Biotechnology Books

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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Book SynopsisTable of ContentsPreface xv 1 Machine Learning–Assisted Remote Patient Monitoring with Data Analytics 1Vinutha D. C., Kavyashree and G. T. Raju 1.1 Introduction 2 1.1.1 Traditional Patient Monitoring System 2 1.1.2 Remote Monitoring System 3 1.1.3 Challenges in RPM 4 1.2 Literature Survey 5 1.2.1 Machine Learning Approaches in Patient Monitoring 7 1.3 Machine Learning in RPM 8 1.3.1 Support Vector Machine 9 1.3.2 Decision Tree 10 1.3.3 Random Forest 11 1.3.4 Logistic Regression 11 1.3.5 Genetic Algorithm 12 1.3.6 Simple Linear Regression 12 1.3.7 KNN Algorithm 13 1.3.8 Naive Bayes Algorithm 14 1.4 System Architecture 15 1.4.1 Data Collection 16 1.4.2 Data Pre-Processing 17 1.4.3 Apply Machine Learning Algorithm and Prediction 18 1.5 Results 21 1.6 Future Enhancement 23 1.7 Conclusion 24 References 24 2 A Survey on Recent Computer-Aided Diagnosis for Detecting Diabetic Retinopathy 27Priyadharsini C., Jagadeesh Kannan R. and Farookh Khadeer Hussain 2.1 Introduction 28 2.2 Diabetic Retinopathy 28 2.2.1 Features of DR 28 2.2.2 Stages of DR 29 2.3 Overview of DL Models 31 2.3.1 Convolution Neural Network 31 2.3.2 Autoencoders 32 2.3.3 Boltzmann Machine and Deep Belief Network 32 2.4 Data Set 33 2.5 Performance Metrics 34 2.6 Literature Survey 36 2.6.1 Segmentation of Blood Vessels 36 2.6.2 Optic Disc Feature 49 2.6.3 Lesion Detections 50 2.6.3.1 Exudate Detection 50 2.6.3.2 MA and HM 51 2.6.4 DR Classification 51 2.7 Discussion and Future Directions 52 2.8 Conclusion 53 References 53 3 A New Improved Cryptography Method-Based e-Health Application in Cloud Computing Environment 59Dipesh Kumar, Nirupama Mandal and Yugal Kumar 3.1 Introduction 60 3.1.1 Contribution 61 3.2 Motivation 62 3.3 Related Works 62 3.4 Challenges 64 3.5 Proposed Work 64 3.6 Proposed Algorithm for Encryption 66 3.6.1 Demonstration of Encryption Algorithm 66 3.6.1.1 When the Number of Columns Selected in the Table is Even 66 3.6.1.2 When the Number of Columns Selected in the Table is Odd 69 3.6.2 Flowchart for Encryption 72 3.7 Algorithm for Decryption 73 3.7.1 Demonstration of Decryption Algorithm 73 3.7.1.1 When the Number of Columns Selected in the Table is Even 73 3.7.1.2 When the Number of Columns Selected in the Table is Odd 75 3.7.2 Flowchart of Decryption Algorithm 78 3.8 Experiment and Result 78 3.9 Conclusion 80 References 80 4 Cutaneous Disease Optimization Using Teledermatology Underresourced Clinics 85Supriya M., Murugan K., Shanmugaraja T. and Venkatesh T. 4.1 Introduction 86 4.2 Materials and Methods 87 4.2.1 Clinical Setting and Teledermatology Workflow 87 4.2.2 Study Design, Data Collection, and Analysis 87 4.3 Proposed System 88 4.3.1 Teledermatology in an Underresourced Clinic 88 4.3.2 Teledermatology Consultations from Uninsured Patients 89 4.3.3 Teledermatology for Patients Lacking Access to Dermatologists 90 4.3.4 Teledermatologist Management from Nonspecialists 92 4.3.5 Segment Factors of Referring PCPs and Their Patients 93 4.3.6 Teledermatology Operational Considerations 94 4.3.7 Instruction of PCPs 94 4.4 Challenges 95 4.5 Results and Discussion 95 4.5.1 Challenges of Referring to Teledermatology Services 96 References 98 5 Cognitive Assessment Based on Eye Tracking Using Device-Embedded Cameras via Tele-Neuropsychology 101Shanmugaraja T., Venkatesh T., Supriya M. and Murugan K. 5.1 Introduction 102 5.2 Materials and Methods 102 5.3 Framework Elements 102 5.3.1 Eye Tracker Camera 102 5.3.2 Test Construction 103 5.3.3 Web Camera 106 5.3.4 Camera for Eye Tracking 106 5.4 Proposed System 106 5.4.1 Camera for Tracking Eye 106 5.4.2 Web Camera 108 5.4.3 Scoring 108 5.4.4 Eye Tracking Camera 108 5.4.5 Web Camera Human-Coded Scoring 108 5.5 Subjects 109 5.5.1 Characteristics of Subject 109 5.6 Methodology 110 5.6.1 Analysis of Data 110 5.7 Results 110 5.8 Discussion 112 5.9 Conclusion 114 References 115 6 Fuzzy-Based Patient Health Monitoring System 117Venkatesh T., Murugan K., Supriya M., Shanmugaraja T. and Rekha Chakravarthi 6.1 Introduction 118 6.1.1 General Problem 119 6.1.2 Existing Patient Monitoring and Diagnosis Systems 119 6.1.3 Fuzzy Logic Systems 120 6.2 System Design 122 6.2.1 Hardware Requirements 122 6.2.1.1 Functional Requirements 123 6.2.1.2 Nonfunctional Specifications 125 6.3 Software Architecture 125 6.3.1 The Data Acquisition Unit (DAQ) Application Programmable Interface (API) 126 6.3.2 Flowchart—API 128 6.3.3 Foreign Tag IDs 129 6.3.4 Database Manager 130 6.3.5 Database Designing 130 6.3.6 The Fuzzy Logic System 131 6.3.6.1 Introduction to Fuzzy Logic 131 6.3.6.2 The Modified Prior Alerting Score (MPAS) 132 6.3.6.3 Structure of the Fuzzy Logic System 134 6.3.7 Designing a System in Fuzzy 135 6.3.7.1 Input Variables 135 6.3.7.2 The Output Variable 138 6.4 Results and Discussion 140 6.4.1 Hardware Sensors Validation 140 6.4.2 Implementations, Testing, and Evaluation of the Fuzzy Logic Engine 141 6.4.3 Normal Group (NRM) 146 6.4.4 Low Risk Group 146 6.4.5 High Risk Group (HRG) 153 6.5 Conclusions and Future Work 155 6.5.1 Summary and Concluding Remarks 155 6.5.2 Future Directions 155 References 155 7 Artificial Intelligence: A Key for Detecting COVID-19 Using Chest Radiography 159C. Vinothini, P. Anitha, Priya J., Abirami A. and Akash S. 7.1 Introduction 160 7.2 Related Work 162 7.2.1 Traditional Approach 162 7.2.2 Deep Learning–Based Approach 163 7.3 Materials and Methods 163 7.3.1 Data Set and Data Pre-Processing 163 7.3.2 Proposed Model 165 7.4 Experiment and Result 171 7.4.1 Experiment Setup 171 7.4.2 Comparison with Other Models 173 7.5 Results 174 7.6 Conclusion 175 References 176 8 An Efficient IoT Framework for Patient Monitoring and Predicting Heart Disease Based on Machine Learning Algorithms 179Shanthi S., Nidhya R., Uma Perumal and Manish Kumar 8.1 Introduction 180 8.2 Literature Survey 182 8.3 Machine Learning Algorithms 183 8.4 Problem Statement 184 8.5 Proposed Work 185 8.5.1 Data Set Description 185 8.5.2 Collection of Values Through Sensor Nodes 186 8.5.3 Storage of Data in Cloud 187 8.5.4 Prediction with Machine Learning Algorithms 188 8.5.4.1 Data Cleaning and Preparation 188 8.5.4.2 Data Splitting 189 8.5.4.3 Training and Testing 189 8.5.5 Machine Learning Algorithms 189 8.5.5.1 Naive Bayes Algorithm 189 8.5.5.2 Decision Tree Algorithm 190 8.5.5.3 K-Neighbors Classifier 191 8.5.5.4 Logistic Regression 192 8.6 Performance Analysis and Evaluation 192 8.7 Conclusion 197 References 197 9 BABW: Biometric-Based Authentication Using DWT and FFNN 201R. Kingsy Grace, M.S. Geetha Devasena and R. Manimegalai 9.1 Introduction 202 9.2 Literature Survey 203 9.3 BABW: Biometric Authentication Using Brain Waves 208 9.4 Results and Discussion 211 9.5 Conclusion 215 References 216 10 Autism Screening Tools With Machine Learning and Deep Learning Methods: A Review 221Pavithra D., Jayanthi A. N., Nidhya R. and Balamurugan S. 10.1 Introduction 222 10.2 Autism Screening Methods 223 10.2.1 Autism Screening Instrument for Educational Planning—3rd Version 224 10.2.2 Quantitative Checklist for Autism in Toddlers 224 10.2.3 Autism Behavior Checklist 224 10.2.4 Developmental Behavior Checklist-Early Screen 225 10.2.5 Childhood Autism Rating Scale Version 2 225 10.2.6 Autism Spectrum Screening Questionnaire (ASSQ) 226 10.2.7 Early Screening for Autistic Traits 226 10.2.8 Autism Spectrum Quotient 226 10.2.9 Social Communication Questionnaire 227 10.2.10 Child Behavior Check List 227 10.2.11 Indian Scale for Assessment of Autism 227 10.3 Machine Learning in ASD Screening and Diagnosis 228 10.4 DL in ASD Diagnosis 238 10.5 Conclusion 242 References 242 11 Drug Target Module Mining Using Biological Multifunctional Score-Based Coclustering 249R. Gowri and R. Rathipriya 11.1 Introduction 249 11.2 Literature Study 250 11.3 Materials and Methods 253 11.3.1 Biological Terminologies 253 11.3.2 Functional Coherence 256 11.3.3 Biological Significances 257 11.3.4 Existing Approach: MR-CoC 257 11.4 Proposed Approach: MR-CoCmulti 258 11.4.1 Biological Score Measures for DTM 259 11.4.2 Multifunctional Score-Based Co-Clustering Approach 259 11.5 Experimental Analysis 264 11.5.1 Experimental Results 265 11.6 Discussion 280 11.7 Conclusion 280 Acknowledgment 281 References 281 12 The Ascendant Role of Machine Learning Algorithms in the Prediction of Breast Cancer and Treatment Using Telehealth 285Jothi K.R., Oswalt Manoj S., Ananya Singhal and Suruchi Parashar 12.1 Introduction 286 12.1.1 Objective 287 12.1.2 Description and Goals 287 12.1.2.1 Data Exploration 288 12.1.2.2 Data Pre-Processing 288 12.1.2.3 Feature Scaling 288 12.1.2.4 Model Selection and Evaluation 288 12.2 Literature Review 289 12.3 Architecture Design and Implementation 304 12.4 Results and Discussion 310 12.5 Conclusion 312 12.6 Future Work 313 References 314 13 Remote Patient Monitoring: Data Sharing and Prediction Using Machine Learning 317Mohammed Hameed Alhameed, S. Shanthi, Uma Perumal and Fathe Jeribi 13.1 Introduction 318 13.1.1 Patient Monitoring in Healthcare System 318 13.2 Literature Survey 321 13.3 Problem Statement 322 13.4 Machine Learning 322 13.4.1 Introduction 322 13.4.2 Cloud Computing 324 13.4.3 Design and Architecture 325 13.5 Proposed System 326 13.6 Results and Discussions 331 13.7 Privacy and Security Challenges 333 13.8 Conclusions and Future Enhancement 334 References 335 14 Investigations on Machine Learning Models to Envisage Coronavirus in Patients 339R. Sabitha, J. Shanthini, R.M. Bhavadharini and S. Karthik 14.1 Introduction 340 14.2 Categories of ML Algorithms in Healthcare 341 14.3 Why ML to Fight COVID-19? Tools and Techniques 343 14.4 Highlights of ML Algorithms Under Consideration 344 14.5 Experimentation and Investigation 349 14.6 Comparative Analysis of the Algorithms 353 14.7 Scope of Enhancement for Better Investigation 354 References 356 15 Healthcare Informatics: Emerging Trends, Challenges, and Analysis of Medical Imaging 359G. Karthick and N.S. Nithya 15.1 Emerging Trends and Challenges in Healthcare Informatics 360 15.1.1 Advanced Technologies in Healthcare Informatics 360 15.1.2 Intelligent Smart Healthcare Devices Using IoT With DL 361 15.1.3 Cyber Security in Healthcare Informatics 362 15.1.4 Trends, Challenges, and Issues in Healthcare IT Analytics 363 15.2 Performance Analysis of Medical Image Compression Using Wavelet Functions 364 15.2.1 Introduction 364 15.2.2 Materials and Methods 366 15.2.3 Wavelet Basis Functions 367 15.2.3.1 Haar Wavelet 367 15.2.3.2 db Wavelet 368 15.2.3.3 bior Wavelet 368 15.2.3.4 rbio Wavelet 368 15.2.3.5 Symlets Wavelet 369 15.2.3.6 coif Wavelet 369 15.2.3.7 dmey Wavelet 369 15.2.3.8 fk Wavelet 369 15.2.4 Compression Methods 370 15.2.4.1 Embedded Zero-Trees of Wavelet Transform 370 15.2.4.2 Set Partitioning in Hierarchical Trees 370 15.2.4.3 Adaptively Scanned Wavelet Difference Reduction 370 15.2.4.4 Coefficient Thresholding 371 15.3 Results and Discussion 371 15.3.1 Mean Square Error 371 15.3.2 Peak Signal to Noise Ratio 371 15.4 Conclusion 380 15.4.1 Summary 380 References 380 Index 383

