Biotechnology Books

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Book SynopsisCOVID-19 and Omics Technologies is a comprehensive, integrative assessment of recent information and knowledge collected on SARS-CoV-2 and COVID-19 during the pandemic based on omics technologies. It demonstrates how omics technologies could better investigate the infectious disease and propose solutions to the current concerns.The value of multi-omics technologies in understanding disease etiology and host response, discovering infection biomarkers and illness prediction, identifying vaccine candidates, discovering therapeutic targets, and tracing pathogen evolution is discussed in this book. These factors combine to make it a valuable resource to enhance understanding of both Omics technology and COVID-19 as a disease. The book covers the most recent understanding of COVID-19 and the applications of cutting-edge studies, making it accessible to a large multidisciplinary readership.The book explains how high-throughput technologies and systems biology might assist to Table of ContentsClinical and Epidemiological Context Of COVID-19. NGS technologies for detection of SARS-CoV-2 strains and mutations. Mass-spectrometry techniques for detection of COVID-19 viral and host proteins using naso-oropharyngeal swab and plasma. Targeted proteomic approaches in context of the COVID-19 pandemic. Metabolomics: Role in pathobiology and therapeutics of COVID-19. Protein microarrays for COVID-19 research: biomarker discovery, humoral response & vaccine targets. COVID-19 pathogenesis and host immune response. Putative role of multi-omics technologies in the investigation of the persistent effects of COVID-19 on vital human organs. Insights on interactomics driven drug repurposing to combat COVID-19. Spectroscopy methods for SARS-CoV-2 detection. Role of AI and ML in empowering and solving problems linked to COVID-19 pandemic.

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Book SynopsisOptogenetics represents a breakthrough technology capable of dynamically modulating molecular and cellular activity in live cells with high precision. This transformative technology made it possible to reversibly interrogate protein actions, cellular events, and animal behaviors with a simple flash of light. Manipulating the temporal and spatial profile of light enabled precise control of membrane potentials. This feature has inspired non-opsin-based optogenetics, which not only inherits the precise spatiotemporal resolution but also expands the targets into a diverse pool of biomolecules such as membrane receptors, ion channels, kinases, GTPases, and transcription factors. This book is unique because it emphasizes the design and applications of opsin-free optogenetic tools. Key Features Describes new developments in non-opsin-based optogenetic tools Introduces cutting-edge methods for precise modulation of cell signaling Trade Review “This book differs markedly from these other, more general volumes by virtue of its concentration on next generation, non-opsin photo-switches. The result is a focused, highly informative, yet compact and easy-to-read volume that offers a model for how these works should be constructed.” Doody Review Peter J. Kennelly, PhD (Virginia Tech) Table of ContentsTable of Content Chapter 1 Optogenetic dissection of a two-component calcium influx pathway Xiaoxuan Liu, Yingshan Wang, Yubin Zhou, and Guolin Ma* Chapter 2 High-throughput engineering of a light-activatable Ca2+ channel Lian He*, Liuqing Wang, and Youjun Wang* Chapter 3 Optogenetic activation of TrkB signaling Peiyuan Huang, Zhihao Zhao, Lei Lei, and Liting Duan* Chapter 4 Spatiotemporal modulation of neural repair Huaxun Fan, Qin Wang, Kai Zhang*, and Yuanquan Song* Chapter 5 Optogenetic control of neural stem cell differentiation Yixun Su, Taida Huang, Kai Zhang, and Chenju Yi* Chapter 6 An optogenetic toolbox for remote control of programmed cell death Ningxia Zhang and Ji Jing* Chapter 7 Control of protein levels in Saccharomyces cerevisiae by optogenetic modules that act on protein synthesis and stability Sophia Hasenjäger, Jonathan Trauth, and Christof Taxis* Chapter 8 Optogenetics as a tool to study neurodegeneration and signal transduction Prabhat Tiwari* and Nicholas S. Tolwinski* Chapter 9 Opsin-free optogenetics: brain and beyond Jongryul Hong, Yeonji Jeong, and Won Do Heo* Chapter 10 Constructing a far-red light-induced split-Cre recombinase system for controllable genome engineering Meiyan Wang, Jiali Wu, and Haifeng Ye* Chapter 11 Tools and Technologies for Wireless and Non-invasive Optogenetics Guangfu Wu, Vagif Abdulla, Yiyuan Yang, Michael Schneider, and Yi Zhang*

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Book SynopsisBiomass is the physical basis of the bioeconomy, the renewable segment of the circular economy, and as a CO2-neutral part of the carbon cycle, biomass is an efficient carbon sink. Demand for biomass is increasing worldwide because of its advantages in replacing fossil-based materials and fuels, which presents the challenge of reconciling this increased demand with the sustainable management of ecosystems, including forests and crops. This reference book discusses the role of biomass in the bioeconomy and focuses on the European Union and the United States, the first two regions to develop a bioeconomy strategy with an obvious effect on the bioeconomy developments in the rest of the world. Significant developments in other areas of the world are addressed.Features: Provides strategies for optimal use of biomass in the bioeconomy Defines and details sources, production, and chemical composition of biomass Describes conversion, uses

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Book SynopsisCOVID-19 is a highly contagious viral illness caused by severe acute respiratory syndrome SARSCoV-2. It has had a devastating effect on the world's demographics with high morbidity and mortality worldwide. After the influenza pandemic of 1918, it has emerged as the most consequential global health crisis. After the first cases of this predominantly respiratory viral illness were first reported in Wuhan, Hubei Province, China, in late December 2019, SARS-CoV- 2 rapidly disseminated across the world in a short span of time, compelling the World Health Organization (WHO) to declare it a global pandemic on March 11, 2020. The outbreak of COVID-19 has proven to be a worldwide unprecedented disaster. It has physically, psychologically, socially, and economically afflicted billions of people across the globe. Its transmission is significantly high. Serious postrecovery has been noticed in a large number of people. The virus is highly mutable and new and new strains are appearing, and many Table of ContentsPreface. Author Biography. 1. Teaching, Learning And Caring In Post-covid Era2. Adoption Of Blended Learning Model In Higher Education Post Covid-193. Ode: Cruising Onto A New Education System4. Covid-19 Pandemic And Paradigms Of Education In Indian Heis: A Mapping Of Tectonic Shifts5. Paradigm Shift In Education And Career Choice Of Students In The New Normalpost Covid -19 Era6. An Impact Assessment Of Covid-19 Pandemic On The Higher Education Institutions Of India7. Academic Administration: Post Pandemic Challenges In Science Education8. Family Life And Education Under The Dark Shadow Of Covid-19 Pandemic In India: Some Observations9. Impact Of Covid -19 Pandemic On Education In Indian Context: Reimagining Education Beyond The Pandemic10. Telecommunication Interventions And Opportunities In Education, Health And Agriculture: Post Covid-19 Scenario 11. Technological Innovations And Challenges In Higher Education During Covid-19 Pandemic 12. Shift In Technology: A Mechanical Engineer’s Perspective In The Post Covid-19 World 13. Architecture Of Covid Era14. Maps, Digitalization And Citizenry (With Special Reference To Covid-19) 15. Covid-19 Pandemic And Environmental Sustainability16. Covid-19 Pandemic And Environmental Pollution: Opportunity To Revisit Environmental Strategies For Public Health Benefits17. Bio-medical Waste Management In Post Covid-19 Pandemic: Need For An Effective Regulation In India 18. Covid - 19 Pandemic : Social Response Through Changing Lifestyles 19. Emerging Life Styles In Urban India Under The Regime Of Covid-19 Pandemic: An Overview Of The Implications 20. Confronting Potential Role Of Yoga In Combatting Covid-19 Pandemic21. Lifestyle Communication, Environment And Development Sustainability: An Analytical Study From Consumption To Information Dissemination During Covid 19 22. Adoption Of Diet Pattern During Covid Pandemic 23. Life Post Covid-19 Pandemic: Opportunities And Challenges For The Decision Makers 24. Post Covid-19 Paradigm Shift: A New Era Of Digital Experience 25. Covid-19: Our Solutions Are In Nature

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Book SynopsisThe book is an introduction to nanomedicine informed by a philosophical reflection about the domain and recent developments. It is an overview of the field, sketching out the main areas of current investment and research. The authors present some case-studies illustrating the different areas of research (nanopharmacy, theranostics and patient monitoring) as well as reflecting on the risks that accompany it, such as unanticipated impacts on human health and environmental toxicity. This introduction to a fast-growing field in modern medical research is of great interest to researchers working in many disciplines as well as the general public. In addition to an overview of the work currently ongoing, the authors critically assess these projects from an ethical and philosophical perspective.Key Features Provides an overview of nanomedicine Employs a reflective and coherent critical evaluation of the benefits and risks of nanomedicine Table of Contents Authors. Introduction. Nanopharmacy: What's New With the Nano? Theranostics: Toward a New Integrative Horizon. Health Under Surveillance. Genetic Nanomedicine. Toxicology of Nanomaterials: A New Toxicology? Organs on Chips, Miniaturization and Medical Specialties: The Different Logics of Nanomedicine. Regenerative Medicine: Mobilizing the Body's Own Repair Mechanisms: Conclusion. Glossary. Index.

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Book SynopsisThis book describes various methods of decontamination and how the methods work. There is a discussion of the various cleaning and disinfection methods utilized, along with details of how to qualify these methods. It also describes new technologies that may be useful in the battle for decontamination across industries. Finally, this book provides a single resource on how one can address contamination issues for a variety of manufacturing processes and industries. Explores new technologies that may be useful in the battle for decontamination Examines various methods of decontamination and how the methods work Addresses contamination issues for a variety of manufacturing processes and industries Describes how to detect contaminants as well as how to deal with contaminants that are present Table of ContentsChapter 1 Introduction Chapter 2 Disinfectants and Biocides Chapter 3 Disinfecting Agents: The Art of Disinfection Chapter 4 The Microbiome and Its Usefulness to Decontamination/ Disinfection Practices Chapter 5 Disinfectant Qualification Testing Considerations for Critical Manufacturing Environments Chapter 6 Methods for Contamination Detection Chapter 7 Residue Removal in Cleanroom Environments Chapter 8 Microbiological Concerns in Non-Sterile Manufacturing Chapter 9 Preservatives and Why They Are Useful Chapter 10 The Problem of Burkholderia cepacia Complex (BCC) in Your Facility Chapter 11 What Is Mold and Why Is It Important? Chapter 12 Sterilization Methods

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Book SynopsisJohn Carreyrou joined the Wall Street Journal in 1999 and was based in Brussels, Paris, and New York for the paper. John has covered a number of topics during his career, ranging from Islamist terrorism when he was on assignment in Europe to the pharmaceutical industry and the US healthcare system. His reporting on Theranos, the blood-testing startup founded by Elizabeth Holmes, was recognized with a George Polk award, and is chronicled in his book Bad Blood: Secrets and Lies in a Silicon Valley Startup.Born in New York and raised in Paris, he currently resides in Brooklyn with his wife and three children.Trade ReviewI couldn’t put down this thriller with a tragic ending . . . a book so compelling that I couldn’t turn away . . . This book has everything: elaborate scams, corporate intrigue, magazine cover stories, ruined family relationships, and the demise of a company once valued at nearly $10 billion -- Bill Gates, '5 books I loved in 2018'A dazzling story of deception in Silicon Valley . . . You will not be able to put this book down. * Washington Post *Carreyrou tells the story virtually to perfection . . . Bad Blood reads like a West Coast version of All the President’s Men. * New York Times Book Review *Riveting . . . a blistering critique of Silicon Valley . . . The real heroes, though, are his sources: the young scientists who worked at the company and risked their reputations and careers by voicing their concerns. Were it not for their courage, Theranos might still be testing blood today -- David Crow * Financial Times *If you’re looking for an engaging non-fiction read, look no further than Bad Blood . . . a pacy, compelling narrative about white-collar crime that’s as incredible as any work of fiction. * Irish Times *In this Silicon Valley drama, he opens his reporter’s notebook to deliver a tale of corporate fraud and legal browbeating that reads like a crime thriller. -- The 10 Best Nonfiction Books of 2018 * TIME *Gripping . . . Carreyrou presents the scientific, human, legal and social sides of the story in full . . . He unveils many dark secrets of Theranos that have not previously been laid bare. * Nature *A parable, with all the usual, delicious ingredients of human folly: greed, pride, vanity, lust, anger. Above all, it is an analysis of the phenomenon of hype. * Daily Telegraph *Simply one of the best books about a startup ever. * Forbes *Bad Blood reveals a crucial truth: outside observers must act as the eyes, the ears and, most importantly, the voice of Silicon Valley’s blind spot . . . It gambled not with our smart phones, our attention or our democracy, but with people’s lives. * Paste *Engaging * The Economist *A beautifully controlled narrative that challenges the gold-rush mentality of Silicon Valley. -- Lionel Barber, Editor of the FT, 'Books of the Year 2018' * Financial Times *[Holmes') story is a parable about Silicon Valley delusion, but the gossipy fun comes from seeing which high-profile man (James Mattis, Joe Biden) gets drawn into Holmes’ scammy web next. -- ‘Best Books of 2018’ * ELLE *Carreyrou tells the full, gripping tale of how he slayed the “unicorn” in a fascinating look at how buzz and billions can blind people to facts. -- ‘Best Books of 2018’ * Marie Claire *You will not be able to put this down. -- Top tech book releases in 2018 * Evening Standard *

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Book SynopsisThis fourth edition explores fully up-to-date standardly used cryopreservation, vitrification, and freeze-drying protocols for specimens that are used for research purposes, conservation of genetic reserves, and applications in agriculture and medicine. Beginning with a section on the fundamentals as well as the use of mathematical modeling to solve cryobiological problems, the book continues with sections on technological aspects of freezing and drying, analytical methods to study protectant loading of cells and tissues, cell behavior during freezing and drying, and thermodynamic properties of preservation solutions, as well as cryopreservation, vitrification, and freeze-drying protocols for a wide variety of samples and different applications. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips oTable of ContentsPart I: Fundamental Aspects of Cryopreservation and Freeze-Drying 1. Principles Underlying Cryopreservation and Freeze-Drying of Cells and Tissues Willem F. Wolkers and Harriëtte Oldenhof 2. Principles of Ice-Free Cryopreservation by Vitrification Gregory M. Fahy and Brian Wowk 3. The Principles of Freeze-Drying and Application of Analytical Technologies Kevin R. Ward and Paul Matejtschuk 4. Mathematical Modeling and Optimization of Cryopreservation in Single Cells James D. Benson 5. Mathematical Modeling of Protectant Transport in Tissues Ross M. Warner and Adam Z. Higgins Part II: Technologies and Methods to Study Freezing and Drying 6. Freezing Technology: Control of Freezing, Thawing, and Ice Nucleation Peter Kilbride and Julie Meneghel 7. Microwave- and Laser-Assisted Drying for the Anhydrous Preservation of Biologics Shangping Wang, Susan Trammell, and Gloria D. Elliott 8. High-Speed Video Cryomicroscopy for Measurement of Intracellular Ice Formation Kinetics Jens O.M. Karlsson 9. Use of Ice Recrystallization Inhibition Assays to Screen for Compounds that Inhibit Ice Recrystallization Anna A. Ampaw, August Sibthorpe, and Robert N. Ben 10. DSC Analysis of Thermophysical Properties for Biomaterials and Formulations Wendell Q. Sun 11. Osmometric Measurements of Cryoprotective Agent Permeation into Tissues Kezhou Wu, Leila Laouar, Nadia Shardt, Janet A.W. Elliott, and Nadr M. Jomha 12. Use of X-Ray Computed Tomography for Monitoring Tissue Permeation Processes Ariadna Corral, Alberto Olmo, and Ramón Risco 13. Use of In Situ Fourier Transform Infrared Spectroscopy in Cryobiological Research Willem F. Wolkers and Harriëtte Oldenhof 14. Raman Cryomicroscopic Imaging and Sample Holder for Spectroscopic Subzero Temperature Measurements Guanglin Yu, Rui Li, and Allison Hubel Part III: Cryopreservation and Freeze-Drying Protocols 15. Cryopreservation of Semen from Domestic Livestock: Bovine, Equine, and Porcine Sperm Harriëtte Oldenhof, Willem F. Wolkers, and Harald Sieme 16. Cryopreservation of Avian Semen Henri Woelders 17. Cryopreservation of Mouse Sperm for Genome Banking Yuksel Agca and Cansu Agca 18. Cryopreservation of Marine Invertebrates: From Sperm to Complex Larval Stages Estefania Paredes, Pablo Heres, Catarina Anjos, and Elsa Cabrita 19. Aseptic Cryoprotectant-Free Vitrification of Human Spermatozoa by Direct Dropping into a Cooling Agent Mengying Wang, Evgenia Isachenko, Gohar Rahimi, Peter Mallmann, and Vladimir Isachenko 20. Cryopreservation of Mammalian Oocytes: Slow Cooling and Vitrification as Successful Methods for Cryogenic Storage Victoria Keros and Barry J. Fuller 21. Vitrification of Porcine Oocytes and Zygotes in Microdrops on a Solid Metal Surface or Liquid Nitrogen Tamas Somfai and Kazuhiro Kikuchi 22. Cryopreservation and Transplantation of Laboratory Rodent Ovarian Tissue for Genome Banking and Biomedical Research Yuksel Agca and Cansu Agca 23. Cryopreservation and Thawing of Human Ovarian Cortex Tissue Slices Jana Liebenthron and Markus Montag 24. Vitrification: A Simple and Successful Method for Cryostorage of Human Blastocysts Juergen Liebermann 25. Vitrification of Equine In Vivo-Derived Embryos, after Blastocoel Aspiration Carolina Herrera 26. Frozen Blood Reserves Johan W. Lagerberg 27. Isolation, Cryopreservation, and Characterization of iPSC-Derived Megakaryocytes Denys Pogozhykh, Rainer Blasczyk, and Constança Figueiredo 28. Chemically Defined, Clinical-Grade Cryopreservation of Human Adipose Stem Cells Melany López and Ali Eroglu 29. Chemically-Defined and Xeno-Free Cryopreservation of Human Induced Pluripotent Stem Cells Juliette Seremak and Ali Eroglu 30. Protocol for Cryopreservation of Endothelial Monolayers Leah A. Marquez-Curtis, Nasim Eskandari, Locksley E. McGann, and Janet A.W. Elliott 31. Vitrification of Heart Valve Tissues Kelvin G.M. Brockbank, Zhenzhen Chen, Elizabeth D. Greene, and Lia H. Campbell 32. Cryopreservation of Algae Estefania Paredes, Angela Ward, Ian Probert, Léna Gouhier, and Christine N. Campbell 33. Cryopreservation of Fern Spores and Pollen Anna Nebot, Victoria J. Philpott, Anna Pajdo, and Daniel Ballesteros 34. Cryopreservation of Plant Cell Lines Using Alginate Encapsulation Heinz Martin Schumacher, Martina Westphal, and Elke Heine-Dobbernack 35. Cryopreservation of Plant Shoot Tips of Potato, Mint, Garlic, and Shallot Using Plant Vitrification Solution 3 Angelika Senula and Manuela Nagel 36. Cryopreservation of Seeds and Seed Embryos in Orthodox, Intermediate, and Recalcitrant Seeded Species Daniel Ballesteros, Natalia Fanega-Sleziak, and Rachael Davies 37. Freeze-Drying of Proteins Baolin Liu and Xinli Zhou 38. Freeze-Drying of Lactic Acid Bacteria: A Stepwise Approach for Developing a Freeze-Drying Protocol Based on Physical Properties Fernanda Fonseca, Amélie Girardeau, and Stéphanie Passot 39. Preservation of Mammalian Sperm by Freeze-Drying Levent Keskintepe and Ali Eroglu 40. Freeze-Drying of Decellularized Heart Valves for Off-the-Shelf Availability Willem F. Wolkers and Andres Hilfiker

