, Classifiers, and Decisions 627 10.10.1 Separability of features 628 10.10.2 Feature selection 630 10.10.3 The training and test steps 631 10.11 Application: Normal versus Ectopic ECG Beats 633 10.11.1 Classification with a linear discriminant function 633 10.11.2 Application of the Bayes classifier 637 10.11.3 Classification using the K-means method 637 10.12 Application: Detection of Knee-joint Cartilage Pathology 637 10.13 Application: Detection of Sleep Apnea 644 10.14 Application: Monitoring Parkinson’s Disease Using Multimodal Signal Analysis 647 10.15 Strengths and Limitations of CAD 650 10.16 Remarks 656 10.17 Study Questions and Problems 657 10.18 Laboratory Exercises and Projects 658 References 659 Index 665

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