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Book SynopsisNANOMATERIALS IN CLINICAL THERAPEUTICS In this rapidly developing field, the book focuses on the practical elements of nanomaterial creation, characterization, and development, as well as their usage in clinical research. Nanotechnology-based applications is a rapidly growing field encompassing a diverse range of disciplines that impact our daily lives. Nanotechnology is being used to carry out large-scale reactions in practically every field of biotechnology and healthcare. The incredible progress being made in these applications is particularly true for the healthcare sector, where they are used in cancer detection and treatment, medical implants, tissue engineering, and so forth. Expansions in this discipline are expected to continue in the future, resulting in the creation of a variety of life-saving medical technology and treatment procedures. The primary goal of this book is to disseminate information on nanotechnology's applications in the biological scieTable of ContentsPreface xix Part 1: History and Basic Principles of Nanotechnology 1 1 Introduction to Nanotechnology 3 Rekha Sharma, Kritika S. Sharma and Dinesh Kumar 1.1 Introduction 4 1.2 Nanoscale Materials: Importance 5 1.3 Nanotechnology: Historical Advances 8 1.4 Nanofabrication Methods in Nanotechnology 9 1.4.1 Top-Down Method 10 1.4.2 Bottom-Up Method 11 1.5 Carbon Nanoallotropes 13 1.5.1 Fullerene 13 1.5.2 Carbon Nanotubes 14 1.5.3 Graphene 15 1.6 Classification of the Nanomaterials 16 1.6.1 Based on Dimensions 16 1.6.2 Based on the Structural Configuration 17 1.7 Applications of Nanotechnology 18 1.7.1 Chip-Based Plasmonic Sensors 18 1.7.2 Nanoparticle-Based Colorimetric Sensors 20 1.7.3 Colloidal Nanoparticle-Based Plasmonic Sensors 21 1.8 Conclusions and Future Perspectives 23 Acknowledgment 23 References 24 2 Functional Principal of Nanotechnology in Clinical Research 33 Kalyanee Bera, Biva Ghosh and Mainak Mukhopadhyay 2.1 Introduction 34 2.2 Nanoparticles 36 2.3 Carbon-Based Nanoparticles 37 2.4 Metal Nanoparticles 37 2.4.1 Gold Nanoparticles 38 2.4.2 Silver Nanoparticles 39 2.4.3 Zinc Nanoparticles 39 2.5 Magnetic Nanoparticles 40 2.6 Ceramic Nanoparticles 41 2.7 Lipid Nanoparticles 41 2.8 Polymeric Nanoparticles (Nanoparticles Made of Polymers) 42 2.8.1 Synthetic 43 2.8.2 Natural 43 2.9 Hydrogel 44 2.10 Nanofibers 45 2.11 Nanocomposites 45 2.12 Nanotechnologies for Clinical Laboratory Diagnosis 46 2.12.1 Nanotechnology-Based Biochips and Microarrays 46 2.12.2 Protein Microarrays/Chips 47 2.12.3 Nanobiosensors 48 2.12.4 PEBBLE Nanosensors (Probes Encapsulated by Biologically Localized Embedding) 48 2.12.5 Quantum Dots 48 2.12.6 Fluorescence Microscopy for Chromosomal Changes 49 2.12.7 Nanobarcodes 49 2.12.8 Protein Biobarcode Assay 50 2.12.9 Cantilever Arrays 50 2.12.10 DNA-Protein and Nanoparticles Conjugates 51 2.12.11 Resonance Light Scattering Technology 52 2.12.12 Method of Colorimetric DNA Detection 52 2.12.13 Upcoming Phosphor Technology Based on Nanoparticles 53 2.13 Clinical Uses of Nanotechnology 53 2.13.1 Application of Nanocrystals in Immunohistochemistry 54 2.13.2 Detection of Illness Biomarkers 54 2.13.3 Disease Gene Detection 54 2.13.4 Detection of Microorganisms 55 2.13.5 Dental Nanotechnology 55 2.14 Nanofilm Applications 56 2.15 Nanomedicine Implementation 57 2.16 Future Prospects 58 2.17 Conclusion 58 References 59 3 Application of Nanotechnology in Clinical Research: Present and Future Prospects 75 Mansi Sharma, Pragati Chauhan, Rekha Sharma and Dinesh Kumar 3.1 Introduction 76 3.2 Scope of Nanotechnology in Clinical Research 77 3.3 Classification 78 3.3.1 Nanomaterials 78 3.3.1.1 Nanocrystal 80 3.3.1.2 Nanostructures 81 3.3.2 Nanodevices 89 3.4 Applications of Nanotechnology 91 3.4.1 Drug Delivery 93 3.4.2 Cancer Treatment 93 3.4.3 Gene Therapy 95 3.4.4 Tissue Engineering 95 3.4.5 Wound Treatment 96 3.4.6 Visualization 96 3.4.7 Tuberculosis Treatment 97 3.4.8 In Ophthalmology 97 3.4.9 Neurodegenerative Treatment 97 3.4.10 Diabetes Treatment 98 3.4.11 Protein Detection 98 3.4.12 In Surgery 99 3.4.13 Antibiotic Resistance 99 3.4.14 Immune Response 99 3.4.15 Operative Dentistry 101 3.4.16 Diagnostic Techniques 102 3.5 Conclusion 103 Acknowledgment 103 References 104 Part 2: Synthesis, Characterization and Applications of Nanomaterials 115 4 Fermentation Process Versus Nanotechnology 117 Nabya Nehal, Anushka Mathur, Modhumita Ganguli and Priyanka Singh 4.1 Overview of Microbial Technology 118 4.1.1 Biological Methodologies for Extraction and Purification of Biomolecules 118 4.1.2 Recent Advancements in Bioprocess Technology 119 4.1.2.1 Genetic Engineering and Random Mutagenesis 120 4.1.2.2 Immobilization Techniques 120 4.2 Nanotechnology 123 4.2.1 Classification of Nanostructures 125 4.2.1.1 Organic Nanocarriers 126 4.2.1.2 Inorganic Nanocarriers 127 4.2.2 Self-Assembly 128 4.2.3 Methodology for Synthesis of Nanoparticles 129 4.3 Biogenic Sources 131 4.3.1 From Bacteria 131 4.3.2 Filamentous Fungi 133 4.3.3 Plants 135 4.3.4 Microalgae 135 4.4 The Extent of Biogenic Nanoparticles in Industrial Sectors 139 4.4.1 Biomedical and Pharmaceutical Sectors 143 4.4.2 Environmental Remediation 146 4.4.3 Food Sectors 148 References 158 5 Application of Geno-Sensors and Nanoparticles in Gene Therapy: A New Avenue for Gene Delivery 177 Sharmili Roy, Monalisha Ghosh Dastidar, Vivek Sharma, Beom Soo Kim and Rajiv Chandra Rajak 5.1 Introduction 178 5.2 Inorganic Nanomaterials and Their Application in Gene Delivery 179 5.2.1 Magnetic Nanoparticles 180 5.2.2 Quantum Dots 181 5.2.3 Gold, Silver, and Platinum Nanoparticles 182 5.2.4 Graphene-Based Nanoparticles 186 5.3 Carbon-Based Nanotubes and Their Applications in Gene Delivery 187 5.4 Polymer-Based Nanomaterials and Their Applications in Gene Delivery 188 5.5 Protein, Lipid, and Peptide-Based Nanomaterials and Their Advantages for Gene Delivery 192 5.6 Conclusion: Challenges and Outlook 194 References 196 6 Flexuous Plant Viruses as Nanomaterials for Biomedical Applications 205 De Swarnalok 6.1 Introduction 205 6.2 Plant Virus Particle Structures 207 6.2.1 Viruses With Icosahedral Symmetry 207 6.2.2 Viruses with Helical Symmetry 208 6.2.2.1 Rigid Rod-Like Viruses 208 6.2.2.2 Flexuous Filament-Like Viruses 209 6.3 Virus Nanoparticles and Virus-Like Particles 209 6.3.1 VNPs 209 6.3.2 VLPs 210 6.4 Production Platforms for VNPs and VLPs 210 6.4.1 VNPs/VLPs in Plants 211 6.4.2 VLPs via In Vitro Assembly 212 6.5 Functionalization of Viruses 212 6.5.1 Genetic Engineering 213 6.5.2 Chemical Conjugation 213 6.5.3 Other Functionalization Strategies 214 6.6 Uses of Flexuous Plant Viruses in Medicine 214 6.6.1 Vaccination and Immunotherapy 214 6.6.2 3D Tissue Engineering 215 6.6.3 Drug Delivery and Targeting 215 6.6.4 Bioimaging 216 6.6.5 Biosensing 217 6.7 Conclusions 217 References 218 7 Role of Plants in Nanoparticle Synthesis 225 Tanya Kapoor, Md Azizur Rahman, Shally Pandit and Anand Prakash 7.1 Introduction 225 7.2 Characterization of Nanoparticles 227 7.3 Classification of Nanoparticles 227 7.4 Biochemical Synthesis of Nanoparticles 228 7.5 Green Synthesis Approach for NPs 232 7.6 Plants’ Role in the Green Synthesis of NPs 232 7.7 Green Synthesis Using Enzymes 234 7.8 Nanoparticles Role in Photosynthesis 235 7.9 Applications of Green Synthesis NPs 235 7.10 Conclusion 237 References 237 8 Static DNA Nanostructures and Their Applications 245 Debalina Bhattacharya 8.1 Introduction 245 8.1.1 DNA Structure 245 8.1.2 Types of DNA Structures 247 8.2 Static DNA Nanostructures 247 8.2.1 DNA Tile Assembly 248 8.2.2 DNA Origami and Brick Assembly 251 8.3 DNA Origami Nanostructure 251 8.4 DNA Polyhedra 252 8.5 DNA-Functionalized Nanoparticles 253 8.6 Stability in Biological Fluid and Cellular Uptake of DNA-NSs and DNA-NPs 254 8.7 Application 255 8.7.1 DNA Nanostructures as Biosensors 255 8.7.2 DNA in Therapeutics 257 8.7.3 Photo Thermal Therapy and Photo Dynamic Therapy 258 8.7.4 DNA-Based Enzyme Reactors 259 8.7.5 DNA-Based Gene Delivery 260 8.7.6 DNA Scaffolds for Nanophotonics 261 8.7.7 Conclusion 261 References 262 9 Protein-Based Nanostructures 269 Ditipriya Hazra and Amlan Roychowdhury 9.1 Introduction 269 9.2 Peptide-Based Nanoparticle 270 9.3 Protein-Based Nanostructure 271 9.3.1 Oligomerization of Protein 272 9.3.2 Repeat Domain Proteins 273 9.3.3 Protein-Based 2D and 3D Lattice Assembly of Nanoparticles 274 9.3.4 Covalently Assembled Single Chain-Based Nanostructure 274 9.4 Application of Protein-Based Nanostructures in Therapeutics 275 9.4.1 Protein Nanoparticle for Drug Delivery 275 9.4.2 Nanoparticle-Based Vaccines 275 9.4.3 Hydrogel 277 References 278 10 Nanocomposites-Based Biodegradable Polymers 285 Pragati Chauhan, Mansi Sharma, Rekha Sharma and Dinesh Kumar 10.1 Introduction 286 10.2 Nanocomposite 287 10.3 Biodegradable Polymer 288 10.4 Biopolymer 289 10.5 Nanofillers 289 10.6 Cellulose and Its Sources 289 10.7 Nanocellulose 291 10.8 Nanocellulose Composite Processing 292 10.8.1 Melt Mixing Method 293 10.8.1.1 Injection Molding Method 294 10.8.1.2 Resin Transfer Molding Method 295 10.8.1.3 Extrusion Method 296 10.8.2 Solution Casting Method 297 10.8.3 Particle Suspensions Method 299 10.8.4 In-Situ Polymerization Method 300 10.8.5 Layer-by-Layer Lamination Method 303 10.9 Nanocomposites Used as Packaging Materials 305 10.10 Future Perspective and Application 306 10.11 Conclusions 307 References 308 11 Instrumentation for the Analysis and Characterization of Nanomaterials 317 Andrea Komesu, Johnatt Oliveira, Débora Kono Taketa Moreira, Yvan Jesus Olortiga Asencios, João Moreira Neto and Luiza Helena da Silva Martins 11.1 Introduction 318 11.2 Scanning Electron Microscopy [SEM] 319 11.3 Energy Dispersive X-Ray Analysis [EDX] 320 11.4 Atomic Force Microscopy [AFM] 322 11.5 Transmission Electron Microscopy [TEM] 323 11.6 Scanning Tunneling Microscopy [STM] 325 11.7 Ultraviolet-Visible Spectroscopy 327 11.8 Raman Spectroscopy 329 11.9 Fourier Transform Infrared Spectroscopy 330 11.10 X-Ray Diffraction [XRD] 332 11.11 X-Ray Photoelectron Spectroscopy [XPS] 333 11.12 Zeta Potential 335 11.13 Conclusions 336 References 337 12 Application of Microbial Nanoparticles 343 Monika Yadav, Sneha Upreti and Priyanka Singh 12.1 Introduction 344 12.2 Categorization of Nanoparticles 346 12.2.1 Polymeric Nanoparticles 346 12.2.1.1 Polymeric Micelles 346 12.2.1.2 Nanosphere 347 12.2.1.3 Nanocapsules 347 12.2.1.4 Polymerosome 347 12.2.1.5 Nanogels 348 12.2.1.6 Dendrimers 348 12.2.1.7 Nanocomplex 349 12.2.2 Lipid-Based Nanoparticles 349 12.2.2.1 Liposomes 349 12.2.2.2 Solid Lipid Nanoparticles 349 12.2.2.3 Lipoplexes 349 12.2.3 Inorganic Nanoparticles 350 12.2.3.1 Gold Nanoparticles 350 12.2.3.2 Magnetic Nanoparticles 350 12.2.3.3 Silica Nanoparticles 351 12.2.3.4 Quantum Dots 351 12.2.3.5 Nanocarbons 351 12.2.4 Bioinspired Nanoparticles 352 12.2.4.1 Exosomes 352 12.2.4.2 Protein Nanoparticles 352 12.2.4.3 DNA Nanostructures 352 12.2.5 Hybrid Nanoparticles 353 12.2.5.1 Cell Membrane-Coated Nanoparticles 353 12.2.5.2 Organic-Inorganic Nanocomposites 353 12.2.5.3 Lipid-Polymer Nanoparticles (LPNs) 354 12.3 Microbial-Mediated Synthesis of Nanoparticles for Therapeutic and Biomedical Applications 354 12.3.1 Bacteria 355 12.3.2 Molds and Yeast 356 12.3.3 Microalgae 357 12.4 Agriculture and Food Nanotechnology 358 12.4.1 Food Nanotechnology 359 12.4.1.1 Food Processing 359 12.4.1.2 Food Packaging 359 12.4.2 Agriculture Nanotechnology 360 12.4.3 Enzyme Nanotechnology 360 12.5 Role of Nanoparticles in the Medical Field 361 12.5.1 Nanoparticles Drug Delivery Applications 362 12.5.1.1 Drug Loading 362 12.5.1.2 Covalent Bonding (Prodrug) 362 12.5.1.3 Noncovalent Encapsulation 363 12.6 Application of Microbial Nanoparticles 363 12.6.1 Application of NPs in Food Industry 364 12.6.2 Applications of Nanoparticles in the Pharmaceuticals Industry 368 12.6.2.1 Biopolymeric Nanoparticles in Detection, Diagnosis and Imaging 369 12.6.2.2 In Drug Liberation 370 12.6.2.3 In Magnetic Partition and Recognition 372 12.6.3 Application of Nanoparticles in Cosmetic Sector 373 12.6.4 Nanoparticles in Bioremediation 375 12.6.4.1 Dendrimers in the Process of Bioremediation 376 12.6.4.2 Carbon Nanoparticles in Bioremediation 377 12.6.4.3 Biogenic Uraninite NMs in Bioremediation 378 12.7 Conclusion 378 References 379 13 Bio-Nanostructures: Applications and Perspectives 393 Tanya Kapoor, Shally Pandit and Anand Prakash 13.1 Introduction 393 13.2 Classification of Nanostructures 394 13.2.1 Self-Assembled Nanostructures 394 13.2.2 Carbon-Based Nanostructures 394 13.2.3 Nanocellulose Nanostructures 395 13.2.4 Graphene Oxide-Based Nanostructures 395 13.2.5 Silica-Based Nanostructures 396 13.3 Characterization Method of Nanostructures 396 13.4 Applications of Bio-Nanoparticles 401 13.5 Conclusion 404 References 405 Part 3: Application of Nanomaterials in Clinical Research 411 14 Nanomaterials for Tissue Grafting 413 Paramjeet Singh, Atanu Kotal and Avik Acharya Chowdhury 14.1 Introduction 414 14.2 Tissue Engineering 415 14.2.1 Bone Tissue Engineering 416 14.2.2 Cartilage Tissue Engineering 418 14.2.3 Tissue Grafting 420 14.3 What is Nanotechnology? 422 14.4 Nanomaterials and Nanoparticles 423 14.4.1 Nanomaterials 423 14.4.1.1 Organic Nanomaterials 423 14.4.1.2 Inorganic Nanomaterials 424 14.4.1.3 Composite Nanomaterials 424 14.4.2 Nanoparticles 425 14.4.2.1 Nanoparticles as Bioactive Agents 431 14.4.2.2 Scaffolds and Nanoparticles 431 14.5 Future Prospects 433 14.6 Conclusion 435 References 436 15 Nanoparticles for Cancer Therapy 441 Kaliyaperumal Rekha, Nalok Dutta, Muthu Thiruvengadam, Mohammad Ali Shariati, Muhammad Usman Khan, Muhammad Usman, Mihir Bhatta, Kunal Ghosh, Shaheer Arif and Muhammad Naeem 15.1 Introduction 442 15.2 Nanoparticles as Drug Delivery in Cancer Treatment 442 15.3 Drug Nanocarriers Classification 444 15.4 Organic Nanocarriers 444 15.4.1 Liposomes 444 15.4.2 Solid Lipid Nanoparticles 445 15.4.3 Polymer Nanoparticles 446 15.4.4 Polymer Micelles 446 15.4.5 Dendrimers 446 15.4.6 Polymersomes 447 15.4.7 Hydrogel Nanoparticles 447 15.4.8 Mineral Nanoparticles 448 15.5 Tumor Targeting by Nanoparticles 448 15.6 Utilization of Nanoparticles in Imaging and Treatment for Cancer 449 15.7 Use of Nanoparticles in the Diagnosis and Treatment of Breast Cancer 450 15.8 The Use of Nanoparticles in the Diagnosis and Treatment of Brain Cancer 451 15.9 Conclusion 452 References 452 16 Nanoantibiotics 459 Rituparna Saha and Mainak Mukhopadhyay 16.1 Introduction 460 16.2 Nanoantibiotics—A Potent Alternative to Antibiotics? 461 16.3 Developmental Strategy of Nanoantibiotics Over Antibiotics 462 16.4 Mechanism of Action of Nanoantibiotics 463 16.5 Common Functions of Nanoantibiotics 463 16.6 Nanomaterials—A Suitable Source of Nanoantibiotics 464 16.7 Types of Nanoantibiotics 465 16.7.1 Through Direct Formulations 465 16.7.1.1 Metal-Based Nanoparticles 465 16.7.1.2 Carbon-Based Nanomaterials 466 16.7.1.3 Nanoemulsions 466 16.7.1.4 Nanocomposites 466 16.7.2 Through Indirect Formulations 467 16.7.2.1 Polymers 467 16.7.2.2 Dendrimers 467 16.7.2.3 Hydrogels 468 16.7.2.4 Liposomes 468 16.8 Advantages of Nanoantibiotics 468 16.9 Disadvantages of Nanoantibiotics 469 16.10 Treatment of Multidrug-Resistant Bacteria with Nanoantibiotics 469 16.11 Treatment of Methicillin-Resistant Staphylococcus aureus with Nanoantibiotics 470 16.12 Development of Targeted Therapy Using Nanoantibiotics 470 16.13 Future Prospects of Nanoantibiotics 471 16.14 Conclusion 471 References 472 17 Theranostic Nanomaterials and Its Use in Biomedicine 479 Arka Mukhopadhyay 17.1 Introduction 480 17.2 Biomedical Payloads 482 17.2.1 Imaging 482 17.2.1.1 Optical Imaging 482 17.2.1.2 Magnetic Resonance Imaging 486 17.2.1.3 Computed Tomography 486 17.2.1.4 Positron Emission Tomography 486 17.2.1.5 Photo Acoustic Tomography 486 17.2.1.6 Ultrasound 488 17.2.1.7 Multimodal Image Therapy 488 17.2.2 Photodynamic Therapy 488 17.2.3 Targeted Gene Therapy 489 17.2.4 Photothermal Therapy 489 17.3 Carrier 490 17.3.1 Polymers 491 17.3.2 Lipids 491 17.3.3 Dendrimers 491 17.3.4 Inorganic Nanocarriers 492 17.4 Theranostic Nanomaterials and Applications 492 17.4.1 Magnetic Nanoparticles 492 17.4.2 Quantum Dots 493 17.4.3 Anisotropic Nanoparticles 494 17.4.4 Upconverting Nanoparticles 494 17.4.5 Carbon Nanotubes 495 17.4.6 Dendrimers 496 17.4.7 Other Nanomaterials 496 17.4.7.1 Gold (Au) Nanoparticles (GNPs) 496 17.4.7.2 Conjugated Polymers 498 17.5 Pharmacokinetics and Pharmacodynamics 499 17.6 Conclusions: Challenges and Future Perspectives 501 References 503 Appendix 509 Index 511