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Book SynopsisThis volume provides detailed technical protocols on current biomedical technologies and examples of their applications and capabilities. Chapters focus on molecular and cellular analytical methods, experimental new drug delivery approaches, guided surgery, implants and tissue engineering.Table of ContentsPart I: Molecular and Cellular analysis and manipulation 1. Development of a Multi-Target Protein Biomarker Assay for Circulating Tumor Cells Diya Li, Ceming Wang, Yingjia Ni, Yaoping Liu, Wei Wang, Siyuan Zhang, Hsueh-Chia Chang, and Satyajyoti Senapati 2. Method to Isolate Dormant Cancer Cells from Heterogeneous Populations Julian A. Preciado, and Alptekin Aksan 3. Label-Free Morphological Phenotyping of in vitro 3D Micro Tumors Zoe Moscato, Devina Jaiswal, Krishna Dixit, Cooper J. Langanis, Kevin P. Claffey, and Kazunori Hoshino 4. High-throughput microenvironment microarray (MEMA) (file #high-resolution imaging Tiina A Jokela, Michael E Todhunter, and Mark A LaBarge 5. Real-Time Analysis of AKT Signaling Activities at Single-Cell Resolution Using Cyclic Peptide-Based Probes Fei Ji, Siwen Wang, Shiqun Shao, Priyanka Sarkar, and Min Xue 6. Microfluidic device technologies for digestion, disaggregation, and filtration of tissue samples for single cell applications Jeremy A. Lombardo, and Jered B. Haun 7. Microdissection methods utilizing single cell subtype analysis and the impact on precision medicine Donald J. Johann, Jr., Sarah Laun, Owen Stephens, Robert Weigman, , Ikjae Shin, , Adam Roberge, Meeiyueh Liu, Valerie Greisman, Mathew Steliga, Jason Muesse, , Erich Peterson, , Michael R. Emmert-Buck and Michael A. Tangrea, 8. Functionalized lineage tracing for the study and manipulation of heterogeneous cell populations Andrea Gardner, Daylin Morgan, Aziz Al’Khafaji, and Amy Brock 9. Fluorescence lifetime imaging probes for cell-based measurements of enzyme activity Sampreeti Jena, and Laurie L. Parker 10. Assessment of intracellular GTP levels using genetically encoded fluorescent sensors’ Anna Bianchi-Smiraglia, and Mikhail. Nikiforov 11. Node-Pore Sensing for characterizing cells and extracellular vesicles Thomas Carey, Brian Li, and Lydia L. Sohn 12. Affinity-Based Enrichment of Extracellular Vesicles with Lipid Nanoprobes Yuan Wan, Mackenzie Maurer, and Si-Yang Zheng 13. Droplet magnetofluidic assay platform for quantitative methylation-specific PCR Alejandro Stark, Alexander Trick, Thomas R Pisanic II, and Tza-Huei Wang 14. Droplette: A Platform Technology to Directly Deliver Nucleic Acid Therapeutics and Other Molecules into Cells and Deep into Tissue Without Transfection Reagents Bao Lin Quek, Rathi L Srinivas, and Madhavi P Gavini 15. Molecular imaging of HER2 in patient tissues with touch prep-quantitative single molecule localization microscopy Devin L. Wakefield, Steven J. Tobin, Daniel Schmolze, and Tijana Jovanovic-Talisman 16. Microchip free-flow electrophoresis for bioanalysis, sensing and purification William E. Arter, Kadi L. Saar, Therese W. Herling, and Tuomas P. J. Knowles 17. Green Chemistry Preservation and Extraction of Biospecimens for Multi-omic Analyses Andrey P. Tikunov, Jeremiah D. Tipton, Timothy J. Garrett, Sachi V. Shinde, Hong Jin Kim, David A. Gerber, Laura E. Herring, Lee M. Graves, and Jeffrey M. Macdonald 18. TdT-UTP DSB End Labeling (TUDEL), for Specific, Direct in situ Labeling of DNA Double Strand Breaks Julian Lutze, Sara E Warrington, and Stephen J. Kron 19. Ligand-directed GPCR Antibody Discovery Qi Zhao, Amanda Chapman, Yan Huang, Mary Ferguson, Shannon McBride, Meghan Kelly, Michael Weiner, and Xiaofeng Li 20. Self-Induced Back-Action Actuated Nanopore Electrophoresis (Sane) (File #Sensor For Label-Free Detection Of Cancer Immunotherapy-Relevant Antibody-Ligand Interactions Sai Santosh Sasank Peri, Muhammad Usman Raza, Manoj K. Sabnani, Soroush Ghaffari, Susanne Gimlin, Debra D. Wawro, Jung Soo Lee, Min Jun Kim, Jon Weidanz, and George Alexandrakis 21. Incorporating, quantifying, and leveraging noncanonical amino acids in yeast Jessica T. Stieglitz, and James A. Van Deventer 22. Nuclease-assisted, multiplexed minor-allele enrichment: application in liquid biopsy of cancer Fangyan Yu, Ka Wai Leong, and G. Mike Makrigiorgos 23. Implementation of Ion Mobility Spectrometry-Based Separations in Structures for Lossless Ion Manipulations (SLIM) Adam L. Hollerbach, Christopher R. Conant, Gabe Nagy, and Yehia M. Ibrahim 24. Pleural Effusion Aspirate for use in 3D Lung Cancer Modeling and Chemotherapy Screening Andrea Mazzocchi, Anthony Dominijanni, and Shay Soker 25. Using Optical Tweezers to Dissect Allosteric Communication Networks in Protein Kinases Yuxin Hao and Rodrigo Maillard Part II: Therapeutics Technologies 26. Focused ultrasound-mediated intranasal brain drug delivery technique (FUSIN) Dezhuang Ye, and Hong Chen 27. Extracellular pH mapping as therapeutic readout of drug delivery in glioblastoma John J. Walsh, and Fahmeed Hyder 28. Charge-Based Multi-Arm Avidin Nano-construct as a Platform Technology for Applications in Drug Delivery Tengfei He, Chenzhen Zhang, and Ambika G. Bajpayee 29. Chemical Modification of Proteins and Their Intracellular Delivery Using Lipidoid Nanoparticles Yamin Li, Zachary Glass, and Qiaobing Xu 30. Generation of Membrane-derived Nanovesicles by Nitrogen Cavitation for Drug Targeting Delivery and Immunization Jin Gao, Mindy Lee, Xinyue Dong, and Zhenjia Wang 31. Laboratory-scale production of sterile targeted microbubbles Guixin Shi, and Yu-Tsueng Liu 32 (file #47). Adeno-associated viral vector immobilization and local delivery from bare metal surfaces. Ben B. Pressly, Bahman Hooshdaran, Ivan S. Alferiev, Michael Chorny, Robert J. Levy, and Ilia Fishbein 33. Decellularization and Recellularization Methods for Avian Lungs: An Alternative Approach for Use in Pulmonary Therapeutics Alicia E. Tanneberger, Daniel J. Weiss, and Juan J. Uriarte 34. Methods for Forming Human Lymphatic Microvessels In Vitro and Assessing Their Drainage Function Joe Tien, and Usman Ghani 35. Natural Polymer Based Micro-Nanostructured Scaffolds for Bone Tissue Engineering Sara Katebifar, Devina Jaiswal, Michael R. Arul, Sanja Novak, Jonathan Nip, Ivo Kalajzic, Swetha Rudraiah, and Sangamesh G. Kumbar 36. Biodegradable electrospun nanofibrous scaffolds for bone tissue engineering Aneela Anwar, Daniel Jerome Petrino Jr., Nicole Van Alstine, and Xiaojun Yu 37. Bio-Tribometer for the Assessment of Cell and Tissue Toxicity of Orthopedic Metal Implant Debris Simona Radice, and Markus A. Wimmer 38. Methods for Quantifying Neutrophil Extracellular Traps on Biomaterials Allison E. Fetz, William E. King III, Benjamin A. Minden-Birkenmaier, and Gary L. Bowlin 39. In Vivo Imaging of Implanted Hyaluronic Acid Hydrogel Biodegradation Shreyas Kuddannaya, Wei Zhu, and Jeff W.M. Bulte 40. Computational modeling and simulation to quantify the effects of obstructions on the performance of ventricular catheters used in hydrocephalus treatment Stephanie C. TerMaath, Douglas L. Stefanski, and James A. Killeffer 41. Selection of Cancer Stem Cell--targeting Agents Using Bacteriophage Display Austin R. Prater, and Susan L. Deutscher 42. Nano-Scintillator-Based X-Ray Induced Photodynamic Therapy Benjamin Cline, and Jin Xie 43. Methods to measure the inhibition of ABCG2 transporter and ferrochelatase activity to enhance aminolevulinic acid-protoporphyrin IX fluorescence-guided tumor detection and resection Matthew Mansi, Richard Howley, and Bin Chen 44. Macroscopic Fluorescence Lifetime Imaging for Monitoring of Drug-Target Engagement Marien Ochoa, Alena Rudkouskaya, Jason T. Smith, Xavier Intes, and Margarida Barroso 45. Tumor in vivo Imaging with a New Peptide-based Fluorescent Probe Samer Naffouje, Masahide Goto, Ingeun Ryoo, Albert Green, Tapas K. Das Gupta, and Tohru Yamada 46. Thermal Ablation Treatment for Cervical Precancer (Cervical Intraepithelial Neoplasia grade 2 or higher [CIN2+]) Montserrat Soler, Rachel Masch, Rakiya Saidu, and Miriam Cremer 47. Employing Novel Porcine Models of Subcutaneous Pancreatic Cancer to Evaluate Oncological Therapies Alissa Hendricks-Wenger, Margaret A Nagai-Singer, Kyungjun Uh, Eli Vlaisavljevich, Kiho Lee, and Irving C Allen

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Book SynopsisThis second edition volume expands on the previous edition by exploring the latest advancements in high throughput screening (HTS) in toxicity studies by using in vitro, ex vivo, and in vivo models. This volume also covers the application of artificial intelligence (AI) and data science to curate, manage, and use HTS data. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, High Throughput Screening Assays in Modern Toxicology, Second Edition is a valuable resource for scientists pursuing chemical toxicology research. This book will aid scientists and researchers in translating new HTS techniques into standardized chemical toxicology assessment tools that can refine, reTable of ContentsAcknowledgement…Preface…Table of Contents…Contributing Authors…Part I In Vitro Toxicological High Throughput Screening Methods1. Cell-Based Assays to Identify ERR and ERR/PGC ModulatorsCaitlin Lynch, Jinghua Zhao, and Menghang Xia2. Mitochondrial Membrane Potential AssaySrilatha Sakamuru, Jinghua Zhao, Matias S. Attene-Ramos, and Menghang Xia3. Cell-Based hERG Inhibition Assay in a High-Throughput FormatJinghua Zhao, and Menghang Xia 4. Identifying CAR Modulators Utilizing a Reporter Gene AssayCaitlin Lynch, Jinghua Zhao, Hongbing Wang, and Menghang Xia5. Study Liver Cytochrome P450 3A4 Inhibition and Hepatotoxicity Using DMSO-Differentiated HuH-7 CellsYitong Liu6. Acetylcholinesterase Inhibition Assays for High-Throughput ScreeningShuaizhang Li, Andrew J. Li, Michael F. Santillo, and Menghang Xia7. Cell-Based Assays to Identify Modulators of Nrf2/ARE PathwayZhengxi Wei, Jinghua Zhao, Li Zhang, and Menghang XiaPart II In Vitro Toxicological High Content Screening Methods8. Cell-Based Imaging Assay for Detection of PhospholipdosisLi Zhang, Shuaizhang Li, and Menghang Xia9. GFP-LC3 High-Content Assay for Screening Autophagy ModulatorsLi Zhang, Jinghua Zhao, Wen-Xing Ding, and Menghang XiaPart III Three-Dimensional Cell System for Toxicological High Throughput Screening10. Generation of iPSC-Derived Brain Organoids for Drug Testing and Toxicological EvaluationHa Nam NguyenPart IV In Vivo Toxicological High Throughput Screening Methods11. Zebrafish Behavioral Assays in ToxicologySubham Dasgupta, Michael T. Simonich, and Robert L. TanguayPart V In Silico High Throughput Screening Toxicity Data Analysis12. High Throughput Screening Assay Profiling for Large Chemical DatabasesDaniel P. Russo and Hao Zhu13. A Quantitative High Throughput Screening Data Analysis Pipeline for Activity ProfilingRuili Huang14. CurveP Method for Rendering High Throughput Screening Dose-Response Data into Digital FingerprintsAlexander Sedykh15. Accounting for Artifacts in High Throughput Toxicity AssaysJui-Hua Hsieh16. Automatic Quantitative Structure-Activity Relationship Modeling to Fill Data Gaps in High-Throughput ScreeningHeather L. Ciallella, Elena Chung, Daniel P. Russo, and Hao Zhu17. Use In Silico and In Vitro Methods to Screen Hepatotoxic Chemicals and CYP450 Enzyme InhibitorsYitong LiuSubject Index List…

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Book SynopsisThis book discusses principles, methodology, and applications of microbiological laboratory techniques . It lays special emphasis on the use of various automated machines that are essential for medical microbiology and diagnostic labs. The book contains eleven major chapters. The first chapter describes the good lab practices which should be followed by the students in all biological, chemistry or microbiology laboratories. The next chapter describes manual and automated characterization of antibiotic resistant microbes, followed by a chapter on genomics based tools and techniques that are integral to research. Further chapters deal with other important techniques like immunology based techniques, spectrophotometry and its various types, MALDI-TOFF and microarrays, each with illustrations and detailed description of the protocols and applications. The book also gives certain important guidelines to the students about the planning the experiment and interpreting results. Table of Contents

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Book SynopsisTaking a unique materials science approach, this text introduces students to the basic concepts and applications of materials and biomedical engineering and prepares them for the challenges of the new interdisciplinary field of biomaterials science. Split into three sections - Basic Biology Principles, Biological Materials, and Bioinspired Materials and Biomimetics - it presents biological materials along with the structural and functional classification of biopolymers, bioelastomers, foams, and ceramic composites. More traditional biomimetic designs such as Velcro are then discussed in conjunction with new developments that mimic the structure of biological materials at the molecular level, mixing nanoscale with biomolecular designs. Bioinspired design of materials and structures is also covered. Focused presentations of biomaterials are presented throughout the text in succinct boxes, emphasising biomedical applications, whilst the basic principles of biology are explained, so no priTrade Review'The union of the physical and biological sciences is in many respects one of the most exciting yet challenging aspects of scientific endeavor today. Nowhere is this more in evidence than in the area of biological materials science and engineering where many materials scientists struggle with the complex puzzle of biological form and function while biologists in turn have to deal with the invariably highly quantitative nature of the physical sciences and engineering. With this book, Meyers and Chen have delivered a true tour de force which takes the reader in clear and precise text from cells to virus-produced Li-ion batteries. This book is a must read for undergraduates, graduates and researchers alike in the rapidly expanding fields of biological, bioinspired and biomaterials science.' Robert Ritchie, Lawrence Berkeley National LaboratoryTable of Contents1. Evolution of materials science and engineering: from natural to bioinspired materials; Part I. Basic Biology Principles: 2. Self assembly, hierarchy, and evolution; 3. Basic building blocks; 4. Cells; 5. Biomineralization; Part II. Biological Materials: 6. Silicate and calcium carbonate-based composites; 7. Calcium phosphate-based composites; 8. Biological polymers and polymer composites; 9. Biological elastomers; 10. Biological foams (porous solids); 11. Functional biological materials; Part III. Bioinspired Materials and Biomimetics: 12. Bioinspired materials; 13. Molecular-based biomimetics.

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Book SynopsisThe first introductory book on the subject, this book will provide a complete grounding to this pioneering field for students and professionals across biomedical engineering, biology and medicine. It features a comprehensive overview of original work in this revolutionary field. Topics discussed include drug delivery, cell-material interaction and gene therapy, accompanied by real-world examples and over 100 illustrations. The book teaches readers how to design and test their own nanomedical systems for real-world applications in biomedical engineering, medicine and pharmacy. Presenting a thorough discussion of the science and engineering of nanomedicine, it discusses vital environmental, social and ethical impacts of this revolutionary technology. Including over 200 thought-provoking study questions, allowing the reader to self-assess their understanding, this book is a rich source of information that will be of interest and importance in nanomedicine.Table of Contents1. The need for new perspectives in medicine; 2. Nanomedicine: Single-cell medicine; 3. Targeted drug delivery; 4. Drug delivery cell entry mechanisms; 5. Nanomaterial cores for non-invasive imaging; 6. Attaching biomolecules to nanoparticles; 7. Characterizing nanoparticles; 8. Nanomedicine drug dosing; 9. Nanodelivery of therapeutic genes; 10. Assessing nanomedical therapies at the single-cell level; 11. Nanotoxicity at the single-cell level; 12. Designing nanodelivery systems for in-vivo use; 13. Designing and testing nanomedical devices; 14. Quality assurance and regulatory issues of nanomedicine for the pharmaceutical industry.

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Book SynopsisBiological systems are extremely complex and have emergent properties that cannot be explained or even predicted by studying their individual parts in isolation. The reductionist approach, although successful in the early days of molecular biology, underestimates this complexity. As the amount of available data grows, so it will become increasingly important to be able to analyse and integrate these large data sets. This book introduces novel approaches and solutions to the Big Data problem in biomedicine, and presents new techniques in the field of graph theory for handling and processing multi-type large data sets. By discussing cutting-edge problems and techniques, researchers from a wide range of fields will be able to gain insights for exploiting big heterogonous data in the life sciences through the concept of ''network of networks''.Trade Review'… Networks of Networks in Biology should be of interest and a good introductory resource for molecular biologists, cell biologists, and biochemists, as well as bioinformaticians not yet acquainted with multilayer networks.' Ingo Brigandt, Quarterly Review of BiologyTable of ContentsPreface; Part I. Networks in Biology: 1. An Introduction to Biological Networks Nuria Planell, Xabier Martinez de Morentin and David Gomez-Cabrero; 2. Graph Theory Akram Dehnokhalaji and Nasim Nasrabadi; Part II. Network Analysis: 3. Structural Analysis of Biological Networks Narsis A. Kiani and Mikko Kivelä; 4. Networks From an Information-Theoretic and Algorithmic Complexity Perspective Hector Zenil and Narsis A. Kiani; 5. Integration and Feature Identification in Multi-layer Network using a Heat Diffusion Approach Gordon Ball and Jesper Tegnér; Part III. Multi-layer Networks: 6. Large Multiplex Networks Ginestra Bianconi; 7. Large Existing Tools for Analysis of Multilayer Networks Manlio De Domenico and Massimo Stella; 8. Large Dynamics on Multilayer Networks Manlio De Domenico and Massimo Stella; Part IV. Applications: 9. The Network of Networks Involved in Human Disease Celine Sin and Jörg Menche; 10. Towards a Multi-Layer Network Analysis of Disease: Challenges and Opportunities Through the Lens of Multiple Sclerosis Jesper Tegnér, Ingrid Kockum, Mika Gustafsson and David Gomez-Cabrero; 11. Microbiome: A Multi-Layer Network View Is Required Rodrigo Bacigalupe, Saeed Shoai and David Gomez-Cabrero; Part V. Conclusion : Concluding Remarks: Open Questions and Challenges Ginestra Bianconi, David Gomez-Cabrero, Jesper Tegnér and Narsis A. Kiani; Index.

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Book SynopsisPractical Techniques in Molecular Biotechnology intends to familiarise students with the basics of the well-known experiments of molecular biotechnology and related courses like chemical biotechnology and cell biology. The content of the book will be useful in strengthening the basic skills and help students to apply the concepts to real-world problems. This book emphasises important concepts like bioanalytical techniques, biochemical analysis of proteins, recombinant DNA, and protein technology etc. The text will help students to understand the theoretical aspects of the techniques and provide experience with hands-on techniques to demonstrate practical troubleshooting and data analysis. The text is supported with diagrams, data, summaries for the quick recap and appendices with useful protocols and calculation methods.Table of ContentsPreface; Acknowledgements; 1. Introduction; 2. Molecular Biology; 3. Recombinant DNA and Protein Technology; 4. Biochemical Analysis of Proteins; 5. Bioanalytical Techniques; 6. Cell Culture and Tissue Engineering; 7. Antibody Technology; Appendix A. Useful Protocols; Appendix B. Practical Applications; Appendix C. Significant Figures and Scientific Notations; Appendix D. Statistical Parameters Used in the Biochemical Measurements.

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Book SynopsisIf you are a biologist and want to get the best out of the powerful methods of modern computational statistics, this is your book. You can visualize and analyze your own data, apply unsupervised and supervised learning, integrate datasets, apply hypothesis testing, and make publication-quality figures using the power of R/Bioconductor and ggplot2. This book will teach you ''cooking from scratch'', from raw data to beautiful illuminating output, as you learn to write your own scripts in the R language and to use advanced statistics packages from CRAN and Bioconductor. It covers a broad range of basic and advanced topics important in the analysis of high-throughput biological data, including principal component analysis and multidimensional scaling, clustering, multiple testing, unsupervised and supervised learning, resampling, the pitfalls of experimental design, and power simulations using Monte Carlo, and it even reaches networks, trees, spatial statistics, image data, and microbial ecology. Using a minimum of mathematical notation, it builds understanding from well-chosen examples, simulation, visualization, and above all hands-on interaction with data and code.Trade Review'This is a gorgeous book, both visually and intellectually, superbly suited for anyone who wants to learn the nuts and bolts of modern computational biology. It can also be a practical, hands-on starting point for life scientists and students who want to break out of 'canned packages' into the more versatile world of R coding. Much richer than the typical statistics textbook, it covers a wide range of topics in machine learning and image processing. The chapter on making high-quality graphics is alone worth the price of the book.' William H. Press, University of Texas, Austin'The book is a timely, comprehensive and practical reference for anyone working with modern quantitative biotechnologies. It can be read at multiple levels. For scientists with a statistics background, it is a thorough review of key methods for design and analysis of high-throughput experiments. For life scientists with a limited exposure to statistics, it offers a series of examples with relevant data and R code. Avoiding buzzwords and hype, the book advocates appropriate statistical practice for reproducible research. I expect it to be as influential for the life sciences community as Modern Applied Statistics with S, by Venables and Ripley or Introduction to Statistical Learning, by James, Witten, Hastie and Tibshirani are for applied statistics.' Olga Vitek, Northeastern University, Boston'Navigating rich data to arrive at sensible insight requires confidence in our biological understanding, informatic ability, statistical sophistication, and skills at effective communication. Fortunately the wisdom and effort of the worldwide research community has been distilled into accessible and rich collections of R and Bioconductor software packages. Holmes and Huber provide a comprehensive guide to navigating modern statistical methods for working with complex, large, and nuanced biological data. The presentation provides a firm conceptual foundation coupled with worked practical examples, extended analysis, and refined discussion of practical and theoretical challenges facing the modern practitioner. This book provides us with the confidence and tools necessary for the analysis and comprehension of modern biological data using modern statistical methods.' Martin Morgan, Roswell Park Comprehensive Cancer Center, leader of the Bioconductor project'Holmes and Huber take an integrated approach to presenting the key statistical concepts and methods needed for the analysis of biological data. Specifically, they do a wonderful job of building these foundations in the context of modern computational tools, genuine scientific questions, and real-world datasets. The code showcases many of the newest features of R and its dynamic package ecosystem, such as using ggplot2 for visualization and dplyr for data manipulation.' Jenny Bryan, RStudio and University of British Columbia'... the book is extremely readable and engaging, it explains complicated concepts in simple terms, and uses illuminating graphics and examples. Any researcher who wants to learn or teach up-to-date statistics to biologists will find this an essential volume for modern teaching of modern statistics to modern biologists.' Noa Pinter-Wollman, The Quarterly Review of BiologyTable of ContentsIntroduction; 1. Generative models for discrete data; 2. Statistical modeling; 3. High-quality graphics in R; 4. Mixture models; 5. Clustering; 6. Testing; 7. Multivariate analysis; 8. High-throughput count data; 9. Multivariate methods for heterogeneous data; 10. Networks and trees; 11. Image data; 12. Supervised learning; 13. Design of high-throughput experiments and their analyses; Statistical concordance; Bibliography; Index.

