Biotechnology Books

Book SynopsisResearch in nano and cell mechanics has received much attention from the scientific community as a result of society needs and government initiatives to accelerate developments in materials, manufacturing, electronics, medicine and healthcare, energy, and the environment. Engineers and scientists are currently engaging in increasingly complex scientific problems that require interdisciplinary approaches. In this regard, studies in this field draw from fundamentals in atomistic scale phenomena, biology, statistical and continuum mechanics, and multiscale modeling and experimentation. As a result, contributions in these areas are spread over a large number of specialized journals, which prompted the Editors to assemble this book. Nano and Cell Mechanics: Fundamentals and Frontiers brings together many of the new developments in the field for the first time, and covers fundamentals and frontiers in mechanics to accelerate developments in nano- and bio-technologies. Table of ContentsAbout the Editors xiii List of Contributors xv Foreword xix Series Preface xxi Preface xxiii Part One BIOLOGICAL PHENOMENA 1 Cell–Receptor Interactions 3 David Lepzelter and Muhammad Zaman 1.1 Introduction 3 1.2 Mechanics of Integrins 4 1.3 Two-Dimensional Adhesion 7 1.4 Two-Dimensional Motility 9 1.5 Three-Dimensional Adhesion 11 1.6 Three-Dimensional Motility 12 1.7 Apoptosis and Survival Signaling 13 1.8 Cell Differentiation Signaling 13 1.9 Conclusions 14 References 15 2 Regulatory Mechanisms of Kinesin and Myosin Motor Proteins: Inspiration for Improved Control of Nanomachines 19 Sarah Rice 2.1 Introduction 19 2.2 Generalized Mechanism of Cytoskeletal Motors 19 2.3 Switch I: A Controller of Motor Protein and G Protein Activation 21 2.4 Calcium-Binding Regulators of Myosins and Kinesins 23 2.5 Phospho-Regulation of Kinesin and Myosin Motors 262.6 Cooperative Action of Kinesin and Myosin Motors as a “Regulator” 28 2.7 Conclusion 29 References 30 3 Neuromechanics: The Role of Tension in Neuronal Growth and Memory 35 Wylie W. Ahmed, Jagannathan Rajagopalan, Alireza Tofangchi, and Taher A. Saif 3.1 Introduction 35 3.1.1 What is a Neuron? 36 3.1.2 How Does a Neuron Function? 38 3.1.3 How Does a Neuron Grow? 40 3.2 Tension in Neuronal Growth 41 3.2.1 In Vitro Measurements of Tension in Neurons 41 3.2.2 In Vivo Measurements of Tension in Neurons 43 3.2.3 Role of Tension in Structural Development 45 3.3 Tension in Neuron Function 48 3.3.1 Tension Increases Neurotransmission 48 3.3.2 Tension Affects Vesicle Dynamics 48 3.4 Modeling the Mechanical Behavior of Axons 52 3.5 Outlook 58 References 58 Part Two NANOSCALE PHENOMENA 4 Fundamentals of Roughness-Induced Superhydrophobicity 65 Neelesh A. Patankar 4.1 Background and Motivation 65 4.2 Thermodynamic Analysis: Classical Problem (Hydrophobic to Superhydrophobic) 67 4.2.1 Problem Formulation 68 4.2.2 The Cassie–Baxter State 71 4.2.3 Predicting Transition from Cassie–Baxter to Wenzel State 73 4.2.4 The Apparent Contact Angle of the Drop 77 4.2.5 Modeling Hysteresis 79 4.3 Thermodynamic Analysis: Classical Problem (Hydrophilic to Superhydrophobic) 84 4.4 Thermodynamic Analysis: Vapor Stabilization 86 4.5 Applications and Future Challenges 90 Acknowledgments 91 References 91 5 Multiscale Experimental Mechanics of Hierarchical Carbon-Based Materials 95 Horacio D. Espinosa, Tobin Filleter, and Mohammad Naraghi 5.1 Introduction 95 5.2 Multiscale Experimental Tools 97 5.2.1 Revealing Atomic-Level Mechanics: In-Situ TEM Methods 98 5.2.2 Measuring Ultralow Forces: AFM Methods 101 5.2.3 Investigating Shear Interactions: In-Situ SEM/AFM Methods 102 5.2.4 Collective and Local Behavior: Micromechanical Testing Methods 103 5.3 Hierarchical Carbon-Based Materials 106 5.3.1 Weak Shear Interactions between Adjacent Graphitic Layers 106 5.3.2 Cross-linking Adjacent Graphitic Layers 110 5.3.3 Local Mechanical Properties of CNT/Graphene Composites 113 5.3.4 High Volume Fraction CNT Fibers and Composites 115 5.4 Concluding Remarks 120 References 123 6 Mechanics of Nanotwinned Hierarchical Metals 129 Xiaoyan Li and Huajian Gao 6.1 Introduction and Overview 129 6.1.1 Nanotwinned Materials 130 6.1.2 Numerical Modeling of Nanotwinned Metals 132 6.2 Microstructural Characterization and Mechanical Properties of Nanotwinned Materials 134 6.2.1 Structure of Coherent Twin Boundary 134 6.2.2 Microstructures of Nanotwinned Materials 135 6.2.3 Mechanical and Physical Properties of Nanotwinned Metals 137 6.3 Deformation Mechanisms in Nanotwinned Metals 145 6.3.1 Interaction between Dislocations and Twin Boundaries 146 6.3.2 Strengthening and Softening Mechanisms in Nanotwinned Metals 147 6.3.3 Fracture of Nanotwinned Copper 155 6.4 Concluding Remarks 156 References 157 7 Size-Dependent Strength in Single-Crystalline Metallic Nanostructures 163 Julia R. Greer 7.1 Introduction 163 7.2 Background 164 7.2.1 Experimental Foundation 164 7.2.2 Models 167 7.3 Sample Fabrication 170 7.3.1 FIB Approach 170 7.3.2 Directional Solidification and Etching 172 7.3.3 Templated Electroplating 173 7.3.4 Nanoimprinting 173 7.3.5 Vapor–Liquid–Solid Growth 174 7.3.6 Nanowire Growth 175 7.4 Uniaxial Deformation Experiments 175 7.4.1 Nanoindenter-Based Systems (Ex Situ) 176 7.4.2 In-Situ Systems 176 7.5 Discussion and Outlook on Size-Dependent Strength in Single-Crystalline Metals 178 7.5.1 Cubic Crystals 178 7.5.2 Non-Cubic Single Crystals 183 7.6 Conclusions and Outlook 184 References 185 Part Three EXPERIMENTATION 8 In-Situ TEM Electromechanical Testing of Nanowires and Nanotubes 193 Horacio D. Espinosa, Rodrigo A. Bernal, and Tobin Filleter 8.1 Introduction 193 8.1.1 Relevance of Mechanical and Electromechanical Testing for One-Dimensional Nanostructures 194 8.1.2 Mechanical and Electromechanical Characterization of Nanostructures: The Need for In-Situ TEM 196 8.2 In-Situ TEM Experimental Methods 197 8.2.1 Overview of TEM Specimen Holders 199 8.2.2 Methods for Mechanical and Electromechanical Testing of Nanowires and Nanotubes 200 8.2.3 Sample Preparation for TEM of One-Dimensional Nanostructures 208 8.3 Capabilities of In-Situ TEM Applied to One-Dimensional Nanostructures 212 8.3.1 HRTEM 212 8.3.2 Diffraction 216 8.3.3 Analytical Techniques 217 8.3.4 In-Situ Specimen Modification 218 8.4 Summary and Outlook 220 Acknowledgments 221 References 221 9 Engineering Nano-Probes for Live-Cell Imaging of Gene Expression 227 Gang Bao, Brian Wile, and Andrew Tsourkas 9.1 Introduction 227 9.2 Molecular Probes for RNA Detection 229 9.2.1 Fluorescent Linear Probes 229 9.2.2 Linear FRET Probes 232 9.2.3 Quenched Auto-ligation Probes 233 9.2.4 Molecular Beacons 234 9.2.5 Dual-FRET Molecular Beacons 236 9.2.6 Fluorescent Protein-Based Probes 237 9.3 Probe Design, Imaging, and Biological Issues 239 9.3.1 Specificity of Molecular Beacons 239 9.3.2 Fluorophores, Quenchers, and Signal-to-Background 241 9.3.3 Target Accessibility 242 9.4 Delivery of Molecular Beacons 244 9.4.1 Microinjection 245 9.4.2 Cationic Transfection Agents 245 9.4.3 Electroporation 245 9.4.4 Chemical Permeabilization 246 9.4.5 Cell-Penetrating Peptide 246 9.5 Engineering Challenges and Future Directions 248 Acknowledgments 249 References 249 10 Towards High-Throughput Cell Mechanics Assays for Research and Clinical Applications 255 David R. Myers, Daniel A. Fletcher, and Wilbur A. Lam 10.1 Cell Mechanics Overview 255 10.1.1 Cell Cytoskeleton and Cell-Sensing Overview 256 10.1.2 Forces Applied by Cells 259 10.1.3 Cell Responses to Force and Environment 260 10.1.4 General Principles of Combined Mechanical and Biological Measurements 261 10.2 Bulk Assays 262 10.2.1 Microfiltration 262 10.2.2 Rheometry 264 10.2.3 Ektacytometry 