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Book SynopsisTable of ContentsAcknowledgments xvii List of Abbreviations xix Introduction 1 Chapter 1 The Basic Physics of Ultrasound 5 Sound Waves 5 Describing Waves 9 Energy in a Sound Wave 11 Ultrasound Pulses 12 Energy Spectrum of a Pulse 13 Bandwidth 14 Speed of Sound (C) 16 Characteristic Acoustic Impedance, Z0 20 Energy in a Sound Wave 22 Decibels 23 Chapter 2 The Interaction of Ultrasound with Tissue 25 Reflection and Transmission at a Plane Interface 25 Poor Visualisation 29 Scattering 30 Attenuation 34 The Journey of the Ultrasound Pulse 37 User Control 37 References 38 Chapter 3 Beam Shapes 39 Simple Beam Shape Model 40 Huygen’s Wavelet Model and Diffraction 43 Focusing 44 Beam Forming with Transducer Arrays 47 Beam Steering 50 Electronic Focusing 52 Resolution 54 Clutter 58 Reference 58 Chapter 4 The Ultrasound Probe 59 The Transducer 59 Backing Layer 62 Matching Layer 63 Front Face Lens 65 Wide Band Transducers 65 Construction of an Array 66 CMUT Technology 66 1-D, 1.5-D, and 2-D Arrays 68 References 72 Chapter 5 Image Formation 73 Image Modes 74 Linear Image Formation 76 3D Imaging 80 Cine Loop 82 Endoprobes 82 Choosing A Probe 84 Focusing 84 Increasing Frame Rate 86 User Control 86 Ultrasound Harmonics 89 Coded Excitation 92 References 94 Chapter 6 The B-Mode Scanner 95 Transmission Side of a Scanner 95 User Controls 96 Receive Side of a Scanner (Rx) 97 Advantages of Digitising 101 Dynamic Range and Transfer Function (Greyscale Mapping) 102 Contrast Resolution 106 User Controls 106 Image Memory 106 Frame Freeze 106 Read and Write Zoom 107 Image Processing 108 User Control 108 Chapter 7 Image Quality and Artefacts 111 Acoustic Window 111 Frame Rate: Frames Per Second (fps) 112 Interlacing Scan Lines 113 Interpolation – Writing in ‘Extra Lines’ 114 Speckle 115 Frame Averaging or Persistence 116 User Control 117 Spatial Compound Imaging 117 Adaptive Filtering 118 Artefacts 122 Speed of Sound Artefacts 122 Attenuation Artefacts 127 Reflection Artefacts 130 Anisotropy 134 Beam Shape Artefacts 135 Temporal Artefacts 137 Final Example 139 References 140 Chapter 8 Principles of Doppler Ultrasound 141 The Doppler Effect 141 The Doppler Equation 143 Duplex Ultrasound 144 CW Doppler 145 CW Doppler Summary 152 Pulsed Wave Doppler (PW Doppler) and Range Gating 152 Intrinsic Spectral Broadening (ISB) 160 Question: What Doppler Angle Should We Use? 162 User Controls 163 Peak Velocity Envelope 165 Average Velocity 167 Doppler Artefacts 170 References 173 Chapter 9 Principles of Colour Doppler Ultrasound 175 Autocorrelation 177 Colour Scale 180 Frame Rate 181 User Controls 181 CDU and the Doppler Angle 183 Colour Aliasing 183 User Controls 185 Discrimination of Stationary Targets 187 User Controls 188 Power Doppler (PD) 188 CDU Artefacts 190 Colour Sensitivity 192 Presets 194 Colour M-Mode 194 Tissue Doppler Imaging (TDI) 194 Myocardial Strain Imaging 197 Speckle Tracking Echocardiography STE 199 References 202 Chapter 10 Making Measurements 203 Accuracy 204 Precision 204 How Accurate or Precise Do We Need To Be? 205 Reproducibility 205 Systematic and Random Errors 206 Ultrasound Measurements in Practice 206 Physical Constraints 207 Sonographer-Based Constraints 209 Principles for Making Reliable Measurements 209 Measurement of Circumference, Area, and Volume 213 Doppler Waveform Measurements 216 Waveform Indices 219 Colour Doppler Ultrasound 221 Measurement of Volume Flow Q 221 References 224 Chapter 11 Safety and Quality Assurance 225 Energy, Power, and Intensity 226 Measuring Intensity 227 Intensity 227 Factors Affecting Damage Potential 230 Thermal Effects 231 Thermal Index (TI) 232 Transducer Self-Heating 234 Nonthermal Effects 235 Radiation Force 235 Streaming 235 Cavitation 236 Mechanical Index (MI) 239 Alara 239 Contrast Agents 240 Quality Assurance and Routine Checks 241 Suggested Routine User Checks 241 The Use of Test Objects 244 Personal Risk Management 245 New Techniques in Ultrasound 246 References 247 Chapter 12 Advanced Topics 249 Contrast Agents (CA) 249 Behaviour of Bubbles in the Ultrasound Field 251 Contrast Agent Harmonics 252 Flashing 254 Advanced Micro-Bubble Techniques 255 B-Flow Blood Vessel Imaging 256 Doppler Measurement of Pressure Gradients 260 Advanced Image Processing 261 Artificial Intelligence 261 Segmentation 262 Examples (1–3) 262 Computer-Aided Diagnosis (CAD) 263 Diagnosis with Cad 268 Fusion Imaging 269 Needle Visualisation and Guidance 271 References 274 Chapter 13 Ultrafast Ultrasound 277 Synthetic Aperture Imaging (SA) 278 Plane-Wave Beamforming 279 Summary 283 Speed of Sound Correction 283 Ultrafast Doppler 286 Vector Flow Imaging (VFI) 291 References 298 Chapter 14 Elastography 301 Background Theory 302 Elastography 303 Methods of Applying The Distorting Force 303 Strain Elastography (SE) 303 User Controls 307 SE Artefacts 310 Acoustic Radiation Force Impulse Imaging (ARFI Imaging) 314 Strain Ratio 316 Shear Wave Elastography (SWE) 316 Point SWE (PSWE) 320 Supersonic Shear Imaging (SSI) 322 Shear Wave Compounding 323 SWE Artefacts 325 References 326 Appendix 1: Knobology 329 Appendix 2: Handling Equations and Decibels 335 Appendix 3: The Unfocused Transducer Beam Shape 345 Index 349