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Book SynopsisLearn how to apply rough-fuzzy computing techniques to solve problems in bioinformatics and medical image processing Emphasizing applications in bioinformatics and medical image processing, this text offers a clear framework that enables readers to take advantage of the latest rough-fuzzy computing techniques to build working pattern recognition models. The authors explain step by step how to integrate rough sets with fuzzy sets in order to best manage the uncertainties in mining large data sets. Chapters are logically organized according to the major phases of pattern recognition systems development, making it easier to master such tasks as classification, clustering, and feature selection. Rough-Fuzzy Pattern Recognition examines the important underlying theory as well as algorithms and applications, helping readers see the connections between theory and practice. The first chapter provides an introduction to pattern recognition and data mining, including the Table of ContentsForeword xiii Preface xv About the Authors xix 1 Introduction to Pattern Recognition and Data Mining 1 1.1 Introduction 1 1.2 Pattern Recognition 3 1.2.1 Data Acquisition 4 1.2.2 Feature Selection 4 1.2.3 Classification and Clustering 5 1.3 Data Mining 6 1.3.1 Tasks, Tools, and Applications 7 1.3.2 Pattern Recognition Perspective 8 1.4 Relevance of Soft Computing 9 1.5 Scope and Organization of the Book 10 References 14 2 Rough-Fuzzy Hybridization and Granular Computing 21 2.1 Introduction 21 2.2 Fuzzy Sets 22 2.3 Rough Sets 23 2.4 Emergence of Rough-Fuzzy Computing 26 2.4.1 Granular Computing 26 2.4.2 Computational Theory of Perception and f -Granulation 26 2.4.3 Rough-Fuzzy Computing 28 2.5 Generalized Rough Sets 29 2.6 Entropy Measures 30 2.7 Conclusion and Discussion 36 References 37 3 Rough-Fuzzy Clustering: Generalized c-Means Algorithm 47 3.1 Introduction 47 3.2 Existing c-Means Algorithms 49 3.2.1 Hard c-Means 49 3.2.2 Fuzzy c-Means 50 3.2.3 Possibilistic c-Means 51 3.2.4 Rough c-Means 52 3.3 Rough-Fuzzy-Possibilistic c-Means 53 3.3.1 Objective Function 54 3.3.2 Cluster Prototypes 55 3.3.3 Fundamental Properties 56 3.3.4 Convergence Condition 57 3.3.5 Details of the Algorithm 59 3.3.6 Selection of Parameters 60 3.4 Generalization of Existing c-Means Algorithms 61 3.4.1 RFCM: Rough-Fuzzy c-Means 61 3.4.2 RPCM: Rough-Possibilistic c-Means 62 3.4.3 RCM: Rough c-Means 63 3.4.4 FPCM: Fuzzy-Possibilistic c-Means 64 3.4.5 FCM: Fuzzy c-Means 64 3.4.6 PCM: Possibilistic c-Means 64 3.4.7 HCM: Hard c-Means 65 3.5 Quantitative Indices for Rough-Fuzzy Clustering 65 3.5.1 Average Accuracy, α Index 65 3.5.2 Average Roughness, ϱ Index 67 3.5.3 Accuracy of Approximation, α⋆ Index 67 3.5.4 Quality of Approximation, γ Index 68 3.6 Performance Analysis 68 3.6.1 Quantitative Indices 68 3.6.2 Synthetic Data Set: X32 69 3.6.3 Benchmark Data Sets 70 3.7 Conclusion and Discussion 80 References 81 4 Rough-Fuzzy Granulation and Pattern Classification 85 4.1 Introduction 85 4.2 Pattern Classification Model 87 4.2.1 Class-Dependent Fuzzy Granulation 88 4.2.2 Rough-Set-Based Feature Selection 90 4.3 Quantitative Measures 95 4.3.1 Dispersion Measure 95 4.3.2 Classification Accuracy, Precision, and Recall 96 4.3.3 κ Coefficient 96 4.3.4 β Index 97 4.4 Description of Data Sets 97 4.4.1 Completely Labeled Data Sets 98 4.4.2 Partially Labeled Data Sets 99 4.5 Experimental Results 100 4.5.1 Statistical Significance Test 102 4.5.2 Class Prediction Methods 103 4.5.3 Performance on Completely Labeled Data 103 4.5.4 Performance on Partially Labeled Data 110 4.6 Conclusion and Discussion 112 References 114 5 Fuzzy-Rough Feature Selection using f -Information Measures 117 5.1 Introduction 117 5.2 Fuzzy-Rough Sets 120 5.3 Information Measure on Fuzzy Approximation Spaces 121 5.3.1 Fuzzy Equivalence Partition Matrix and Entropy 121 5.3.2 Mutual Information 123 5.4 f -Information and Fuzzy Approximation Spaces 125 5.4.1 V -Information 125 5.4.2 Iα-Information 126 5.4.3 Mα-Information 127 5.4.4 χα-Information 127 5.4.5 Hellinger Integral 128 5.4.6 Renyi Distance 128 5.5 f -Information for Feature Selection 129 5.5.1 Feature Selection Using f -Information 129 5.5.2 Computational Complexity 130 5.5.3 Fuzzy Equivalence Classes 131 5.6 Quantitative Measures 133 5.6.1 Fuzzy-Rough-Set-Based Quantitative Indices 133 5.6.2 Existing Feature Evaluation Indices 133 5.7 Experimental Results 135 5.7.1 Description of Data Sets 136 5.7.2 Illustrative Example 137 5.7.3 Effectiveness of the FEPM-Based Method 138 5.7.4 Optimum Value of Weight Parameter β 141 5.7.5 Optimum Value of Multiplicative Parameter η 141 5.7.6 Performance of Different f -Information Measures 145 5.7.7 Comparative Performance of Different Algorithms 152 5.8 Conclusion and Discussion 156 References 156 6 Rough Fuzzy c-Medoids and Amino Acid Sequence Analysis 161 6.1 Introduction 161 6.2 Bio-Basis Function and String Selection Methods 164 6.2.1 Bio-Basis Function 164 6.2.2 Selection of Bio-Basis Strings Using Mutual Information 166 6.2.3 Selection of Bio-Basis Strings Using Fisher Ratio 167 6.3 Fuzzy-Possibilistic c-Medoids Algorithm 168 6.3.1 Hard c-Medoids 168 6.3.2 Fuzzy c-Medoids 169 6.3.3 Possibilistic c-Medoids 170 6.3.4 Fuzzy-Possibilistic c-Medoids 171 6.4 Rough-Fuzzy c-Medoids Algorithm 172 6.4.1 Rough c-Medoids 172 6.4.2 Rough-Fuzzy c-Medoids 174 6.5 Relational Clustering for Bio-Basis String Selection 176 6.6 Quantitative Measures 178 6.6.1 Using Homology Alignment Score 178 6.6.2 Using Mutual Information 179 6.7 Experimental Results 181 6.7.1 Description of Data Sets 181 6.7.2 Illustrative Example 183 6.7.3 Performance Analysis 184 6.8 Conclusion and Discussion 196 References 196 7 Clustering Functionally Similar Genes from Microarray Data 201 7.1 Introduction 201 7.2 Clustering Gene Expression Data 203 7.2.1 k-Means Algorithm 203 7.2.2 Self-Organizing Map 203 7.2.3 Hierarchical Clustering 204 7.2.4 Graph-Theoretical Approach 204 7.2.5 Model-Based Clustering 205 7.2.6 Density-Based Hierarchical Approach 206 7.2.7 Fuzzy Clustering 206 7.2.8 Rough-Fuzzy Clustering 206 7.3 Quantitative and Qualitative Analysis 207 7.3.1 Silhouette Index 207 7.3.2 Eisen and Cluster Profile Plots 207 7.3.3 Z Score 208 7.3.4 Gene-Ontology-Based Analysis 208 7.4 Description of Data Sets 209 7.4.1 Fifteen Yeast Data 209 7.4.2 Yeast Sporulation 211 7.4.3 Auble Data 211 7.4.4 Cho et al. Data 211 7.4.5 Reduced Cell Cycle Data 211 7.5 Experimental Results 212 7.5.1 Performance Analysis of Rough-Fuzzy c-Means 212 7.5.2 Comparative Analysis of Different c-Means 212 7.5.3 Biological Significance Analysis 215 7.5.4 Comparative Analysis of Different Algorithms 215 7.5.5 Performance Analysis of Rough-Fuzzy-Possibilistic c-Means 217 7.6 Conclusion and Discussion 217 References 220 8 Selection of Discriminative Genes from Microarray Data 225 8.1 Introduction 225 8.2 Evaluation Criteria for Gene Selection 227 8.2.1 Statistical Tests 228 8.2.2 Euclidean Distance 228 8.2.3 Pearson’s Correlation 229 8.2.4 Mutual Information 229 8.2.5 f -Information Measures 230 8.3 Approximation of Density Function 230 8.3.1 Discretization 231 8.3.2 Parzen Window Density Estimator 231 8.3.3 Fuzzy Equivalence Partition Matrix 233 8.4 Gene Selection using Information Measures 234 8.5 Experimental Results 235 8.5.1 Support Vector Machine 235 8.5.2 Gene Expression Data Sets 236 8.5.3 Performance Analysis of the FEPM 236 8.5.4 Comparative Performance Analysis 250 8.6 Conclusion and Discussion 250 References 252 9 Segmentation of Brain Magnetic Resonance Images 257 9.1 Introduction 257 9.2 Pixel Classification of Brain MR Images 259 9.2.1 Performance on Real Brain MR Images 260 9.2.2 Performance on Simulated Brain MR Images 263 9.3 Segmentation of Brain MR Images 264 9.3.1 Feature Extraction 265 9.3.2 Selection of Initial Prototypes 274 9.4 Experimental Results 277 9.4.1 Illustrative Example 277 9.4.2 Importance of Homogeneity and Edge Value 278 9.4.3 Importance of Discriminant Analysis-Based Initialization 279 9.4.4 Comparative Performance Analysis 280 9.5 Conclusion and Discussion 283 References 283 Index 287

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Book SynopsisA comprehensive introduction to using modeling and simulation programs in drug discovery and development Biopharmaceutical modeling has become integral to the design and development of new drugs. Influencing key aspects of the development process, including drug substance design, formulation design, and toxicological exposure assessment, biopharmaceutical modeling is now seen as the linchpin to a drug''s future success. And while there are a number of commercially available software programs for drug modeling, there has not been a single resource guiding pharmaceutical professionals to the actual tools and practices needed to design and test safe drugs. A guide to the basics of modeling and simulation programs, Biopharmaceutics Modeling and Simulations offers pharmaceutical scientists the keys to understanding how they work and are applied in creating drugs with desired medicinal properties. Beginning with a focus on the oral absorption of drugs, the bookTrade Review“This book serves as an invaluable source of information for the formulation scientist, the preclinical, translational or clinical pharmacokineticist, as well as the modeling and simulation scientist.” (ChemMedChem, 1 April 2013)Table of ContentsPREFACE xxv LIST OF ABBREVIATIONS xxix 1 INTRODUCTION 1 1.1 An Illustrative Description of Oral Drug Absorption: The Whole Story 1 1.2 Three Regimes of Oral Drug Absorption 2 1.3 Physiology of the Stomach, Small Intestine, and Colon 5 1.4 Drug and API Form 6 1.4.1 Undissociable and Free Acid Drugs 6 1.4.2 Free Base Drugs 6 1.4.3 Salt Form Cases 6 1.5 The Concept of Mechanistic Modeling 7 References 8 2 THEORETICAL FRAMEWORK I: SOLUBILITY 10 2.1 Definition of Concentration 10 2.1.1 Total Concentration 11 2.1.2 Dissolved Drug Concentration 11 2.1.3 Effective Concentration 12 2.2 Acid–Base and Bile-Micelle-Binding Equilibriums 13 2.2.1 Monoprotic Acid and Base 14 2.2.2 Multivalent Cases 16 2.2.3 Bile-Micelle Partitioning 17 2.2.4 Modified Henderson–Hasselbalch Equation 18 2.2.5 Kbm from Log Poct 19 2.3 Equilibrium Solubility 19 2.3.1 Definition of Equilibrium Solubility 19 2.3.2 pH–Solubility Profile (pH-Controlled Region) 21 2.3.3 Solubility in a Biorelevant Media with Bile Micelles (pH-Controlled Region) 23 2.3.4 Estimation of Unbound Fraction from the Solubilities with and without Bile Micelles 25 2.3.5 Common Ionic Effect 25 2.3.6 Important Conclusion from the pH–Equilibrium Solubility Profile Theory 27 2.3.7 Yalkowsky’s General Solubility Equation 27 2.3.8 Solubility Increase by Converting to an Amorphous Form 29 2.3.9 Solubility Increase by Particle Size Reduction (Nanoparticles) 30 2.3.10 Cocrystal 31 References 31 3 THEORETICAL FRAMEWORK II: DISSOLUTION 33 3.1 Diffusion Coefficient 34 3.1.1 Monomer 34 3.1.2 Bile Micelles 35 3.1.3 Effective Diffusion Coefficient 36 3.2 Dissolution and Particle Growth 36 3.2.1 Mass Transfer Equations: Pharmaceutical Science Versus Fluid Dynamics 37 3.2.2 Dissolution Equation with a Lump Sum Dissolution Rate Coefficient (kdiss) 38 3.2.3 Particle Size and Surface Area 39 3.2.3.1 Monodispersed Particles 39 3.2.3.2 Polydispersed Particles 41 3.2.4 Diffusion Layer Thickness I: Fluid Dynamic Model 41 3.2.4.1 Reynolds and Sherwood Numbers 42 3.2.4.2 Disk (Levich Equation) 45 3.2.4.3 Tube (Graetz Problem) 45 3.2.4.4 Particle Fixed to Space (Ranz–Marshall Equation) 46 3.2.4.5 Floating Particle 47 3.2.4.6 Nonspherical Particle 49 3.2.4.7 Minimum Agitation Speed for Complete Suspension 51 3.2.4.8 Other Factors 52 3.2.5 Diffusion Layer Thickness II: Empirical Models for Particles 52 3.2.6 Solid Surface pH and Solubility 53 3.3 Nucleation 56 3.3.1 General Description of Nucleation and Precipitation Process 56 3.3.2 Classical Nucleation Theory 57 3.3.2.1 Concept of Classical Nucleation Theory 58 3.3.2.2 Mathematical Expressions 58 3.3.3 Application of a Nucleation Theory for Biopharmaceutical Modeling 61 References 61 4 THEORETICAL FRAMEWORK III: BIOLOGICAL MEMBRANE PERMEATION 64 4.1 Overall Scheme 64 4.2 General Permeation Equation 66 4.3 Permeation Rate Constant, Permeation Clearance, and Permeability 66 4.4 Intestinal Tube Flatness and Permeation Parameters 68 4.5 Effective Concentration for Intestinal Membrane Permeability 70 4.5.1 Effective Concentration for Unstirred Water Layer Permeation 70 4.5.2 Effective Concentration for Epithelial Membrane Permeation: the Free Fraction Theory 70 4.6 Surface Area Expansion by Plicate and Villi 71 4.7 Unstirred Water Layer Permeability 73 4.7.1 Basic Case 73 4.7.2 Particles in the UWL (Particle Drifting Effect) 74 4.8 Epithelial Membrane Permeability (Passive Processes) 76 4.8.1 Passive Transcellular Membrane Permeability: pH Partition Theory 76 4.8.2 Intrinsic Passive Transcellular Permeability 77 4.8.2.1 Solubility–Diffusion Model 77 4.8.2.2 Flip-Flop Model 79 4.8.2.3 Relationship between Ptrans,0 and log Poct 80 4.8.3 Paracellular Pathway 83 4.8.4 Relationship between log Doct, MW, and Fa% 84 4.9 Enteric Cell Model 84 4.9.1 Definition of Papp 86 4.9.2 Enzymatic Reaction: Michaelis–Menten Equation 87 4.9.3 First-Order Case 1: No Transporter and Metabolic Enzymes 88 4.9.4 First-Order Case 2: Efflux Transporter in Apical Membrane 91 4.9.5 Apical Efflux Transporter with Km and Vmax 95 4.9.6 Apical Influx Transporter with Km and Vmax 100 4.9.7 UWL and Transporter 100 4.9.7.1 No Transporter 101 4.9.7.2 Influx Transporter and UWL 101 4.9.7.3 Efflux Transporter 101 4.10 Gut Wall Metabolism 103 4.10.1 The Qgut Model 104 4.10.2 Simple Fg Models 104 4.10.3 Theoretical Consideration on Fg 104 4.10.3.1 Derivation of the Fg Models 105 4.10.3.2 Derivation of the Anatomical Fg Model 107 4.10.4 Interplay between CYP3A4 and P-gp 108 4.11 Hepatic Metabolism and Excretion 114 References 115 5 THEORETICAL FRAMEWORK IV: GASTROINTESTINAL TRANSIT MODELS AND INTEGRATION 122 5.1 GI Transit Models 122 5.1.1 One-Compartment Model/Plug Flow Model 122 5.1.2 Plug Flow Model 123 5.1.3 Three-Compartment Model 124 5.1.4 S1I7CX (X = 1–4) Compartment Models 124 5.1.5 Convection–Dispersion Model 126 5.1.6 Tapered Tube Model 126 5.2 Time-Dependent Changes of Physiological Parameters 127 5.2.1 Gastric Emptying 127 5.2.2 Water Mass Balance 128 5.2.3 Bile Concentration 129 5.3 Integration 1: Analytical Solutions 129 5.3.1 Dissolution Under Sink Condition 130 5.3.1.1 Monodispersed Particles 130 5.3.1.2 Polydispersed Particles 131 5.3.2 Fraction of a Dose Absorbed (Fa%) 132 5.3.3 Approximate Fa% Analytical Solutions 1: Case-by-Case Solution 133 5.3.3.1 Permeability-Limited Case 134 5.3.3.2 Solubility-Permeability-Limited Case 135 5.3.3.3 Dissolution-Rate-Limited Case 137 5.3.4 Approximate Fa% Analytical Solutions 2: Semi-General Equations 137 5.3.4.1 Sequential First-Order Kinetics of Dissolution and Permeation 137 5.3.4.2 Minimum Fa% Model 138 5.3.5 Approximate Fa% Analytical Solutions 3: FaSS Equation 139 5.3.5.1 Application Range 140 5.3.5.2 Derivation of Fa Number Equation 140 5.3.5.3 Refinement of the FaSS Equation 141 5.3.5.4 Advantage of FaSS Equation 146 5.3.5.5 Limitation of FaSS Equation 146 5.3.6 Interpretations of Fa Equations 146 5.3.7 Approximate Analytical Solution for Oral PK Model 147 5.4 Integration 2: Numerical Integration 147 5.4.1 Virtual Particle Bins 149 5.4.2 The Mass Balance of Dissolved Drug Amount in Each GI Position 149 5.4.3 Controlled Release of Virtual Particle Bin 150 5.5 In Vivo FA From PK Data 150 5.5.1 Absolute Bioavailability and Fa 151 5.5.2 Relative Bioavailability Between Solid and Solution Formulations 151 5.5.3 Relative Bioavailability Between Low and High Dose 152 5.5.4 Convolution and Deconvolution 152 5.5.4.1 Convolution 153 5.5.4.2 Deconvolution 154 5.6 Other Administration Routes 156 5.6.1 Skin 156 References 157 6 PHYSIOLOGY OF GASTROINTESTINAL TRACT AND OTHER ADMINISTRATION SITES IN HUMANS AND ANIMALS 160 6.1 Morphology of Gastrointestinal Tract 160 6.1.1 Length and Tube Radius 160 6.1.2 Surface Area 161 6.1.2.1 Small Intestine 161 6.1.2.2 Colon 163 6.1.3 Degree of Flatness 164 6.1.3.1 Small Intestine 164 6.1.3.2 Colon 164 6.1.4 Epithelial Cells 165 6.1.4.1 Apical and Basolateral Lipid Bilayer Membranes 165 6.1.4.2 Tight Junction 168 6.1.4.3 Mucous Layer 168 6.2 Movement of the Gastrointestinal Tract 170 6.2.1 Transit Time 170 6.2.1.1 Gastric Emptying Time (GET) 170 6.2.1.2 Small Intestinal Transit Time 170 6.2.1.3 Colon Transit Time 171 6.2.2 Migrating Motor Complex 171 6.2.3 Agitation 173 6.2.3.1 Mixing Pattern 173 6.2.3.2 Agitation Strength 175 6.2.3.3 Unstirred Water Layer on the Intestinal Wall 176 6.3 Fluid Character of the Gastrointestinal Tract 178 6.3.1 Volume 178 6.3.1.1 Stomach 178 6.3.1.2 Small Intestine 178 6.3.1.3 Colon 179 6.3.2 Bulk Fluid pH and Buffer Concentration 179 6.3.2.1 Stomach 181 6.3.2.2 Small Intestine 181 6.3.2.3 Colon 181 6.3.3 Microclimate pH 181 6.3.3.1 Small Intestine 181 6.3.3.2 Colon 182 6.3.4 Bile Micelles 182 6.3.4.1 Stomach 183 6.3.4.2 Small Intestine 183 6.3.4.3 Colon 185 6.3.5 Enzymes and Bacteria 185 6.3.6 Viscosity, Osmolality, and Surface Tension 185 6.4 Transporters and Drug-Metabolizing Enzymes in the Intestine 186 6.4.1 Absorptive Drug Transporters 186 6.4.1.1 PEP-T1 186 6.4.1.2 OATP 186 6.4.2 Efflux Drug Transporters 186 6.4.2.1 P-gp 186 6.4.3 Drug-Metabolizing Enzymes 186 6.4.3.1 CYP3A4 186 6.4.3.2 Glucuronyl Transferase and Sulfotransferase 188 6.5 Intestinal and Liver Blood Flow 188 6.5.1 Absorption Sites Connected to Portal Vein 188 6.5.2 Villous Blood Flow (Qvilli) 188 6.5.3 Hepatic Blood Flow (Qh) 188 6.6 Physiology Related to Enterohepatic Recirculation 189 6.6.1 Bile Secretion 189 6.6.2 Mass Transfer into/from the Hepatocyte 190 6.6.2.1 Sinusoidal Membrane (Blood to Hepatocyte) 190 6.6.2.2 Canalicular Membrane (Hepatocyte to Bile Duct) 191 6.7 Nasal 191 6.8 Pulmonary 193 6.8.1 Fluid in the Lung 193 6.8.2 Mucociliary Clearance 193 6.8.3 Absorption into the Circulation 194 6.9 Skin 194 References 196 7 DRUG PARAMETERS 206 7.1 Dissociation Constant (pKa) 206 7.1.1 pH Titration 207 7.1.2 pH–UV Shift 207 7.1.3 Capillary Electrophoresis 207 7.1.4 pH–Solubility Profile 208 7.1.5 Calculation from Chemical Structure 208 7.1.6 Recommendation 208 7.2 Octanol–Water Partition Coefficient 208 7.2.1 Shake Flask Method 209 7.2.2 HPLC Method 210 7.2.3 Two-Phase Titration Method 210 7.2.4 PAMPA-Based Method 210 7.2.5 In Silico Method 210 7.2.6 Recommendation 210 7.3 Bile Micelle Partition Coefficient (Kbm) 211 7.3.1 Calculation from Solubility in Biorelevant Media 211 7.3.2 Spectroscopic Method 212 7.3.3 Recommendations 212 7.4 Particle Size and Shape 212 7.4.1 Microscope 213 7.4.2 Laser Diffraction 215 7.4.3 Dynamic Laser Scattering (DLS) 215 7.4.4 Recommendations 215 7.5 Solid Form 215 7.5.1 Nomenclature 215 7.5.1.1 Crystalline and Amorphous 215 7.5.1.2 Salts, Cocrystals, and Solvates 216 7.5.1.3 Hydrate 217 7.5.2 Crystal Polymorph 217 7.5.2.1 True Polymorph and Pseudopolymorph 217 7.5.2.2 Kinetic Resolution versus Stable Form 217 7.5.2.3 Dissolution Profile Advantages of Less Stable Forms 218 7.5.2.4 Enantiotropy 218 7.5.3 Solid Form Characterization 219 7.5.3.1 Polarized Light Microscopy (PLM) 219 7.5.3.2 Powder X-Ray Diffraction (PXRD) 219 7.5.3.3 Differential Scanning Calorimeter (DSC) and Thermal Gravity (TG) 220 7.5.3.4 High Throughput Solid Form Screening 221 7.5.4 Wettability and Surface Free Energy 222 7.5.5 True Density 222 7.6 Solubility 223 7.6.1 Terminology 223 7.6.1.1 Definition of Solubility 223 7.6.1.2 Intrinsic Solubility 223 7.6.1.3 Solubility in Media 223 7.6.1.4 Initial pH and Final pH 224 7.6.1.5 Supersaturable API 224 7.6.1.6 Critical Supersaturation Concentration and Induction Time 224 7.6.1.7 Dissolution Rate and Dissolution Profile 225 7.6.2 Media 225 7.6.2.1 Artificial Stomach Fluids 225 7.6.2.2 Artificial Small Intestinal Fluids 225 7.6.3 Solubility Measurement 225 7.6.3.1 Standard Shake Flask Method 225 7.6.3.2 Measurement from DMSO Sample Stock Solution 227 7.6.3.3 Solid Surface Solubility 228 7.6.3.4 Method for Nanoparticles 228 7.6.4 Recommendation 228 7.6.4.1 Early Drug Discovery Stage (HTS to Early Lead Optimization) 229 7.6.4.2 Late Lead Optimization Stage 229 7.6.4.3 Transition Stage between Discovery and Development 229 7.7 Dissolution Rate/Release Rate 230 7.7.1 Intrinsic Dissolution Rate 230 7.7.2 Paddle Method 230 7.7.2.1 Apparatus 231 7.7.2.2 Fluid Condition 231 7.7.2.3 Agitation 232 7.7.3 Flow-Through Method 233 7.7.4 Multicompartment Dissolution System 233 7.7.5 Dissolution Permeation System 233 7.7.6 Recommendation 235 7.8 Precipitation 235 7.8.1 Kinetic pH Titration Method 235 7.8.2 Serial Dilution Method 236 7.8.3 Two-Chamber Transfer System 236 7.8.4 Nonsink Dissolution Test 236 7.9 Epithelial Membrane Permeability 240 7.9.1 Back-Estimation from Fa% 241 7.9.2 In Situ Single-Pass Intestinal Perfusion 241 7.9.3 Cultured Cell Lines (Caco-2, MDCK, etc.) 243 7.9.4 PAMPA 244 7.9.5 Estimation of Ptrans,0 from Experimental Apparent Membrane Permeability 246 7.9.6 Estimation of Ptrans,0 from Experimental log Poct 247 7.9.7 Mechanistic Investigation 247 7.9.8 Limitation of Membrane Permeation Assays 247 7.9.8.1 UWL Adjacent to the Membrane 249 7.9.8.2 Membrane Binding 250 7.9.8.3 Low Solubility 250 7.9.8.4 Differences in Paracellular Pathway 251 7.9.8.5 Laboratory to Laboratory Variation 251 7.9.8.6 Experimental Artifacts in Carrier-Mediated Membrane Transport 251 7.9.9 Recommendation for Pep and Peff Estimation 251 7.9.9.1 Hydrophilic Drugs 251 7.9.9.2 Lipophilic Drugs 252 7.9.9.3 Drugs with Medium Lipophilicity 252 7.10 In Vivo Experiments 252 7.10.1 P.O 252 7.10.2 I.V 253 7.10.3 Animal Species 253 7.10.4 Analysis 254 References 254 8 VALIDATION OF MECHANISTIC MODELS 266 8.1 Concerns Related to Model Validation Using In Vivo Data 267 8.2 Strategy for Transparent and Robust Validation of Biopharmaceutical Modeling 267 8.3 Prediction Steps 268 8.4 Validation for Permeability-Limited Cases 279 8.4.1 Correlation Between Fa% and Peff Data for Humans (Epithelial Membrane Permeability-Limited Cases PL-E) 279 8.4.2 Correlation Between In Vitro Permeability and Peff and/or Fa% (PL-E Cases) 283 8.4.2.1 Caco-2 283 8.4.2.2 PAMPA 285 8.4.2.3 Experimental log Poct and pKa 285 8.4.3 Peff for UWL Limited Cases 287 8.4.4 Chemical Structure to Peff, Fa%, and Caco-2 Permeability 288 8.5 Validation for Dissolution-Rate and Solubility-Permeability-Limited Cases (without the Stomach Effect) 290 8.5.1 Fa% Prediction Using In Vitro Dissolution Data 290 8.5.2 Fa% Prediction Using In Vitro Solubility and Permeability Data 292 8.6 Validation for Dissolution-Rate and Solubility-Permeability-Limited Cases (with the Stomach Effect) 305 8.6.1 Difference Between Free Base and Salts 305 8.6.2 Simulation Model for Free Base 305 8.6.3 Simulation Results 307 8.7 Salts 307 8.8 Reliability of Biopharmaceutical Modeling 311 References 311 9 BIOEQUIVALENCE AND BIOPHARMACEUTICAL CLASSIFICATION SYSTEM 322 9.1 Bioequivalence 322 9.2 The History of BCS 324 9.3 Regulatory Biowaiver Scheme and BCS 326 9.3.1 Elucidation of BCS Criteria in Regulatory Biowaiver Scheme 327 9.3.1.1 Congruent Condition of Bioequivalence 328 9.3.1.2 Equivalence of Dose Number (Do) 329 9.3.1.3 Equivalence of Permeation Number (Pn) 329 9.3.1.4 Equivalence of Dissolution Number (Dn) 329 9.3.2 Possible Extension of the Biowaiver Scheme 331 9.3.2.1 Dose Number Criteria 331 9.3.2.2 Permeability Criteria 332 9.3.3 Another Interpretation of the Theory 332 9.3.3.1 Another Assumption about Dissolution Test 332 9.3.3.2 Assessment of Suitability of Dissolution Test Based on Rate-Limiting Process 333 9.3.4 Validation of Biowaiver Scheme by Clinical BE Data 333 9.3.5 Summary for Regulatory BCS Biowaiver Scheme 334 9.4 Exploratory BCS 335 9.5 In Vitro–In Vivo Correlation 335 9.5.1 Levels of IVIVC 335 9.5.2 Judgment of Similarity Between Two Formulations (f2 Function) 336 9.5.3 Modeling the Relationship Between f2 and Bioequivalence 336 9.5.4 Point-to-Point IVIVC 337 References 338 10 DOSE AND PARTICLE SIZE DEPENDENCY 340 10.1 Definitions and Causes of Dose Nonproportionality 340 10.2 Estimation of the Dose and Particle Size Effects 341 10.2.1 Permeability-Limited Cases (PL) 341 10.2.2 Dissolution-Rate-Limited (DRL) Cases 341 10.2.3 Solubility–Epithelial Membrane Permeability Limited (SL-E) Cases 342 10.2.4 Solubility-UWL-Permeability-Limited Cases 344 10.3 Effect of Transporters 344 10.4 Analysis of In Vivo Data 345 References 346 11 ENABLING FORMULATIONS 347 11.1 Salts and Cocrystals: Supersaturating API 347 11.1.1 Scenarios of Oral Absorption of Salt 349 11.1.2 Examples 350 11.1.2.1 Example 1: Salt of Basic Drugs 350 11.1.2.2 Example 2: Salt of Acid Drugs 352 11.1.2.3 Example 3: Other Supersaturable API Forms 353 11.1.3 Suitable Drug for Salts 353 11.1.3.1 pKa Range 353 11.1.3.2 Supersaturability of Drugs 355 11.1.4 Biopharmaceutical Modeling of Supersaturable API Forms 357 11.2 Nanomilled API Particles 358 11.3 Self-Emulsifying Drug Delivery Systems (Micelle/Emulsion Solubilization) 360 11.4 Solid Dispersion 363 11.5 Supersaturable Formulations 364 11.6 Prodrugs to Increase Solubility 365 11.7 Prodrugs to Increase Permeability 365 11.7.1 Increasing Passive Permeation 366 11.7.2 Hitchhiking the Carrier 366 11.8 Controlled Release 366 11.8.1 Fundamentals of CR Modeling 367 11.8.2 Simple Convolution Method 368 11.8.3 Advanced Controlled-Release Modeling 368 11.8.4 Controlled-Release Function 368 11.8.5 Sustained Release 368 11.8.5.1 Objectives to Develop a Sustained-Release Formulation 368 11.8.5.2 Suitable Drug Character for Sustained Release 369 11.8.5.3 Gastroretentive Formulation 369 11.8.6 Triggered Release 369 11.8.6.1 Time-Triggered Release 369 11.8.6.2 pH-Triggered Release 369 11.8.6.3 Position-Triggered Release 371 11.9 Communication with Therapeutic Project Team 371 References 373 12 FOOD EFFECT 379 12.1 Physiological Changes Caused by Food 379 12.1.1 Food Component 380 12.1.2 Fruit Juice Components 380 12.1.3 Alcohol 382 12.2 Types of Food Effects and Relevant Parameters in Biopharmaceutical Modeling 382 12.2.1 Delay in Tmax and Decrease in Cmax 382 12.2.2 Positive Food Effect 383 12.2.2.1 Bile Micelle Solubilization 383 12.2.2.2 Increase in Hepatic Blood Flow 388 12.2.2.3 Increase in Intestinal Blood Flow 388 12.2.2.4 Inhibition of Efflux Transporter and Gut Wall Metabolism 389 12.2.2.5 Desaturation of Influx Transporter 391 12.2.3 Negative Food Effect 391 12.2.3.1 Bile Micelle Binding/Food Component Binding 391 12.2.3.2 Inhibition of Uptake Transporter 392 12.2.3.3 Desaturation of First-Pass Metabolism and Efflux Transport 394 12.2.3.4 Viscosity 398 12.2.3.5 pH Change in the Stomach 398 12.2.3.6 pH Change in the Small Intestine 398 12.3 Effect of Food Type 398 12.4 Biopharmaceutical Modeling of Food Effect 401 12.4.1 Simple Flowchart and Semiquantitative Prediction 401 12.4.2 More Complicated Cases 402 References 403 13 BIOPHARMACEUTICAL MODELING FOR MISCELLANEOUS CASES 412 13.1 Stomach pH Effect on Solubility and Dissolution Rate 412 13.1.1 Free Bases 413 13.1.2 Free Acids and Undissociable Drugs 413 13.1.3 Salts 413 13.1.4 Chemical and Enzymatic Degradation in the Stomach and Intestine 413 13.2 Intestinal First-Pass Metabolism 414 13.3 Transit Time Effect 415 13.3.1 Gastric Emptying Time 415 13.3.2 Intestinal Transit Time 415 13.4 Other Chemical and Physical Drug–Drug Interactions 415 13.4.1 Metal Ions 415 13.4.2 Cationic Resins 416 13.5 Species Difference 417 13.5.1 Permeability 417 13.5.2 Solubility/Dissolution 418 13.5.3 First-Pass Metabolism 419 13.6 Validation of GI Site-Specific Absorption Models 421 13.6.1 Stomach 421 13.6.2 Colon 422 13.6.3 Regional Difference in the Small Intestine: Fact or Myth? 422 13.6.3.1 Transporter 422 13.6.3.2 Bile-Micelle Binding and Bimodal Peak Phenomena 422 References 426 14 INTESTINAL TRANSPORTERS 430 14.1 Apical Influx Transporters 431 14.1.1 Case Example 1: Antibiotics 431 14.1.2 Case Example 2: Valacyclovir 433 14.1.3 Case Example: Gabapentin 434 14.2 Efflux Transporters 435 14.2.1 Effect of P-gp 435 14.2.2 Drug–Drug Interaction (DDI) via P-gp 437 14.3 Dual Substrates 438 14.3.1 Talinolol 438 14.3.2 Fexofenadine 441 14.4 Difficulties in Simulating Carrier-Mediated Transport 442 14.4.1 Absorptive Transporters 442 14.4.1.1 Discrepancies Between In Vitro and In Vivo Km Values 442 14.4.1.2 Contribution of Other Pathways 443 14.4.2 Efflux Transporters 443 14.5 Summary 445 References 446 15 STRATEGY IN DRUG DISCOVERY AND DEVELOPMENT 452 15.1 Library Design 452 15.2 Lead Optimization 453 15.3 Compound Selection 455 15.4 API Form Selection 455 15.5 Formulation Selection 455 15.6 Strategy to Predict Human Fa% 456 References 457 16 EPISTEMOLOGY OF BIOPHARMACEUTICAL MODELING AND GOOD SIMULATION PRACTICE 459 16.1 Can Simulation be so Perfect? 459 16.2 Parameter Fitting 460 16.3 Good Simulation Practice 461 16.3.1 Completeness 461 16.3.2 Comprehensiveness 462 References 463 APPENDIX A GENERAL TERMINOLOGY 464 A.1 Biopharmaceutic 464 A.2 Bioavailability (BA% or F) 464 A.3 Drug Disposition 465 A.4 Fraction of a Dose Absorbed (Fa) 465 A.5 Modeling/Simulation/In Silico 465 A.6 Active Pharmaceutical Ingredient (API) 465 A.7 Drug Product 465 A.8 Lipophilicity 465 A.9 Acid and Base 466 A.10 Solubility 466 A.11 Molecular Weight (MW) 466 A.12 Permeability of a Drug 466 APPENDIX B FLUID DYNAMICS 468 B.1 Navier–Stokes Equation and Reynolds Number 468 B.2 Boundary Layer Approximation 469 B.3 The Boundary Layer and Mass Transfer 470 B.4 The Thickness of the Boundary Layer 470 B.4.1 99% of Main Flow Speed 471 B.4.2 Displacement Thickness 471 B.4.3 Momentum Thickness 471 B.5 Sherwood Number 471 B.6 Turbulence 473 B.7 Formation of Eddies 474 B.8 Computational Fluid Dynamics 474 References 476 INDEX 477