266 10.2.4 Parallel-Plate Flow Chambers 267 10.3 Single-Cell Techniques 268 10.3.1 Micropipette Aspiration 268 10.3.2 Atomic Force Microscopy 270 10.3.3 Microplate Stretcher 272 10.3.4 Optical Tweezers 273 10.4 Existing High-Throughput Cell Mechanical-Based Assays 274 10.4.1 Optical Stretchers 274 10.4.2 Traction Force Microscopy via Bead-Embedded Gels 275 10.4.3 Traction Force Microscopy via Micropost Arrays 275 10.4.4 Substrate Stretching Assays 277 10.4.5 Magnetic Twisting Cytometry 277 10.4.6 Microfluidic Pore and Deformation Assays 278 10.5 Cell Mechanical Properties and Diseases 280 References 284 11 Microfabricated Technologies for Cell Mechanics Studies 293 Sri Ram K. Vedula, Man C. Leong, and Chwee T. Lim 11.1 Introduction 293 11.2 Microfabrication Techniques 294 11.2.1 Photolithography and Soft Lithography 294 11.2.2 Microphotopatterning (μPP) 297 11.3 Applications to Cell Mechanics 298 11.3.1 Micropatterned Substrates 298 11.3.2 Micropillared Substrates 301 11.3.3 Microfluidic Devices 304 11.4 Conclusions 307 References 307 Part Four MODELING 12 Atomistic Reaction Pathway Sampling: The Nudged Elastic BandMethod and Nanomechanics Applications 313 Ting Zhu, Ju Li, and Sidney Yip 12.1 Introduction 313 12.1.1 Reaction Pathway Sampling in Nanomechanics 314 12.1.2 Extending the Time Scale in Atomistic Simulation 314 12.1.3 Transition-State Theory 315 12.2 The NEB Method for Stress-Driven Problems 315 12.2.1 The NEB method 315 12.2.2 The Free-End NEB Method 317 12.2.3 Stress-Dependent Activation Energy and Activation Volume 320 12.2.4 Activation Entropy and Meyer–Neldel Compensation Rule 322 12.3 Nanomechanics Case Studies 324 12.3.1 Crack Tip Dislocation Emission 324 12.3.2 Stress-Mediated Chemical Reactions 326 12.3.3 Bridging Modeling with Experiment 327 12.3.4 Temperature and Strain-Rate Dependence of Dislocation Nucleation 329 12.3.5 Size and Loading Effects on Fracture 330 12.4 A Perspective on Microstructure Evolution at Long Times 332 12.4.1 Sampling TSP Trajectories 333 12.4.2 Nanomechanics in Problems of Materials Ageing 334 References 336 13 Mechanics of Curvilinear Electronics 339 Shuodao Wang, Jianliang Xiao, Jizhou Song, Yonggang Huang, and John A. Rogers 13.1 Introduction 339 13.2 Deformation of Elastomeric Transfer Elements during Wrapping Processes 342 13.2.1 Strain Distribution in Stretched Elastomeric Transfer Elements 342 13.2.2 Deformed Shape of Elastomeric Transfer Elements 344 13.3 Buckling of Interconnect Bridges 347 13.4 Maximum Strain in the Circuit Mesh 351 13.5 Concluding Remarks 355 Acknowledgments 355 References 355 14 Single-Molecule Pulling: Phenomenology and Interpretation 359 Ignacio Franco, Mark A. Ratner, and George C. Schatz 14.1 Introduction 359 14.2 Force–Extension Behavior of Single Molecules 360 14.3 Single-Molecule Thermodynamics 364 14.3.1 Free Energy Profile of the Molecule Plus Cantilever 365 14.3.2 Extracting the Molecular Potential of Mean Force φ(ξ ) 366 14.3.3 Estimating Force–Extension Behavior from φ(ξ ) 369 14.4 Modeling Single-Molecule Pulling Using Molecular Dynamics 370 14.4.1 Basic Computational Setup 370 14.4.2 Modeling Strategies 371 14.4.3 Examples 373 14.5 Interpretation of Pulling Phenomenology 376 14.5.1 Basic Structure of the Molecular Potential of Mean Force 377 14.5.2 Mechanical Instability 378 14.5.3 Dynamical Bistability 381 14.6 Summary 384 Acknowledgments 385 References 385 15 Modeling and Simulation of Hierarchical Protein Materials 389 Tristan Giesa, Graham Bratzel, and Markus J. Buehler 15.1 Introduction 389 15.2 Computational and Theoretical Tools 391 15.2.1 Molecular Simulation from Chemistry Upwards 391 15.2.2 Mesoscale Methods for Modeling Larger Length and Time Scales 392 15.2.3 Mathematical Approaches to Biomateriomics 394 15.3 Case Studies 400 15.3.1 Atomistic and Mesoscale Protein Folding and Deformation in Spider Silk 400 15.3.2 Coarse-Grained Modeling of Actin Filaments 402 15.3.3 Category Theoretical Abstraction of a Protein Material and Analogy to an Office Network 403 15.4 Discussion and Conclusion 406 Acknowledgments 406 References 406 16 Geometric Models of Protein Secondary-Structure Formation 411 Hendrik Hansen-Goos and Seth Lichter 16.1 Introduction 411 16.2 Hydrophobic Effect 412 16.2.1 Variable Hydrogen-Bond Strength 415 16.3 Prior Numerical and Coarse-Grained Models 415 16.4 Geometry-Based Modeling: The Tube Model 416 16.4.1 Motivation 416 16.4.2 Impenetrable Tube Models 417 16.4.3 Including Finite-Sized Particles Surrounding the Protein 419 16.4.4 Models Using Real Protein Structure 421 16.5 Morphometric Approach to Solvation Effects 422 16.5.1 Hadwiger’s Theorem 422 16.5.2 Applications 424 16.6 Discussion, Conclusions, Future Work 429 16.6.1 Results 429 16.6.2 Discussion and Speculations 430 Acknowledgments 433 References 433 17 Multiscale Modeling for the Vascular Transport of Nanoparticles 437 Shaolie S. Hossain, Adrian M. Kopacz, Yongjie Zhang, Sei-Young Lee, Tae-Rin Lee, Mauro Ferrari, Thomas J.R. Hughes, Wing Kam Liu, and Paolo Decuzzi 17.1 Introduction 437 17.2 Modeling the Dynamics of NPs in the Macrocirculation 438 17.2.1 The 3D Reconstruction of the Patient-Specific Vasculature 439 17.2.2 Modeling the Vascular Flow and Wall Adhesion of NPs 440 17.2.3 Modeling NP Transport across the Arterial Wall and Drug Release 440 17.3 Modeling the NP Dynamics in the Microcirculation 448 17.3.1 Semi-analytical Models for the NP Transport 449 17.3.2 An IFEM for NP and Cell Transport 452 17.4 Conclusions 456 Acknowledgments 456 References 457 Index 461

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Book SynopsisAn in-depth treatment of cutting-edge work being done internationally to develop new techniques in crop nutritional quality improvement Phytonutritional Improvement of Crops explores recent advances in biotechnological methods for the nutritional enrichment of food crops.Table of ContentsList of Contributors xv Foreword xxi 1 Important Plant-Based Phytonutrients 1Avik Basu, Saikat Kumar Basu, Ratnabali Sengupta, Muhammad Asif, Xianping Li, Yanshan Li, Arvind Hirani, Peiman Zandi, Muhammad Sajad, Francisco Solorio-Sánchez, Ambrose Obongo Mbuya, William Cetzal-Ix, Sonam Tashi, Tshitila Jongthap,Danapati Dhungyel and Mukhtar Ahmad List of Abbreviations 1 1.1 Introduction 2 1.2 Nutraceuticals and Functional Foods in Human Health 3 1.3 Plants with Potential for Use as Nutraceutical Source and Functional Food Component 49 1.4 Nutraceutical Values of Fenugreek 49 1.4.1 Fenugreek Possesses the Following Medicinal Properties 50 1.5 Coloured Potatoes as Functional Food 51 1.6 Red Wine as Functional Food 54 1.7 Tea as Functional Food 54 1.8 Cereals as Nutraceuticals 55 1.9 Nutraceutical Properties of Wheat Bran and Germ 58 1.9.1 Wheat Bran 58 1.9.2 Wheat Germ 59 1.10 Barley and Oat as Nutraceuticals 59 1.11 Value-Added Products 59 1.12 Conclusion 61 Acknowledgements 61 References 61 2 Biotechnological Interventions for Improvement of Plant Nutritional Value: From Mechanisms to Applications 83 Rajan Katoch, Sunil Kumar Singh and Neelam Thakur 2.1 Introduction 83 2.2 Improvement of Food Nutrition 84 2.3 Improvement of Nutritional Value Through Crop Improvement 85 2.4 Identification of Genes With the Potential to Improve the Nutritional Quality 86 2.5 Genetic Engineering for the Introduction of Nutritionally Potential Genes 90 2.6 Nutritional Improvement Through Recent Biotechnological Advances 92 2.7 Production of Health Care Products 94 2.7.1 The Development of Oral Vaccines in Plant System 95 2.7.2 Advantages of Plant System in the Development of Oral Vaccines 96 2.7.3 Edible Vaccine against Hepatitis B Virus 98 2.8 Major Biotechnological Advances in Nutritional Improvement of