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Book SynopsisFUNCTIONALIZED CARBON NANOTUBES FOR BIOMEDICAL APPLICATIONS The book highlights established research and technology on current and emerging trends and biomedical applications of functionalized carbon nanotubes by providing academic researchers and scientists in industry, as well as high-tech start-ups, with knowledge of the modern practices that will revolutionize using functionalized carbon nanotubes. Nanotechnology suggests fascinating opportunities for a variety of applications in biomedical fields, including bioimaging and targeted delivery of biomacromolecules into cells. Numerous strategies have been recommended to functionalize carbon nanotubes with raised solubility for efficient use in biomedical applications. Functionalized carbon nanotubes have unique arrangements and extravagant mechanical, thermal, magnetic, optical, electrical, surface, and chemical properties, and the combination of these features gives them widespread biomedical applications. Functionalized carbon nanotTable of ContentsPreface xv Part 1: Overview of Functionalized Carbon Nanotubes 1 1 Functionalized Carbon Nanotubes: An Introduction 3 Sheerin Masroor 1.1 Introduction 4 1.2 Carbon Nanotube’s Classification 6 1.3 Structural and Morphological Analysis of Carbon Nanotubes 7 1.4 Synthetic Techniques of Carbon Nanotubes 8 1.5 Functionalization of Carbon Nanotubes 9 1.6 Commercial Scale Use of Functionalized Carbon Nanotubes 12 1.7 Conclusion and Future Prospects 14 References 15 2 Functionalized Carbon Nanotubes: Synthesis and Characterization 21 Neelam Sharma, Shubhra Pareek, Rahul Shrivastava and Debasis Behera 2.1 Introduction 22 2.2 Synthesis Methods 24 2.2.1 Arc Discharge 24 2.2.2 Laser Ablation 25 2.2.3 Chemical Vapor Deposition 26 2.3 Characterization 27 2.3.1 Raman Spectroscopy 27 2.3.2 Fourier Transform Infrared Spectroscopy (FT-IR) 28 2.3.3 Thermogravimetric Analysis (TGA) 29 2.3.4 Scanning Electron Microscopy (SEM) 29 2.3.5 Transmission Electron Microscopy (TEM) 30 2.3.6 X-Ray Diffraction (XRD) 31 2.3.7 X-Ray Photoelectron Spectroscopy (XPS) 32 2.4 Functionalized Routes of CNTs 33 2.4.1 Surface Oxidation 33 2.4.2 Doping Heteroatoms 33 2.4.3 Alkali Activation 33 2.4.4 Sulfonation 34 2.4.5 Halogenation 34 2.4.6 Grafting 34 2.4.6.1 Grafting via Oxygen-Containing Groups 35 2.4.6.2 Grafting via Diazonium Compounds 36 2.4.6.3 Other Grafting Methods 37 2.4.7 Non-Covalent Functionalization of CNTs 37 2.4.8 Deposition on Functionalized CNTs 37 2.4.9 Physiochemical Approaches 38 2.4.10 Electrochemical Deposition 38 2.4.11 Electroless Deposition 39 2.5 Conclusion 39 References 40 3 Carbon Nanotubes: Types of Functionalization 49 Manilal Murmu, Debanjan Dey, Naresh Chandra Murmu and Priyabrata Banerjee 3.1 Introduction 50 3.2 Carbon Nanotubes 50 3.3 Functionalization of Carbon Nanotubes 52 3.3.1 Covalent Functionalization 52 3.3.2 Non-Covalent Functionalization of Carbon Nanotubes 58 3.3.2.1 Reversibility in Non-Covalent Functionalization 63 3.3.2.2 Solvent Variation in Non-Covalent Functionalization 64 3.3.3.3 pH of the System in Non-Covalent Functionalization 64 3.3.3.4 Temperature Responsive System in Non-Covalent Functionalization 65 3.4 Conclusion and Future Outlook 65 Acknowledgements 65 Web Links 66 References 66 4 Functionalization Carbon Nanotubes Innovate on Medical Technology 75 Afroz Aslam, Jeenat Aslam, Hilal Ahmad Parray and Chaudhery Mustansar Hussain 4.1 Introduction 75 4.2 Functionalization CNTs for Biomedical Applications 78 4.3 Potential Applications of CNTs in Cancer Therapy 79 4.3.1 Anti-Tumor Immunotherapy 80 4.3.2 Anti-Tumor Hyperthermia Therapy 80 4.3.3 Anti-Tumor Chemotherapy 81 4.3.4 Other Cancer Treatment Strategies 82 4.4 Treatment of Central Nervous System Disorders 82 4.5 Treatment of Infectious Diseases 84 4.6 CNTs-Based Transdermal Drug Delivery 85 4.7 f-CNTs for Vaccination 86 4.8 Application of f-CNTs in Tissue Engineering 86 4.9 Conclusion 88 Important Websites 89 References 89 Part 2: Functionalized Carbon Nanotubes: Current and Emerging Biomedical Applications 95 5 Functionalized Carbon Nanotubes: Applications in Biosensing 97 N. Palaniappan, Nidhi Vashistha and Ruby Aslam 5.1 Introduction 97 5.2 CNTs-Based Biosensors 99 5.2.1 Electrochemical Biosensors 100 5.2.1.1 Electrochemical Enzyme Sensors 100 5.2.1.2 Electrochemical Immunosensors 101 5.2.1.3 Electrochemical DNA Sensors 102 5.2.1.4 Non-Biomolecule Based Electrochemical Sensors 104 5.2.2 Optical CNT Sensors 105 5.2.3 Field-Effect CNTs Sensors 106 5.2.4 CNT Human Strain Sensor 107 5.3 Conclusion 108 References 108 6 Applications of Functionalized Carbon Nanotubes in Drug Delivery Systems 117 N. Palaniappan, Małgorzata Kujawska and Kader Poturcu 6.1 Introduction 118 6.2 Nanoparticles-Doped Carbon Nanotubes 121 6.3 Brain-Targeted Delivery 123 6.4 The Organic Molecules Functionalized CNTs as Drug Delivery Vehicles 125 6.5 Functionalized CNTs with Nanoparticles for Drug Active Molecular Mechanism 126 6.5.1 Future of Scope of Functionalized Carbon Nanotube Drug Delivery Application 126 6.6 Conclusion 127 References 127 7 Functionalized Carbon Nanotubes for Gene Therapy 139 Tejas Agnihotri, Tanuja Shinde, Manoj Gitte, Pankaj Kumar Paradia, Rakesh Kumar Tekade and Aakanchha Jain 7.1 Introduction 140 7.2 Functionalized CNTs and Gene Therapy 141 7.3 Cellular Uptake of CNT 146 7.4 Functionalized Carbon Nanotubes and Cancer 147 7.5 Miscellaneous Diseases and Gene Delivery Through Functionalized CNT 150 7.6 Toxicology and Environmental Aspects of Functionalized CNT 158 7.6.1 Cellular Toxicity 159 7.6.2 Liver Toxicity 159 7.6.3 Central Nervous System Toxicity 160 7.6.4 Cardiovascular Toxicity 161 7.7 Regulatory Concerns Over Functionalized Carbon Nanotubes 162 7.8 Conclusion and Future Prospects 164 Important Website 165 References 165 8 Applications of Functionalized Carbon Nanotubes in Cancer Therapy and Diagnosis 171 Irshad Ahmad, Talat Parween, Lina Khandare, Aafaq Tantray and Weqar Ahmad Siddiqi 8.1 Introduction 172 8.2 Characteristic Properties of CNTs and Their Performance 175 8.2.1 Physicochemical Properties of CNTs 176 8.3 The Techniques of CNTs Functionalization 177 8.4 Application of Carbon Nanotubes in Cancer Therapy and Diagnostic 180 8.4.1 The Use of Carbon Nanotubes in Cancer Treatment 180 8.4.2 Intracellular Targeting Using Carbon Nanotubes 180 8.4.2.1 Nucleus Targeting 181 8.4.2.2 Cytoplasm Targeting 181 8.4.2.3 Mitochondria Targeting 181 8.4.3 CNTs for Immunotherapy 182 8.4.4 Cancer Stem Cell Inhibition 183 8.5 Carbon Nanotubes in Cancer Diagnosis 183 8.5.1 CNTs in Cancer Imaging 184 8.5.1.1 Raman Imaging 184 8.5.1.2 Nuclear Magnetic Resonance Imaging 184 8.5.1.3 Ultrasonography 184 8.5.1.4 Photoacoustic Imaging 185 8.5.1.5 Near‐Infrared Fluorescence Imaging 185 8.6 Future Prospects 186 8.7 Conclusion 186 Important Websites 187 References 188 9 Functionalized Carbon Nanotubes for Biomedical Imaging: The Recent Advances 197 Alina Abbas, Saman Zehra, Ruby Aslam, Mohammad Mobin and Shahidul Islam bhat 9.1 Introduction 198 9.2 CNT-Based Imaging Methods 199 9.2.1 Fluorescence Imaging 200 9.2.2 Raman Imaging 204 9.2.3 Photoacoustic Imaging 207 9.2.4 Magnetic Resonance Imaging 209 9.2.5 Nuclear Imaging 212 9.3 Prospects and Challenges 212 9.4 Conclusion 214 References 214 10 Functionalized Carbon Nanotubes for Artificial Bone Tissue Engineering 225 Sougata Ghosh and Ebrahim Mostafavi 10.1 Introduction 226 10.2 CNT-Based Scaffolds and Implants 230 10.2.1 Hydroxyapatite 231 10.2.2 Polymers 234 10.2.2.1 Poly(ε-Caprolactone) 235 10.2.2.2 Polymethyl-Methacrylate 237 10.2.2.3 Poly(Lactide-Co-Glycolide) 238 10.2.2.4 Poly-L-Lactic Acid 240 10.2.2.5 Polyvinyl Alcohol 241 10.2.2.6 Others 242 10.2.3 Biopolymers 242 10.2.3.1 Chitosan 244 10.2.3.2 Collagen 244 10.2.3.3 Others 247 10.3 Intellectual Property Rights and Commercialization Aspects 248 10.4 Conclusion and Future Perspectives 251 References 252 11 Application of Functionalized Carbon Nanotubes in Biomimetic/Bioinspired Systems 257 Mohammad Mobin, Ruby Aslam, Saman Zehra, Jeenat Aslam and Shahidul Islam bhat 11.1 Introduction 258 11.2 Naturally Occurring Materials 259 11.2.1 Nacre and Bone 259 11.2.2 Petal Effect and Gecko Feet 259 11.2.3 Lotus Effect 260 11.2.4 Structural Colors, Antireflection, and Light Collection 261 11.3 Bioinspired Functionalized CNTs Material 261 11.4 Challenges and Solutions in Using CNTs 272 11.5 Conclusion and Perspectives 272 References 274 12 Functionalized Carbon Nanotubes: Applications in Tissue Engineering 281 Ajahar Khan, Khalid A. Alamry and Raed H. Althomali 12.1 Introduction 282 12.2 Structural, Physical, and Chemical Properties 284 12.3 Interactions and Biodegradation of CNTs with Biomolecule 287 12.4 Bio-Security of CNT-Based Scaffolds Toward In Vivo Analyses 288 12.5 CNTs Towards the Bone Compatibility 293 12.6 Applications of Functionalized CNTs in Tissue Engineering 294 12.6.1 Functionalized CNTs for Cardiac Tissue Engineering 294 12.6.2 Functionalized CNTs for Neuronal Tissue Regeneration 297 12.6.3 Functionalized CNT for Cartilage Tissue Engineering 298 12.6.4 CNT for Bone Tissue Regeneration 300 12.7 Future Perspectives and Challenges 303 12.8 Conclusion 304 Important Websites 305 References 305 13 Functionalized Carbon Nanotubes for Cell Tracking 319 Sagar Salave, Dhwani Rana, Jyotsna Vitore and Aakanchha Jain Abbreviations 319 13.1 Introduction 320 13.2 Carbon Nanotubes 321 13.2.1 Cellular Interaction of CNTs 325 13.3 Cellular Tracking via CNT 325 13.3.1 Effect of the Surface Coating of CNTs in Single-Particle Tracking 328 13.4 3D Tracking Using CNTs 328 13.4.1 Detection of Single Protein Molecules Through CNTs 329 13.4.2 Stem Cell Labeling and Tracking Through CNTs 330 13.4.3 Labelling and Tracking of Human Pancreatic Cells Through CNTs 330 13.4.4 CNT as Macrophage Carrying Microdevices 331 13.4.4.1 Intracellular Fluctuations and CNT 331 13.4.5 Limitations of CNTs 332 13.5 Concluding Remarks and Future Perspective 332 Important Links 333 Acknowledgment 333 References 333 14 Functionalized Carbon Nanotubes for Treatment of Various Diseases 339 Ajahar Khan, Khalid A. Alamry and Raed H. Althomali 14.1 Introduction 340 14.2 CNTs: Basic Structure, and Synthesis Methods 342 14.2.1 Structure and Synthesis of CNTs 342 14.2.2 Arc Discharge Technique 342 14.2.3 Laser Ablation Technique 342 14.2.4 Catalytic Chemical Vapor Deposition Technique 343 14.3 Functionalization of CNTs 343 14.3.1 Covalent Functionalization 344 14.3.2 Non-Covalent Functionalization 344 14.4 Toxicity/Bio-Safety Profile of Carbon Nanotubes 346 14.5 Investigating the Promising Biomedical Effects of Functionalized CNTs 349 14.5.1 Functionalized CNTs-Based Remediation of Infectious Diseases 350 14.5.2 Functionalized CNTs for the Treatment of Central Nervous System Disorders (CNS) 350 14.5.3 Functionalized CNTs for Gene Delivery 351 14.5.4 Implication of Functionalized CNTs in Cancer Diagnosis and Treatment 354 14.5.5 Functionalized CNTs for Drug Targeting and Release 357 14.6 Future Prospective 362 14.7 Conclusion 363 Important Websites 364 References 365 15 Role of Functionalized Carbon Nanotubes in Antimicrobial Activity: A Review 377 Monika Aggarwal, Samina Husain and Basant Kumar 15.1 Introduction 378 15.2 Introduction to CNTs 378 15.2.1 Classification of CNTs 379 15.2.2 Structure of CNTs 381 15.3 Overview on CNTs Functionalization 382 15.3.1 Types of Functionalization 384 15.4 Anti-Microbial Activity of f-CNTs: Interaction and Action 387 15.5 Antifungal Activity of f-CNTs 388 15.6 Antibacterial Activity of f-CNTs 390 15.6.1 For SWNTs 390 15.6.2 For MWCNTs 392 15.7 Commercial Application of Antimicrobial Activity of f-CNTs 400 15.8 Overview on Antimicrobial Activity of f-CNTs 401 15.9 Future Scope 405 15.10 Conclusion 405 Acknowledgement 406 References 406 Index 413

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Book SynopsisBioelectronics is a rich field of research involving the application of electronics engineering principles to biology, medicine, and the health sciences. With its interdisciplinary nature, bioelectronics spans state-of-the-art research at the interface between the life sciences, engineering and physical sciences.Table of ContentsAbout the Authors xiii Foreword xv Preface xvii Acknowledgements xix 1 Basic Chemical and Biochemical Concepts 1 1.1 Chapter Overview 1 1.2 Energy and Chemical Reactions 1 1.3 Water and Hydrogen Bonds 15 1.4 Acids, Bases and pH 18 1.5 Summary of Key Concepts 25 2 Cells and their Basic Building Blocks 29 2.1 Chapter Overview 29 2.2 Lipids and Biomembranes 29 2.3 Carbohydrates and Sugars 32 2.4 Amino Acids, Polypeptides and Proteins 34 2.5 Nucleotides, Nucleic Acids, DNA, RNA and Genes 43 2.6 Cells and Pathogenic Bioparticles 51 2.7 Summary of Key Concepts 70 3 Basic Biophysical Concepts and Methods 73 3.1 Chapter Overview 73 3.2 Electrostatic Interactions 74 3.3 Hydrophobic and Hydration Forces 90 3.4 Osmolarity, Tonicity and Osmotic Pressure 91 3.5 Transport of Ions and Molecules across Cell Membranes 94 3.6 Electrochemical Gradients and Ion Distributions Across Membranes 99 3.7 Osmotic Properties of Cells 103 3.8 Probing the Electrical Properties of Cells 105 3.9 Membrane Equilibrium Potentials 111 3.10 Nernst Potential and Nernst Equation 112 3.11 The Equilibrium (Resting) Membrane Potential 114 3.12 Membrane Action Potential 116 3.13 Channel Conductance 120 3.14 The Voltage Clamp 121 3.15 Patch-Clamp Recording 122 3.16 Electrokinetic Effects 124 4 Spectroscopic Techniques 147 4.1 Chapter Overview 147 4.2 Introduction 148 4.3 Classes of Spectroscopy 151 4.4 The Beer-Lambert Law 165 4.5 Impedance Spectroscopy 170 5 Electrochemical Principles and Electrode Reactions 177 5.1 Chapter Overview 177 5.2 Introduction 178 5.3 Electrochemical Cells and Electrode Reactions 180 5.4 Electrical Control of Electron Transfer Reactions 194 5.5 Reference Electrodes 203 5.6 Electrochemical Impedance Spectroscopy (EIS) 208 6 Biosensors 215 6.1 Chapter Overview 215 6.2 Introduction 215 6.3 Immobilisation of the Biosensing Agent 217 6.4 Biosensor Parameters 218 6.5 Amperometric Biosensors 228 6.6 Potentiometric Biosensors 233 6.7 Conductometric and Impedimetric Biosensors 237 6.8 Sensors Based on Antibody–Antigen Interaction 240 6.9 Photometric Biosensors 242 6.10 Biomimetic Sensors 245 6.11 Glucose Sensors 247 6.12 Biocompatibility of Implantable Sensors 252 7 Basic Sensor Instrumentation and Electrochemical Sensor Interfaces 259 7.1 Chapter Overview 259 7.2 Transducer Basics 260 7.3 Sensor Amplification 262 7.4 The Operational Amplifier 264 7.5 Limitations of Operational Amplifiers 269 7.6 Instrumentation for Electrochemical Sensors 271 7.7 Impedance Based Biosensors 278 7.8 FET Based Biosensors 284 8 Instrumentation for Other Sensor Technologies 297 8.1 Chapter Overview 297 8.2 Temperature Sensors and Instrumentation 298 8.3 Mechanical Sensor Interfaces 304 8.4 Optical Biosensor Technology 325 8.5 Transducer Technology for Neuroscience and Medicine 335 9 Microfluidics: Basic Physics and Concepts 343 9.1 Chapter Overview 343 9.2 Liquids and Gases 343 9.3 Fluids Treated as a Continuum 346 9.4 Basic Fluidics 354 9.5 Fluid Dynamics 356 9.6 Navier-Stokes Equations 365 9.7 Continuum versus Molecular Model 369 9.8 Diffusion 378 9.9 Surface Tension 383 10 Microfluidics: Dimensional Analysis and Scaling 391 10.1 Chapter Overview 391 10.2 Dimensional Analysis 391 10.3 Dimensionless Parameters 400 10.4 Applying Nondimensional Parameters to Practical Flow Problems 411 10.5 Characteristic Time Scales 412 10.6 Applying Micro- and Nano-Physics to the Design of Microdevices 413 Problems 415 References 416 Appendix A: SI Prefixes 417 Appendix B: Values of Fundamental Physical Constants 419 Appendix C: Model Answers for Self-study Problems 421 Index 435

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Book SynopsisCOMPUTATIONAL INTELLIGENCE IN BIOPRINTING The book provides a comprehensive exploration of the evolving field of bioprinting in regenerative medicine and is an essential guide for professionals seeking a thorough understanding of the field. Computational Intelligence in Bioprinting provides a comprehensive overview of the evolving field of bioprinting in reformative medicine, defining the process of printing structures using viable cells, biomaterials, and living molecules. The primary goal is to provide substitutes for tissue implants, which might lead to eliminating the requirement for organ donors, as well as to transform animal testing for the learning and analysis of disease and the growth of treatments. The book offers a comprehensive overview of bioprinting technologies and their applications, emphasizing the integration of computation intelligence, artificial intelligence, and other computer science advancements in the field. By harnessing the power

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Book SynopsisThis book is a comprehensive exploration of bio-inspired optimization techniques and their potential applications in healthcare. Bio-Inspired Optimization for Medical Data Mining is a groundbreaking book that delves into the convergence of nature's ingenious algorithms and cutting-edge healthcare technology. Through a comprehensive exploration of state-of-the-art algorithms and practical case studies, readers gain unparalleled insights into optimizing medical data processing, enabling more precise diagnosis, optimizing treatment plans, and ultimately advancing the field of healthcare. Organized into 15 chapters, readers learn about the theoretical foundation of pragmatic implementation strategies and actionable advice. In addition, it addresses current developments in molecular subtyping and how they can enhance clinical care. By bridging the gap between cutting-edge technology and critical healthcare challenges, this book is a pivotal contribution, providing a r