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Book SynopsisThe functional materials with the most promising outlook have the ability to precisely adjust the biological phenomenon in a controlled mode.Table of ContentsPreface xv Part I: Biomedical Materials 1. Application of the Collagen as Biomaterials 3 Kwangwoo Nam and Akio Kishida 1.1 Introduction 3 1.2 Structural Aspect of Native Tissue 5 1.3 Processing of Collagen Matrix 8 1.4 Conclusions and Future Perspectives 14 2. Biological and Medical Significance of Nanodimensional and Nanocrystalline Calcium Orthophosphates 19 Sergey V. Dorozhkin 2.1 Introduction 19 2.2 General Information on ?Nano? 21 2.3 Micron- and Submicron-Sized Calcium Orthophosphates versus the Nanodimensional Ones 23 2.4 Nanodimensional and Nanocrystalline Calcium Orthophosphates in Calcified Tissues of Mammals 26 2.5 The Structure of the Nanodimensional and Nanocrystalline Apatites 28 2.6 Synthesis of the Nanodimensional and Nanocrystalline Calcium Orthophosphates 34 2.7 Biomedical Applications of the Nanodimensional and Nanocrystalline Calcium Orthophosphates 47 2.8 Other Applications of the Nanodimensional and Nanocrystalline Calcium Orthophosphates 58 2.9 Summary and Perspectives 58 2.10 Conclusions 61 3. Layer-by-Layer (LbL) Thin Film: From Conventional To Advanced Biomedical and Bioanalytical Applications 101 Wing Cheung MAK 3.1 State-of-the-art LbL Technology 101 3.2 Principle of Biomaterials Based Lbl Architecture 102 3.3 LbL Thin Film for Biomaterials and Biomedical Implantations 103 3.4 LbL Thin Film for Biosensors and Bioassays 105 3.5 LbL Thin Film Architecture on Colloidal Materials 107 3.6 LbL Thin Film for Drug Encapsulation and Delivery 108 3.7 LbL Thin Film Based Micro/Nanoreactor 110 4. Polycaprolactone based Nanobiomaterials 115 Narendra K. Singh and Pralay Maiti 4.1 Introduction 115 4.2 Preparation of Polycaprolactone Nanocomposites 118 4.3 Characterization of Poly(caprolactone) Nanocomposites 119 4.4 Properties 123 4.5 Biocompatibility and Drug Delivery Application 141 4.6 Conclusion 150 Acknowledgement 150 5. Bone Substitute Materials in Trauma and Orthopedic Surgery ? Properties and Use in Clinic 157 Esther M.M. Van Lieshout 5.1 Introduction 158 5.2 Types of Bone Grafts 159 5.3 Bone Substitute Materials 161 5.4 Combinations with Osteogenic and Osteoinductive Materials 171 5.5 Discussion and Conclusion 173 6. Surface Functionalized Hydrogel Nanoparticles 191 Mehrdad Hamidi, Hajar Ashrafi and Amir Azadi 6.1 Hydrogel Nanoparticles 191 6.2 Hydrogel Nanoparticles Based on Chitosan 193 6.3 Hydrogel Nanoparticles Based on Alginate 194 6.4 Hydrogel Nanoparticles Based on Poly(vinyl Alcohol) 195 6.5 Hydrogel Nanoparticles Based on Poly(ethylene Oxide) and Poly(ethyleneimine) 196 6.6 Hydrogel Nanoparticles Based on Poly(vinyl Pyrrolidone) 198 6.7 Hydrogel Nanoparticles Based on Poly-N-Isopropylacrylamide 198 6.8 Smart Hydrogel Nanoparticles 199 6.9 Self-assembled Hydrogel Nanoparticles 200 6.10 Surface Functionalization 201 6.11 Surface Functionalized Hydrogel Nanoparticles 205 Part II: Diagnostic Devices 7. Utility and Potential Application of Nanomaterials in Medicine 215 Ravindra P. Singh, Jeong -Woo Choi, Ashutosh Tiwari and Avinash Chand Pandey 7.1 Introduction 215 7.2 Nanoparticle Coatings 218 7.3 Cyclic Peptides 220 7.4 Dendrimers 221 7.5 Fullerenes/Carbon Nanotubes/Graphene 227 7.6 Functional Drug Carriers 229 7.7 MRI Scanning Nanoparticles 233 7.8 Nanoemulsions 235 7.9 Nanofibers 236 7.10 Nanoshells 239 7.11 Quantum Dots 240 7.12 Nanoimaging 248 7.13 Inorganic Nanoparticles 248 7.14 Conclusion 250 8. Gold Nanoparticle-based Electrochemical Biosensors for Medical Applications 261 Ülkü Anik 8.1 Introduction 261 8.2 Electrochemical Biosensors 262 8.3 Conclusion 272 9. Impedimetric DNA Sensing Employing Nanomaterials 277 Manel del Valle and Alessandra Bonanni 9.1 Introduction 277 9.2 Electrochemical Impedance Spectroscopy for Genosensing 280 9.3 Nanostructured Carbon Used in Impedimetric Genosensors 286 9.4 Nanostructured Gold Used in Impedimetric Genosensors 290 9.5 Quantum Dots for Impedimetric Genosensing 293 9.6 Impedimetric Genosensors for Point-of-Care Diagnosis 293 9.7 Conclusions (Past, Present and Future Perspectives) 294 10. Bionanocomposite Matrices in Electrochemical Biosensors 301 Ashutosh Tiwari, Atul Tiwari 10.1 Introduction 301 10.2 Fabricationof SiO2-CHIT/CNTs Bionanocomposites 303 10.3 Preparation of Bioelectrodes 304 10.4 Characterizations 305 10.5 Electrocatalytic Properties 307 10.6 Photometric Response 315 10.7 Conclusions 316 11. Biosilica? Nanocomposites - Nanobiomaterials for Biomedical Engineering and Sensing Applications 321 Nikos Chaniotakis, Raluca Buiculescu 11.1 Introduction 321 11.2 Silica Polymerization Process 323 11.3 Biocatalytic Formation of Silica 325 11.4 Biosilica Nanotechnology 327 11.5 Applications 328 11.6 Conclusions 334 12. Molecularly Imprinted Nanomaterial-based Highly Sensitive and Selective Medical Devices 337 Bhim Bali Prasad and Mahavir Prasad Tiwari 12.1 Introduction 337 12.2 Molecular Imprinted Polymer Technology 340 12.3 Molecularly Imprinted Nanomaterials 360 12.4 Molecularly Imprinted Nanomaterial-based Sensing Devices 362 12.5 Conclusion 379 13. Immunosensors for Diagnosis of Cardiac Injury 391 Swapneel R. Deshpande, Aswathi Anto Antony, Ashutosh Tiwari, Emilia Wiechec, Ulf Dahlström, Anthony P.F. Turner 13.1 Immunosensor 391 13.2 Myocardial Infarction and Cardiac Biomarkers 392 13.3 Immunosensors for Troponin 399 13.4 Conclusions 404 Part III: Drug Delivery and Therapeutics 14. Ground-Breaking Changes in Mimetic and Novel Nanostructured Composites for Intelligent-, Adaptive- and In vivo-responsive Drug Delivery Therapies 411 Dipak K. Sarker 14. 1 Introduction 411 14.2 Obstacles to the Clinician 420 14.3 Hurdles for the Pharmaceuticist 428 14.4 Nanostructures 431 14.5 Surface Coating 435 14.7 Formulation Conditions and Parameters 439 14.8 Delivery Systems 440 14.9 Evaluation 443 14.10 Conclusions 447 15. Progress of Nanobiomaterials for Theranostic Systems 451 Dipendra Gyawali, Michael Palmer, Richard T. Tran and Jian Yang 15.1 Introduction 451 15.2 Design Concerns for Theranostic Nanosystems 456 15.3 Designing a Smart and Functional Theranostic System 459 15.4 Materials for Theranostic System 462 15.5 Theranostic Systems and Applications 474 15.6 Future Outlook 481 16. Intelligent Drug Delivery Systems for Cancer Therapy 493 Mousa Jafari, Bahram Zargar, M. Soltani, D. Nedra Karunaratne, Brian Ingalls, P. Chen 16.1 Introduction 493 16.2 Peptides for Nucleic Acid and Drug Delivery in Cancer Therapy 494 16.3 Lipid Carriers 499 16.4 Polymeric Carriers 506 16.5 Bactria Mediated Cancer Therapy 514 16.6 Conclusion 519 Part IV: Tissue Engineering and Organ Regeneration 531 17. The Evolution of Abdominal Wall Reconstruction and the Role of Nonobiotecnology in the Development of Intelligent Abdominal Wall Mesh 533 Cherif Boutros, Hany F. Sobhi and Nader Hanna 17.1 The Complex Structure of the Abdominal Wall 534 17.2 Need for Abdominal Wall Reconstruction 535 17.3 Failure of Primary Repair 535 17.4 Limitations of the Synthetic Meshes 536 17.5 Introduction of Biomaterials To Overcome Synthetic Mesh Limitations 537 17.6 Ideal Material for Abdominal Wall Reconstruction 538 17.7 Role of Bionanotechnology in Providing the 17.7 Future Directions 542 18. Poly(Polyol Sebacate)-based Elastomeric Nanobiomaterials for Soft Tissue Engineering 545 Qizhi Chen 18.1 Introduction 545 18.2 Poly(polyol sebacate) Elastomers 547 18.3 Elastomeric Nanocomposites 562 18.4 Summary 569 19. Electrospun Nanomatrix for Tissue Regeneration 577 Debasish Mondal and Ashutosh Tiwari 19.1 Introduction 577 19.2 Electrosun Nanomatrix 578 19.3 Polymeric Nanomatrices for Tissue Engineering 580 19.4 Biocompatibility of the Nanomatrix 581 19.5 Electrospun Nanomatrices for Tissue Engineering 583 19.6 Status and Prognosis 592 20. Conducting Polymer Composites for Tissue Engineering Scaffolds 597 Yashpal Sharma, Ashutosh Tiwari and Hisatoshi Kobayashi 20.1 Introduction 598 20.3 Synthesis of Conducting Polymers 599 20.4 Application of Conducting Polymer in Tissue Engineering 600 20.5 Polypyrrole 600 20.6 Poly(3,4-ethylene dioxythiophene) 602 20.7 Polyaniline 603 20.8 Carbon Nanotube 605 20.9 Future Prospects and Conclusions 607 21. Cell Patterning Technologies for Tissue Engineering 611 Azadeh Seidi and Murugan Ramalingam 21.1 Introduction 611 21.2 Patterned Co-culture Techniques 612 21.3 Applications of Co-cultures in Tissue Engineering 618 21.4 Concluding Remarks 619 Acknowledgements 619 References 620 Index 000