Plants 99 2.9 Conclusion 100 References 100 3 Nutrient Biofortification of Staple Food Crops: Technologies, Products and Prospects 113Chavali Kameswara Rao and Seetharam Annadana 3.1 Introduction 113 3.2 The Concepts of Nutrition and Malnutrition 114 3.2.1 Nutrition, Macronutrients, Micronutrients and Balanced Diets 114 3.2.2 Hunger, Nutritional Security, Undernutrition and Malnutrition 116 3.2.3 The Metabolic Syndrome 116 3.3 Strategies to Enhance Nutrient Intake and Nutrient Content of Plant Foods 118 3.3.1 Interventions to Enhance Nutrient Intake 118 3.3.2 Technologies for Biofortification 119 3.3.3 Common Genetic Engineering Technologies 120 3.3.4 Alternative Genetic Engineering Technologies 122 3.3.5 Recent Genetic Engineering Technologies 123 3.3.6 Moral and Ethical Arguments Against Genetic Engineering Technologies 124 3.4 Quantitative and Qualitative Modification of Dietary Carbohydrates 125 3.4.1 The Carbohydrates 125 3.4.2 Modifying Levels of Components of Starch 128 3.4.3 Engineering Levels of Fructans 129 3.4.4 Quantitative and Qualitative Enhancement Dietary Fibre 130 3.5 Quantitative and Qualitative Enhancement of Proteins and Amino Acids 131 3.5.1 The Proteins and Amino Acids 131 3.5.2 Enhancement of Total Protein 132 3.5.3 Enhancement of Levels of Lysine 132 3.5.4 Enhancement of Levels of Methionine 133 3.5.5 Simultaneous Enhancement of levels Several Amino Acids 133 3.5.6 Artificial Storage Protein 133 3.5.7 Alternate Interventions 134 3.5.8 Non]Proteinogenic Amino Acids 135 3.6 Quantitative and Qualitative Enhancement of Fatty Acids in Oil Seed Crops 136 3.6.1 Lipids, Fats and Oils 136 3.6.2 Cholesterol 136 3.6.3 Characterisation of Fatty Acids, Dietary Fats and Oils 136 3.6.4 Quantitative and Qualitative Improvement of Oil Seed Crops 137 3.6.5 The New Shift in Fat Paradigm and Its Implications 140 3.7 Enhancement of Levels of Vitamins 141 3.7.1 The Vitamins 141 3.7.2 Retinoids (Vitamin A) 142 3.7.3 Folate (Vitamin B9) 145 3.7.4 Ascorbic Acid (Vitamin C) 146 3.7.5 Tocopherols (Vitamin E) 147 3.7.6 Multi]vitamin Corn 148 3.8 Enhancement of Levels of Mineral Elements 148 3.8.1 Role of Mineral Elements in Human Health 148 3.8.2 Iron (Fe) 150 3.8.3 Zinc (Zn) 152 3.8.4 Calcium (Ca) 154 3.8.5 Selenium (Se) 155 3.8.6 Iodine (I) 156 3.8.7 Fluoride (Fl) 157 3.9 Enhancement of Antioxidants 157 3.9.1 The Antioxidants 157 3.9.2 Lycopene 158 3.9.3 Flavonoids 159 3.9.4 Carotenoids 159 3.9.5 Other Antioxidants 160 3.9.6 Thermal Stability of Antioxidants 160 3.10 Mitigation of Levels of Antinutritional Factors 160 3.10.1 The Antinutritional Factors 160 3.10.2 Phytate 160 3.10.3 Inhibitors of Digestive Enzymes 162 3.10.4 Reducing Levels of Allergens 162 3.10.5 Other Significant Antinutritional Factors 163 3.11 Conclusions and Recommendations 163 Acknowledgement 167 References 167 4 Applications of RNA-Interference and Virus-Induced Gene Silencing (VIGS) for Nutritional Genomics in Crop Plants 185Subodh Kumar Sinha and Basavaprabhu L. Patil 4.1 Introduction 185 4.2 RNA Interference 186 4.2.1 RNAi in Modification of Primary Metabolism 186 4.2.2 RNAi for Modification of Secondary Metabolism 188 4.3 Virus-Induced Gene Silencing (VIGS) for Biofortification 192 4.4 Conclusions 195 References 196 5 Strategies for Enhancing Phytonutrient Content in Plant-Based Foods 203Carla S. Santos, Noureddine Benkeblia and Marta W. Vasconcelos 5.1 Introduction 203 5.2 What are Phytonutrients? 204 5.3 Which Plant-Based Foods are the Best Known Sources of Phytonutrients? 205 5.4 How Can We Enhance Phytonutrients? 207 5.4.1 Conventional Breeding 207 5.4.2 Molecular Breeding 208 5.4.3 Metabolic Engineering and Genetic Modification 208 5.5 Phenotyping for Phytonutrients at Different Levels 210 5.5.1 Low Throughput Techniques 210 5.5.2 High]Throughput Techniques 213 5.6 The Future Ahead/Concluding Remarks 216 Acknowledgements 217 References 217 6 The Use of Genetic Engineering to Improve the Nutritional Profile of Traditional Plant Foods 233Marta R.M. Lima, Carla S. Santos and Marta W. Vasconcelos 6.1 Introduction 233 6.1.1 Nutrients in Plant Foods 233 6.1.2 Consequences of Malnutrition 235 6.1.3 Strategies to Overcome Malnutrition 235 6.2 What Are Genetically Engineered Crops? 236 6.2.1 Plant Genetic Transformation Technologies 236 6.2.2 Traditional Foods with Enhanced Nutritional Profiles: Case Studies 238 6.3 GM Plant Foods Under Approval for Commercial Utilisation 245 6.4 Socioeconomic Impact and Safety of GM Foods 247 Acknowledgements 248 References 248 7 Carotenoids: Biotechnological Improvements for Human Health and Sustainable Development 259George G. Khachatourians 7.1 Introduction 259 7.2 Occurrence 260 7.3 Discovery and Early History 260 7.4 Carotenoids Use in Human Foods and Biotechnology 262 7.5 Use of Carotenoids in Animal Feed 264 7.6 Global Market Situation and Sustainability 264 7.7 Carotenoid Biosynthesis and Function in Plants 266 7.8 Conclusion and Perspectives 268 References 268 8 Progress in Enrichment and Metabolic Profiling of Diverse Carotenoids in Tropical Fruits: Importance of Hyphenated Techniques 271Bangalore Prabhashankar Arathi, Poorigali Raghavendra]Rao Sowmya, Kariyappa Vijay, Vallikannan Baskaran and Rangaswamy Lakshminarayana 8.1 Introduction 271 8.2 Trends in Biosynthesis of Carotenoids and their Profiling in Plants and Tropical Fruits 274 8.3 Biotechnological Approaches to Enrich Carotenoids in Tropical Fruits 281 8.3.1 Conventional Approaches to Enrich Carotenoids in Tropical Fruits 283 8.3.2 Pre] and Post]Harvest Technology to Improve Carotenoids Contents in Tropical Fruits 283 8.4 Bioaccessibility and Bioavailability of Carotenoids From Fruits and Their Products 285 8.5 Techniques to Characterise Carotenoids from Fruits 291 8.6 Conclusion 294 Acknowledgements 294 References 295 9 Improvement of Carotenoid Accumulation in Tomato Fruit 309Lihong Liu, Zhiyong Shao, Min Zhang, Tianyu Liu, Haoran Liu, Shuo Li, Yuanyuan Liu and Qiaomei Wang List of Abbreviations 309 9.1 Introduction 310 9.2 Metabolism of Carotenoid in Tomato 312 9.2.1 Biosynthesis of Carotenoid 312 9.2.2 Catabolism of Carotenoid 315 9.3 The Biosynthetic Capacities of the Plastid 316 9.4 Hormonal Regulatory Network of Carotenoid Metabolism 317 9.4.1 Ethylene 317 9.4.2 Jasmonates 318 9.4.3 Brassinosteroids 319 9.4.4 Abscisic acid 319 9.4.5 Gibberellin 320 9.4.6 Auxin 320 9.5 Environmental Regulation of Carotenoid Metabolism 320 9.5.1 Light 320 9.5.2 Temperature 322 9.5.3 Carbon Dioxide (CO2) 322 9.5.4 Post]Harvest Regulation 322 9.6 Bioavailability of Carotenoid 322 9.7 Food Omics 324 Acknowledgements 324 References 327 10 Modern Biotechnologies and Phytonutritional Improvement of Grape and Wine 339Atanas Atanassov, Teodora Dzhambazova, Ivanka Kamenova, Ivan Tsvetkov, Vasil Georgiev, Ivayla Dincheva, Ilian Badjakov, Dasha Mihaylova, Miroslava Kakalova, Atanas Pavlov and Plamen Mollov 10.1 Grape Genomics 339 10.1.1 Identifying Genes Behind the Main Secondary Metabolites 340 10.1.2 Identifying Disease Resistance Genes in Vitis sp.—a New Level of Grapevine Breeding 341 10.2 Marker Assisted Selection (MAS) and Genomic Selection (GS) of Grapevine 342 10.3 Engineered Resistance to Viruses 343 10.4 Diagnosis of Grapevine Viruses 350 10.4.1 Biological Assays 350 10.4.2 Serological Assays 350 10.4.3 Molecular Assays 351 10.5 Phytonutritional Compounds with Biological Activity in Grape and Wine and Their Target Analyses 353 10.5.1 Biologically Active Substances Found in Grape and Wine 353 10.5.2 LC]MS and GC]MS Based Analysis and Metabolomics 358 10.5.3 NMR–Based Metabolomic Analysis of Grape and Wine 360 10.6 Wine Quality 361 10.6.1 What is the Particular Meaning We Imply to the Term ‘Quality of Wine’? 