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Book SynopsisThis book provides a comprehensive exploration of the exciting intersection between technology and biology and delves into the principles, applications, and future directions of IoT in the realm of bioelectronics; it serves as both an introduction for those new to the field and as a detailed reference for experienced professionals seeking to deepen their knowledge. The rapid convergence of technology and biology heralds a new era of evolution in the Internet of Things (IoT), a transformative force enabling interconnected devices to communicate and operate with unparalleled synergy. This is particularly true in the groundbreaking field of bioelectronics, where the fusion of biological systems with electronic devices and IoT is reshaping the landscape of bioelectronics, promising to open up new frontiers in healthcare, diagnostics, and personalized medicine. This timely book explores the numerous ways in which IoT-enabled bioelectronic devices are used to monitor and enhance human health

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Book SynopsisThis book covers a wide range of advanced techniques and approaches for designing and implementing computationally intelligent methods in different application domains which is of great use to not only researchers but also academicians and industry experts. Optimized Computational Intelligence (OCI) is a new, cutting-edge, and multidisciplinary research area that tackles the fundamental problems shared by modern informatics, biologically-inspired computation, software engineering, AI, cybernetics, cognitive science, medical science, systems science, philosophy, linguistics, economics, management science, and life sciences. OCI aims to apply modern computationally intelligent methods to generate optimum outcomes in various application domains. This book presents the latest technologies-driven material to explore optimized various computational intelligence domains. includes real-life case studies highlighting different advanced technologies in computational intellig

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Book SynopsisBiotechnology has become one of the most important issues in public policy and governance, altering the boundaries between the public and the private, the economic and the social, and further complicating the divide between what is scientifically possible and ethically preferred. Given the importance of biotechnology in shaping relations between the state, science, the economy, and the citizenry, a book that explores the Canadian biotechnology regime and its place in our democracy is timelier than ever.Three Bio-Realms provides the first integrated examination of the thirty-year story of the democratic governance of biotechnology in Canada. G. Bruce Doern and Michael J. Prince, two recognized specialists in governance innovation and social policy, look at particular ‘network-based’ factors that seek to promote and to regulate biotechnology inside the state as well as at broader levels. Unmatched by any other book in its historical scope and range, ThrTable of ContentsPreface Abbreviations List of Tables INTRODUCTION: THREE REALMS OF BIOTECHNOLOGY Purposes and Contribution The Three Bio-Realms and Related Products and Processes Main Arguments Foundational Concepts and Analytical Framework Structure of the Book PART I: ANALYTICAL FRAMEWORK AND HISTORICAL POLICY CONTEXT CHAPTER 1- THE STATE, NETWORKED DEMOCRACY AND SCIENCE-BASED GOVERNANCE Introduction Conceptual Foundations * Governance and Regulation* Networked Democracy and Interests* The Nature of Biotechnology and Science-based Governance The Analytical Framework: Three Core Elements * The State as Biotech Supporter and Biotech Regulator* Networked Biotech Governance Interests and Democracy* Science-based and Precautionary Governance Conclusions CHAPTER 2- NATIONAL AND INTERNATIONAL BIOTECHNOLOGY POLICY IN LIBERAL AND CONSERVATIVE GOVERNMENT ERAS Introduction Biotech Policy in the Trudeau and Mulroney Eras: Early Support and Major Trade and Patent Policy Impacts Biotech Policy in the Chretien Liberal Era: Towards Better Balance amidst Extended Trade and Precautionary Norms Biotech Policy in the Chretien, Martin and Harper Eras Since 2000: Towards a Genome-Centred Bio-Economy? The Core Politics Underlying International Biotech Policy Conclusions PART II: EMPIRICAL ANALYSIS OF THE CHANGING BIOTECH-GOVERNANCE REGIME CHAPTER 3: SCIENCE AND SUPPORTIVE GOVERNANCE Introduction Federal and Related Biotech Research Agencies: Networked Governance, Support and Research Conduct * National Research Council (NRC)* The Granting Councils' Networks of Centres of Excellence* Canada Foundation for Innovation* The Canadian Institutes of Health Research (CIHR)* Genome Canada Biotech Policy and Advisory Bodies and Arenas of Partial Support, Debate, Criticism and Engagement * Industry Canada and Its Innovation and Related Intellectual Policy Agenda* Engaging Ministers in The Interdepartmental Bio-Policy and Bio-Governance Structure* CBAC, External Advice and Governance Through Citizen Engagement* Periodic Parliamentary and Opposition Party Involvement, Criticism and Inquiries. Biotech Policy and the Search for Technology Assessment Arenas Conclusions CHAPTER 4 - THE BIO-FOOD REALM: BUSINESS DOMINATED PLURALISTC POWER Introduction Bio-Food Regulation Making: Initial Design and Congealment under Institutionalized Pluralistic Power Pre-Market Bio-Food Product Assessment and Approvals under Novel Food Concepts and Regulations Product Regulation on Research on Plants with Novel Traits (PNT) and Potential Unconfined Environmental Release Bio-Food Post Market Regulatory Monitoring Conclusions CHAPTER 5- THE BIO-HEALTH REALM: NETWORKED POWER AND GOVERANCE Introduction Changing Bio-Health Regulation and Related Policy Development Pre-Market Assessment and Approvals of Biologics and Genetic Therapies Post Market Regulatory Monitoring and Assessment for Funding under Medicare and Health Care Plans Conclusions CHAPTER 6- THE BIO-LIFE REALM: PLAYING CATCH-UP WITH SELF-DISCIPLINED POWER RELATIONS Introduction Bio-life Civic Regulation, Bio-Power and Bio-Politics Bio-life Regulation and Rule-Making Regulating Bio-life Products and Activities: The Case of Assisted Human Reproduction Inspection, Enforcement and Post- Monitoring Bio-life Activities Outstanding Issues, Genetic Testing, AHRA Inertia and the Politics of Implementation Conclusions CHAPTER 7- POWER, CHANGING BIOTECH GOVERNANCE AND EXTENDING DEMOCRACY Introduction Key Arguments and Related Explanations of Biotechnology Governance Regime Change Biotechnology Governance Challenges and Extending Democracy REFERENCES

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Book SynopsisBiotechnology has become one of the most important issues in public policy and governance, altering the boundaries between the public and the private, the economic and the social, and further complicating the divide between what is scientifically possible and ethically preferred. Given the importance of biotechnology in shaping relations between the state, science, the economy, and the citizenry, a book that explores the Canadian biotechnology regime and its place in our democracy is timelier than ever.Three Bio-Realms provides the first integrated examination of the thirty-year story of the democratic governance of biotechnology in Canada. G. Bruce Doern and Michael J. Prince, two recognized specialists in governance innovation and social policy, look at particular ‘network-based’ factors that seek to promote and to regulate biotechnology inside the state as well as at broader levels. Unmatched by any other book in its historical scope and range, ThrTable of ContentsPreface Abbreviations List of Tables INTRODUCTION: THREE REALMS OF BIOTECHNOLOGY Purposes and Contribution The Three Bio-Realms and Related Products and Processes Main Arguments Foundational Concepts and Analytical Framework Structure of the Book PART I: ANALYTICAL FRAMEWORK AND HISTORICAL POLICY CONTEXT CHAPTER 1- THE STATE, NETWORKED DEMOCRACY AND SCIENCE-BASED GOVERNANCE Introduction Conceptual Foundations * Governance and Regulation* Networked Democracy and Interests* The Nature of Biotechnology and Science-based Governance The Analytical Framework: Three Core Elements * The State as Biotech Supporter and Biotech Regulator* Networked Biotech Governance Interests and Democracy* Science-based and Precautionary Governance Conclusions CHAPTER 2- NATIONAL AND INTERNATIONAL BIOTECHNOLOGY POLICY IN LIBERAL AND CONSERVATIVE GOVERNMENT ERAS Introduction Biotech Policy in the Trudeau and Mulroney Eras: Early Support and Major Trade and Patent Policy Impacts Biotech Policy in the Chretien Liberal Era: Towards Better Balance amidst Extended Trade and Precautionary Norms Biotech Policy in the Chretien, Martin and Harper Eras Since 2000: Towards a Genome-Centred Bio-Economy? The Core Politics Underlying International Biotech Policy Conclusions PART II: EMPIRICAL ANALYSIS OF THE CHANGING BIOTECH-GOVERNANCE REGIME CHAPTER 3: SCIENCE AND SUPPORTIVE GOVERNANCE Introduction Federal and Related Biotech Research Agencies: Networked Governance, Support and Research Conduct * National Research Council (NRC)* The Granting Councils' Networks of Centres of Excellence* Canada Foundation for Innovation* The Canadian Institutes of Health Research (CIHR)* Genome Canada Biotech Policy and Advisory Bodies and Arenas of Partial Support, Debate, Criticism and Engagement * Industry Canada and Its Innovation and Related Intellectual Policy Agenda* Engaging Ministers in The Interdepartmental Bio-Policy and Bio-Governance Structure* CBAC, External Advice and Governance Through Citizen Engagement* Periodic Parliamentary and Opposition Party Involvement, Criticism and Inquiries. Biotech Policy and the Search for Technology Assessment Arenas Conclusions CHAPTER 4 - THE BIO-FOOD REALM: BUSINESS DOMINATED PLURALISTC POWER Introduction Bio-Food Regulation Making: Initial Design and Congealment under Institutionalized Pluralistic Power Pre-Market Bio-Food Product Assessment and Approvals under Novel Food Concepts and Regulations Product Regulation on Research on Plants with Novel Traits (PNT) and Potential Unconfined Environmental Release Bio-Food Post Market Regulatory Monitoring Conclusions CHAPTER 5- THE BIO-HEALTH REALM: NETWORKED POWER AND GOVERANCE Introduction Changing Bio-Health Regulation and Related Policy Development Pre-Market Assessment and Approvals of Biologics and Genetic Therapies Post Market Regulatory Monitoring and Assessment for Funding under Medicare and Health Care Plans Conclusions CHAPTER 6- THE BIO-LIFE REALM: PLAYING CATCH-UP WITH SELF-DISCIPLINED POWER RELATIONS Introduction Bio-life Civic Regulation, Bio-Power and Bio-Politics Bio-life Regulation and Rule-Making Regulating Bio-life Products and Activities: The Case of Assisted Human Reproduction Inspection, Enforcement and Post- Monitoring Bio-life Activities Outstanding Issues, Genetic Testing, AHRA Inertia and the Politics of Implementation Conclusions CHAPTER 7- POWER, CHANGING BIOTECH GOVERNANCE AND EXTENDING DEMOCRACY Introduction Key Arguments and Related Explanations of Biotechnology Governance Regime Change Biotechnology Governance Challenges and Extending Democracy REFERENCES

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Book SynopsisBioCoder is a quarterly newsletter for DIYbio, synthetic bio, and anything related. You'll discover: Articles about interesting projects and experiments, such as the glowing plantArticles about tools, both those you buy and those you buildVisits to DIYbio laboratoriesProfiles of key people in the communityAnnouncements of events and other items of interestSafety pointers and tips about good laboratory practiceAnything that's interesting or useful: you tell us!And BioCoder is free (for the time being), unless you want a dead-tree version. We'd like BioCoder to become self supporting (maybe even profitable), but we'll worry about that after we've got a few issues under our belt.If you'd like to contribute, send email to BioCoder@oreilly.com. Tell us what you'd like to do, and we'll get you started.

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Book SynopsisLab Manual for Biomedical Engineering: Devices and Systems examines key concepts in biomedical systems and signals in a laboratory setting. The book gives students the opportunity to complete both measurement and math modeling exercises, thus demonstrating that the experimental real-world setting directly corresponds with classroom theory.All the experiments in the lab manual have been extensively class-tested and cover concepts such as wave math, Fourier transformation, electronic and random noise, transfer functions, and systems modeling. Each experiment builds on knowledge acquired in previous experiments, allowing the level of difficulty to increase at an appropriate pace. In completing the lab work, students enhance their understanding of the lecture course.The third edition features expanded exercises, additional sample data and measurements, and lab modifications for increased ease and simple adaptation to the online teaching and learning environment. Individual activities have also been added to aid with independent learning.Lab Manual for Biomedical Engineering is ideal for undergraduate courses in biomedical engineering comprised of students who have completed introductory electrical and mechanical physics courses. A two-semester background in calculus is recommended.

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Book SynopsisResveratrol (3,5,4'-trihydroxy-trans-stilbene) is a phenol phytoalexin derived from grapes, berries, and other plants possessing a spectrum of pharmacologic properties. Resveratrol has been shown to modulate LDL levels, a major risk factor for cardiovascular disease, to interfere with or inhibit oncogenesis and tumor proliferation in in vivo animal cancer models and in human tumor cells in vitro, to significantly extend the lifespan of the yeastSaccharomyces cerevisiae, Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and to produce wide-ranging benefits in animal models of obsesity and diabetes.Resveratrol has gained mainstream attention as “the red wine pill,” with widespread claims made of human health benefits that have outpaced the existing evidence. Over the past few years, many clinical trials have been conducted to evaluate the health effects of resveratrol in humans, in the treatment of cancer, cardiovascular disease, obesity, diabetes, osteopenia and osteoporosis, and others. Considerable work is also underway exploring the optimization of resveratrol delivery and bioavailability in nutraceutical and pharmaceutical paradigms. NOTE: Annals volumes are available for sale as individual books or as a journal. For more information on institutional journal subscriptions, please visit: http://ordering.onlinelibrary.wiley.com/subs.asp?ref=1749-6632&doi=10.111/(ISSN)1749-6632 ACADEMY MEMBERS: Please contact the New York Academy of Sciences directly to place your order (www.nyas.org). Members of the New York Academy of Science receive full-text access to Annals online and discounts on print volumes. Please visit http://www.nyas.org/MemberCenter/Join.aspx for more information on becoming a member.

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Book SynopsisWorld populations are increasing, as are pathogens capable of causing human disease. These infectious diseases contribute to global "wicked problems". As infection numbers rise, and dangerous pathogens evolve, the complexity of these problems increase. Current biotechnological advances can be used to design more effective methods of combatting infectious diseases, and this book documents a core set of infectious agents, as a method of describing ways to update diagnostic and therapeutic tools. The book begins with an introduction to the pathogenic mechanisms displayed by various diseases. Pathogen descriptions of are followed up by such topics as use assays for low-level detection, application of nanosized agents for drug delivery, and design of vaccines for emerging infections, including Ebola and Zika. New technologies are being developed as fast as infectious evolve. The key to taming these wicked pathogens will be in finding commonalities between organisms and applying biotechnological advances.

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Book SynopsisBiotechnology is a fascinating interdisciplinary field uniquely poised to take on some of the world's most complex problems. With this thesis at its core, Modern Biotechnology takes a refreshing problems-based approach to exploring the field. The novice will come away with a broad appreciation for the significance of current and emerging biotechnologies - from regenerative medicine, to genetically enhanced crops, to biofuels. Experts will benefit from the concise review of timely game-changing technologies such as DNA sequence-by-synthesis and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease-mediated genome editing technologies. Despite being set within a conceptual framework of "wicked" problems (i.e., disease, food production, environmental spoilage), insights into the current state and future potential of biotechnologies make this book both optimistic and forward thinking. This is not just an informative text, it's a jumping off point for engaging with a discipline that has the potential to change the world.

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Book SynopsisConcise, yet comprehensive, coverage of various endoscopic forms as provided in this book will help the reader generate new knowledge in this field. Endoscopy has been in practice for many years in diagnostic medicine. From a simple image collection device, the endoscope has grown into an instrument that incorporates multiple imaging modalities to extract structural and functional information from different parts of the human body. Multimodality endoscopes are discussed in detail in this book, along with their clinical applications. The book is intended for graduate-level students as a quick reference to understand the evolving trends in endoscopic design research. The challenges that remain unaddressed could potentially be explored by biomedical researchers to advance this technology to realize the concept of optical biopsy during routine endoscopic examinations. The book portrays the endoscope as a purely optical instrument, and hence hybrid modes of endoscopic imaging are not covered.