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Book SynopsisMedical Coatings and Deposition Technologies is an important new addition to the libraries of medical device designers and manufacturers. Coatings enable the properties of the surface of a device to be controlled independently from the underlying bulk properties; they are often critical to the performance of the device and their use is rapidly growing. This book provides an introduction to many of the most important types of coatings used on modern medical devices as well as descriptions of the techniques by which they are applied and methods for testing their efficacy. Developers of new medical devices and those responsible for producing them will find it an important reference when deciding if a particular functionality can be provided by a coating and what limitations may apply in a given application. Written as a practical guide and containing many specific coating examples and a large number of references for further reading, the book will also be useful to students in materials science & engineering with an interest in medical devices. Chapters on antimicrobial coatings as well as coatings for biocompatibility, drug delivery, radiopacity and hardness are supported by chapters describing key liquid coating processes, plasma-based processes and chemical vapor deposition. Many types of coatings can be applied by more than one technique and the reader will learn the tradeoffs given the relevant design, manufacturing and economic constraints. The chapter on regulatory considerations provides important perspectives regarding the marketing of these coatings and medical devices.Table of ContentsPreface xxi Part 1 Introduction 1 1 Historical Perspectives on Biomedical Coatings in Medical Devices 3 M. Hendriks and P.T. Cahalan 1.1 Introduction 4 1.2 Improving Physical Properties of Biomaterials: Hydrophilic, Lubricious Coatings 7 1.3 Modulating Host-Biomaterial Interactions: Biologically Active Coatings 7 1.4 Bioinert Coatings Redressed: Nonfouling Coatings 15 1.5 Future Biomedical Coatings 16 References 18 Part 2 Coating Applications 27 2 Antimicrobial Coatings and Other Surface Modifications for Infection Prevention 29 Marc W. Mittelman and Nimisha Mukherjee 2.1 Introduction 29 2.2 Genesis of Device-Related Infections 35 2.3 Antimicrobial Coatings 38 2.4 Non-Eluting Antimicrobial Surfaces 49 2.5 Coating and Surface Modification Technologies 53 2.6 Regulatory Considerations 57 2.7 Future Challenges 58 References 61 3 Drug Delivery Coatings for Coronary Stents 75 Shrirang V. Ranade and Kishore Udipi 3.1 Introduction 75 3.2 Polymer Coatings for DES 81 3.3 Biostable (Non-Bioabsorbable) Polymers 86 3.4 Bioabsorbable Polymers 99 3.5 Concluding Remarks 103 References 104 4 Coatings for Radiopacity 115 Scott Schewe and David Glocker 4.1 Principles of Radiography 115 4.2 Use of Radiopaque Materials in Medical Devices 116 4.3 Radiopaque Fillers 117 4.4 Types of Radiopaque Fillers 117 4.5 Other Radiographic Materials and Coating Systems 121 4.6 Radiopaque Coatings by Physical Vapor Deposition 122 4.7 Challenges in Producing Radiopaque Coatings Using PVD 124 4.8 Gold Radiopaque Coatings 125 4.9 Tantalum Radiopaque Coatings 126 4.10 Summary 129 References 130 5 Biocompatibility and Medical Device Coatings 131 Joe McGonigle, Thomas J. Webster, and Garima Bhardwaj 5.1 Introduction 131 5.2 Challenges with Medical Devices 134 5.3 Examples of Products Coated to Improve Biocompatibility 148 5.4 Types of Biocompatible Coatings 157 5.5 Commercialization 170 5.6 Summary 172 References 172 6 Tribological Coatings for Biomedical Devices 181 Peter Martin 6.1 Introduction 181 6.2 Hard Thin Film Coatings for Implants 187 6.3 Binary Carbon-Based Thin Film Materials: Diamond, Hard Carbon and Amorphous Carbon 194 6.4 Progress of DLC, ta-C and a-C:H Films for Hip and Knee Implants 200 6.5 Wear-Resistant Coatings for Stents and Catheters 208 6.6 Wear-Resistant Coatings for Angioplasty Devices 210 6.7 Scalpel Blades and Surgical Instruments 211 6.8 Multifunctional, Nanostructured, Nanolaminate, and Nanocomposite Tribological Materials 211 References 222 Part 3 Coating and Surface Modification Methods 233 7 Dip Coating 235 Donald M. Copenhagen 7.1 Description and Basic Steps 235 7.2 Equipment and Coating Application 236 7.3 Coating Solution Containers 237 7.4 Coating Parameters and Controls 238 7.5 Role of Solution Viscosity 240 7.6 Coating Problems 241 7.7 Process Considerations 244 8 Inkjet Technology and Its Application in Biomedical Coating Bogdan V. Antohe, David B. Wallace, and Patrick W. Cooley 247 8.1 Introduction 247 8.2 Inkjet Background 248 8.3 Equipment Used 260 8.4 Capabilities 268 8.5 Limitations and Ways around Them 280 8.6 Manufacturing Advantages and Future Directions 293 8.7 Conclusions 299 References 300 9 Direct Capillary Printing in Medical Device Manufacture 309 William J. Grande 9.1 Introduction 309 9.2 Fundamental Elements of Direct Capillary Printing 320 9.3 Practical Operational Considerations 337 9.4 Manufacturing Considerations 349 9.5 Medical Device Examples 352 9.6 Conclusions 367 Acknowledgments 369 References 369 10 Sol-Gel Coating Methods in Biomedical Systems 373 Bakul C. Dave 10.1 Introduction 374 10.2 Overview of Sol-Gel Coatings in Biomedical Systems 377 10.3 The Sol-Gel Process 381 10.4 Coating Methods and Processes 385 10.5 Factors influencing Coatings Characteristics/Performance 390 10.6 Summary and Concluding Remarks 394 References 395 11 Chemical Vapor Deposition 403 Kenneth K. S. Lau 11.1 Introduction 403 11.2 Process Description 405 11.3 Process Mechanism 410 11.4 Technology Advances 414 11.5 Future Outlook 442 References 443 12 Introduction to Plasmas Used for Coating Processes 457 David A. Glocker 12.1 Introduction 457 12.2 DC Glow Discharges 459 12.3 RF Glow Discharges 463 12.4 RF Diode Glow Discharges 464 12.5 Ionization in RF Diode Glow Discharges 466 12.6 Inductively Coupled RF Discharges 466 12.7 Mid-Frequency AC Discharges 468 12.8 Pulsed DC Discharges 469 12.9 Comparison of Plasma Properties 470 12.10 Plasma Species 470 12.11 Summary 471 References 472 13 Ion Implantation: Tribological Applications 473 Peter Martin 13.1 Introduction 473 13.2 Applications 474 13.3 Nanocrystalline Diamond 487 Reference 492 14 Plasma-Enhanced Chemical Vapor Deposition 495 Kenneth K. S. Lau 14.1 Introduction 495 14.2 Process Description 497 14.3 Plasma Effects on Materials Deposition 501 14.4 Future Outlook 520 References 521 15 Sputter Deposition and Sputtered Coatings for Biomedical Applications 531 David A. Glocker 15.1 Introduction 531 15.2 Overview of Sputter Coating 533 15.3 Characteristics of Sputtered Atoms 536 15.4 Sputtering Cathodes 539 15.5 Relationship between Process Parameters and Coating Properties 541 15.6 Biased Sputtering 544 15.7 Adhesion and Stress in Sputtered Coatings 545 15.8 Sputtering Electrically Insulating Materials 546 15.9 Recent Developments 549 15.10 Summary and Conclusions 549 References 550 16 Cathodic Arc Vapor Deposition 553 Gary Vergason 16.1 Introduction 553 16.2 Medical Uses of Cathodic Arc Titanium Nitride Coatings 556 16.3 Brief History and Commercial Advancement of Cathodic Arcs 557 16.4 Review of Arc Devices 559 16.5 Description of PVD Coating Manufacturing 561 16.6 Macroparticle Generation and Mitigation 567 16.7 Considerations for Coating Success 568 16.8 Materials Used in Biomedical PVD Coatings 576 References 576 Part 4 Functional Tests 581 17 Antimicrobial Coatings Efficacy Evaluation 583 Nimisha Mukherjee and Marc W. Mittelman 17.1 Introduction 583 17.2 In-Vitro Methods 584 17.3 In-Vivo (Animal) Methods 590 17.4 Equipment and Laboratory Resources 590 17.5 Human Clinical Trial Considerations 590 17.6 Regulatory Considerations 590 References 596 18 Mechanical Characterization of Biomaterials: Functional Tests for Hardness 605 Vincent Jardret 18.1 Introduction 605 18.2 Basic Principles of Hardness and Indentation Testing 607 18.3 Depth-Sensing Indentation Testing 611 18.4 Dynamic Indentation Testing: A More Advanced Hardness Measurement Technique for More Complex Material Behavior 617 18.5 Special Case of Coatings Configuration under Indentation Testing 626 18.6 Conclusions 628 References 629 19 Adhesion Measurement of Thin Films and Coatings: Relevance to Biomedical Applications 631 Wei-Sheng Lei, Kash Mittal, and Ajay Kumar 19.1 Introduction 631 19.2 Mechanical Test Methods of Adhesion Measurement 634 19.3 Summary and Remarks 654 Appendix 656 References 665 20 Functional Tests for Biocompatability 671 Joe McConigle and Thomas J. Webster 20.1 Introduction 671 20.2 Inflammation 672 20.3 Blood Compatibility 675 20.4 Wound Healing 685 20.5 Encapsulation 688 20.6 Tissue Integration 691 20.7 Vascularization 692 20.8 Toxicity 699 20.9 Infection 700 20.10 When to Move In Vivo? 701 References 702 21 Analytical Requirements for Drug Eluting Stents 707 Lori Alquier and Shrirang Ranade 21.1 Introduction 707 21.2 Instrumentation 708 21.3 API and Excipient Characterization 709 21.4 Analytical Methods 712 21.5 Conclusion 719 References 719 Part 5 Regulatory Overview 723 22 Regulations for Medical Devices and Coatings 725 Robert J. Klepinski 22.1 Introduction 725 22.2 Types of Regulated Products 726 22.3 Scope of Regulation 732 22.4 Marketing Clearance of Medical Devices 733 22.5 Comparison to EU Regulation 737 22.6 Good Manufacturing Practices 737 Part 6 Future of Coating Technologies 743 23 The Future of Biomedical Coatings Technologies 745 Shrirang Ranade and David Glocker 23.1 Introduction 745 23.2 The Continuing Evolution of Biomaterials 749 23.3 Tissue Engineering and Regenerative Medicine 749 23.4 Coating Process Development 750 References 751

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Book SynopsisBiogas Production covers the most cutting-edge pretreatment processes being used and studied today for the production of biogas. As an increasingly important piece of the energy pie, biogas and other biofuels are being used more and more around the world in every conceivable area of industry and could be a partial answer to the energy problem and the elimination of global warming. This book will highlight the recent advances in the pretreatment and value addition of lignocellulosic wastes (LCW) with the main focus on domestic and agro-industrial residues. Mechanical, physical, and biological treatment systems are brought into perspective. The main value-added products from lignocellulosic wastes are summarized in a manner that pinpoints the most recent trends and the future directions. Physico-chemical and biological treatment systems seem to be the most favored options while biofuels, biodegradable composites, and biosorbents production paint a brTable of ContentsPreface xv Acknowledgements xvii Special Contributor xviii Editor xix List of Contributors xxi 1. Anaerobic Digestion: Pretreatments of Substrates 1 Tanta Forster-Carnetro, Ricardo Isaac, Montserrat Pérez, and Ciarita Schvartz 1.1 Pretreatments in Anaerobic Digestion Process 2 1.2 Physical Pretreatment 6 1.3 Chemical Pretreatment 15 1.4 Biological Pretreatment 17 1.5 Combined Pretreatment 18 1.6 Concluding Note 19 2. Recalcitrance of Lignocellulosic Biomass to Anaerobic Digestion 27 Mohammad J. Taherzadeh and Azam Jeihanipour 2.1 Introduction 27 2.2 Plant Cell Wall Anatomy 28 2.3 Chemistry of Cell Wall Polymers 30 2.4 Molecular Interactions Between Cell Wall Polymers 39 2.5 Plant Cell Wall Molecular Architecture 40 2.6 Recalcitrance of Plant Cell Wall Cellulose 42 2.7 Reduction of Biomass Recalcitrance 46 2.8 Concluding Note 50 3. The Effect of Physical, Chemical, and Biological Pretreatments of Biomass on its Anaerobic Digestibility and Biogas Production 55 Katerina Stamatelatou, Georgia Antonopoulou, loanna Ntaikou, and Gerasimos Lyberatos 3.1 Introduction 56 3.2 Pretreatment Methods for Lignocellulosic Biomass 57 3.3 Pretreatment Methods for Sewage Sludge 77 3.4 Concluding Note 84 4. Application of Ultrasound Pretreatment for Sludge Digestion 91 Show Kuan Yeow and Wong Lai Peng 4.1 Introduction 91 4.2 Anaerobic Digestion 93 4.3 Overview of Pretreatment Methods for Anaerobic Digestion 95 4.4 Fundamental of Ultrasound 100 4.5 Bubbles Dynamic 103 4.6 Effects of Ultrasound 106 4.7 Ultrasound Applications 109 4.8 Ultrasonication for Anaerobic Digesion 116 4.9 Evaluation on Sludge Disintegration 126 4.10 Conclusions 131 5. Microwave Sludge Irradiation 137 Cigdetn Esktctoglu and Giampiero Galvagno 5.1 Introduction 137 5.2 Microwave Theory 139 5.3 Microwave Irradiation for Waste Sludge Treatment 144 5.4 Industrial Microwave Applications 147 5.5 Microwave Absorbing Materials and Ionic Liquids 148 5.6 Sludge Pretreatment Similar to Microwave Irradiation 151 5.7 Concluding Notes 151 6. Hydrolytic Enzymes Enhancing Anaerobic Digestion 157 Teresa Suárez Quiñones, Matthias Plöchl, Katrin Päzolt, Jörn Budde, Robert Kausmann, Edith Nettmann, and Monika Heiermann 6.1 Introduction 158 6.2 Where and How can Enzymes be Applied? 170 6.3 Impact of Enzyme Application 178 6.4 Economic Assessment 191 6.5 Concluding Note 192 7. Oxidizing Agents and Organic Solvents as Pretreatment for Anaerobic Digestion 199 Lise Appels, Jan Van Impe, and Raf Dewil 7.1 Oxidative Pretreatment Methods 199 7.2 Organic Solvents 210 7.3 Concluding Note 212 8. Anaerobic Digestion and Biogas Utilization in Greece: Current Status and Perspectives 215 Avraam Karagiannidis, George Perkoultdts, and Apostólos Malamakts 8.1 Assessment of Existing Biogas Installations 215 8.2 Use of Waste Material for Biogas Production 217 8.3 Feedstock Availability and Agricultural Structures 219 8.4 Purification of Biogas for Insertion in the Natural Gas Grid 224 8.5 Biogas Utilization 226 8.6 Concluding Note 227 9. Original Research: Investigating the Potential of Using Biogas in Cooking Stove in Rodrigues 229 Dinesh Surroop and Osman Dina Bégué 9.1 Energy Crisis and Future Challenges 230 9.2 Case Study of Rodrigues 231 9.3 Rationale of Research Study 233 9.4 Research Methodology 234 9.5 Reactor Design Considerations 241 9.6 Results, Findings and Discussions 247 9.7 Conclusions 257 10. Optimizing and Modeling the Anaerobic Digestion of Lignocellulosic Wastes by Rumen Cultures 259 Zhen-Hu Hu and Han-Qing Yu 10.1 Introduction 260 10.2 Materials and Methods 262 10.3 Optimizing the Anaerobic Digestion of Microwave-Pretreated Cattail by Rumen Cultures 266 10.4 Modeling the Anaerobic Digestion of Cattail by Rumen Cultures 275 10.5 Concluding Note 287 11. Pretreatment of Biocatalyst as Viable Option for Sustained Production of Biohydrogen from Wastewater Treatment 291 S. Venkata Mohan and R. Kannatah Goud 11.1 Introduction 292 11.2 Pretreatment of Biocatalyst 294 11.3 Combined Pretreatment 300 11.4 Influence of Pretreatment on Wastewater Treatment 302 11.5 Microbial Diversity 303 11.6 Summary and Future Scope 304 Acknowledgements 305 References 305 Index 313

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Book SynopsisSets the stage for the design and application of new protein cages Featuring contributions from a team of international experts in the coordination chemistry of biological systems, this book enables readers to understand and take advantage of the fascinating internal molecular environment of protein cages. With the aid of modern organic and polymer techniques, the authors explain step by step how to design and construct a variety of protein cages. Moreover, the authors describe current applications of protein cages, setting the foundation for the development of new applications in biology, nanotechnology, synthetic chemistry, and other disciplines. Based on a thorough review of the literature as well as the authors'' own laboratory experience, Coordination Chemistry in Protein Cages Sets forth the principles of coordination reactions in natural protein cages Details the fundamental design of coordination sites of small artificial metTable of ContentsForeword xiii Preface xv Contributors xvii PART I COORDINATION CHEMISTRY IN NATIVE PROTEIN CAGES 1 The Chemistry of Nature’s Iron Biominerals in Ferritin Protein Nanocages 3 Elizabeth C. Theil and Rabindra K. Behera 1.1 Introduction 3 1.2 Ferritin Ion Channels and Ion Entry 6 1.2.1 Maxi- and Mini-Ferritin 6 1.2.2 Iron Entry 7 1.3 Ferritin Catalysis 8 1.3.1 Spectroscopic Characterization of -1,2 Peroxodiferric Intermediate (DFP) 8 1.3.2 Kinetics of DFP Formation and Decay 12 1.4 Protein-Based Ferritin Mineral Nucleation and Mineral Growth 13 1.5 Iron Exit 16 1.6 Synthetic Uses of Ferritin Protein Nanocages 17 1.6.1 Nanomaterials Synthesized in Ferritins 18 1.6.2 Ferritin Protein Cages in Metalloorganic Catalysis and Nanoelectronics 19 1.6.3 Imaging and Drug Delivery Agents Produced in Ferritins 19 1.7 Summary and Perspectives 20 Acknowledgments 20 References 21 2 Molecular Metal Oxides in Protein Cages/Cavities 25 Achim M¨uller and Dieter Rehder 2.1 Introduction 25 2.2 Vanadium: Functional Oligovanadates and Storage of VO2+ in Vanabins 26 2.3 Molybdenum and Tungsten: Nucleation Process in a Protein Cavity 28 2.4 Manganese in Photosystem II 33 2.5 Iron: Ferritins, DPS Proteins, Frataxins, and Magnetite 35 2.6 Some General Remarks: Oxides and Sulfides 38 References 38 PART II DESIGN OF METALLOPROTEIN CAGES 3 De Novo Design of Protein Cages to Accommodate Metal Cofactors 45 Flavia Nastri, Rosa Bruni, Ornella Maglio, and Angela Lombardi 3.1 Introduction 45 3.2 De Novo-Designed Protein Cages Housing Mononuclear Metal Cofactors 47 3.3 De Novo-Designed Protein Cages Housing Dinuclear Metal Cofactors 59 3.4 De Novo-Designed Protein Cages Housing Heme Cofactor 66 3.5 Summary and Perspectives 79 Acknowledgments 79 References 80 4 Generation of Functionalized Biomolecules Using Hemoprotein Matrices with Small Protein Cavities for Incorporation of Cofactors 87 Takashi Hayashi 4.1 Introduction 87 4.2 Hemoprotein Reconstitution with an Artificial Metal Complex 89 4.3 Modulation of the O2 Affinity of Myoglobin 90 4.4 Conversion of Myoglobin into Peroxidase 95 4.4.1 Construction of a Substrate-Binding Site Near the Heme Pocket 95 4.4.2 Replacement of Native Heme with Iron Porphyrinoid in Myoglobin 99 4.4.3 Other Systems Used in Enhancement of Peroxidase Activity of Myoglobin 100 4.5 Modulation of Peroxidase Activity of HRP 102 4.6 Myoglobin Reconstituted with a Schiff Base Metal Complex 103 4.7 A Reductase Model Using Reconstituted Myoglobin 106 4.7.1 Hydrogenation Catalyzed by Cobalt Myoglobin 106 4.7.2 A Model of Hydrogenase Using the Heme Pocket of Cytochrome c 107 4.8 Summary and Perspectives 108 Acknowledgments 108 References 108 5 Rational Design of Protein Cages for Alternative Enzymatic Functions 111 Nicholas M. Marshall, Kyle D. Miner, Tiffany D. Wilson, and Yi Lu 5.1 Introduction 111 5.2 Mononuclear Electron Transfer Cupredoxin Proteins 112 5.3 CuA Proteins 116 5.4 Catalytic Copper Proteins 118 5.4.1 Type 2 Red Copper Sites 118 5.4.2 Other T2 Copper Sites 120 5.4.3 Cu, Zn Superoxide Dismutase 121 5.4.4 Multicopper Oxygenases and Oxidases 122 5.5 Heme-Based Enzymes 124 5.5.1 Mb-Based Peroxidase and P450 Mimics 124 5.5.2 Mimicking Oxidases in Mb 125 5.5.3 Mimicking NOR Enzymes in Mb 127 5.5.4 Engineering Peroxidase Proteins 128 5.5.5 Engineering Cytochrome P450s 129 5.6 Non-Heme ET Proteins 131 5.7 Fe and Mn Superoxide Dismutase 132 5.8 Non-Heme Fe Catalysts 133 5.9 Zinc Proteins 134 5.10 Other Metalloproteins 135 5.10.1 Cobalt Proteins 135 5.10.2 Manganese Proteins 136 5.10.3 Molybdenum Proteins 137 5.10.4 Nickel Proteins 137 5.10.5 Uranyl Proteins 138 5.10.6 Vanadium Proteins 138 5.11 Summary and Perspectives 139 References 142 PART III COORDINATION CHEMISTRY OF PROTEIN ASSEMBLY CAGES 6 Metal-Directed and Templated Assembly of Protein Superstructures and Cages 151 F. Akif Tezcan 6.1 Introduction 151 6.2 Metal-Directed Protein Self-Assembly 152 6.2.1 Background 152 6.2.2 Design Considerations for Metal-Directed Protein Self-Assembly 153 6.2.3 Interfacing Non-Natural Chelates with MDPSA 155 6.2.4 Crystallographic Applications of Metal-Directed Protein Self-Assembly 159 6.3 Metal-Templated Interface Redesign 162 6.3.1 Background 162 6.3.2 Construction of a Zn-Selective Tetrameric Protein Complex Through MeTIR 163 6.3.3 Construction of a Zn-Selective Protein Dimerization Motif Through MeTIR 166 6.4 Summary and Perspectives 170 Acknowledgments 171 References 171 7 Catalytic Reactions Promoted in Protein Assembly Cages 175 Takafumi Ueno and Satoshi Abe 7.1 Introduction 175 7.1.1 Incorporation of Metal Compounds 176 7.1.2 Insight into Accumulation Process ofMetal Compounds 177 7.2 Ferritin as a Platform for Coordination Chemistry 177 7.3 Catalytic Reactions in Ferritin 179 7.3.1 Olefin Hydrogenation 179 7.3.2 Suzuki–Miyaura Coupling Reaction in Protein Cages 182 7.3.3 Polymer Synthesis in Protein Cages 185 7.4 Coordination Processes in Ferritin 188 7.4.1 Accumulation of Metal Ions 188 7.4.2 Accumulation of Metal Complexes 192 7.5 Coordination Arrangements in Designed Ferritin Cages 194 7.6 Summary and Perspectives 197 Acknowledgments 198 References 198 8 Metal-Catalyzed Organic Transformations Inside a Protein Scaffold Using Artificial Metalloenzymes 203 V. K. K. Praneeth and Thomas R. Ward 8.1 Introduction 203 8.2 Enantioselective Reduction Reactions Catalyzed by Artificial Metalloenzymes 204 8.2.1 Asymmetric Hydrogenation 204 8.2.2 Asymmetric Transfer Hydrogenation of Ketones 206 8.2.3 Artificial Transfer Hydrogenation of Cyclic Imines 208 8.3 Palladium-Catalyzed Allylic Alkylation 211 8.4 Oxidation Reaction Catalyzed by Artificial Metalloenzymes 212 8.4.1 Artificial Sulfoxidase 212 8.4.2 Asymmetric cis-Dihydroxylation 215 8.5 Summary and Perspectives 216 References 218 PART IV APPLICATIONS IN BIOLOGY 9 Selective Labeling and Imaging of Protein Using Metal Complex 223 Yasutaka Kurishita and Itaru Hamachi 9.1 Introduction 223 9.2 Tag–Probe Pair Method Using Metal-Chelation System 225 9.2.1 Tetracysteine Motif/Arsenical Compounds Pair 225 9.2.2 Oligo-Histidine Tag/Ni(ii)-NTA Pair 227 9.2.3 Oligo-Aspartate Tag/Zn(ii)-DpaTyr Pair 230 9.2.4 Lanthanide-binding Tag 235 9.3 Summary and Perspectives 237 References 237 10 Molecular Bioengineering of Magnetosomes for Biotechnological Applications 241 Atsushi Arakaki, Michiko Nemoto, and Tadashi Matsunaga 10.1 Introduction 241 10.2 Magnetite Biomineralization Mechanism in Magnetosome 242 10.2.1 Diversity of Magnetotactic Bacteria 242 10.2.2 Genome and Proteome Analyses of Magnetotactic Bacteria 244 10.2.3 Magnetosome Formation Mechanism 246 10.2.4 Morphological Control of Magnetite Crystal in Magnetosomes 250 10.3 Functional Design of Magnetosomes 251 10.3.1 Protein Display on Magnetosome by Gene Fusion Technique 252 10.3.2 Magnetosome Surface Modification by In Vitro System 255 10.3.3 Protein-mediated Morphological Control of Magnetite Particles 257 10.4 Application 258 10.4.1 Enzymatic Bioassays 259 10.4.2 Cell Separation 260 10.4.3 DNA Extraction 262 10.4.4 Bioremediation 264 10.5 Summary and Perspectives 266 Acknowledgments 266 References 266 PART V APPLICATIONS IN NANOTECHNOLOGY 11 Protein Cage Nanoparticles for Hybrid Inorganic–Organic Materials 275 Shefah Qazi, Janice Lucon, Masaki Uchida, and Trevor Douglas 11.1 Introduction 275 11.2 Biomineral Formation in Protein Cage Architectures 277 11.2.1 Introduction 277 11.2.2 Mineralization 278 11.2.3 Model for Synthetic Nucleation-Driven Mineralization 279 11.2.4 Mineralization in Dps: A 12-Subunit Protein Cage 279 11.2.5 Icosahedral Protein Cages: Viruses 282 11.2.6 Nucleation of Inorganic Nanoparticles Within Icosahedral Viruses 282 11.3 Polymer Formation Inside Protein Cage Nanoparticles 283 11.3.1 Introduction 283 11.3.2 Azide–Alkyne Click Chemistry in sHsp and P22 285 11.3.3 Atom Transfer Radical Polymerization in P22 287 11.3.4 Application as Magnetic Resonance Imaging Contrast Agents 290 11.4 Coordination Polymers in Protein Cages 292 11.4.1 Introduction 292 11.4.2 Metal–Organic Branched Polymer Synthesis by Preforming Complexes 292 11.4.3 Coordination Polymer Formation from Ditopic Ligands and Metal Ions 295 11.4.4 Altering Protein Dynamics by Coordination: Hsp-Phen-Fe 296 11.5 Summary and Perspectives 298 Acknowledgments 298 References 298 12 Nanoparticles Synthesized and Delivered by Protein in the Field of Nanotechnology Applications 305 Ichiro Yamashita, Kenji Iwahori, Bin Zheng, and Shinya Kumagai 12.1 Nanoparticle Synthesis in a Bio-Template 305 12.1.1 NP Synthesis by Cage-Shaped Proteins for Nanoelectronic Devices and Other Applications 305 12.1.2 Metal Oxide or Hydro-Oxide NP Synthesis in the Apoferritin Cavity 307 12.1.3 Compound Semiconductor NP Synthesis in the Apoferritin Cavity 308 12.1.4 NP Synthesis in the Apoferritin with the Metal-Binding Peptides 311 12.2 Site-Directed Placement of NPs 312 12.2.1 Nanopositioning of Cage-Shaped Proteins 312 12.2.2 Nanopositioning of Au NPs by Porter Proteins 313 12.3 Fabrication of Nanodevices by the NP and Protein Conjugates 317 12.3.1 Fabrication of Floating Nanodot Gate Memory 318 12.3.2 Fabrication of Single-Electron Transistor Using Ferritin 321 References 326 13 Engineered “Cages” for Design of Nanostructured Inorganic Materials 329 Patrick B. Dennis, Joseph M. Slocik, and Rajesh R. Naik 13.1 Introduction 329 13.2 Metal-Binding Peptides 331 13.3 Discrete Protein Cages 332 13.4 Heat-Shock Proteins 334 13.5 Polymeric Protein and Carbohydrate Quasi-Cages 340 13.6 Summary and Perspectives 346 References 347 PART VI COORDINATION CHEMISTRY INSPIRED BY PROTEIN CAGES 14 Metal–Organic Caged Assemblies 353 Sota Sato and Makoto Fujita 14.1 Introduction 353 14.2 Construction of Polyhedral Skeletons by Coordination Bonds 355 14.2.1 Geometrical Effect on Products 356 14.2.2 Structural Extension Based on Rigid, Designable Framework 358 14.2.3 Mechanistic Insight into Self-Assembly 366 14.3 Development of Functions via Chemical Modification 366 14.3.1 Chemistry in the Hollow of Cages 367 14.3.2 Chemistry on the Periphery of Cages 368 14.4 Metal–Organic Cages for Protein Encapsulation 370 14.5 Summary and Perspectives 370 References 371 Index 375