361 10.6.2 How is the Wine Quality Created? 362 10.7 Grapevine Genetic Resources] Prospects in Management and Sustainable Use 367 10.7.1 European Policy, Regulation and Coordination Initiatives 367 10.7.2 Vitis Grapevine Genebanks, Collections and Databases 368 10.7.3 European Scientific Achievements 369 References 370 11 Phytonutrient Improvements of Sweetpotato 391 Noureddine Benkeblia 391 11.1 Introduction 391 11.2 Nutritional Qualities of Sweetpotato 393 11.3 Phytonutrient Improvements of Sweetpotato 396 10.3.1 Sweetpotato Improvement for β]Carotene 396 10.3.2 Sweetpotato Improvement for Anthocyanins and Phenolics 397 10.3.3 Other Nutrient Improvements 399 11.4 Conclusion and Future Perspectives 399 Acknowledgements 400 References 400 12 Improvement of Glucosinolate in Cruciferous Crops 407Huiying Miao, Bo Sun, Yanting Zhao, Hongmei Qian, Congxi Cai, Jiaqi Chang, Mingdan Deng, Xin Zhang and Qiaomei Wang List of Abbreviations 407 12.1 Introduction 408 12.2 Glucosinolate Breakdown 408 12.2.1 Glucosinolate Breakdown Upon Tissue Damage 409 12.2.2 Glucosinolate Breakdown in Living Plant Cell 410 12.2.3 Glucosinolate Hydrolysis in Mammalian 411 12.3 Biological Functions of Glucosinolates and Their Hydrolysis Products 411 12.3.1 Anticarcinogenic Mechanism 411 12.3.2 Other Chemopeventive Effects 413 12.3.3 Adverse Effects 413 12.4 Glucosinolate Biosynthesis 414 12.4.1 Side-Chain Elongation 414 12.4.2 Formation of Core Glucosinolate Structure 414 12.4.3 Secondary Modifications 416 12.4.4 Regulators of Glucosinolate Biosynthetic Pathway 416 12.5 Metabolic Engineering of Glucosinolates in Brassica Crops 418 12.6 Glucosinolate Accumulation under Pre-Harvest and Post-Harvest Handlings 421 12.6.1 Effects of Light on Glucosinolate Accumulation 422 12.6.2 Chemical Regulation of Glucosinolate Accumulation 423 12.6.3 Glucosinolate Changes upon Post-Harvest Handlings 427 12.7 Conclusions and Future Prospects 432 Acknowledgements 433 References 433 13 Development of the Transgenic Rice Accumulating Flavonoids in Seed by Metabolic Engineering 451Yuko Ogo and Fumio Takaiwa 13.1 Introduction 451 13.2 Production of Flavonoids in Rice Seed by Ectopic Expression of the Biosynthetic Enzymes 454 13.3 Production of Flavonoids in Rice Seed by Ectopic Expression of the Transcription Factors 458 13.4 Characterisation of Flavonoids in Transgenic Rice Seed by LC–MS-based Metabolomics 460 13.5 Future Prospects 461 References 463 14 Nutrient Management for High Efficiency Sweetpotato Production 471Yong]Chun Zhang, Ji]Dong Wang, Yan]Xi Shi and Dai]Fu Ma 14.1 Patterns of Growth and Development and Nutrient Absorption in Sweetpotato 471 14.1.1 Area under Sweetpotato 471 14.1.2 Growth Characteristics 471 14.1.3 Nutrient Requirements 472 14.1.4 Factors Affecting Nutrient Absorption 472 14.2 Screening of High Efficient of Potassium Uptake and Utilised Genotypes 474 14.2.1 Potassium Deficiency 474 14.2.2 Potassium Use Efficiency and Utilisation Efficiency 476 14.2.3 Screening of High Uptake Efficiency Genotypes 476 14.2.4 Screening of High Use Efficiency Genotypes 478 14.3 Effect of Fertilisers 480 14.3.1 Effect of Nitrogen Application 480 14.3.2 Effect of Phosphorus Application 482 14.3.3 Effect of Potassium Application 482 14.3.4 Effect of Nitrogen, Phosphorus, and Potassium Application on Yield 483 14.4 Balanced Fertiliser Management in Sweetpotato at Sishui, Shandong: A Case Study 483 14.4.1 General Description of Area 483 14.4.2 Major Steps Towards Balanced Application of Fertilisers 485 14.4.3 Establishment and Application of an Expert Consultation System 491 14.5 Application of Fertilisers Through Drip Irrigation (‘Fertigation’) 493 14.5.1 Effect of Supplying Fertilisers Through Drip Irrigation on Sweetpotato 494 14.5.2 Input/output Ratio in Application of Fertilisers Through Drip Irrigation 495 Acknowledgements 495 References 495 Index 499

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Book SynopsisPresents the methodology and applications of ODE and PDE models within biomedical science and engineering With an emphasis on the method of lines (MOL) for partial differential equation (PDE) numerical integration, Method of Lines PDE Analysis in Biomedical Science and Engineering demonstrates the use of numerical methods for the computer solution of PDEs as applied to biomedical science and engineering (BMSE). Written by a well-known researcher in the field, the book provides an introduction to basic numerical methods for initial/boundary value PDEs before moving on to specific BMSE applications of PDEs. Featuring a straightforward approach, the book's chapters follow a consistent and comprehensive format. First, each chapter begins by presenting the model as an ordinary differential equation (ODE)/PDE system, including the initial and boundary conditions. Next, the programming of the model equations is introduced through a series of R routines that primarily implement MOL for PDETrade Review"This book demonstrates the use of numerical methods for the computer solution of partial differential equations (PDEs) as applied to biomedical science and engineering...The book is worth reading not only for mathematicians but also for, e.g., chemical engineers, medical researchers, clinicians, epidemiologists and statisticians." (Mathematical Reviews/MathSciNet June 2017)Table of ContentsPreface xiAbout the Companion Website xiii1 An Introduction to MOL Analysis of PDEs: Wave Front Resolution in Chromatography 11.1 1D 2-PDE model, 21.2 MOL routines, 71.2.1 Main program, 71.2.2 MOL/ODE routine, 161.2.3 Subordinate routines, 201.3 Model output, single component chromatography, 211.3.1 FDs, step BC, 211.3.2 Flux limiters, step BC, 391.3.3 FDs, pulse BC, 481.3.4 Flux limiters, pulse BC, 501.4 Multi component model, 531.5 MOL routines, 541.5.1 Main program, 541.5.2 MOL/ODE routine, 621.6 Model output, multi component chromatography, 67References, 682 Wave Front Resolution in VEGF Angiogenesis 692.1 1D 2-PDE model, 702.2 MOL routines, 722.2.1 Main program, 722.2.2 MOL/ODE routine, 812.2.3 Subordinate routines, 852.3 Model output, 862.3.1 Comparison of numerical and analytical solutions, 862.3.2 Effect of diffusion on the traveling-wave solution, 882.4 Conclusions, 88References, 893 Thermographic Tumor Location 913.1 2D, 1-PDE model, 923.2 MOL analysis, 943.2.1 ODE routine, 943.2.2 Main program, 1003.3 Model output, 1053.4 Summary and conclusions, 110References, 1114 Blood-Tissue Transport 1134.1 1D 2-PDE model, 1144.2 MOL routines, 1154.2.1 MOL/ODE routine, 1154.2.2 Main program, 1194.2.3 Bessel function routine, 1284.3 Model output, 1294.4 Model extensions, 1334.5 Conclusions and summary, 142References, 1435 Two-Fluid/Membrane Model 1455.1 2D, 3-PDE model, 1465.2 MOL analysis, 1475.2.1 MOL/ODE routine, 1485.2.2 Main program, 1535.3 Model output, 1605.4 Summary and conclusions, 1626 Liver Support Systems 1656.1 2-ODE patient model, 1666.2 Patient ODE model routines, 1676.2.1 Main program, 1676.2.2 ODE routine, 1726.3 Model output, 1746.4 8-PDE ALSS model, 1766.4.1 Membrane unit MU1, 1776.4.2 Adsorption unit AU1, 1776.4.3 Adsorption unit AU2, 1786.4.4 Membrane unit MU2, 1796.5 Patient-ALSS ODE/PDE model routines, 1806.5.1 Main program, 1806.5.2 ODE routine, 1886.6 Model output, 1956.7 Summary and conclusions, 196Appendix - Derivation of PDEs for Membrane and Adsorption Units, 200A.1 PDEs for Membrane Units, 200A.2 PDEs for Adsorption Units, 202References, 2037 Cross Diffusion Epidemiology Model 2057.1 2-PDE model, 2057.2 Model routines, 2077.2.1 Main program, 2077.2.2 ODE routine, 2157.3 Model output, 2187.3.1 ncase = 1, time-invariant solution, 2187.3.2 ncase = 2, transient solution, no cross diffusion, 2207.3.3 ncase = 3, transient