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Book SynopsisThe past five decades have witnessed a rapid growth of computer models for simulating ecosystem functions and dynamics. This has been fuelled by the availability of remote sensing data, computation capability, and cross-disciplinary knowledge. These models contain many submodules for simulating different processes and forcing mechanisms, albeit it has become challenging to truly understand the details due to their complexity. Most ecosystem models, fortunately, are rooted in a few core biophysical foundations, such as the widely recognized Farquhar model, Ball-Berry-Leuning and Medlyn family models, Penman-Monteith equation, Priestley-Taylor model, and Michaelis-Menten kinetics.an introduction of biophysical essentials, four chapters present the core algorithms and their behaviors in modeling ecosystem production, respiration, evapotranspiration, and global warming potentials. Each chapter is composed of a brief introduction of the literature, in which model algorithms, their assumptions, and performances are described in detail. Spreadsheet (or Python codes) templates are included in each chapter for modeling exercises with different input parameters as online materials, which include datasets, parameter estimation, and real-world applications (e.g., calculations of global warming potentials). Users can also apply their own datasets. The materials included in this volume serve as effective tools for users to understand model behaviours and uses with specified conditions and in situ applications.

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Book SynopsisOver the course of the last few decades, the incorporation of genetics, genomics, proteomics, and statistics into the field of bioinformatics has had a significant impact on both the field of biology and the field of medicine. The primary application for it is in assisting with the modeling, forecasting, and analysis of enormous amounts of multidimensional biological data utilizing the most recent and cutting-edge computational technologies. The majority of life science students and researchers do not have the skills necessary to make effective use of this sophisticated technology, which is why bioinformatics is not yet widely incorporated in academic courses despite the fact that it holds enormous promise. This book was written after realizing that there was a void in the market for a resource that could provide students and researchers with prior knowledge of the biosciences with a place to begin their studies. The book is an excellent resource that students and young professionals can use in their pursuit of knowledge on this ever-changing topic.Table of Contents Chapter 1 Elements of Biology Chapter 2 History of Bioinformatics Chapter 3 Integral Component of Bioinformatics Chapter 4 Types of Biological Data? Chapter 5 Tools for DNA Analysis Chapter 6 Tools for RNA Analysis Chapter 7 Tools for Protein Analysis Chapter 8 Bioinformatics Databases and Tools for Whole Genome Analysis Chapter 9 Main Challenges in the Field of Bioinformatics Chapter 10 Applications of Bioinformatics

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Book SynopsisThis comprehensive book covers the underlying scientific principles, state-of-the-art technologies and methodologies of plant mutagenesis. It covers historical development and commonly used terminologies, chemical and physical mutagenesis, mutation induction, mutation breeding and mutations in functional genomics research. Suitable both as a manual for professionals and a resource for students in plant breeding and research, the book includes exemplary cases of practical applications and an appendix of recommended doses of gamma and fast neutron irradiation for almost 200 plant species.Table of ContentsSECTION I: Concepts, Historical Development and Genetic Basis 1: Plant Mutagenesis in Crop Improvement: Basic Terms and Applications 2: A Brief History of Plant Mutagenesis 3: The Structure and Regulation of Genes and Consequences of Genetic Mutations 4: Mutation Categories 5: DNA Repair Pathways and Genes in Plant 6: Double-Stranded DNA Break, Repair and Associated Mutations SECTION II: Mutagens and Induced Mutagenesis 7: Mutagenic Radiations: X-Rays, Ionizing Particles and Ultra Violet 8: Gamma Irradiation 9: Ion Beam Radiation Mutagenesis 10: Ion Implantation Mutagenesis 11: Effects of Radiation on Living Cells and Plants 12: Chemical Mutagenesis 13: Sodium Azide as a Mutagen SECTION III: Mutation Induction and Mutant Development 14: Methodology for Physical and Chemical Mutagenic Treatments 15: Chimeras and Mutant Gene Transmission 16: Chimeras: Properties and Dissociation in Vegetatively Propagated Plants 17: Mutation Induction in Cytoplasmic Genomes 18: Strategies and Approaches in Mutant Population Development for Mutant Selection in Seed Propagated Crops 19: Irradiation - Facilitated Chromosomal Translocation: Wheat As An Example 20: Molecular Techniques and Methods for Mutation Detection and Screening in Plants 21: Discovery of Chemically Induced Mutations by TILLING 22: A Protocol for TILLING and EcoTILLING 23: Applications of DNA Marker Techniques in Plant Mutation Research SECTION IV: Mutation Breeding 24: Principles and Applications of Plant Mutation Breeding 25: Mutant Phenotyping and Pre-Breeding in Barley 26: Mutation Breeding of Vegetatively Propagated Crops 27: Uses of TILLING® For Crop Improvement 28: Applications of in vitro Techniques in Mutation Breeding of Vegetatively Propagated Crops 29: Haploid Mutagenesis 30: Use of Irradiated Pollen to Induce Parthenogenesis and Haploid Production in Fruit Crops 31: Herbicide - Tolerant Crops Developed from Mutations 32: Mutation Breeding for Fatty Acid Composition in Soybean 33: Genetic Improvement of Basmati RiceThrough Mutation Breeding 34: Mutation Breeding of Sweet Cherry (Prunus avium L.) var. 0900 Ziraat SECTION V: Mutations in Functional Genomics 35: Cloning Genes for Mineral Uptake: Examples Using Rice Mutants 36: Molecular Genetics of Symbiotic Plant-Microbe Interactions in a Model Legume, Lotus Japonicus 37: Mutational Dissection of the Phytochrome Genetic Systems in Rice 38: T-DNA Insertion Mutagenesis 39: Transposon Mutagenesis for Functional Genomics 40: Site-Directed Mutagenesis in Higher Plants 41: Phenomics in Plant Biological Research and Mutation Breeding"

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Book SynopsisDescribing recent developments in the engineering and generation of plants as production platforms for biopharmaceuticals, this book includes both vaccines and monoclonal antibodies. It has a particular emphasis on targeting diseases which predominate in less developed countries, encompassing the current state of technologies and describing expression systems and applications. This book also includes a variety of vaccine case studies, protecting against pervasive infectious diseases such as rabies, influenza and HIV.Table of Contents1: Introduction, and the Promise of a Plant-derived Vaccine for Hepatitis B Virus 2: Protein Body-inducing Fusions for Recombinant Protein Production in Plants 3: Expression of Recombinant Proteins in Plant Cell Culture 4: Plant-derived Monoclonal Antibodies as Human Biologics for Infectious Disease and Cancer 5: Plant-produced Virus-like Particles 6: Expression of the Capsid Protein of Human Papillomavirus in Plants as an Alternative for the Production of Vaccines 7: Patenting of Plant-made Recombinant Pharmaceuticals and Access in the Developing World 8: Case Study 1: Rabies 9: Case Study 2: Plant-made HIV Vaccines and Neutralizing Antibodies 10: Case Study 3: The Search for a Plant-made Vaccine for Pandemic Influenza Virus

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Book SynopsisBiotechnology of Major Cereals focuses on the recent advances and future prospects in cereal biotechnology. The first part of the book covers the world's major cereals and focus on new developments and trends. The second part is technology rather than species-led, detailing fundamental developments in technologies and significant target traits.Table of Contents1: Biotechnology of Major Cereals 2: Genetic Transformation of Maize: Conventional Methods and Precision Genome Modification 3: Biotech Maize: Industry Development & Impact 4: Sorghum Genetic Transformation: Current Status and Future Target Traits 5: Barley as a Cereal Model for Biotechnology Applications 6: Wheat Biotechnology; Recent Developments and Future Trends 7: The Long and Winding Road of Rice Genetic Modification Technology and its Potential 8: Setaria Viridis; A Model for C4 Crop Biotechnology 9: Genome Editing in Cereals 10: Anther Culture for Doubled Haploids 11: Chloroplast Transformation in Cereals 12: Cross-species Silencing: Plant-mediated RNAi for Insect Control 13: Acrylamide in Cereals: The Problem and Potential Genetic and Agronomic Solutions 14: Engineering Cereal Endosperm 15: Key molecular and Metabolic Processes used for Genetic Engineering to Improve Freezing 16: Mergers and Acquisitions in Global Ag-Biotech

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Book SynopsisMicrobial technology plays an integral role in the biotechnology, bioengineering, biomedicine/biopharmaceuticals and agriculture sector. This book provides a detailed compendium of the methods, biotechnological routes, and processes used to investigate different aspects of microbial resources and applications. It covers the fundamental and applied aspects of microorganisms in the health, industry, agriculture and environmental sectors, reviewing subjects as varied and topical as pest control, health and industrial developments and animal feed.Trade ReviewEdited by one of the most renowned experts in bioprocesses, [this book] is extremely opportune not just to meet a growing demand in the sector, but also for its comprehensiveness and indisputable competence. --Professor Helen Treichel"Table of Contents-: Foreword 1: Microbial Resources for Improved Crop Productivity 2: The contributions of mycorrhizal fungi 3: Trichoderma: Utilization for Agriculture Management and Biotechnology 4: The Role of Bacillus Bacterium in Formation of Plant Defence: Mechanism and Reaction 5: Biofilm Formation on Plant Surface by Rhizobacteria: Impact on Plant Growth and Ecological Significance 6: Biofilmed Biofertilizers Application in Agroecosystems 7: Microbial nanoformulation: Exploring potential for coherent nano-farming 8: Bacillus thuringiensis: A Natural Tool in the Insect Pest Control 9: Pleurotus as an Exclusive Eco-Friendly Modular Bio-Tool 10: Use of Biotechnology in Promoting Novel Food and Agriculture Important Microorganisms 11: Endophytes: An Emerging Microbial Tool for Plant Diseases Management 12: Role of L: monocytogenes in Human Health: Disadvantages and Advantages 13: Natural Weapons against Cancer From Bacteria 14: Giardia and Giardiasis: An Overview On Recent Developments 15: Power of Bifidobacteria in Food Applications for the Health Promotion 16: Probiotic and Dental Carries: A Recent Outlook on Conventional Therapy 17: Human Microbiota for Human Health 18: Biotechnological Production of Polyunsaturated Fatty Acids 19: Functional Enzymes for Animal Feed Applications 20: Microbial Xylanases: Production, Applications and Challenges 21: Microbial Chitinase: Production and Potential Applications 22: Characteristics of microbial inulinases: physical and chemical bases of their activity 23: Microbial Resources for Biopolymer Production 24: Microbial Metabolites in Cosmetic Industries 25: Fungi of the Genus Pleurotus: Importance and Applications 26: Useful Microorganisms for Environmental Sustainability: Application of Heavy Metal Tolerant Consortia for Surface Water Decontamination in Natural and Artificial Wetlands 27: Exopolysaccharide (EPS) producing bacteria: an ideal source of biopolymers 28: Microbial Process Development for Fermentation Based Biosurfactant Production 29: Recent Developments on Algal Biofuel Technology 30: Microbial lipases: Emerging Biocatalyst 31: Bioremediation of Gaseous and Liquid Hydrogen Sulfide Pollutants by Microbial Oxidation 32: Archaea, A Useful Group for Energy Unconventional Production: Methane Production from Sugarcane Secondary Distillation Effluents Using Thermotolerant Strains 33: Industrial Additives Obtained Through Microbial Biotechnology: Biosurfactants and Prebiotics Carbohydrates 34: Industrial Additives Obtained Through Microbial Biotechnology: Bioflavors and Biocolorants 35: Actinomycetes in Biodiscovery: Genomic Advances and New Horizons 36: Molecular Strategies for the Studies of the Expression of Gene Variation by Real-time PCR 37: Whole Genome Sequence Typing Strategies for Enterohemorrhagic Escherichia coli of the O157:H7 Serotype 38: Microbial Keratinases: Characteristics, Biotechnological Applications and Potential 39: Philippine Fungal Diversity: Benefits and Threats to Food Security

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Book SynopsisThis book integrates a science and business approach to provide an introduction and an insider view of intellectual property issues within the biotech industry, with case studies and examples from developing economy markets. Broad in scope, this book covers key principles in pharmaceutical, industrial, and agricultural biotechnology within four parts. Part 1 details the principles of intellectual property and biotechnology. Part 2 covers plant biotechnology, including biotic and abiotic stress tolerance, GM foods in sustainable agriculture, microbial biodiversity and bioprospecting for improving crop health and productivity, and production and regulatory requirements of biopesticides and biofertilizers. The third part describes recent advances in industrial biotechnology, such as DNA patenting, and commercial viability of the CRISPR/Cas9 system in genome editing. The final part describes intellectual property issues in drug discovery and development of personalized medicine, and vaccines in biodefence. This book is an ideal resource for all postgraduates and researchers working in any branch of biotechnology that requires an overview of the recent developments of intellectual property frameworks in the biotech sector.Table of ContentsPart 1: Biotechnology and Intellectual Property Issues 1: Biotechnology in Agriculture, Medicine and Industry: An Overview 2: Biotechnology and its Development in Developing Countries: Can IPR’s Foster Innovation in the Field? 3: Patent Eligibility Issues in Life Science Innovations: Contentious Court Cases 4: Checks and Balances in Biotechnology Related Patents: In Agreement to the Indian Patents (Amendment) Act, 2005 5: Intellectual Property in Biotechnology Sector. The Importance of “Star Scientists” in the Entrepreneurship and Universities Environment Part 2: Intellectual Property Issues in Agricultural Biotechnology 6: Intellectual Property in Agricultural Biotechnology: From Patent Thickets to Generics 7: Bioprospecting for Improving Soil Health and Crop Productivity: Indian Patent Landscape 8: Seeds of Change: Genetically Modified Crops, Canada’s Agricultural Growth Act and the Erosion of Farmers’ Privilege 9: Recent Innovations in Agricultural Biotechnology: Challenging the Status Quo 10: Chinese Innovation System: The Case of Agricultural Knowledge Sharing 11: IPR Regime for Agricultural Biotechnology in India Part 3: Intellectual Property Issues in Industrial Biotechnology 12: DNA Patenting 13: The Development of Patentability of Genetic Patent in Mainland China and Taiwan 14: Bioprospecting Microbial Diversity: IPR Issues 15: CRISPR/Cas9 system, A Revolutionary Technology for Genome Editing: Applications and IP Disputes Part 4: Intellectual Property Issues in Pharmaceutical Biotechnology 16: Healthcare Innovation, Personalization, and the Patent System: Where is the Public Interest? 17: Patentability of Human Embryo Stem Cell: A Comparative Analyse of Case WARF in United States and Europe 18: Innovation and Intellectual Property Issues in the “Decade of Vaccines”: a Brazilian Perspective 19: Promoting Access To Health Care Through Biosimilars: Addressing Intellectual Property Rights And Regulatory Barriers 20: Changing Paradigm for IPR Protection in Drug Discovery Research: Where India Stands 21: Intellectual Property Rights in Drug Development and Biotechnology 22: Leishmaniasis: Drug Development and IP Issues

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Book SynopsisPlant gene silencing is a crucially important phenomenon in gene expression and epigenetics. This book describes the way small RNA is produced and acts to silence genes, its likely origins in defence against viruses, and also its potential to improve plants. Plant gene silencing can be used to improve industrial traits, make plants more nutritious or more valuable to consumers, to remove allergens, and to improve resistance to weeds and pathogens.Table of Contents1: Diversity of RNA Silencing Pathways in Plants 2: Induction and Suppression of Silencing by Plant Viruses 3: Artificial Induction and Maintenance of Epigenetic Variations in Plants 4: Gene Silencing in Archaeplastida Algae 5: Gene Silencing in Fungi: A Diversity of Pathways and Functions 6: Artificial Small RNA-based Strategies for Effective and Specific Gene Silencing in Plants 7: Application of RNA Silencing in Improving Plant Traits for Industrial Use 8: Increasing Nutritional Value by RNA Silencing 9: RNA-based Control of Plant Diseases: A Case Study with Fusarium graminearum 10: Targeting Nematode Genes by RNA Silencing 11: Gene Silencing Provides Efficient Protection against Plant Viruses