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Book SynopsisReviews and compares the major types of bioreactors, defines their pros and cons, and identifies research needs and figures of merit that have yet to be addressed Describes common modes of operation in bioreactors Covers the three common bioreactor types, including stirred-tank bioreactors, bubble column bioreactors, and airlift bioreactors Details less common bioreactors types, including fixed bed bioreactors and novel bioreactor designs Discusses advantages and disadvantages of each bioreactor and provides a procedure for optimal bioreactor selection based on current process needs Reviews the problems of bioreactor selection globally while considering all bioreactor options rather than concentrating on one specific bioreactor type Table of Contents1 INTRODUCTION 1 2 MODES OF OPERATION 3 2.1 Batch Bioreactors 3 2.2 Continuous Bioreactors 9 2.3 Summary 15 3 GAS-LIQUID MASS TRANSFER MODELS 17 4 EXPERIMENTAL MEASUREMENT TECHNIQUES 28 4.1 Measuring Bioreactor Hydrodynamic Characteristics 28 4.1.1 Flow regime measurements 29 4.1.2 Local pressure drop 30 4.1.3 Mixing or residence time 32 4.1.4 Axial diffusion coefficient 33 4.1.5 Gas-liquid interfacial area 34 4.1.6 Bubble size and velocity 35 4.1.7 Global and local liquid velocity 37 4.1.8 Gas holdup 40 4.1.8.1 Bed expansion 41 4.1.8.2 Pressure drop measurements 41 4.1.8.3 Dynamic gas disengagement (DGD) 46 4.1.8.4 Tomographic techniques 47 4.1.9 Liquid holdup 50 4.1.10 Power measurements 51 4.2 Gas-Liquid Mass Transfer 53 4.2.1 Dissolved oxygen measurement techniques 54 4.2.1.1 Chemical method 54 4.2.1.2 Volumetric method 56 4.2.1.3 Tubing method 56 4.2.1.4 Optode method 57 4.2.1.5 Electrochemical electrode method 58 4.2.1.5.1 Polarographic electrodes 59 4.2.1.5.2 Galvanic probes 61 4.2.1.5.3 Electrochemical electrode time constant 61 4.2.1.5.4 Electrochemical electrode response time (τe) 64 4.2.1.5.5 Electrochemical electrode response models 66 4.2.1.5.6 Summary of electrochemical electrode response models 72 4.2.2 Dissolved carbon monoxide measurements 72 4.2.2.1 Bioassay overview 74 4.2.2.2 Needed materials 75 4.2.2.3 Liquid sample collection 76 4.2.2.4 Identifying the concentrated myoglobin solution concentration 77 4.2.2.5 Sample preparation for analysis 78 4.2.2.6 Determining the dissolved CO concentration 79 4.2.3 Determining volumetric gas-liquid mass transfer coefficient, kLa 80 4.2.3.1 Gas balance method 81 4.2.3.2 Dynamic method 82 4.2.3.2.1 Biological dynamic method 82 4.2.3.2.2 Non-biological dynamic method 85 4.2.3.2.3 Variations of the inlet step change 86 4.2.3.2.4 Dynamic method drawbacks 91 4.2.3.3 Chemical sorption methods 92 4.2.3.3.1 Sulfite oxidation method 92 4.2.3.3.2 The hydrazine method 94 4.2.3.3.3 Peroxide method 95 4.2.3.3.4 Carbon dioxide absorption method 95 4.3 Summary 95 5 MODELING BIOREACTORS 97 5.1 Multiphase Flow CFD Modeling 97 5.1.1 Governing equations for gas-liquid flows 100 5.1.2 Turbulence modeling 101 5.1.3 Interfacial momentum exchange 104 5.1.4 Bubble pressure model 105 5.1.5 Bubble-induced turbulence 106 5.1.6 Modeling bubble size distribution 107 5.2 Biological Process Modeling 109 5.2.1 Simple bioprocess models 111 5.3 Summary 113 6 STIRRED TANK BIOREACTORS 114 6.1 Introduction 114 6.2 Stirred Tank Reactor Flow Regimes 116 6.2.1 Radial Flow Impellers 117 6.2.2 Axial Flow Impellers 122 6.3 Effects of Impeller Design and Arrangement 127 6.3.1 Radial Flow Impellers 129 6.3.2 Axial flow impellers 134 6.3.3 Multiple Impeller Systems 139 6.3.4 Surface Aeration 148 6.3.5 Self-Inducing Impellers 150 6.4 Superficial Gas Velocity 152 6.5 Power Input 155 6.6 Baffle Design 158 6.7 Sparger Design 161 6.7.1 Axial Flow Impellers 162 6.7.2 Radial Flow Impellers 164 6.8 Microbial Cultures 165 6.9 Correlation Forms 172 6.10 Summary 184 7 BUBBLE COLUMN BIOREACTORS 191 7.1 Introduction 191 7.2 Flow Regimes 194 7.3 Column Geometry 202 7.3.1 Column Diameter 202 7.3.2 Unaerated Liquid Height 205 7.3.3 Aspect Ratio 206 7.4 Other Operating Conditions 207 7.4.1 Pressure 207 7.4.2 Temperature 210 7.4.3 Viscosity 212 7.4.4 Surface Tension and Additives 213 7.5 Gas Distributor Design 215 7.6 Correlations 221 7.7 Needed Bubble Column Research 226 7.8 Summary 227 8 AIRLIFT BIOREACTORS 243 8.1 Introduction 243 8.2 Circulation Regimes 247 8.3 Configuration 253 8.3.1 Bioreactor Height 255 8.3.2 Area Ratio 258 8.3.3 Gas Separator 261 8.3.4 Internal-Loop Airlift Bioreactor 266 8.3.5 External-Loop Airlift Bioreactor 268 8.4 Sparger Design 272 8.5 Correlations 277 8.6 Needed Research 280 8.7 Summary 284 9 FIXED BED BIOREACTORS 295 9.1 Introduction 295 9.2 Column Geometry and Components 299 9.3 Flow Regime 307 9.4 Liquid Properties 314 9.5 Packing Material 316 9.5.1 Random Packing 319 9.5.2 Structured Packing 321 9.6 Biological Considerations 324 9.7 Correlations 325 9.8 Needed Research 327 9.9 Summary 328 10 NOVEL BIOREACTORS 333 10.1 Introduction 333 10.2 Novel Bubble-Induced Flow Designs 333 10.3 Miniaturized Bioreactors 341 10.3.1 Microreactors 343 10.3.2 Nanoreactors 348 10.4 Membrane Reactor 349 10.5 Summary 353 11 FIGURES OF MERIT 355 12 CONCLUDING REMARKS 363 13 NOMENCLATURE 367 Abbreviations 375 Greek Symbols 377 Dimensionless numbers 379 14 BIBLIOGRAPHY 382

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Book SynopsisProviding an introduction to the fundamentals of body area communications, this book covers the key topics of channel modeling, modulation and demodulation, and performance evaluation A systematic introduction to body area networks (BAN), this book focuses on three major parts: channel modeling, modulation/demodulation communications performance, and electromagnetic compatibility considerations. The content is logically structured to lead readers from an introductory level through to in-depth and more advanced topics. Provides a concise introduction to this emerging topic based on classroom-tested materials Details the latest IEEE 802.15.6 standard activities Moves from very basic physics, to useful mathematic models, and then to practical considerations Covers not only EM physics and communications, but also biological applications Topics approached include: link budget, bit error rate performance, RAKE and diversityTable of ContentsPreface ix 1 Introduction to Body Area Communications 1 1.1 Definition 1 1.2 Promising Applications 2 1.2.1 Medical and Healthcare Applications 3 1.2.2 Assistance to People with Disabilities 7 1.2.3 Consumer Electronics and User Identification 7 1.3 Available Frequency Bands 8 1.3.1 UWB Band 8 1.3.2 MICS Band 10 1.3.3 ISM Band 10 1.3.4 HBC Band 11 1.4 Standardization (IEEE Std 802.15.6-2012) 11 1.4.1 Narrow Band PHY Specification 12 1.4.2 UWB PHY Specification 13 1.4.3 HBC PHY Specification 15 References 18 2 Electromagnetic Characteristics of the Human Body 21 2.1 Human Body Composition 21 2.2 Frequency-Dependent Dielectric Properties 22 2.3 Tissue Property Modeling 23 2.4 Aging Dependence of Tissue Properties 30 2.5 Penetration Depth versus Frequency 35 2.6 In-Body Absorption Characteristic 39 2.7 On-Body Propagation Mechanism 43 2.8 Diffraction Characteristic 49 References 52 3 Electromagnetic Analysis Methods 55 3.1 Finite-Difference Time-Domain Method 55 3.1.1 Formulation 55 3.1.2 Absorbing Boundary Conditions 59 3.1.3 Field Excitation 64 3.1.4 FDTD Flow Chart and Code 65 3.1.5 Frequency-Dependent FDTD Method 67 3.2 MoM-FDTD Hybrid Method 71 3.2.1 MoM Formulation 73 3.2.2 Scattered Field FDTD Formulation 75 3.2.3 Hybridization of MoM and FDTD Method 76 3.3 Finite Element Method 78 3.4 Numerical Human Body Model 83 References 87 4 Body Area Channel Modeling 89 4.1 Introduction 89 4.2 Path Loss Model 91 4.2.1 Free-Space Path Loss 91 4.2.2 On-Body UWB Path Loss 92 4.2.3 In-Body UWB Path Loss 98 4.2.4 In-Body MICS Band Path Loss 104 4.2.5 HBC Band Path Loss and Equivalent Circuit Expression 107 4.3 Multipath Channel Model 118 4.3.1 Saleh–Valenzuela Impulse Response Model 119 4.3.2 On-Body UWB Channel Model 119 4.3.3 In-Body UWB Channel Model 135 References 141 5 Modulation/Demodulation 143 5.1 Introduction 143 5.2 Modulation Schemes 144 5.2.1 ASK, FSK and PSK 144 5.2.2 IR-UWB 147 5.2.3 MB-OFDM 151 5.3 Demodulation and Error Probability 155 5.3.1 Optimum Demodulation for ASK, FSK and PSK 155 5.3.2 Noncoherent Detection for ASK, FSK and PSK 159 5.3.3 Optimum Demodulation for IR-UWB 161 5.3.4 Noncoherent Detection for IR-UWB 164 5.3.5 MB-OFDM Demodulation 167 5.4 RAKE Reception 168 5.5 Diversity Reception 174 References 179 6 Body Area Communication Performance 181 6.1 Introduction 181 6.2 On-Body UWB Communication 182 6.2.1 Bit Error Rate 182 6.2.2 Link Budget 194 6.2.3 Maximum Communication Distance 198 6.3 In-Body UWB Communication 201 6.3.1 Bit Error Rate 201 6.3.2 Link Budget 206 6.4 In-Body MICS-Band Communication 212 6.4.1 Bit Error Rate 212 6.4.2 Link Budget 213 6.5 Human Body Communication 216 6.5.1 Bit Error Rate 216 6.5.2 Link Budget 217 6.6 Dual Mode Body Area Communication 219 References 221 7 Electromagnetic Compatibility Considerations 223 7.1 Introduction 223 7.2 SAR Analysis 225 7.2.1 Safety Guidelines 225 7.2.2 Analysis and Assessment Methods 227 7.2.3 Transmitting Power versus SAR 234 7.3 Electromagnetic Interference Analysis for the Cardiac Pacemaker 245 7.3.1 Cardiac Pacemaker Model and Interference Mechanism 245 7.3.2 Electromagnetic Field Approach 249 7.3.3 Electric Circuit Approach 250 7.3.4 Transmitting Signal Strength versus Interference Voltage 255 7.3.5 Experimental Assessment System 262 References 266 8 Summary and Future Challenges 267 Index 273

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Book SynopsisA comprehensive and timely review of developments in the field, Cell and Molecular Biology of Stem Cell Imaging features original and review articles written by experts in their fields.Table of ContentsContributors vii Preface xi 1 Cell and Molecular Biology and Imaging of Stem Cells: Stem Cells from the Amniotic Fluid and Placenta 1Amritha Kidiyoor, Sean V. Murphy, and Anthony Atala 2 Biomaterials as Artificial Niches for Pluripotent Stem Cell Engineering 21Kyung Min Park and Sharon Gerecht 3 Low-Intensity Ultrasound in Stem Cells and Tissue Engineering 45Byung Hyune Choi, Kil Hwan Kim, Mrigendra Bir Karmacharya, Byoung-Hyun Min and So Ra Park 4 Mammalian Neo-Oogenesis from Ovarian Stem Cells In Vivo and In Vitro 67Antonin Bukovsky and Michael R. Caudle 5 Oct4-EGFP Transgenic Pigs as a New Tool for Visualization of Pluripotent and Reprogrammed Cells 137Monika Nowak-Imialek and Heiner Niemann 6 Regulation of Adult Intestinal Stem Cells through Thyroid Hormone-Induced Tissue Interactions during Amphibian Metamorphosis 153Atsuko Ishizuya-Oka 7 Stem Cell Therapy for Veterinary Orthopedic Lesions 173Anna Paula Balesdent Barreira and Ana Liz Garcia Alves 8 Sex Steroid Combinations in Regenerative Medicine for Brain and Heart Diseases: The Vascular Stem Cell Niche and a Clinical Proposal 193Antonin Bukovsky and Michael R. Caudle 9 Hair Follicle Stem Cells 211Hilda Amalia Pasolli 10 The Potential of Using Induced Pluripotent Stem Cells in Skin Diseases 223Shigeki Ohta, Ophelia Veraitch, Hideyuki Okano, Manabu Ohyama, and Yutaka Kawakami 11 Mitochondrial Differentiation in Early Embryo Cells and Pluripotent Stem Cells 247Heide Schatten, Qing-Yuan Sun, and Randall S. Prather 12 The Role of Centrosomes in Cancer Stem Cell Functions 259Heide Schatten Index 281

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Book SynopsisAn in-depth look at the latest research, methods, and applications in the field of protein bioinformatics This book presents the latest developments in protein bioinformatics, introducing for the first time cutting-edge research results alongside novel algorithmic and AI methods for the analysis of protein data.Table of ContentsPREFACE ix CONTRIBUTORS xv I FROM PROTEIN SEQUENCE TO STRUCTURE 1 EMPHASIZING THE ROLE OF PROTEINS IN CONSTRUCTION OF THE DEVELOPMENTAL GENETIC TOOLKIT IN PLANTS 3 Anamika Basu and Anasua Sarkar 2 PROTEIN SEQUENCE MOTIF INFORMATION DISCOVERY 41 Bernard Chen 3 IDENTIFYING CALCIUM BINDING SITES IN PROTEINS 57 Hui Liu and Hai Deng 4 REVIEW OF IMBALANCED DATA LEARNING FOR PROTEIN METHYLATION PREDICTION 71 Zejin Ding and Yan-Qing Zhang 5 ANALYSIS AND PREDICTION OF PROTEIN POSTTRANSLATIONAL MODIFICATION SITES 91 Jianjiong Gao, Qiuming Yao, Curtis Harrison Bollinger, and Dong Xu II PROTEIN ANALYSIS AND PREDICTION 6 PROTEIN LOCAL STRUCTURE PREDICTION 109 Wei Zhong, Jieyue He, Robert W. Harrison, Phang C. Tai, and Yi Pan 7 PROTEIN STRUCTURAL BOUNDARY PREDICTION 125 Gulsah Altun 8 PREDICTION OF RNA BINDING SITES IN PROTEINS 153 Zhi-Ping Liu and Luonan Chen 9 ALGORITHMIC FRAMEWORKS FOR PROTEIN DISULFIDE CONNECTIVITY DETERMINATION 171 Rahul Singh, William Murad, and Timothy Lee 10 PROTEIN CONTACT ORDER PREDICTION: UPDATE 205 Yi Shi, Jianjun Zhou, David S. Wishart, and Guohui Lin 11 PROGRESS IN PREDICTION OF OXIDATION STATES OF CYSTEINES VIA COMPUTATIONAL APPROACHES 217 Aiguo Du, Hui Liu, Hai Deng, and Yi Pan 12 COMPUTATIONAL METHODS IN CRYOELECTRON MICROSCOPY 3D STRUCTURE RECONSTRUCTION 231 Fa Zhang, Xiaohua Wan, and Zhiyong Liu III PROTEIN STRUCTURE ALIGNMENT AND ASSESSMENT 13 FUNDAMENTALS OF PROTEIN STRUCTURE ALIGNMENT 255 Mark Brandt, Allen Holder, and Yosi Shibberu 14 DISCOVERING 3D PROTEIN STRUCTURES FOR OPTIMAL STRUCTURE ALIGNMENT 281 Tomáš Novosád, Václav Snášel, Ajith Abraham, and Jack Y. Yang 15 ALGORITHMIC METHODOLOGIES FOR DISCOVERY OF NONSEQUENTIAL PROTEIN STRUCTURE SIMILARITIES 299 Bhaskar DasGupta, Joseph Dundas, and Jie Liang 16 FRACTAL RELATED METHODS FOR PREDICTING PROTEIN STRUCTURE CLASSES AND FUNCTIONS 317 Zu-Guo Yu, Vo Anh, Jian-Yi Yang, and Shao-Ming Zhu 17 PROTEIN TERTIARY MODEL ASSESSMENT 339 Anjum Chida, Robert W. Harrison, and Yan-Qing Zhang IV PROTEIN–PROTEIN ANALYSIS OF BIOLOGICAL NETWORKS 18 NETWORK ALGORITHMS FOR PROTEIN INTERACTIONS 357 Suely Oliveira 19 IDENTIFYING PROTEIN COMPLEXES FROM PROTEIN–PROTEIN INTERACTION NETWORKS 377 Jianxin Wang, Min Li, and Xiaoqing Peng 20 PROTEIN FUNCTIONAL MODULE ANALYSIS WITH PROTEIN–PROTEIN INTERACTION (PPI) NETWORKS 393 Lei Shi, Xiujuan Lei, and Aidong Zhang 21 EFFICIENT ALIGNMENTS OF METABOLIC NETWORKS WITH BOUNDED TREEWIDTH 413 Qiong Cheng, Piotr Berman, Robert W. Harrison, and Alexander Zelikovsky 22 PROTEIN–PROTEIN INTERACTION NETWORK ALIGNMENT: ALGORITHMS AND TOOLS 431 Valeria Fionda V APPLICATION OF PROTEIN BIOINFORMATICS 23 PROTEIN-RELATED DRUG ACTIVITY COMPARISON USING SUPPORT VECTOR MACHINES 451 Wei Zhong and Jieyue He 24 FINDING REPETITIONS IN BIOLOGICAL NETWORKS: CHALLENGES, TRENDS, AND APPLICATIONS 461 Simona E. Rombo 25 MeTaDoR: ONLINE RESOURCE AND PREDICTION SERVER FOR MEMBRANE TARGETING PERIPHERAL PROTEINS 481 Nitin Bhardwaj, Morten Källberg, Wonhwa Cho, and Hui Lu 26 BIOLOGICAL NETWORKS–BASED ANALYSIS OF GENE EXPRESSION SIGNATURES 495 Gang Chen and Jianxin Wang INDEX 507