solution with cross diffusion, 2227.4 Summary and conclusions, 224Reference, 2258 Oncolytic Virotherapy 2278.1 1D 4-PDE model, 2288.2 MOL routines, 2298.2.1 Main program, 2308.2.2 MOL/ODE routine, 2408.2.3 Subordinate routine, 2458.3 Model output, 2468.4 Summary and conclusions, 273Reference, 2749 Tumor Cell Density in Glioblastomas 2759.1 1D PDE model, 2769.2 MOL routines, 2779.2.1 Main program, 2779.2.2 MOL/ODE routine, 2869.3 Model output, 2899.3.1 Output for ncase = 1, linear, 2909.3.2 Output for ncase = 2, logistic, 2959.3.3 Output for ncase = 3, Gompertz, 2969.4 p-refinement error analysis, 2999.5 Summary and conclusions, 301References, 30110 MOL Analysis with a Variable Grid: Antigen-Antibody Binding Kinetics 30310.1 ODE/PDE model, 30310.2 MOL routines, 30610.2.1 Main program, 30610.2.2 MOL/ODE routine, 31410.3 Model output, 31810.3.1 Uniform grid, 31810.3.2 Variable grid, 32110.4 Summary and conclusions, 325Appendix: Variable Grid Analysis, 327A.1 Derivation of numerical differentiators, 327A.2 Testing of numerical differentiators, 331A.2.1 Differentiation matrix, 331A.2.2 Test functions, 332References, 340AppendicesAppendix A Derivation of Convection-Diffusion-ReactionPartial Differential Equations 341Appendix B Functions dss012, dss004, dss020, vanl 345Index 351

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Book SynopsisA comprehensive reference on biochemistry, bioimaging, bioanalysis, and therapeutic applications of carbon nanomaterials Carbon nanomaterials have been widely applied for biomedical applications in the past few decades, because of their unique physical properties, versatile functionalization chemistry, and biological compatibility. This book provides background knowledge at the entry level into the biomedical applications of carbon nanomaterials, focusing on three applications: bioimaging, bioanalysis, and therapy. Carbon Nanomaterials for Bioimaging, Bioanalysis and Therapy begins with a general introduction to carbon nanomaterials for biomedical applications, including a discussion about the pros and cons of various carbon nanomaterials for the respective therapeutic applications. It then goes on to cover fluorescence imaging; deep tissue imaging; photoacoustic imaging; pre-clinical/clinical bioimaging applications; carbon nanomaterial sensors for canceTable of ContentsList of Contributors xiii Series Preface xix Preface xxi Part I Basics of Carbon Nanomaterials 1 1 Introduction to Carbon Structures 3 Meng-Chih Su and Yuen Yung Hui 1.1 Carbon Age 3 1.2 Classification 4 1.3 Fullerene 4 1.4 Carbon Nanotubes 6 1.4.1 Structure 6 1.4.2 Electronics 8 1.5 Graphene 10 1.5.1 Structure 10 1.5.2 Electronics 11 1.6 Nanodiamonds and Carbon Dots 12 Acknowledgment 13 References 13 2 Using Polymers to Enhance the Carbon Nanomaterial Biointerface 15 Goutam Pramanik, Jitka Neburkova, Vaclav Vanek, Mona Jani, Marek Kindermann, and Petr Cigler 2.1 Introduction 15 2.2 Colloidal Stability of CNMs 16 2.3 Functionalization of CNMs with Polymers 18 2.3.1 Noncovalent Approaches 18 2.3.2 Covalent Approaches 18 2.4 Influence of Polymers on the Spectral Properties of CNMs 19 2.5 Functionalizing CNMs with Antifouling Polymers for Bioapplications 22 2.6 Functionalization of CNMs with Stimuli‐Responsive Polymers 26 2.6.1 Carbon Nanoparticles with Thermoresponsive Polymers 27 2.6.2 pH‐Responsive Carbon Nanoparticles 27 2.6.3 Redox‐Responsive Carbon Nanoparticles 28 2.6.4 Multi‐Responsive Carbon Nanoparticles 28 2.7 Functionalization of CNMs with Polymers for Delivery of Nucleic Acids 29 2.8 Outlook 32 Acknowledgments 34 References 34 3 Carbon Nanomaterials for Optical Bioimaging and Phototherapy 43 Haifeng Dong and Yu Cao 3.1 Introduction 43 3.2 Surface Functionalization of Carbon Nanomaterials 43 3.3 Carbon Nanomaterials for Optical Imaging 45 3.3.1 Intrinsic Fluorescence of Carbon Nanomaterials 45 3.3.2 Imaging Utilizing Intrinsic Fluorescence Features of Carbon Nanomaterials 46 3.3.3 Imaging with Fluorescently Labeled Carbon Nanomaterials 51 3.4 Carbon Nanomaterials for Phototherapies of Cancer 51 3.4.1 Photothermal Therapy 52 3.4.2 Photodynamic Therapy 53 3.5 Conclusions and Outlook 56 References 56 Part II Bioimaging and Bioanalysis 63 4 High‐Resolution and High‐Contrast Fluorescence Imaging with Carbon Nanomaterials for Preclinical and Clinical Applications 65 John Czerski and Susanta K. Sarkar 4.1 Introduction 65 4.2 Survey of Carbon Nanomaterials 66 4.2.1 Fluorescent Nanodiamonds 66 4.2.2 Carbon Nanotubes 66 4.2.3 Graphene 69 4.2.4 Carbon Nanodots 69 4.3 Fluorescent Properties of FNDs and SWCNTs 69 4.3.1 FNDs 69 4.3.2 SWCNTs 71 4.4 Survey of High‐Resolution and High‐Contrast Imaging 71 4.4.1 General Considerations for Eventual Human Use 71 4.4.2 General Considerations for Achieving High‐Resolution and High‐Contrast Imaging 72 4.4.2.1 Photoacoustic Imaging (PAI) 72 4.4.2.2 X‐ray Computed Tomographic (CT) Imaging 73 4.4.2.3 Magnetic Resonance Imaging (MRI) 73 4.4.2.4 Image Alignment and Drift Correction 74 4.4.3 Preclinical and Clinical Optical Imaging with CNMs 74 4.4.4 Optical Imaging in the Short‐Wavelength Window (~650–950 nm) 74 4.4.4.1 Optical Imaging beyond the Diffraction Limit 75 4.4.4.2 Selective Modulation of Emission 75 4.4.4.3 Time‐Gated Fluorescence Lifetime Imaging 77 4.4.5 Optical Imaging in the Long‐Wavelength Window (~950–1400 nm) 77 4.5 Conclusions 78 References 79 5 Carbon Nanomaterials for Deep‐Tissue Imaging in the NIR Spectral Window 87 Stefania Lettieri and Silvia Giordani 5.1 Introduction 87 5.1.1 Transparent Optical Windows in Biological Tissue 87 5.1.2 Near‐Infrared Imaging Materials 88 5.2 Carbon Nanomaterials for NIR Imaging 89 5.2.1 Biocompatibility of CNMs 90 5.2.2 Fluorescence of CNMs Probes 91 5.2.3 Covalent and Noncovalent Functionalization 91 5.2.4 CNMs as Bioimaging Platforms 91 5.2.4.1 Fullerene 91 5.2.4.2 Carbon Nanotubes 93 5.2.4.3 Graphene Derivatives 99 5.2.4.4 Carbon Dots 100 5.2.4.5 Carbon Nano-onions 102 5.2.4.6 Nanodiamonds 104 5.3 Conclusions and Outlook 105 Acknowledgments 106 References 106 6 Tracking Photoluminescent Carbon Nanomaterials in Biological Systems 115 Simon Haziza, Laurent Cognet, and François Treussart Chapter Summary 115 6.1 Introduction 115 6.2 Tracking Cells in Organisms with Fluorescent Nanodiamonds 116 6.3 Monitoring Inter and Intra Cellular Dynamics with Fluorescent Nanodiamonds 120 6.4 Single‐Walled Carbon Nanotubes: A Near‐Infrared Optical Probe of the Nanoscale Extracellular Space in Live Brain Tissue 127 6.5 Conclusion 131 References 132 7 Photoacoustic Imaging with Carbon Nanomaterials 139 Seunghyun Lee, Donghyun Lee, and Chulhong Kim Chapter Summary 139 7.1 Introduction 139 7.2 Photoacoustic Imaging Systems 140 7.2.1 Photoacoustic Microscopy 141 7.2.2 Photoacoustic Computed Tomography 142 7.3 Photoacoustic Application of Carbon Nanomaterials 145 7.3.1 Carbon Nanomaterials for Photoacoustic Imaging Contrast Agents 146 7.3.2 Carbon Nanomaterials for Multimodal Photoacoustic Imaging 149 7.3.3 Carbon Nanomaterials for Photoacoustic Image‐Guided Therapy 156 7.3.4 Conclusions and Future Perspective 160 Acknowledgments 161 References 162 8 Carbon Nanomaterial Sensors for Cancer and Disease Diagnosis 167 Tran T. Tung, Kumud M. Tripathi, TaeYoung Kim, Melinda Krebsz, Tibor Pasinszki, and Dusan Losic 8.1 Introduction 167 8.2 Detection of VOC by Using Gas/Vapor Sensors for Cancer and Disease Diagnosis 169 8.2.1 Carbon Nanodots (CNDs) and Graphene Quantum Dots (GQDs) for VOC Sensors 171 8.2.2 Carbon Nanotubes (CNTs) for VOC Sensors 173 8.2.3 Graphene for VOC Sensors 176 8.3 Detection of Biomarkers Using Biosensors for Cancer and Disease Diagnosis 179 8.3.1 Carbon Nanodot‐ and Graphene Quantum Dot‐Based