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Book SynopsisThis book covers the biotechnology of all the major perennial fruit and nut species. Since the publication of the first edition of this book in 2005, there has been significant progress in cell culture, genomics and genetic transformation for many of these species. This book covers these biotechnologies and also traditional ones, such as regeneration pathways, protoplast culture, in vitro mutagenesis, and ploidy manipulation that have been applied to many of these species. Three species, Diospyros kaki (persimmon), Punica granatum (pomegranate) and Eriobotrya japonica (loquat) are included for the first time, and several Prunus species now receive separate coverage. The species are organized by plant family to facilitate comparisons among related ones. Each species is discussed in relation to its family and its related wild forms, and most are accompanied by full colour illustrations. This book is a vital resource for those working on the improvement of perennial fruit, nut and plantation crops. The book features: Detailed coverage of major perennial fruit and crop species. Coverage of traditional and new biotechnologies. Full colour illustrations to aid identification This book is an essential resource for scientists and postgraduate students who are engaged in the improvement of perennial fruit, nut and plantation crops and will also be an important accession for university and agricultural research libraries.Table of Contents1: Actinidiaceae 1.1: Actinidia deliciosa Kiwifruit 2: Anacardiaceae 2.1: Anacardium occidentale Cashew 2.2: Mangifera indica L. Mango 2.3: Pistacia vera L. Pistachio 3: Annonaceae 3.1: Annona squamosa Sugar Apple, Annona cherimola Cherimoya and Annona muricata Soursop 4: Arecaceae 4.1: Cocos nucifera L. Coconut 4.2: Elaeis guineensis Oil Palm 4.3: Phoenix dactylifera L. Date Palm 5: Bromeliaceae 5.1: Ananas comosus Pineapple 6: Caricaceae 6.1: Carica papaya L. Papaya 7: Clusiaceae 7.1: Garcinia mangostana Mangosteen 8: Ebenaceae 8.1: Diospyros kaki Persimmon 9: Ericaceae 9.1: Vaccinium spp. Blueberry and Cranberry 10: Fagaceae 10.1: Castanea spp. Chestnut 11: Juglandaceae 11.1: Carya illinoensis Pecan 11.2: Juglans regia L. Walnut 12: Lauraceae 12.1: Persea americana Avocado 13: Malvaceae 13.1: Theobroma cacao L. Cacao 14: Musaceae 14.1: Musa Banana and Plantain 15: Myrtaceae 15.1: Psidium guajaba L. Guava 16: Oleaceae 16.1: Olea europaea Olive 17: Oxalidaceae 17.1: Averrhoa carambola L. Carambola 18: Passifloraceae 18.1: Passiflora edulis Passionfruit 19: Rosaceae 19.1: Eriobotrya japonica Loquat 19.2: Fragaria × ananassa Strawberry 19.3: Malus × domestica Apple 19.4: Prunus sp. Peach and Nectarine 19.5: Prunus sp. Apricot 19.6: Prunus sp. Plum 19.7: Prunus Cherry 19.8: Prunus sp. Almond 19.9: Pyrus Pear and Quince 19.10: Rubus spp. Cane Fruit 20: Rutaceae 20.1: Citrus 21: Sapindaceae 21.1: Dimocarpus longan Longan and Litchi chinensis Litchi 22: Vitaceae 22.1: Vitis spp. Grape

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Book SynopsisThis book explores how policies targeting public research institutions, such as universities, contribute to the appropriation of biotechnology through national innovation systems. Around the world, biotechnology has become a driving force for dramatic change in systems and policies intended to spur innovation. The leading contributors expertly construct a detailed picture of policy approaches that support biotechnology and how such approaches work under different economic and social conditions. They also provide an insight into the role of universities in this process. Researchers, academics, students, policy advisors, decision makers and other professionals involved in the fields of biotechnology, innovation systems, higher education and development will find this book an invaluable resource.Contributors: A. Adamsone-Fiskovica, S.G. Antunes de Souza, I. Bortagaray, T.N. Ca, J.E. Cassiolato, L.V. Chuong, A.M. da Graça Mondjana, B.D. Diyamett, B. Göransson, B. Gregersen, J. Kristapsons, R. Lindner, A. Lulle, P. Macucule, N.P. Mai, E. Mneney, L.F. Montalvo Arriete, B.L.M. Mwamila, L. Neves, J. Núñez Jover, C.M. Palsson, I. Pérez Ones, T.T. Phuong, M.S. Rapini, T. Reiss, C.M. Ribeiro, G. Sagieva, U. Schmoch, J. Sutz, E. Tjunina, L. Van Chuong, H. Wang, Z. Yuan, G.F. ZucolotoTable of ContentsContents: 1. Strategies for Appropriation of Biotechnology Bo Göransson and Carl Magnus Pålsson PART I: LATIN AMERICA 2. The Recent Evolution of the Biotech Local Innovation System of Minas Gerais: University, Local Firms and Transnational Corporations José Eduardo Cassiolato, Graziela Ferrero Zucoloto, Márcia Siqueira Rapini and Sara Gonçalves Antunes de Souza 3. Linkages between Bio-Innovation, Knowledge Production and Policy in Uruguay Isabel Bortagaray, Isarelis Pérez Ones and Judith Sutz 4. Biotechnology, University and Scientific and Technological Policy in Cuba: A Look at Progress and Challenges Jorge Núñez Jover, Isarelis Pérez Ones and Luis Félix Montalvo Arriete PART II: AFRICA 5. The Role of Product Development Partnerships for the Appropriation of Knowledge and Innovation in Biotechnology in Tanzania Emmarold Mneney, Bitrina D. Diyamett and Burton L.M. Mwamila 6. Biotechnology in Mozambique: Present Situation and Future Trends Luis Neves, Paula Macucule, Carlos Miguel Ribeiro and Ana Maria da Graça Mondjana PART III: ASIA 7. Appropriation of Technology in Universities: The Case of Biotechnology Transfer in Vietnam Tran Ngoc Ca, Nguyen Phuong Mai, Tran Thi Phuong and Le Van Chuong 8. Biotechnology Transfer and Application in China: Background and Case Study Wang Haiyan and Zhou Yuan PART IV: EUROPE 9. Biotechnology in Europe: Background Information on Biotechnology Industry Characteristics and Policy Environment in Denmark, Germany, Latvia, Russia and Sweden Thomas Reiss, Ralf Lindner and Ulrich Schmoch 10. Biotechnology in Denmark and Sweden Carl Magnus Pålsson and Birgitte Gregersen 11. Biotechnology Appropriation in a Small Country: From Historical Legacies to Contemporary Challenges in Latvia Anda Adamsone-Fiskovica, Janis Kristapsons, Aija Lulle and Erika Tjunina 12. Biotechnology in Germany Thomas Reiss, Ralf Lindner and Ulrich Schmoch 13. Biotechnology: National Policy and Development Priorities in Russia Galina Sagieva PART V: IMPLICATIONS FOR PUBLIC POLICY AND INDUSTRY DEVELOPMENT 14. Implications for Public Policy and Industry Development Bo Göransson and Carl-Magnus Pålsson Index

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Book SynopsisOn the heels of his earlier work Medical Patent Law - The Challenges of Medical Treatment, Ventose makes another significant contribution to the literature. In his earlier work, he devoted a chapter to medical patents under US law. In Patenting Medical and Genetic Diagnostic Methods he expands that chapter into an entire text. No easy feat, to be sure. Nonetheless, his 'treatment' of the jurisprudential terrain is sophisticated and rigorous. Scholars, practitioners and students seriously interested in the evolution of medical patents under US law will find Ventose's latest work to be invaluable.'- Emir Crowne, University of Windsor, Canada, Law Society of Upper Canada and Harold G. Fox Intellectual Property Moot'This work provides a timely exploration of patent battles over biotechnology, medicine, diagnostic testing, and pharmacogenomics. Such conflicts are critically important at the dawn of a new era of personalised medicine.'- Matthew Rimmer, The Australian National University College of Law and ACIPA, Australia'The debate on the patent eligibility of diagnostic and medical methods has raged recently in the United States and there seemed to be far less certainty about the outcome than in Europe. Gene patents for diagnostic methods clearly stirred the debate, but this is not a new debate. It goes back a century. This book gets to the bottom of the debate and provides an in depth insight, both of the history and of the recent developments. A fascinating tale.'- Paul Torremans, University of Nottingham, UKThis well-researched book explores in detail the issue of patenting medical and genetic diagnostic methods in the United States.It examines decisions of the Patent Office Boards of Appeal and the early courts on the question of whether medical treatments were eligible for patent protection under section 101 of the Patents Act. It then traces the legislative history of the Medical Procedures and Affordability Act that provided immunity for physicians from patent infringement suits. After considering the Supreme Court's jurisprudence on patent eligibility, the book then comprehensively sets out how the Federal Circuit and the Supreme Court have dealt with the issue, paying close attention to the Supreme Court's recent decision in Bilski and Prometheus.Being the first book to comprehensively cover patenting medical methods, it will appeal to patent agents, patent attorneys, solicitors and barristers working in patent and medical law worldwide, medical practitioners and healthcare professionals, in-house legal and regulatory departments of pharmaceutical companies. Researchers and managers in the chemical, medical, pharmaceutical and biotechnology industries, as well as academics specializing in medical law or patent law, will also find much to interest them in this book.Contents: Preface 1. Introduction 2. Initial Determination 3. Legislative Intervention 4. Patent-Eligibility 5. Consideration by the Federal Circuit 6. Consideration by the Supreme Court 7. Conclusions Bibliography IndexTrade Review‘On the heels of his earlier work Medical Patent Law – The Challenges of Medical Treatment, Ventose makes another significant contribution to the literature. In his earlier work, he devoted a chapter to medical patents under US law. In Patenting Medical and Genetic Diagnostic Methods he expands that chapter into an entire text. No easy feat, to be sure. Nonetheless, his “treatment” of the jurisprudential terrain is sophisticated and rigorous. Scholars, practitioners and students seriously interested in the evolution of medical patents under US law will find Ventose’s latest work to be invaluable.’ -- Emir Crowne, University of Windsor, Canada, Law Society of Upper Canada and Harold G. Fox Intellectual Property Moot‘This work provides a timely exploration of patent battles over biotechnology, medicine, diagnostic testing, and pharmacogenomics. Such conflicts are critically important at the dawn of a new era of personalised medicine.’ -- Matthew Rimmer, The Australian National University College of Law and ACIPA, Australia‘The debate on the patent eligibility of diagnostic and medical methods has raged recently in the United States and there seemed to be far less certainty about the outcome than in Europe. Gene patents for diagnostic methods clearly stirred the debate, but this is not a new debate. It goes back a century. This book gets to the bottom of the debate and provides an in depth insight, both of the history and of the recent developments. A fascinating tale. . .’ -- Paul Torremans, University of Nottingham, UK‘For researchers, the tables of cases and of national and international legislation are particularly useful and of course, there’s a host of handy references to be gleaned from the bibliography and the footnotes throughout. For anyone involved in intellectual property, medical law or patents, this book should be considered an essential purchase.’ -- Phillip Taylor MBE and Elizabeth Taylor, The Barrister MagazineTable of ContentsContents: Preface 1. Introduction 2. Initial Determination 3. Legislative Intervention 4. Patent-Eligibility 5. Consideration by the Federal Circuit 6. Consideration by the Supreme Court 7. Conclusions Bibliography Index