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Book SynopsisThis publication offers a unique approach that links the materials science of bioceramics to clinical needs and applications.Providing a structured account of this highly active area of research, the book reviews the clinical applications in bone tissue engineering, bone regeneration, joint replacement, drug-delivery systems and biomimetism, this book is an ideal resource for materials scientists and engineers, as well as for clinicians.From the contents:Part I Introduction1. Bioceramics2. Biomimetics Part II Materials 3. Calcium Phosphate Bioceramics4. Silica-based Ceramics: Glasses5. Silica-based Ceramics: Mesoporous Silica6. Alumina, Zirconia, and Other Non-oxide Inert Bioceramics7. Carbon-based Materials in Biomedicine Part III Material Shaping 8. Cements9. Bioceramic Coatings for Medical Implants10. Scaffold Designing Part IV Research on Future CeraTable of ContentsList of Contributors xiii Preface xv Part I Introduction 1 1. Bioceramics 3 María Vallet-Regí 1.1 Introduction 3 1.2 Reactivity of the Bioceramics 4 1.3 First, Second, and Third Generations of Bioceramics 6 1.4 Multidisciplinary Field 7 1.5 Solutions for Bone Repairing 8 1.6 Biomedical Engineering 13 Recommended Reading 15 2. Biomimetics 17 María Vallet-Regí 2.1 Biomimetics 17 2.2 Formation of Hard Tissues 18 2.3 Biominerals versus Biomaterials 19 Recommended Reading 22 Part II Materials 23 3. Calcium Phosphate Bioceramics 25 Daniel Arcos 3.1 History of Calcium Phosphate Biomaterials 25 3.2 Generalities of Calcium Phosphates 26 3.3 In vivo Response of Calcium Phosphate Bioceramics 28 3.4 Calcium Hydroxyapatite-Based Bioceramics 30 3.4.1 Stoichiometric Hydroxyapatite (HA) 31 3.4.2 Calcium Deficient Hydroxyapatites (CDHA) 37 3.4.3 Carbonated Hydroxyapatites (CHA) 39 3.4.4 Silicon-Substituted Hydroxyapatite (Si-HA) 40 3.4.5 Hydroxyapatites of Natural Origin 45 3.5 Tricalcium Phosphate-Based Bioceramics 50 3.5.1 -Tricalcium Phosphate (-TCP) 50 3.5.2 -Tricalcium Phosphate (-TCP) 53 3.6 Biphasic Calcium Phosphates (BCP) 55 3.6.1 Chemical and Structural Properties 55 3.6.2 Preparation Methods 56 3.6.3 Clinical Applications 56 3.7 Calcium Phosphate Nanoparticles 57 3.7.1 General Properties and Scope of Calcium Phosphate Nanoparticles 57 3.7.2 Preparation Methods of CaP Nanoparticles 58 3.7.3 Clinical Applications 60 3.8 Calcium Phosphate Advanced Biomaterials 60 3.8.1 Scaffolds for in situ Bone Regeneration and Tissue Engineering 60 3.8.2 Drug Delivery Systems 62 References 65 4. Silica-based Ceramics: Glasses 73 Antonio J. Salinas 4.1 Introduction 73 4.1.1 What Is a Glass? 73 4.1.2 Properties of Glasses 75 4.1.3 Structure of Glasses 75 4.1.4 Synthesis of Glasses 76 4.2 Glasses as Biomaterials 78 4.2.1 First Bioactive Glasses (BGs): Melt-Prepared Glasses (MPGs) 79 4.2.2 Other Bioactive MPGs 80 4.2.3 Bioactivity Index and Network Connectivity 80 4.2.4 Mechanism of Bioactivity 81 4.3 Increasing the Bioactivity of Glasses: New Methods of Synthesis 82 4.3.1 Sol–Gel Glasses (SGGs) 82 4.3.2 Composition, Texture, and Bioactivity of SSGs 84 4.3.3 Biocompatibility of SGGs 86 4.3.4 SGGs as Bioactivity Accelerators in Biphasic Materials 86 4.3.5 Template Glasses (TGs) Bioactive Glasses with Ordered Mesoporosity 88 4.3.6 Atomic Length Scale in BGs: How the Local Structure Affects Bioactivity 91 4.3.7 New Reformulation of Hench’s Mechanism for TGs 93 4.3.8 Including Therapeutic Inorganic Ions in the Glass Composition 94 4.4 Strengthening and Adding New Capabilities to Bioactive Glasses 95 4.4.1 Glass Ceramics (GCs) 95 4.4.2 Composites Containing Bioactive Glasses 97 4.4.3 Sol–Gel Organic–Inorganic Hybrids (O-IHs) 98 4.5 Non-silicate Glasses 99 4.5.1 Phosphate Glasses 99 4.5.2 Borate Glasses 100 4.6 Clinical Applications of Glasses 101 4.6.1 Bioactive Silica Glasses 101 4.6.2 Inert Silica Glasses 106 4.6.3 Phosphate Glasses 106 4.6.4 Borate Glasses 107 Recommended Reading 107 5. Silica-based Ceramics: Mesoporous Silica 109 Montserrat Colilla 5.1 Introduction 109 5.2 Discovery of Ordered Mesoporous Silicas 110 5.3 Synthesis of Ordered Mesoporous Silicas 111 5.3.1 Hydrothermal Synthesis 112 5.3.2 Evaporation-Induced Self-Assembly (EISA) Method 119 5.4 Mechanisms of Mesostructure Formation 119 5.5 Tuning the Structural Properties of Mesoporous Silicas 122 5.5.1 Micellar Mesostructure 123 5.5.2 Type of Mesoporous Structure 128 5.5.3 Mesopore Size 131 5.6 Structural Characterization of Mesoporous Silicas 132 5.7 Synthesis of Spherical Mesoporous Silica Nanoparticles 135 5.7.1 Aerosol-Assisted Synthesis 136 5.7.2 Modified Stöber Method 137 5.8 Organic Functionalization of Ordered Mesoporous Silicas 138 5.8.1 Post-synthesis Functionalization (“Grafting”) 139 5.8.2 Co-condensation (“One-Pot” Synthesis) 140 5.8.3 Periodic Mesoporous Organosilicas 141 References 141 6. Alumina, Zirconia, and Other Non-oxide Inert Bioceramics 153 Juan Peña López 6.1 A Perspective on the Clinical Application of Alumina and Zirconia 153 6.1.1 Alumina 155 6.1.2 Zirconia 158 6.2 Novel Strategies Based on Alumina and Zirconia Ceramics 160 6.2.1 From Alumina Toughened Zirconia to Alumina Matrix Composite 160 6.2.2 Introduction of Different Species in Zirconia 161 6.2.3 Improvement of Surface Adhesion 162 6.3 Non-oxidized Ceramics 163 6.3.1 Silicon Nitride (Si3N4) 163 6.3.2 Silicon Carbide (SiC) 164 References 164 7. Carbon-based Materials in Biomedicine 175 Mercedes Vila 7.1 Introduction 175 7.2 Carbon Allotropes 175 7.2.1 Pyrolytic Carbon 176 7.2.2 Carbon Fibers 177 7.2.3 Fullerenes 177 7.2.4 Carbon Nanotubes 179 7.2.5 Graphene 181 7.2.6 Diamond and Amorphous Carbon 184 7.3 Carbon Compounds 186 7.3.1 Silicon Carbide 186 7.3.2 Boron Carbide 187 7.3.3 Tungsten Carbide 188 References 188 Part III Material Shaping 193 8. Cements 195 Oscar Castaño and Josep A. Planell Abbreviations 195 Glossary 196 8.1 Introduction 197 8.1.1 Brief History 197 8.1.2 Definition and Chemistry 199 8.1.3 Description of the Different CaP Cements 200 8.1.4 State of the Art 201 8.2 Calcium Phosphate Cements 206 8.2.1 Types 206 8.2.2 Mechanisms 206 8.2.3 Relevant Experimental Variables 207 8.2.4 Material Characterization 211 8.2.5 Reaction Evolution of Cements 220 8.2.6 Additives and Strategies to Enhance Properties 222 8.2.7 Biological Characterization and Bioactive Behavior 224 8.3 Applications 229 8.3.1 Bone Defect Repair 229 8.3.2 Drug Delivery Systems 232 8.4 Future Trends 232 8.5 Conclusions 233 References 234 9. Bioceramic Coatings for Medical Implants 249 M. Victoria Cabañas 9.1 Introduction 249 9.2 Methods to Modify the Surface of an Implant 250 9.2.1 Deposited Coatings 251 9.2.2 Conversion Coatings 257 9.3 Bioactive Ceramic Coatings 258 9.3.1 Clinical Applications 259 9.3.2 Calcium Phosphates-Based Coatings 260 9.3.3 Silica-based Coatings: Glass and Glass-Ceramics 268 9.3.4 Bioactive Ceramic Layer Formation on a Metallic Substrate 270 9.4 Bioinert Ceramic Coatings 272 9.4.1 Titanium Nitride and Zirconia Coatings 273 9.4.2 Carbon-based Coatings 275 References 279 10. Scaffold Designing 291 Isabel Izquierdo-Barba 10.1 Introduction 291 10.2 Essential Requirements for Bone Tissue Engineering Scaffolds 293 10.3 Scaffold Processing Techniques 296 10.3.1 Foam Scaffolds 297 10.3.2 Rapid Prototyping Scaffolds 301 10.3.3 Electrospinning Scaffolds 305 References 307 Part IV Research on Future Ceramics 315 11. Bone Biology and Regeneration 317 Soledad Pérez-Amodio and Elisabeth Engel 11.1 Introduction 317 11.2 The Skeleton 318 11.3 Bone Remodeling 320 11.4 Bone Cells 322 11.4.1 Bone Lining Cells 322 11.4.2 Osteoblasts 323 11.4.3 Osteocytes 323 11.4.4 Osteoclasts 324 11.5 Bone Extracellular Matrix 327 11.6 Bone Diseases 327 11.6.1 Osteoporosis 328 11.6.2 Paget’s Disease 329 11.6.3 Osteomalacia 329 11.6.4 Osteogenesis Imperfecta 329 11.7 Bone Mechanics 329 11.8 Bone Tissue Regeneration 333 11.8.1 Calcium Phosphate and Silica-based Bioceramics 333 11.8.2 Bioactive Glasses 334 11.8.3 Calcium Phosphate Cements 335 11.9 Conclusions 336 References 336 12. Ceramics for Drug Delivery 343 Miguel Manzano 12.1 Introduction 343 12.2 Drug Delivery 344 12.3 Drug Delivery from Calcium Phosphates 346 12.3.1 Drug Delivery from Hydroxyapatite 346 12.3.2 Drug Delivery from Tricalcium Phosphates 348 12.3.3 Drug Delivery from Calcium Phosphate Cements 348 12.4 Drug Delivery from Silica-based Ceramics 351 12.4.1 Drug Delivery from Glasses 351 12.4.2 Drug Delivery from Mesoporous Silica 355 12.5 Drug Delivery from Carbon Nanotubes 363 12.6 Drug Delivery from Ceramic Coatings 365 References 366 13. Ceramics for Gene Transfection 383 Blanca González 13.1 Gene Transfection 383 13.2 Gene Transfection Based on Nonviral Vectors 386 13.3 Ceramic Nanoparticles for Gene Transfection 388 13.3.1 Calcium Phosphate Nanoparticles 391 13.3.2 Mesoporous Silica Nanoparticles 393 13.3.3 Carbon Allotropes (Fullerenes, CNTs, Graphene Oxide) 397 13.3.4 Magnetic Iron Oxide Nanoparticles 403 References 410 14. Ceramic Nanoparticles for Cancer Treatment 421 Alejandro Baeza 14.1 Delivery of Nanocarriers to Solid Tumors 421 14.1.1 Special Issues of Tumor Vasculature: Enhanced Permeation and Retention Effect (EPR) 422 14.1.2 Tumor Microenvironment 423 14.2 Ceramic Nanoparticle Pharmacokinetics in Cancer Treatment 424 14.2.1 Biodistribution and Excretion/Clearance Pathways 424 14.2.2 Toxicity of the Ceramic Nanoparticles 426 14.3 Cancer-targeted Therapy 428 14.3.1 Endocytic Mechanism of Targeted Drug Delivery 428 14.3.2 Specific Tumor Active Targeting 430 14.3.3 Angiogenesis-associated Active Targeting 432 14.4 Ceramic Nanoparticles for Cancer Treatment 434 14.4.1 Mesoporous Silica Nanoparticles 434 14.4.2 Calcium Phosphates Nanoparticles 440 14.4.3 Carbon Allotropes 440 14.4.4 Iron Oxide Nanoparticles and Hyperthermia 442 14.5 Imaging and Theranostic Applications 443 References 446 Index 457

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Book SynopsisPractical Multiscaling covers fundamental modelling techniques aimed at bridging diverse temporal and spatial scales ranging from the atomic level to a full-scale product level. It focuses on practical multiscale methods that account for fine-scale (material) details but do not require their precise resolution.Table of ContentsPreface xi Acknowledgments xv 1 Introduction to Multiscale Methods 1 1.1 The Rationale for Multiscale Computations 1 1.2 The Hype and the Reality 2 1.3 Examples and Qualification of Multiscale Methods 3 1.4 Nomenclature and definitions 5 1.5 Notation 6 1.5.1 Index and matrix notation 6 1.5.2 M ultiple Spatial Scale Coordinates 8 1.5.3 Domains and boundaries 9 1.5.4 Spatial and Temporal Derivatives 9 1.5.5 Special symbols 10 References 11 2 Upscaling/Downscaling of Continua 13 2.1 Introduction 13 2.2 Homogenizaton of Linear Heterogeneous Media 16 2.2.1 Two-Scale Formulation 16 2.2.2 Two-Scale Formulation – Variational Form 23 2.2.3 Hill–Mandel Macrohomogeneity Condition and Hill–Reuss–Voigt Bounds 25 2.2.4 N umerical Implementation 27 2.2.5 B oundary Layers 38 2.2.6 Convergence Estimates 41 2.3 Upscaling Based on Enhanced Kinematics 47 2.3.1 M ultiscale Finite Element Method 48 2.3.2 Variational Multiscale Method 48 2.3.3 M ultiscale Enrichment Based on Partition of Unity 49 2.4 Homogenization of Nonlinear Heterogeneous Media 50 2.4.1 Asymptotic Expansion for Nonlinear Problems 50 2.4.2 Formulation of the Coarse-Scale Problem 54 2.4.3 Formulation of the Unit Cell Problem 58 2.4.4 Example Problems 61 2.5 Higher Order Homogenization 64 2.5.1 Introduction 64 2.5.2 Formulation 65 2.6 Multiple-Scale Homogenization 69 2.7 Going Beyond Upscaling – Homogenization-Based Multigrid 71 2.7.1 Relaxation 73 2.7.2 Coarse-grid Correction 77 2.7.3 Two-grid Convergence for a Model Problem in a Periodic Heterogeneous Medium 79 2.7.4 Upscaling-Based Prolongation and Restriction Operators 81 2.7.5 Homogenization-based Multigrid and Multigrid Acceleration 83 2.7.6 N onlinear Multigrid 84 2.7.7 M ultigrid for Indefinite Systems 86 Problems 87 References 91 3 Upscaling/Downscaling of Atomistic/Continuum Media 95 3.1 Introduction 95 3.2 Governing Equations 96 3.2.1 M olecular Dynamics Equation of Motion 96 3.2.2 M ultiple Spatial and Temporal Scales and Rescaling of the MD Equations 98 3.3 Generalized Mathematical Homogenization 100 3.3.1 M ultiple-Scale Asymptotic Analysis 100 3.3.2 The Dynamic Atomistic Unit Cell Problem 102 3.3.3 The Coarse-Scale Equations of Motion 103 3.3.4 Continuum Description of Equation of Motion 106 3.3.5 The Thermal Equation 107 3.3.6 Extension to Multi-Body Potentials 112 3.4 Finite Element Implementation and Numerical Verification 113 3.4.1 Weak Forms and Semidiscretization of Coarse-Scale Equations 113 3.4.2 The Fine-Scale (Atomistic) Problem 115 3.5 Statistical Ensemble 118 3.6 Verification 120 3.7 Going Beyond Upscaling 126 3.7.1 Spatial Multilevel Method Versus Space–Time Multilevel Method 127 3.7.2 The WR Scheme 129 3.7.3 Space–Time FAS 130 Problems 131 References 133 4 Reduced Order Homogenization 137 4.1 Introduction 137 4.2 Reduced Order Homogenization for Two-Scale Problems 139 4.2.1 Governing Equations 139 4.2.2 Residual-Free Fields and Model Reduction 141 4.2.3 Reduced Order System of Equations 148 4.2.4 One-Dimensional Model Problem 150 4.2.5 Computational Aspects 154 4.3 Lower Order Approximation of Eigenstrains 156 4.3.1 The Pitfalls of a Piecewise Constant One-Partition-Per-Phase Model 157 4.3.2 Impotent Eigenstrain 159 4.3.3 Hybrid Impotent-Incompatible Eigenstrain Mode Estimators 163 4.3.4 Chaboche Modification 164 4.3.5 Analytical Relations for Various Approximations of Eigenstrain Influence Functions 165 4.3.6 Eigenstrain Upwinding 172 4.3.7 Enhancing Constitutive Laws of Phases 175 4.3.8 Validation of the Hybrid Impotent-Incompatible Reduced Order Model with Eigenstrain Upwinding and Enhanced Constitutive Model of Phases 180 4.4 Extension to Nonlocal Heterogeneous Media 184 4.4.1 Staggered Nonlocal Model for Homogeneous Materials 186 4.4.2 Staggered Nonlocal Multiscale Model 188 4.4.3 Validation of the Nonlocal Model 189 4.4.4 Rescaling Constitutive Equations 193 4.5 Extension to Dispersive Heterogeneous Media 197 4.5.1 Dispersive Coarse-Scale Problem 199 4.5.2 The Quasi-Dynamic Unit Cell Problem 201 4.5.3 Linear Model Problem 204 4.5.4 N onlinear Model Problem 205 4.5.5 Implicit and Explicit Formulations 208 4.6 Extension to Multiple Spatial Scales 209 4.6.1 Residual-Free Governing Equations at Multiple Scales 210 4.6.2 M ultiple-Scale Reduced Order Model 211 4.7 Extension to Large Deformations 214 4.8 Extension to Multiple Temporal Scales with Application to Fatigue 219 4.8.1 Temporal Homogenization 220 4.8.2 M ultiple Temporal and Spatial Scales 224 4.8.3 Fatigue Constitutive Equation 225 4.8.4 Verfication of the Multiscale Fatigue Model 226 4.9 Extension to Multiphysics Problems 227 4.9.1 Reduced Order Coupled Vector-Scalar Field Model at Multiple Scales 228 4.9.2 Environmental Degradation of PMC 232 4.9.3 Validation of the Multiphysics Model 235 4.10 Multiscale Characterization 239 4.10.1 Formulation of the Inverse Problem 239 4.10.2 Characterization of Model Parameters in ROH 241 Problems 241 References 243 5 Scale-separation-free Upscaling/Downscaling of Continua 249 5.1 Introduction 249 5.2 Computational Continua (C2) 251 5.2.1 N onlocal Quadrature 251 5.2.2 Coarse-Scale Problem 254 5.2.3 Computational Unit Cell Problem 257 5.2.4 One-dimensional model problem 260 5.3 Reduced Order Computational Continua (RC2) 265 5.3.1 Residual-Free Computational Unit Cell Problem 266 5.3.2 The Coarse-Scale Weak Form 274 5.3.3 Coarse-Scale Consistent Tangent Stiffness Matrix 275 5.4 Nonlocal Quadrature in Multidimensions 278 5.4.1 Tetrahedral Elements 278 5.4.2 Triangular Elements 287 5.4.3 Quadrilateral and Hexahedral Elements 292 5.5 Model Verification 297 5.5.1 The Beam Problem 300 Problems 302 References 303 6 Multiscale Design Software 305 6.1 Introduction 305 6.2 Microanalysis with MDS-Lite 308 6.2.1 Familiarity with the GUI 309 6.2.2 Labeling Data Files 312 6.2.3 The First Walkthrough MDS-Micro Example 312 6.2.4 The Second Walkthrough MDS-Micro Example 318 6.2.5 Parametric Library of Unit Cell Models 331 6.3 Macroanalysis with MDS-Lite 340 6.3.1 First Walkthrough MDS-Macro Example 341 6.3.2 Second Walkthrough MDS-Macro Example 362 6.3.3 Third Walkthrough Example 373 6.3.4 Fourth Walkthrough Example 379 Problems 391 References 393 Index 395