Biosensors for Disease Biomarkers Detection 179 8.3.2 Carbon Nanotube‐Based Biosensors for Cancer Biomarker Detection 182 8.3.3 Carbon Nanotube‐Based Biosensors for Disease Biomarker Detection 186 8.3.4 Graphene‐Based Biosensors for Cancer Biomarker Detection 188 8.3.5 Graphene‐Based Biosensors for Disease Biomarker Detection 190 8.4 Conclusions and Perspectives 192 Acknowledgments 193 References 193 9 Recent Advances in Carbon Dots for Bioanalysis and the Future Perspectives 203 Jessica Fung Yee Fong, Yann Huey Ng, and Sing Muk Ng 9.1 Introduction 203 9.2 Fundamentals of CDs 205 9.2.1 Synthesis Approaches 205 9.2.2 Optical Properties 206 9.2.2.1 Absorbance and Photoluminescence (PL) 206 9.2.2.2 Quantum Yield (QY) 210 9.2.2.3 Photoluminescence Origins 210 9.2.2.4 Up‐Conversion Photoluminescence (UCPL) 211 9.2.2.5 Phosphorescence 212 9.2.3 Physical and Chemical Properties 213 9.2.4 Biosafety Assessments 214 9.3 Bioengineering of CDs for Bioanalysis 216 9.3.1 Functionalization Mechanism and Strategies 216 9.3.1.1 Chemical Functionalization 216 9.3.1.2 Doping 217 9.3.1.3 Coupling with Gold Nanoparticles 217 9.3.1.4 Fabrication onto Solid Polymeric Matrices 218 9.3.2 Biomolecules Grafted on CDs as Sensing Receptors 218 9.3.2.1 Deoxyribonucleic Acid (DNA) 218 9.3.2.2 Aptamers 219 9.3.2.3 Proteins/Peptides 219 9.3.2.4 Biopolymers 220 9.4 Bioanalysis Applications of CDs 221 9.4.1 Biosensing Mechanism/Transduction Schemes 221 9.4.1.1 Fluorescence 222 9.4.1.2 Chemiluminescence (CL) 223 9.4.1.3 Electrochemiluminescence (ECL) 224 9.4.1.4 Electrochemical 224 9.4.2 Uses of CDs in Bioanalysis 225 9.4.2.1 Heavy Metals/Elements 225 9.4.2.2 Reactive Oxygen/Nitrogen Species (ROS/RNS) 226 9.4.2.3 Oligonucleotides 227 9.4.2.4 Small Molecules/Pharmaceutical Drugs/Natural Compounds 228 9.4.2.5 Proteins 230 9.4.2.6 Enzyme Activities and Inhibitor Screening 231 9.4.2.7 pH 232 9.4.2.8 Temperature 234 9.4.3 Solid‐State Sensing for Point‐of‐Care Diagnostic Kits 234 9.4.4 Bioimaging/Real‐Time Monitoring 236 9.4.5 Theranostics 238 9.5 Future Perspectives 240 9.5.1 Better Understanding of PL Mechanisms 240 9.5.2 Establishment of Systematic Synthesis Protocol 241 9.5.3 QY Improvement and Spectral Expansion to Longer Wavelength 241 9.5.4 Sensitivity Improvement for Solid‐State Sensing 242 9.6 Conclusions 242 References 242 Part III Therapy 265 10 Functionalized Carbon Nanomaterials for Drug Delivery 267 Naoki Komatsu 267 10.1 Introduction 267 10.2 Direct Fabrication of Graphene‐Based Composite with Photosensitizer for Cancer Phototherapy 268 10.2.1 Fabrication of Graphene‐Based Composite with Chlorin e6 (G‐Ce6) 268 10.2.2 Characterization of G‐Ce6 268 10.2.3 In vitro Evaluation of G‐Ce6 for Cancer Phototherapy 272 10.3 Polyglycerol‐Functionalized Nanodiamond Conjugated with Platinum‐Based Drug for Cancer Chemotherapy 274 10.3.1 Synthesis of Polyglycerol‐Functionalized Nanodiamond Conjugated with Platinum‐Based Drug and Targeting Peptide 274 10.3.2 Characterization of Polyglycerol‐Functionalized Nanodiamond and the Derivatives 276 10.3.3 In vitro Evaluation of Polyglycerol‐Functionalized Nanodiamond Conjugated with Platinum‐Based Drug for Cancer Chemotherapy 279 10.4 Polyglycerol‐Functionalized Nanodiamond Hybridized with DNA for Gene Therapy 280 10.4.1 Synthesis and Characterization of Polyglycerol‐Functionalized Nanodiamond Conjugated with Basic Polypeptides 280 10.4.2 Characterization of Polyglycerol‐Functionalized Nanodiamond Hybridized with Plasmid DNA 280 10.5 Conclusions and Perspectives 283 Acknowledgments 285 References 285 11 Multifunctional Graphene‐Based Nanocomposites for Cancer Diagnosis and Therapy 289 Ayuob Aghanejad, Parinaz Abdollahiyan, Jaleh Barar, and Yadollah Omidi 11.1 Introduction 289 11.2 Multifunctional Graphene‐Based Composites for the Diagnosis/Therapy of Cancer 291 11.2.1 Metal‐Graphene Nanocomposites 292 11.2.1.1 Gold‐Graphene Composites 292 11.2.1.2 Magnetic Graphene Nanocomposites 294 11.2.2 Polymeric Graphene Nanocomposites 295 11.2.3 Graphene Biomaterials for MR Imaging 299 11.3 Multimodal Graphene‐Based Composites for the Radiotherapy of Cancer 300 11.4 Graphene‐Based Nanobiomaterials for Cancer Diagnosis 302 11.5 Conclusion 302 Acknowledgment 303 References 303 12 Carbon Nanomaterials for Photothermal Therapies 309 Jiantao Yu, Lingyan Yang, Junyan Yan, Wen‐Cheng Wang, Yi‐Chun Chen, Hung‐Hsiang Chen, and Chia‐Hua Lin 12.1 Introduction 309 12.2 GO for PTT 311 12.2.1 PTT‐Related Physical and Chemical Properties of GO 311 12.2.2 GO for in vitro PTT 312 12.2.3 GO for in vivo PTT 314 12.3 CNTs and CNHs for PTT 314 12.3.1 Physical and Chemical Properties of CNTs and CNHs Related to PTT 315 12.3.2 CNTs and CNHs for in vitro PTT 316 12.3.3 CNTs and CNHs for in vivo PTT 316 12.4 CDs and GDs for PTT 318 12.4.1 Physical and Chemical Properties of CDs and GDs Related to PTT 318 12.4.2 CDs and GDs for in vitro PTT 319 12.4.3 CDs and GDs for in vivo PTT 319 12.5 Fullerenes for PTT 320 12.5.1 Physical and Chemical Properties of Fullerenes Related to PTT 320 12.5.2 Fullerenes for in vitro PTT 320 12.5.3 Fullerenes for in vivo PTT 321 12.6 Carbon Nanomaterial‐Based Nanocomposites for PTT 321 12.6.1 GO‐Based Nanocomposites for PTT 322 12.6.2 CNT‐Based Nanocomposites for PTT 323 12.6.3 CD‐ and GD‐Based Nanocomposites for PTT 323 12.7 Carbon Nanomaterial‐Based Combined Therapy with PTT 324 12.7.1 Chemotherapy 324 12.7.2 RT 324 12.7.3 Photodynamic Therapy (PDT) 325 12.7.4 Gene Therapy 325 12.7.5 Immune Therapy 327 12.7.6 Theranostic Applications 328 12.8 Conclusions and Perspectives 329 References 330 Index 341

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Book SynopsisWritten by leading experts in the field, Cyanobacteria: An Economic Perspective is a comprehensive edited volume covering all areas of an important field and its application to energy, medicine and agriculture. Issues related to environment, food and energy have presented serious challenge to the stability of nation-states. Increasing global population, dwindling agriculture and industrial production, and inequitable distribution of resources and technologies have further aggravated the problem. The burden placed by increasing population on environment and especially on agricultural productivity is phenomenal. To provide food and fuel to such a massive population, it becomes imperative to find new ways and means to increase the production giving due consideration to biosphere's ability to regenerate resources and provide ecological services. Cyanobacteria are environment friendly resource for commercial production of active biochemicals, drugs and future energy Table of ContentsList of contributors ix Preface xiii About the editors xv Acknowledgements xvii About the book xix Introduction xxi Naveen K. Sharma, Ashwani K. Rai, and Lucas J. Stal About the companion website xxv PART I: BIOLOGY AND CLASSIFICATION OF CYANOBACTERIA 1 Chapter 1 Cyanobacteria: biology, ecology and evolution 3 Aharon Oren Chapter 2 Modern classification of cyanobacteria 21 Ji¢§r´©¥ Kom´arek PART II: ECOLOGICAL SERVICES RENDERED BY CYANOBACTERIA 41 Chapter 3 Ecological importance of cyanobacteria 43 Beatriz D´©¥ez and Karolina Ininbergs Chapter 4 Cyanobacteria and carbon sequestration 65 Eduardo Jacob-Lopes, Leila Queiroz Zepka, and Maria Isabel Queiroz Chapter 5 Ecology of cyanobacteria on stone monuments, biodeterioration, and the conservation of cultural heritage 73 Nitin Keshari and Siba Prasad Adhikari PART III: CYANOBACTERIAL PRODUCTS 91 Chapter 6 Therapeutic applications of cyanobacteria with emphasis on their economics 93 Rathinam Raja, Shanmugam Hemaiswarya, Isabel S. Carvalho, and Venkatesan Ganesan Chapter 7 Spirulina: an example of