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Book SynopsisRecent innovations in agriculture and food technologies have brought benefits to many countries, particularly in developing regions, but information about the extent of these has often been sparse. This research review examines the best papers on the subject to form a comprehensive, global perspective on the impacts of agricultural biotechnology around the world. With an emphasis on the economic, environmental, health and food security aspects of agbiotech, Biotechnology, Agriculture and Development will prove to be an invaluable resource for academics, students and researchers alike.Table of ContentsContents: Acknowledgements Introduction Peter W.B. Phillips, Stuart J. Smyth and David Castle 1. Philipp Aerni (2011), ‘Do Political Attitudes Affect Consumer Choice? Evidence from a Large-Scale Field Study with Genetically Modified Bread in Switzerland’, Sustainability, 3 (9), September, 1555–72 2. Akhter Ali and Awudu Abdulai (2010), ‘The Adoption of Genetically Modified Cotton and Poverty Reduction in Pakistan’, Journal of Agricultural Economics, 61 (1), February, 175–92 3. Julian M. Alston, Michele C. Marra, Philip G. Pardey and T.J. Wyatt (2000), ‘Research Returns Redux: A Meta-Analysis of the Returns to Agricultural R&D’, Australian Journal of Agricultural and Resource Economics, 44 (2), June, 185–215 4. Klaus Ammann (2007), ‘Reconciling Traditional Knowledge with Modern Agriculture: A Guide for Building Bridges’, in Anatole Krattiger, Richard T. Mahoney, Lita Nelsen, Jennifer A. Thomson, Alan B. Bennett, Kanikaram Satyanarayana, Gregory D. Graff, Carlos Fernandez and Stanley P. Kowalski (eds), Intellectual Property Management in Health and Agricultural Innovation: A Handbook of Best Practices, Chapter 16.7, Oxford, UK: MIHR (Centre for the Management of Intellectual Property in Health Research and Development) and Davis, CA: PIPRA (Public Intellectual Property Resource for Agriculture), 1539–62 5. Kym Anderson (2010), ‘Economic Impacts of Policies Affecting Crop Biotechnology and Trade’, New Biotechnology, 27 (5), November, 558–64 6. Arnab K. Basu and Matin Qaim (2007), ‘On The Adoption of Genetically Modified Seeds in Developing Countries and the Optimal Types of Government Intervention’, American Journal of Agricultural Economics, 89 (3), August, 784–804 7. Volker Beckmann, Claudio Soregaroli and Justus Wesseler (2006), ‘Coexistence Rules and Regulations in the European Union’, American Journal of Agricultural Economics, 88 (5), December, 1193–9 8. Richard Bennett, Stephen Morse and Yousouf Ismael (2006), ‘The Economic Impact of Genetically Modified Cotton on South African Smallholders: Yield, Profit and Health Effects’, Journal of Development Studies, 42 (4), May, 662–77 9. Graham Brookes and Peter Barfoot (2012), ‘Global Impact of Biotech Crops: Environmental Effects, 1996–2010’, GM Crops and Food: Biotechnology in Agriculture and the Food Chain, 3 (2), April/May/June, 129–37 10. Derek Byerlee and Ken Fischer (2002), ‘Accessing Modern Science: Policy and Institutional Options for Agricultural Biotechnology in Developing Countries’, World Development, 30 (6), June, 931–48 11. Carl Pray, Danmeng Ma, Jikun Huang and Fangbin Qiao (2001), ‘Impact of Bt Cotton in China’, World Development, 29 (5), May, 813–25 12. Carl K. Eicher, Karim Maredia and Idah Sithole-Niang (2006), ‘Crop Biotechnology and the African Farmer’, Food Policy, 31 (6), December, 504–27 13. José Benjamin Falck-Zepeda, Greg Traxler and Robert G. Nelson (2000), ‘Surplus Distribution from the Introduction of a Biotechnology Innovation’, American Journal of Agricultural Economics, 82 (2), May, 360–9 14. Jose Falck-Zepeda, Jose Yorobe, Jr., Bahagiawati Amir Husin, Abraham Manalo, Erna Lokollo, Godfrey Ramon, Patricia Zambrano (2012), ‘Estimates and Implications of the Costs of Compliance with Biosafety Regulations in Developing Countries’, GM Crops and Food: Biotechnology in Agriculture and the Food Chain, 3 (1), January/February/March, 52–9 15. Jorge Fernandez-Cornejo and Margriet Caswell, with contributions from Lorraine Mitchell, Elise Golan and Fred Kuchler (2006), ‘The First Decade of Genetically Engineered Crops in the United States’, United States Department of Agriculture Economic Information Bulletin Number 11 (EIB-11), April, 1–36 16. George B. Frisvold and Jeanne M. Reeves (2010), ‘Resistance Management and Sustainable Use of Agricultural Biotechnology’, AgBioForum: The Journal of Agrobiotechnology Management and Economics, 13 (4), 343–59 17. Guillaume Gruère and Debdatta Sengupta (2011), ‘Bt Cotton and Farmer Suicides in India: An Evidence-Based Assessment’, Journal of Development Studies, 47 (2), February, 316–37 18. Ronald J. Herring (2007), ‘Stealth Seeds: Bioproperty, Biosafety, Biopolitics’, Journal of Development Studies, 43 (1), January, 130–57 19. Jikun Huang, Scott Rozelle, Carl Pray and Qinfang Wang (2002), ‘Plant Biotechnology in China’, Science, 295 (5555), January, 674–7 20. Jikun Huang, Deliang Zhang, Jun Yang, Scott Rozelle and Nicholas Kalaitzandonakes (2008), ‘Will the Biosafety Protocol Hinder or Protect the Developing World: Learning from China’s Experience’, Food Policy, 33 (1), February, 1–12 21. Jikun Huang, Ruifa Hu, Scott Rozelle and Carl Pray (2008), ‘Genetically Modified Rice, Yields, and Pesticides: Assessing Farm-Level Productivity Effects in China’, Economic Development and Cultural Change, 56 (2), January, 241–63 22. W.D. Hutchison, E.C. Burkness, P.D. Mitchell, R.D. Moon, T.W. Leslie, S.J. Fleischer, M. Abrahamson, K.L. Hamilton, K.L. Steffey, M.E. Gray, R.L. Hellmich, L.V. Kaster, T.E. Hunt, R.J. Wright, K. Pecinovsky, T.L. Rabaey, B.R. Flood and E.S. Raun (2010), ‘Areawide Suppression of European Corn Borer with Bt Maize Reaps Savings to Non-Bt Maize Growers’, Science, 330 (6001), October, 222–5 23. Calestous Juma (2011), ‘Science Meets Farming in Africa’, Science, 334 (6061), December, 1323 24. Nicholas Kalaitzandonakes, Richard Maltsbarger and James Barnes (2001), ‘Global Identity Preservation Costs in Agricultural Supply Chains’, Canadian Journal of Agricultural Economics, 49 (4), December, 605–15 25. Michael Lipton (2001), ‘Reviving Global Poverty Reduction: What Role for Genetically Modified Plants?’, Journal of International Development, 13 (7), October, 823–46 26. GianCarlo Moschini (2001), ‘Biotech—Who Wins? Economic Benefits and Costs of Biotechnology Innovations in Agriculture’, Estey Centre Journal of International Law and Trade Policy, 2 (1), Spring, 93–117 27. Giancarlo Moschini and Harvey Lapan (1997), ‘Intellectual Property Rights and the Welfare Effects of Agricultural R&D’, American Journal of Agricultural Economics, 79 (4), November, 1229–42 28. Carl E. Pray, Jikun Huang, Ruifa Hu and Scott Rozelle (2002), ‘Five Years of Bt Cotton in China – The Benefits Continue’, Plant Journal, 31 (4), August, 423–30 29. Carl E. Pray (2001), ‘Public-Private Sector Linkages in Research and Development: Biotechnology and the Seed Industry in Brazil, China and India’, American Journal of Agricultural Economics, 83 (3), August, 742–7 30. Carl E. Pray and Anwar Naseem (2007), ‘Supplying Crop Biotechnology to the Poor: Opportunities and Constraints’, Journal of Development Studies, 43 (1), January, 192–217 31. Matin Qaim and Greg Traxler (2005), ‘Roundup Ready Soybeans in Argentina: Farm Level and Aggregate Welfare Effects’, Agricultural Economics, 32 (1), January, 73–86 32. Matin Qaim (2009), ‘The Economics of Genetically Modified Crops’, Annual Review of Resource Economics, 1, June, 665–93 33. Matin Qaim (2003), ‘Bt Cotton in India: Field Trial Results and Economic Projections’, World Development, 31 (12), December, 2115–27 34. Matin Qaim and Alain de Janvry (2003), ‘Genetically Modified Crops, Corporate Pricing Strategies, and Farmers’ Adoption: The Case of Bt Cotton in Argentina’, American Journal of Agricultural Economics, 85 (4), November, 814–28 35. Melinda Smale, Patricia Zambrano and Mélodie Cartel (2006), ‘Bales and Balance: A Review of the Methods Used to Assess the Economic Impact of Bt Cotton on Farmers in Developing Economies’, AgBioForum: The Journal of Agrobiotechnology Management and Economics, 9 (3), 195–212 36. Stuart J. Smyth and Drew L. Kershen (2006), ‘Agricultural Biotechnology: Legal Liability Regimes from Comparative and International Perspectives’, Global Jurist, 6 (2), October, i, 1–80 37. Stuart J. Smyth, George G. Khachatourians and Peter W.B. Phillips (2002), ‘Liabilities and Economics of Transgenic Crops’, Nature Biotechnology, 20 (6), June, 537–41 38. Stuart J. Smyth, William A. Kerr and Peter W.B. Phillips (2011), ‘Recent Trends in the Scientific Basis of Sanitary and Phytosanitary Trade Rules and their Potential Impact on Investment’, Journal of World Investment and Trade, 12 (1), 5–26 39. Arjunan Subramanian and Matin Qaim (2010), ‘The Impact of Bt Cotton on Poor Households in Rural India’, Journal of Development Studies, 46 (2), February, 295–311 40. Felicia Wu (2006), ‘Mycotoxin Reduction in Bt Corn: Potential Economic, Health, and Regulatory Impacts’, Transgenic Research, 15 (3), June, 277–89 41. David Zilberman, Holly Ameden and Matin Qiam (2007), ‘The Impact of Agricultural Biotechnology on Yields, Risks, and Biodiversity in Low-Income Countries’, Journal of Development Studies, 43 (1), January, 63–78 42. David Zilberman, Holly Ameden, Gregory D. Graff and Matin Qaim (2004), ‘Agricultural Biotechnology: Productivity, Biodiversity, and Intellectual Property Rights’, Journal of Agricultural and Food Industrial Organization, 2 (2), May, i, 1–16 43. Roukayatou Zimmermann and Matin Qaim (2004), ‘Potential Health Benefits of Golden Rice: A Philippine Case Study’, Food Policy, 29 (2), April, 147–68 Index

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Book SynopsisRapid advances in the life sciences means that there is now a far more detailed understanding of biological systems on the cellular, molecular and genetic levels. Sited at the intersection between the life sciences, the engineering sciences and the design sciences, innovations in the biomaterials industry are expected to garner increasing attention and play a key role in future development. This book examines the biomaterials innovations taking place in corporations and in academic research settings today.Biomaterials Innovation offers a comprehensive overview of life science innovation and presents empirical research in the field of biomaterials innovation. Alexander Styhre examines innovation management practices in the field of biomaterials development and explains institutional changes in the biomaterials industry. The demand for accomplishing biocompatibility between the human body and the materials developed is highlighted, as is the relationship between financial markets and biomaterials companies. Finally, the author discusses the therapeutic, regulatory and managerial implications of biomaterials innovation.Biomaterials Innovation will be required reading for any researcher, policy-maker or student interested in innovation management, the life sciences and the development of health care therapies.Contents: 1. Life and Materiality, Nature and Artifice: Transgressing the Divide 2. Bios, Materiality, and Biomateriality 3. Innovation Management and Innovation in the Life Sciences 4. Shifting Institutional Logics in Biomaterial Companies 5. The Epistemology of Biomaterials: How Biomaterials Become Embodied 6. Financing Biomaterials Innovation: Selling Science in Venture Capital Markets 7. Biomaterials Innovation: Re-creating the Human Body Appendix: Methodology of the Studies Bibliography IndexTable of ContentsContents: 1. Life and Materiality, Nature and Artifice: Transgressing the Divide 2. Bios, Materiality, and Biomateriality 3. Innovation Management and Innovation in the Life Sciences 4. Shifting Institutional Logics in Biomaterial Companies 5. The Epistemology of Biomaterials: How Biomaterials Become Embodied 6. Financing Biomaterials Innovation: Selling Science in Venture Capital Markets 7. Biomaterials Innovation: Re-creating the Human Body Appendix: Methodology of the Studies Bibliography Index

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Book SynopsisRapid advances in the life sciences means that there is now a far more detailed understanding of biological systems on the cellular, molecular and genetic levels. Sited at the intersection between the life sciences, the engineering sciences and the design sciences, innovations in the biomaterials industry are expected to garner increasing attention and play a key role in future development. This book examines the biomaterials innovations taking place in corporations and in academic research settings today.Biomaterials Innovation offers a comprehensive overview of life science innovation and presents empirical research in the field of biomaterials innovation. Alexander Styhre examines innovation management practices in the field of biomaterials development and explains institutional changes in the biomaterials industry. The demand for accomplishing biocompatibility between the human body and the materials developed is highlighted, as is the relationship between financial markets and biomaterials companies. Finally, the author discusses the therapeutic, regulatory and managerial implications of biomaterials innovation.Biomaterials Innovation will be required reading for any researcher, policy-maker or student interested in innovation management, the life sciences and the development of health care therapies.Contents: 1. Life and Materiality, Nature and Artifice: Transgressing the Divide 2. Bios, Materiality, and Biomateriality 3. Innovation Management and Innovation in the Life Sciences 4. Shifting Institutional Logics in Biomaterial Companies 5. The Epistemology of Biomaterials: How Biomaterials Become Embodied 6. Financing Biomaterials Innovation: Selling Science in Venture Capital Markets 7. Biomaterials Innovation: Re-creating the Human Body Appendix: Methodology of the Studies Bibliography IndexTable of ContentsContents: 1. Life and Materiality, Nature and Artifice: Transgressing the Divide 2. Bios, Materiality, and Biomateriality 3. Innovation Management and Innovation in the Life Sciences 4. Shifting Institutional Logics in Biomaterial Companies 5. The Epistemology of Biomaterials: How Biomaterials Become Embodied 6. Financing Biomaterials Innovation: Selling Science in Venture Capital Markets 7. Biomaterials Innovation: Re-creating the Human Body Appendix: Methodology of the Studies Bibliography Index

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Book SynopsisIn this book, the authors present in detail several recent methodologies and algorithms that we have developed during the last fifteen years. The deterministic methods account for uncertainties through empirical safety factors, which implies that the actual uncertainties in materials, geometry and loading are not truly considered. This problem becomes much more complicated when considering biomechanical applications where a number of uncertainties are encountered in the design of prosthesis systems. This book implements improved numerical strategies and algorithms that can be applied only in biomechanical studies.Table of ContentsPreface ix Introduction xi Chapter 1. Basic Tools for Reliability Analysis 1 1.1. Introduction 1 1.2. Advantages of numerical simulation and optimization 2 1.3. Numerical simulation by finite elements 3 1.3.1. Use 3 1.3.2. Principle 4 1.3.3. General approach 5 1.4. Optimization process 6 1.4.1. Basic concepts 7 1.4.2. Problem classification 10 1.4.3. Optimization methods 22 1.4.4. Unconstrained methods 23 1.4.5. Constrained methods 43 1.5. Sensitivity analysis 56 1.5.1. Importance of sensitivity 56 1.5.2. Sensitivity methods 57 1.6. Conclusion 61 Chapter 2. Reliability Concept 63 2.1. Introduction 63 2.1.1. Preamble 63 2.1.2. Reliability history 63 2.1.3. Reliability definition 65 2.1.4. Importance of reliability 66 2.2. Basic functions and concepts for reliability analysis 66 2.2.1. Failure concept 67 2.2.2. Uncertainty concept 67 2.2.3. Random variables 68 2.2.4. Probability density function 69 2.2.5. Cumulative distribution function 69 2.2.6. Reliability function 70 2.3. System reliability 71 2.3.1. Series conjunction 71 2.3.2. Parallel conjunction 72 2.3.3. Mixed conjunction 73 2.3.4. Delta-star conjunction 74 2.4. Statistical measures 77 2.5. Probability distributions 81 2.5.1. Uniform distribution 82 2.5.2. Normal distribution 86 2.5.3. Lognormal distribution 91 2.6. Reliability analysis 97 2.6.1. Definitions 97 2.6.2. Algorithms 105 2.6.3. Reliability analysis methods 106 2.6.4. Optimality criteria 110 2.7. Conclusion 112 Chapter 3. Integration of Reliability Concept into Biomechanics 113 3.1. Introduction 113 3.2. Origin and categories of uncertainties 115 3.3. Uncertainties in biomechanics 116 3.3.1. Uncertainty in loading 117 3.3.2. Uncertainty in geometry 118 3.3.3. Uncertainty in materials 118 3.4. Bone-related uncertainty 119 3.4.1. Bone behavior law 120 3.4.2. Contribution to the characterization of the bone’s mechanical properties 125 3.5. Bone developments and formulations 126 3.5.1. Current formulation 126 3.5.2. Generalized formulation 127 3.5.3. Optimized formulation 128 3.5.4. Extension to orthotropic behavior formulation 130 3.6. Characterization by experimentation of the bone’s mechanical properties 133 3.6.1. Characterization by bending test 134 3.6.2. Characterization by compression test 135 3.7. Conclusion 136 Chapter 4. Reliability Analysis of Orthopedic Prostheses 137 4.1. Introduction to orthopedic prostheses 137 4.1.1. History of prostheses 139 4.1.2. Evolution of prostheses 139 4.1.3. Examples of orthopedic prostheses 140 4.2. Reliability analysis of the intervertebral disk 140 4.2.1. Functional anatomy 140 4.2.2. The lumbar functional spinal unit 141 4.2.3. Intervertebral disk prosthesis 145 4.2.4. Numerical application on the intervertebral disk 147 4.3. Reliability analysis of the hip prosthesis 154 4.3.1. Anatomy 154 4.3.2. Presentation of the total hip prosthesis 158 4.3.3. Numerical application of the hip prosthesis 161 4.3.4. Boundary conditions 164 4.3.5. Direct simulation 164 4.3.6. Probabilistic sensitivity analysis 166 4.3.7. Integration of reliability analysis 167 4.4. Conclusion 173 Chapter 5. Reliability Analysis of Orthodontic Prostheses 175 5.1. Introduction to orthodontic prostheses 175 5.2. Anatomy of the temporomandibular joint 176 5.2.1. Articular bone regions and meniscus 177 5.2.2. Ligaments 179 5.2.3. Myology, elevator muscles and depressor muscles 179 5.3. Numerical simulation of a non-fractured mandible 183 5.3.1. Description of the studied mandible 183 5.3.2. Numerical results 185 5.4. Reliability analysis of the fixation system of the fractured mandible 188 5.4.1. Description of a fractured mandible 188 5.4.2. Fixation strategy using mini-plates 189 5.4.3. Study of a homogeneous and isotropic structure 190 5.4.4. Study of a composite and orthotropic structure 198 5.4.5. Result discussion 207 5.5. Conclusion 208 Appendices 209 Appendix 1: Matrix Calculation 211 Appendix 2: ANSYS Code for the Disk Implant 217 Appendix 3: ANSYS Code for the Stem Implant 221 Appendix 4: Probability of Failure/Reliability Index 235 Bibliography 237 Index 245

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