cyanobacteria as nutraceuticals 103 Masayuki Ohmori and Shigeki Ehira Chapter 8 Ultraviolet photoprotective compounds from cyanobacteria in biomedical applications 119 Tanya Soule and Ferran Garcia-Pichel Chapter 9 Cyanobacteria as a ‘‘green’’ option for sustainable agriculture 145 Radha Prasanna, Anjuli Sood, Sachitra Kumar Ratha, and Pawan K. Singh Chapter 10 The economics of cyanobacteria-based biofuel production: challenges and opportunities 167 Naveen K. Sharma and Lucas J. Stal Chapter 11 Cyanobacterial cellulose synthesis in the light of the photanol concept 181 R. Milou Schuurmans, Hans C.P. Matthijs, Lucas J. Stal, and Klaas J. Hellingwerf Chapter 12 Exopolysaccharides from cyanobacteria and their possible industrial applications 197 Giovanni Colica and Roberto De Philippis Chapter 13 Phycocyanins 209 Ruperto Bermejo Chapter 14 Cyanobacterial polyhydroxyalkanoates: an alternative source for plastics 227 Shilalipi Samantaray, Ranjana Bhati, and Nirupama Mallick PART IV: HARMFUL ASPECTS 245 Chapter 15 Costs of harmful blooms of freshwater cyanobacteria 247 David P. Hamilton, Susanna A. Wood, Daniel R. Dietrich, and Jonathan Puddick Chapter 16 Cyanotoxins 257 Jason N. Woodhouse, Melissa Rapadas, and Brett A. Neilan PART V: TOOLS, TECHNIQUES, AND PATENTS 269 Chapter 17 Photobioreactors for cyanobacterial culturing 271 A. Catarina Guedes, Nadpi G. Katkam, Jo˜ao Varela, and Francisco XavierMalcata Chapter 18 Commercial-scale culturing of cyanobacteria: an industrial experience 293 Hiroyuki Takenaka and Yuji Yamaguchi Chapter 19 Engineering cyanobacteria for industrial products 303 Timo H.J. Niedermeyer, Ekaterina Kuchmina, and Annegret Wilde Chapter 20 Cryopreservation of cyanobacteria 319 John G. Day Chapter 21 Patents on cyanobacteria and cyanobacterial products and uses 329 Michael A. Borowitzka Index 339

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Book SynopsisCarbohydrates are ubiquitous, essential molecules, as important as nucleic acids and proteins yet less well understood. Mounting data demonstrate that microbial and mammalian glycans and their protein-binding partners (lectins) play central roles in all innate and adaptive immune responses. Indeed, programmed remodeling of host glycans can modulate infection, autoimmunity, and cancer, while microbial glycoconjugates can serve as canonical innate receptor agonists that induce B cell and T cell activation. Glycobiology of the Immune Response explores the integration of state-of-the-art glycobiology and immunology to raise awareness of the multifaceted roles of glycans and lectins in the immune system NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit http://ordering.onlinelibrary.wiley.com/subs.asp?ref=1749-6632&doi=10.1111/(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 about becoming a member.Trade Review“Glycobiology of the Immune Response explores the integration of state-of-the art glycobiology and immunology to raise awareness of the multifaceted roles of glycans and lectins in the immune system.” (European Journal of Immunology, 1 December 2012) Table of ContentsGlycobiology of immune responses 1 Gabriel A. Rabinovich, Yvette van Kooyk and Brian A. Cobb Multifarious roles of sialic acids in immunity 16 Ajit Varki and Pascal Gagneux Siglecs as sensors of self in innate and adaptive immune responses 37 James C. Paulson, Matthew S. Macauley and Norihito Kawasaki Interleukin-2, Interleukin-7, T cell-mediated autoimmunity, and N-glycosylation 49 Ari Grigorian, Haik Mkhikian and Michael Demetriou T cells modulate glycans on CD43 and CD45 during development and activation, signal regulation, and survival 58 Mary C. Clark and Linda G. Baum Interplay between carbohydrate and lipid in recognition of glycolipid antigens by natural killer T cells 68 Bo Pei, Jose Luis Vella, Dirk Zajonc and Mitchell Kronenberg Gelectins in acute and chronic inflammation 80 Fu-Tong Liu, Ri-Yao Yang and Daniel K. Hsu Mechanisms underlying in vivo polysaccharide-specific immunoglobulin responses to intact extracellular bacteria 92 Clifford M. Snapper CD33-related siglecs as potential modulators of inflammatory responses 102 Paul R. Crocker, Sarah J. McMillan and Hannah E. Richards Sulfated glycans control lymphocyte homing 112 Hiroto Kawashima and Minoru Fukuda Acute phase glycoproteins: bystanders or participants in carcinogenesis? 122 Eugene Dempsey and Pauline M. Rudd Glycans, galectins, and HIV-1 infection 133 Sachiko Sato, Michel Ouellet, Christian St-Pierre and Michel J. Tremblay An evolutionary perspective on C-type lectins in infection and immunity 149 Linda M. van den Berg, Sonja I. Gringhuis and Teunis B. H. Geijtenbeck Integrated approach toward the discovery of glycol-biomarkers of inflammation-related diseases 159 Takashi Angata, Reiko Fuijinawa, Ayako Kurimoto, Kazuki Nakajima, Masaki Kato, Shinji Takamatsu, Hiroaki Korekane, Cong-Xiao Gao, Kazuaki Ohtsubo, Shinobu Kitazume and Naoyuki Taniguchi Novel roles for the IgG Fc Glycan 170 Robert M. Anthony, Fredrik Wermeling and Jeffrey V. Ravetch The effect of galectins on leukocyte trafficking in inflammation: sweet or sour? 181 Dianne Cooper, Asif J. Iqbal, Beatrice R, Grittens, Carmela Cervone and Mauro Perretti Engineering cellular trafficking via glycosyltransferase-programmed stereosubstitution 193 Robert Sackstein The expanding role of α2-3 sialylation for leukocyte trafficking in vivo 201 Markus Sperandio Beyond glycoproteins as galectin counterreceptors: effector T cell growth control of tumors via ganglioside GM1 206 Robert W. Ledeen, Gusheng Wu, Sabine André, David Bleich, Guillementte Huet, Herbert Kaltner, Jürgen Kopitz and Hans-Joachim Gabius Online only Polarization of host immune responses by helminth-expressed glycans Donald Harn Jr., Smanla Tundup and Leena Srivastava Carbohydrate-recognition in the immune system: contributions of NGL-based microarrays to ligand discovery Ten Feizi Diversity in recognition of glycans by F-type lectins and galectins: molecular, structural, and biophysical aspects Gerardo R. Vasta, Hafiz Ahmed, Mario A. Bianchet, José A. Fernández-Robledo and L. Mario Amzel

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Book SynopsisThe Global Medical Excellence Cluster (GMEC) and the New York Academy of Sciences, in collaboration with Imperial College London and King's College London, sponsored the conference "Animal Models and Their Value in Predicting Drug Efficacy and Toxicity." The goal was to provide a neutral forum to critically examine and discuss the traditional role of pre-clinical animal models in drug discovery, and how these models most effectively contribute to translational medicine and therapeutic development. International, multi-disciplinary clinical and basic science investigators convened to discuss and identify changes needed to increase the predictive power of various models for drug efficacy and toxicity in humans, and ways in which to further refine, reduce, and replace animal models in biomedical research in areas such as metabolic and cardiovascular disease, inflammation, pain. Other topics discussed included new technologies in bioimaging, biosimulation, bioinformatics, the generation of genetically modified animals, phenotype screening, alternatives to rodent models, the use of embryonic stem cells, patient-specific induced pluripotent stem cells, and humanized animal models. This volume presents a collection of short papers on some of the topics discussed at this important conference. NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit http://ordering.onlinelibrary.wiley.com/subs.asp?ref=1749-6632&doi=10.1111/(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 about becoming a member.

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Book SynopsisTribology is the “science and technology of interacting surfaces in relative motion” and encompasses the study of friction, wear and lubrication. By extension biotribology is usually defined as the tribological phenomena occurring in either the human body or in animals. Therefore, it is possible to consider tribological processes that may occur after implantation of an artificial device in the human body and the tribological processes naturally occurring in or on the tissues and organ of animals. Animals, including humans, possess a wide variety of sliding and frictional interfaces. The authors aim to provide some advances in research in biotribology. They cover several aspects of biotribology such as tribology of synovial joints and artificial replacements; wear of screws and plates in bone fractures repair; wear of denture and restorative materials; friction of the skin and comfort of clothing; wear of replacement heart valves; tribology of contact lenses and ocular tribology; biotribology on the microscale and nanoscale levels, etc. This book can be used as a research text for final undergraduate engineering courses (for example, materials, biomedical, etc.) or for those studying the subject of biotribology at the postgraduate level. It can also serve as a useful reference for academics, biomechanical researchers, biologists, chemists, physicists, biomedicals and materials engineers, and other professionals in related engineering, medicine and biomedical industries.Table of ContentsChapter 1. Biotribology of Total Hip Replacement: the Metal-on-Metal Articulation 1 J. Philippe KRETZER 1.1. Introduction 1 1.2. Historical development of metal-on-metal bearings in total hip replacements 3 1.3. Design and materials 4 1.3.1. Implant geometry 4 1.3.2. Manufacturing methods and metallurgy 5 1.4. Tribology of metal-on-metal bearings in total hip replacement 10 1.4.1. Wear and types of friction 10 1.4.2. EHL theory of lubrication 12 1.4.3. Friction in physiological joints 17 1.4.4. Friction in artificial joints 17 1.5. Wear testing 18 1.5.1. Simulation in hip simulators 18 1.5.2. Wear determination 21 1.5.3. Wear properties 23 1.5.4. Results of wear tests 24 1.5.5. Summary of results from simulator studies 30 1.5.6. Wear mode 31 1.6. Clinical relevance of metal wear particles and metal ions 33 1.7. Conclusion 35 1.8. Acknowledgments 36 1.9. Bibliography 36 Chapter 2. Experimental Wear Studies of Total Joint Replacements 51 Claire BROCKETT and John FISHER 2.1. Introduction 51 2.2. Methods for assessing tribology in total joint replacement 52 2.2.1. Lubrication 53 2.2.2. Friction 54 2.2.3. Wear 57 2.3. Effects of material and design on the tribology of total joint replacements 62 2.3.1. Total hip and resurfacing replacements 62 2.3.2. Total knee replacement 73 2.4. Conclusion 78 2.5. Bibliography 79 Chapter 3. Influence of Temperature on Creep and Deformation in UHMWPE under Tribological Loading in Artificial Joints 87 Mathias Christian GALETZ and Uwe GLATZEL 3.1. Temperature in artificial joints 87 3.1.1. Artificial knee joints 87 3.1.2. Why does temperature affect the performance of artificial joints? 89 3.1.3. Mathematical approaches to estimate the contact temperature during friction 91 3.1.4. Temperature rise during cyclic tribological sliding 95 3.2. Temperature influence on creep and fatigue mechanisms of UHMWPE under tribological loading 102 3.2.1. Temperature dependence of the yield strength of UHMWPE 102 3.2.2. Temperature dependence of the creep strength of UHMWPE 107 3.2.3. Temperature-dependent deformation under tribological loads 109 3.2.4. Wear and deformation mechanisms of ultra-high molecular weight polyethylene 113 3.3. Deformation behavior of polyethylene on the molecular scale 115 3.3.1. Deformation mechanisms in polyethylene 115 3.3.2. Tribologically-induced molecular changes 119 3.4. Importance for artificial knee joints 127 3.5. Acknowledgments 131 3.6. Bibliography 132 Chapter 4. Large Capacity Wear Testing 143 Vesa SAIKKO 4.1. Introduction 143 4.2. Categories of test devices 144 4.3. CTPOD principle 144 4.4. SuperCTPOD test procedure 147 4.5. SuperCTPOD validation 149 4.6. Further SuperCTPOD studies 150 4.7. Summary 151 4.8. Concluding remarks 153 4.9. Acknowledgments 153 4.10. Bibliography 154 Chapter 5. Biotribology of Titanium Alloys 157 Yong LUO 5.1. Introduction 157 5.1.1. History of titanium alloys 157 5.1.2. The properties of titanium alloys 158 5.1.3. The application of titanium alloys 159 5.2. Surface modification of titanium alloys 161 5.2.1. Ion implantation 161 5.2.2. Carburization 166 5.3. Biotribological properties of titanium alloys 175 5.3.1. Fretting wear 175 5.3.2. Sliding wear 184 5.3.3. Artificial joint simulation 190 5.4. Acknowledgments 195 5.5. Bibliography 195 List of Authors 199 Index 201

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Book SynopsisMost books dedicated to the issues of bio-sensing are organized by the well-known scheme of a biosensor. In this book, the authors have deliberately decided to break away from the conventional way of treating biosensing research by uniquely addressing biomolecule immobilization methods on a solid surface, fluidics issues and biosensing-related transduction techniques, rather than focusing simply on the biosensor. The aim is to provide a contemporary snapshot of the biosensing landscape without neglecting the seminal references or products where needed, following the downscaling (from the micro- to the nanoscale) of biosensors and their respective best known applications. To conclude, a brief overview of the most popularized nanodevices applied to biology is given, before comparing biosensor criteria in terms of targeted applications.Table of ContentsINTRODUCTION vii CHAPTER 1. TRANSDUCTION TECHNIQUES FOR MINIATURIZED BIOSENSORS 1 1.1. Definition of bioMEMS 1 1.2. Transduction techniques 2 1.2.1. Optical transduction 2 1.2.2. Electro (chemical) transduction 6 1.2.3. Mechanical transduction 10 1.3. MEMS transducers 17 1.4. One specific application of MEMS biosensors: detection of pathogen agents 20 1.5. Bibliography 25 CHAPTER 2. BIORECEPTORS AND GRAFTING METHODS 35 2.1. Types of bioreceptor 35 2.1.1. Catalytic receptors 36 2.1.2. Affinity receptors 37 2.1.3. Nucleic acid-based receptors 40 2.1.4. Molecularly imprinted polymers 41 2.2. Immobilization strategies 43 2.2.1. Adsorption and antifouling strategies 44 2.2.2. Entrapment methods 49 2.2.3. Covalent coupling 51 2.2.4. Other capture systems 54 2.2.5. Immobilization strategies: summary 56 2.3. Conclusion 57 2.4. Bibliography 57 CHAPTER 3. PATTERNING TECHNIQUES FOR THE BIOFUNCTIONALIZATION OF MEMS 65 3.1. What is surface patterning? 65 3.2. Direct biopatterning in liquid phase 66 3.2.1. Ink delivery by non-contact methods 67 3.2.2. Ink delivery by contact methods 71 3.3. Replication of patterns 80 3.3.1. Photolithography 81 3.3.2. Light-induced patterning strategies 81 3.3.3. Microcontact printing 82 3.3.4. In-flux functionalization 83 3.4. Conclusions 84 3.5. Bibliography 85 CHAPTER 4. FROM MEMS TO NEMS BIOSENSORS 93 4.1. Importance of downscaling 93 4.2. Challenges faced by NEMS for biosensing applications 95 4.2.1. Issues related to nanomechanical transducers 97 4.2.2. Issues related to the functionalization of NEMS 99 4.2.3. On the importance of packaging and sample preparation 103 4.3. Economic considerations 106 4.4. Bibliography 107 CHAPTER 5. COMPARING PERFORMANCES OF BIOSENSORS: IMPOSSIBLE MISSION? 113 5.1. Bibliography 117 INDEX 119

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Book SynopsisSystems Biology is the systematic study of the interactions between the components of a biological system and studies how these interactions give rise to the function and behavior of the living system. Through this, a life process is to be understood as a whole system rather than the collection of the parts considered separately. Systems Biology is therefore more than just an emerging field: it represents a new way of thinking about biology with a dramatic impact on the way that research is performed. The logical approach provides an intuitive method to provide explanations based on an expressive relational language. This book covers various aspects of logical modeling of biological systems, bringing together 10 recent logic-based approaches to Systems Biology by leading scientists. The chapters cover the biological fields of gene regulatory networks, signaling networks, metabolic pathways, molecular interaction and network dynamics, and show logical methods for these domains based on propositional and first-order logic, logic programming, answer set programming, temporal logic, Boolean networks, Petri nets, process hitting, and abductive and inductive logic programming. It provides an excellent guide for all scientists, biologists, bioinformaticians, and engineers, who are interested in logic-based modeling of biological systems, and the authors hope that new scientists will be encouraged to join this exciting scientific endeavor.Table of ContentsForeword xiii Luis Fariñas Del Cerro Chapter 1 Symbolic Representation and Inference or Regulatory Network Structures 1 Nataly Maimari, Krysia Broda, Antonis Kakas, Rob Krams and Alessandra Russo Chapter 2 Reasoning on the Response of Logical Signaling Networks with ASP 49 Torsten Schaub, Anne Siegek and Santiago Videla Chapter 3 A Logical Model for Molecular Interaction Maps 93 Robert DeMolombe, Luis Farinas Del Cerro and Naji Obeid Chapter 4 Analyzing Large Network Dynamics with Process Hitting 125 Loic Paulevé, Courtney Chancellor, Maxime Folschette, Morgan Magnin and Olivier Roux Chapter 5 ASP for Construction and Validation of Regulatory Biological Networks Alexandre Rocca, Nicolas Mobilia, Éric Fanchon, Tony Ribeiro, Laurent Trilling and Katsumi Inoue Chapter 6 Simulation-Based Reasoning about Biological Pathways Using Petri Nets and ASP 207 Saadat Anwar, Chitta Barbal and Katsumi Inoue Chapter 7 Formal Methods Applied to Gene Networks Modeling 245 Gilles Bernot, Jean-Paul Comet and El Houssine Snaussi Chapter 8 Temporal Logic Modeling of Dynamical Behaviors: First-Order Patterns and Solvers 291 François Fages and Pauline Traynard Chapter 9 Analyzing SBGN-AF Networks Using Normal Logic Programs 325 Adrien Rougny, Christine Froidevaux, Yoshitaka Yamamoto and Katsumi Inoue Chapter 10 Machine Learning of Biological Networks Using Abductive ILP 363 Alireza Tamassoni, Diahuan Lin, Hiroaki Watanabe, Jianzhong Chen and Stephen Muggleton List of Authors 403 Index 407

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