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Book SynopsisThis cutting edge book provides all the important aspects dealing with the basic science involved in materials in biomedical technology, especially structure and properties, techniques and technological innovations in material processing and characterizations, as well as the applications.Table of ContentsPreface xi 1. 1D~3D Nano-engineered Biomaterials for Biomedical Applications 1 Hui Chen, Xiaokang Li and Yanan Du 1.1 Introduction 1 1.2 3D Nanomaterials Towards Biomedical Applications 2 1.3 Structural and Functional Modification 6 1.4 Properties of Nanoparticles for Biomedical Application 8 1.5 Applications of NPs 10 1.6 2D Nanomaterials Towards Biomedical Applications 15 1.7 1D Nanomaterial Towards Biomedical Applications 21 1.8 Conclusion 28 References 28 2. Porous Biomaterials 35 Nasim Annabi 2.1 Introduction 35 2.2 Porosity and Pore Architecture of Biomaterial Scaffolds 36 2.3 Methods to Measure Porosity and Pore Size 38 2.4 Porosity Generation Techniques 39 2.5 Summary 60 References 61 3. Bioactive and Biocompatible Polymeric Composites Based on Amorphous Calcium Phosphate 67 Joseph M. Antonucci and Drago Skrtic 3.1 Introduction 68 3.2 Experimental Approach 75 3.3 Results and Discussion 91 3.4 Concluding Remarks/Future Directions 108 Acknowledgements 109 References 109 Appendix 1. List of Acronyms used Throughout the Proposal 117 4. Calcium Phosphates and Nanocrystalline Apatites for Medical Applications 121 Sunita Prem Victor and Chandra P. Sharma 4.1 Introduction 121 4.2 Chemistry of Calcium Phosphates 123 Contents vii 4.4 Properties of Calcium Orthophosphates 128 4.5 Biomedical Applications of Calcium Phosphates 133 4.6 Conclusion 138 References 138 5. SiO2 Particles with Functional Nanocrystals: Design and Fabrication for Biomedical Applications 145 Ping Yang 5.1 Introduction 145 5.2 Fabrication Methods of SiO2 Particles with NCs 156 5.3 Main Research Results for SiO2 Particles with NCs 170 5.4 Multifunctional SiO2 Particles for Biomedical Applications 229 5.5 Conclusions and Outlook 243 Acknowledgements 244 References 244 6. New Kind of Titanium Alloys for Biomedical Application 253 Yufeng Zheng, Binbin Zhang, Benli Wang and Li Li 6.1 Introduction 253 6.2 Dental Cast Titanium Alloys 254 6.3 Low Modulus Titanium Alloys 262 6.4 Nickel Free Shape Memory Titanium Alloys 266 6.5 Summary 270 References 270 7. BMP-based Bone Tissue Engineering 273 Ziyad S Haidar and Murugan Ramalingam 7.1 Introduction 274 7.2 Challenges in Protein Therapy 277 7.3 BMP Delivery Requirements 279 7.4 BMP-specific Carrier Types and Materials 282 7.5 Summary 289 Acknowledgements 290 References 290 8. Impedance Sensing of Biological Processes in Mammalian Cells 293 Lamya Ghenim, Hirokazu Kaji, Matsuhiko Nishizawa, Xavier Gidrol 8.1 Introduction 293 8.2 Cell Attachment and Spreading Processes 295 8.3 Cell Motility 299 8.4 Apoptosis 302 8.5 Mitosis 303 8.6 Single Cell Analysis 303 8.7 Conclusion 307 References 307 9. Hydrogel Microbeads for Implantable Glucose Sensors 309 Yun Jung Heo and Shoji Takeuchi 9.1 Introduction 9.2 Fabrication Methods of Hydrogel Microbeads 311 9.3 Fluorescence-based Glucose Monitoring 318 9.4 Biocompatibility 325 9.5 Summary 328 References 328 10. Molecular Design of Multifunctional Polymers for Gene Transfection 333 Chao Lin, Bo Lou and Rong Jin 333 10.1 Introduction 333 10.2 Barriers to Non-viral Gene Delivery 335 10.3 Molecular Design of Polymer Vectors for Efficient Gene Delivery 338 10.4 Molecular Design of Polymer Vectors with Low Cytotoxicity 348 10.5 Summary 354 Acknowledgements 355 Appendix: List of Abbreviations 355 References 355 11. Injectable in situ Gelling Hydrogels as Biomaterials 361 Hardeep Singh and Lakshmi S. Nair 11.1 Introduction 362 11.2 Injectable in situ Gelling Hydrogels 365 11.3 Clinical Applications of Hydrogels 369 11.4 Injectable Hydrogels for Biomedical Applications 370 11.5 Conclusions 393 References 393 12. Metal-polymer Hybrid Biomaterials with High Mechanical and Biological Compatibilities 399 Masaaki Nakai and Mitsuo Niinomi 12.1 Introduction 399 12.2 Fabrication Methods of Porous Titanium Filled with Medical Polymer 401 12.3 Mechanical Properties of Porous Titanium Filled with Medical Polymer 403 12.4 Biological Properties of Porous Titanium Filled with Medical Polymer 407 12.5 Summary 409 References 409

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Book SynopsisA full-colour undergraduate textbook, based on a two semester course, that presents the fundamentals of biological physics, introducing essential modern topics that include cells, polymers, polyelectrolytes, membranes, liquid crystals, phase transitions, self-assembly, photonics, fluid mechanics, motility, chemical kinetics, and enzyme kinetics.Table of ContentsPreface xiii Acknowledgements xvii I Building Blocks 1 1 Molecules 3 1.1 Chemical Bonds and Molecular Interactions 3 1.2 Chirality 7 1.3 Proteins 7 1.4 Lipids 15 1.5 Nucleic Acids 16 1.6 Carbohydrates 21 1.7 Water 24 1.8 Proteoglycans and Glycoproteins 25 1.9 Viruses 26 1.10 Other Molecules 28 Suggested Reading 28 Tutorial Questions 1 29 2 Cells 31 2.1 The First Cell 32 2.2 Metabolism 33 2.3 Central Dogma of Biology 34 2.4 Darwin’s Theory of Natural Selection 38 2.5 Mutations and Cancer 40 2.6 Prokaryotic Cells 41 2.7 Eukaryotic Cells 41 2.8 Chromosomes 44 2.9 Cell Cycle 45 2.10 Genetic Code 45 2.11 Genetic Networks 45 2.12 Human Genome Project 47 2.13 Genetic Fingerprinting 49 2.14 Genetic Engineering 50 2.15 Tissues 51 2.16 Cells as Experimental Models 51 2.17 Stem Cells 52 Suggested Reading 53 Tutorial Questions 2 54 II Soft Condensed-Matter Techniques in Biology 55 3 Introduction to Statistics in Biology 57 3.1 Statistics 57 3.2 Entropy 60 3.3 Information 61 3.4 Free Energy 62 3.5 Partition Function 63 3.6 Conditional Probability 65 3.7 Networks 66 Suggested Reading 67 Tutorial Questions 3 67 4 Mesoscopic Forces 69 4.1 Cohesive Forces 69 4.2 Hydrogen Bonding 71 4.3 Electrostatics 73 4.3.1 Unscreened Electrostatic Interactions 73 4.3.2 Screened Electrostatic Interactions 74 4.3.3 The Force Between Charged Aqueous Spheres 77 4.4 Steric and Fluctuation Forces 79 4.5 Depletion Forces 82 4.6 Hydrodynamic Interactions 84 4.7 Bell’s Equation 84 4.8 Direct Experimental Measurements 86 Suggested Reading 89 Tutorial Questions 4 89 5 Phase Transitions 91 5.1 The Basics 91 5.2 Helix–Coil Transition 94 5.3 Globule–Coil Transition 98 5.4 Crystallisation 101 5.5 Liquid–Liquid Demixing (Phase Separation) 104 Suggested Reading 108 Tutorial Questions 5 109 6 Liquid Crystallinity 111 6.1 The Basics 111 6.2 Liquid Nematic–Smectic Transitions 123 6.3 Defects 125 6.4 More Exotic Possibilities for Liquid-Crystalline Phases 130 Suggested Reading 132 Tutorial Questions 6 132 7 Motility 135 7.1 Diffusion 135 7.2 Low Reynolds Number Dynamics 142 7.3 Motility of Cells and Micro-Organisms 144 7.4 First-Passage Problem 148 7.5 Rate Theories of Chemical Reactions 152 7.6 Subdiffusion 153 Suggested Reading 155 Tutorial Questions 7 155 8 Aggregating Self-Assembly 157 8.1 Surface-Active Molecules (Surfactants) 160 8.2 Viruses 163 8.3 Self-Assembly of Proteins 167 8.4 Polymerisation of Cytoskeletal Filaments (Motility) 167 Suggested Reading 172 Tutorial Questions 8 172 9 Surface Phenomena 173 9.1 Surface Tension 173 9.2 Adhesion 175 9.3 Wetting 177 9.4 Capillarity 180 9.5 Experimental Techniques 183 9.6 Friction 184 9.7 Adsorption Kinetics 186 9.8 Other Physical Surface Phenomena 188 Suggested Reading 188 Tutorial Questions 9 188 10 Biomacromolecules 189 10.1 Flexibility of Macromolecules 189 10.2 Good/Bad Solvents and the Size of Flexible Polymers 198 10.3 Elasticity 203 10.4 Damped Motion of Soft Molecules 206 10.5 Dynamics of Polymer Chains 209 10.6 Topology of Polymer Chains – Supercoiling 214 Suggested Reading 216 Tutorial Questions 10 217 11 Charged Ions and Polymers 219 11.1 Electrostatics 222 11.2 Deybe–Huckel Theory 226 11.3 Ionic Radius 229 11.4 The Behaviour of Polyelectrolytes 232 11.5 Donnan Equilibria 234 11.6 Titration Curves 236 11.7 Poisson–Boltzmann Theory for Cylindrical Charge Distributions 238 11.8 Charge Condensation 239 11.9 Other Polyelectrolyte Phenomena 243 Suggested Reading 244 Tutorial Questions 11 245 12 Membranes 247 12.1 Undulations 248 12.2 Bending Resistance 250 12.3 Elasticity 253 12.4 Intermembrane Forces 258 12.5 Passive/Active Transport 260 12.6 Vesicles 267 Suggested Reading 268 Tutorial Questions 12 268 13 Continuum Mechanics 269 13.1 Structural Mechanics 270 13.2 Composites 273 13.3 Foams 275 13.4 Fracture 277 13.5 Morphology 278 Suggested Reading 278 Tutorial Questions 13 279 14 Fluid Mechanics 281 14.1 Newton’s Law of Viscosity 282 14.2 Navier–Stokes Equations 282 14.3 Pipe Flow 283 14.4 Vascular Networks 285 14.5 Haemodynamics 285 14.6 Circulatory Systems 289 14.7 Lungs 289 Suggested Reading 291 Tutorial Questions 14 291 15 Rheology 293 15.1 Storage and Loss Moduli 295 15.2 Rheological Functions 298 15.3 Examples from Biology: Neutral Polymer Solutions, Polyelectrolytes, Gels, Colloids, Liquid Crystalline Polymers, Glasses, Microfluidics 299 15.3.1 Neutral Polymer Solutions 299 15.3.2 Polyelectrolytes 303 15.3.3 Gels 305 15.3.4 Colloids 309 15.3.5 Liquid-Crystalline Polymers 310 15.3.6 Glassy Materials 310 15.3.7 Microfluidics in Channels 312 15.4 Viscoelasticity of the Cell 312 Suggested Reading 314 Tutorial Questions 15 314 16 Motors 315 16.1 Self-Assembling Motility – Polymerisation of Actin and Tubulin 317 16.2 Parallelised Linear Stepper Motors – Striated Muscle 320 16.3 Rotatory Motors 325 16.4 Ratchet Models 327 16.5 Other Systems 329 Suggested Reading 329 Tutorial Questions 16 330 17 Structural Biomaterials 331 17.1 Cartilage – Tough Shock Absorbers in Human Joints 331 17.2 Spider Silk 341 17.3 Elastin and Resilin 342 17.4 Bone 343 17.5 Adhesive Proteins 343 17.6 Nacre and Mineral Composites 345 Suggested Reading 346 Tutorial Questions 17 346 18 Phase Behaviour of DNA 347 18.1 Chromatin – Naturally Packaged DNA Chains 347 18.2 DNA Compaction – An Example of Polyelectrolyte Complexation 350 18.3 Facilitated Diffusion 351 Suggested Reading 354 III Experimental Techniques 355 19 Experimental Techniques 357 19.1 Mass Spectroscopy 357 19.2 Thermodynamics 359 19.2.1 Differential Scanning Calorimetry 360 19.2.2 Isothermal Titration Calorimetry 360 19.2.3 Surface Plasmon Resonance and Interferometry-Based Biosensors 360 19.3 Hydrodynamics 362 19.4 Optical Spectroscopy 363 19.4.1 Rayleigh Scattering 363 19.4.2 Brillouin Scattering 364 19.4.3 Terahertz/Microwave Spectroscopy 364 19.4.4 Infrared Spectroscopy 365 19.4.5 Raman Spectroscopy 366 19.4.6 Nonlinear Spectroscopy 367 19.4.7 Circular Dichroism and UV Spectroscopy 369 19.5 Optical Microscopy 369 19.5.1 Fluorescence Microscopy 376 19.5.2 Super-Resolution Microscopy 378 19.5.3 Nonlinear Microscopy 382 19.5.4 Polarisation Microscopy 382 19.5.5 Optical Coherence Tomography 382 19.5.6 Holographic Microscopy 383 19.5.7 Other Microscopy Techniques 383 19.6 Single-Molecule Detection 384 19.7 Single-Molecule Mechanics and Force Measurements 384 19.8 Electron Microscopy 395 19.9 Nuclear Magnetic Resonance Spectroscopy 396 19.10 Static Scattering Techniques 397 19.11 Dynamic Scattering Techniques 408 19.12 Osmotic Pressure 412 19.13 Chromatography 415 19.14 Electrophoresis 415 19.15 Sedimentation 420 19.16 Rheology 424 19.17 Tribology 431 19.18 Solid Mechanical Properties 432 Suggested Reading 432 Tutorial Questions 19 433 IV Systems Biology 437 20 Chemical Kinetics 439 20.1 Conservation Laws 440 20.2 Free Energy 440 20.3 Reaction Rates 441 20.4 Consecutive Reactions 449 20.5 Case I and II Reactions 450 20.6 Parallel Reactions 452 20.7 Approach to Chemical Equilibrium 453 20.8 Quasi-Steady-State Approximation 456 20.9 General Kinetic Equation Analysis 459 Suggested Reading 459 Tutorial Questions 20 460 21 Enzyme Kinetics 461 21.1 Michaelis–Menten Kinetics 461 21.2 Lineweaver–Burke Plot 465 21.3 Enzyme Inhibition 466 21.4 Competitive Inhibition 466 21.5 Allosteric Inhibition 467 21.6 Cooperativity 468 21.7 Hill Plot 470 21.8 Single Enzyme Molecules 470 Suggested Reading 472 Tutorial Questions 21 472 22 Introduction to Systems Biology 473 22.1 Integrative Model of the Cell 473 22.2 Transcription Networks 474 22.3 Gene Regulation 474 22.4 Lac Operon 477 22.5 Repressilator 479 22.6 Autoregulation 481 22.7 Network Motifs 483 22.8 Robustness 489 22.9 Morphogenesis 490 22.10 Kinetic Proofreading 492 22.11 Temporal Programs 493 22.12 Nonlinear Models 494 22.13 Population Dynamics 497 Suggested Reading 498 Tutorial Questions 22 499 V Spikes, Brains and the Senses 501 23 Spikes 503 23.1 Structure and Function of a Neuron 503 23.2 Membrane Potential 503 23.3 Ion Channels 506 23.4 Voltage Clamps and Patch Clamps 508 23.5 Nernst Equation 509 23.6 Electrical Circuit Model of a Cell Membrane 511 23.7 Cable Equation 513 23.8 Hodgkin–Huxley Model 515 23.9 Action Potential 518 23.10 Spikes – Travelling Electrical Waves 520 23.11 Cell Signalling 523 Suggested Reading 524 Tutorial Questions 23 525 24 Physiology of Cells and Organisms 527 24.1 Feedback Loops 528 24.2 Nonlinear Behaviour 533 24.3 Potential Outside an Axon 533 24.4 Electromechanical Properties of the Heart 535 24.5 Electrocardiogram 536 24.6 Electroencephalography 537 Suggested Reading 539 Tutorial Questions 24 540 25 The Senses 541 25.1 Biological Senses 541 25.2 Weber’s Law 542 25.3 Information Processing and Hyperacuity 543 25.4 Mechanoreceptors 543 25.5 Chemoreceptors 545 25.6 Photoreceptors 549 25.7 Thermoreceptors 551 25.8 Electroreceptors 552 25.9 Magnetoreceptors 552 Suggested Reading 553 Tutorial Questions 25 554 26 Brains 555 26.1 Neural Encoding Inverse Problem 558 26.2 Memory 560 26.3 Motor Processes 564 26.4 Connectome 565 26.5 Cohesive Properties 566 Suggested Reading 567 Tutorial Questions 26 568 Appendix A: Physical Constants 569 Appendix B: Answers to Tutorial Questions 571 Index 593

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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 SynopsisFeaturing chapters from specialists in endocrinology, physiology, pathology, and nuclear medicine, this book provides a multidisciplinary approach to a wide variety of issues concerning somatostatin and its analogues. The book: Provides the most up-to-date coverage of somatostatin analog use in diagnostic and therapy Integrating the specialties of endocrinology, physiology, pathology, and nuclear medicine, providing the multidisciplinary approach to the topic Focuses on future applications, novel compounds, and areas for further research Covers topics by authors who are renowned experts and researchers in the field Table of ContentsContributors viii Preface xii Acknowledgements xv 1 Somatostatin: The History of Discovery 1Malgorzata Trofimiuk‐Müldner and Alicja Hubalewska‐Dydejczyk 2 Physiology of Endogenous Somatostatin Family: Somatostatin Receptor Subtypes, Secretion, Function and Regulation, and Organ Specific Distribution 6Marily Theodoropoulou 3 Somatostatin Receptors in Malignancies and Other Pathologies 21Marco Volante, Adele Cassenti, Ida Rapa, Luisella Righi, and Mauro Papotti 4 The Use of Radiolabeled Somatostatin Analogue in Medical Diagnosis: Introduction 31Alberto Signore 4.1 Somatostatin Receptor Scintigraphy‐SPECT 35Renata Mikołajczak and Alberto Signore 4.2 Molecular Imaging of Somatostatin Receptor‐Positive Tumors Using PET/CT 55 Richard P. Baum and Harshad R. Kulkarni4.3 Other Radiopharmaceuticals for Imaging GEP‐NET 75Klaas Pieter Koopmans, Rudi A. Dierckx, Philip H. Elsinga, Thera P. Links, Ido P. Kema, Helle-Brit Fiebrich, Annemieke M.E. Walekamp, Elisabeth G.E. de Vries, and Adrienne H. Brouwers 4.4 The Place of Somatostatin Receptor Scintigraphy in Clinical Setting: Introduction 86Alicja Hubalewska‐Dydejczyk 4.4.1 Somatostatin Receptor Scintigraphy in Management of Patients with Neuroendocrine Neoplasms 90Anna Sowa‐Staszczak, Agnieszka Stefańska, Agata Jabrocka‐Hybel, and Alicja Hubalewska‐Dydejczyk 4.4.2 The Place of Somatostatin Receptor Scintigraphy and Other Functional Imaging Modalities in the Setting of Pheochromocytoma and Paraganglioma 112Alicja Hubalewska‐Dydejczyk, Henri J.L.M. Timmers, and Malgorzata Trofimiuk‐Müldner 4.4.3 Somatostatin Receptor Scintigraphy in Medullary Thyroid Cancer 127Anouk N.A. van der Horst‐Schrivers, Adrienne H. Brouwers, and Thera P. Links 4.4.4 Somatostatin Receptor Scintigraphy in Other Tumors Imaging 135Malgorzata Trofimiuk‐Müldner and Alicja Hubalewska‐Dydejczyk 4.4.5 Somatostatin Receptor Scintigraphy in Inflammation and Infection Imaging 153Alberto Signore, Kelly Luz Anzola Fuentes, and Marco Chianelli 5 Somatostatin Analogues in Pharmacotherapy: Introduction 164Wouter W. de Herder 5.1 Somatostatin Analogues in Pharmacotherapy 166Wouter W. de Herder 5.2 Pituitary Tumor Treatment with Somatostatin Analogues 169Alicja Hubalewska-Dydejczyk, Aleksandra Gilis-Januszewska, and Malgorzata Trofimiuk-Müldner 5.3 Somatostatin Analogues in Pharmacotherapy of Gastroenteropancreatic Neuroendocrine Tumors 189Frédérique Maire and Philippe Ruszniewski 5.4 Somatostatin Analogue Use in Other than Endocrine Tumor Indications 198Aleksandra Gilis‐Januszewska, Malgorzata Trofimiuk‐Müldner, Agata Jabrocka‐Hybel,, and Dorota Pach 6 Peptide Receptor Radionuclide Therapy Using Radiolabeled Somatostatin Analogues: An Introduction 207John Buscombe 6.1 Somatostatin Analogues and Radionuclides Used in Therapy 214Esther I. van Vliet, Boen L.R. Kam, Jaap J.M. Teunissen, Marion de Jong, Eric P. Krenning, and Dik J. Kwekkeboom 6.2 PRRT Dosimetry 230Mark Konijnenberg 6.3 Peptide Receptor Radionuclide Therapy (PRRT): Clinical Application 252Lisa Bodei, and Giovanni Paganelli 6.4 Duo‐PRRT of Neuroendocrine Tumors Using Concurrent and Sequential Administration of Y‐90‐ and Lu‐177‐Labeled Somatostatin Analogues 264Richard P. Baum and Harshad R. Kulkarni 6.5 N onsystemic Treatment of Liver Metastases from Neuroendocrine Tumor 273Daniel Putzer, Gerlig Widmann, Dietmar Waitz, Werner Jaschke, and Irene J. Virgolini 6.6 Peptide Receptor Radionuclide Therapy: Other Indications 282Agnieszka Stefańska, Alicja Hubalewska‐Dydejczyk, Agata Jabrocka‐Hybel, and Anna Sowa‐Staszczak 7 Somatostatin Analogs: Future Perspectives and Preclinical Studies—Pansomatostatins 291Aikaterini Tatsi Berthold A. Nock, Theodosia Maina, and Marion de Jong 8 Radiolabeled Somatostatin Receptor Antagonists 305Melpomeni Fani and Helmut R. Maecke 9 Cortistatins and Dopastatins 321Manuela Albertelli and Diego Ferone Index 000

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Book SynopsisThis book explores the structure-property-process relationship of biomaterials from engineering and biomedical perspectives, and the potential of bio-inspired materials and their applications. A large variety of natural materials with outstanding physical and mechanical properties have appeared in the course of evolution.Table of ContentsPreface xi 1 General Introduction 1 1.1 Historical Perspectives 1 1.2 Biomimetic Materials Science and Engineering 2 1.2.1 Biomimetic Materials from Biology to Engineering 2 1.2.2 Two Aspects of Biomimetic Materials Science and Engineering 3 1.2.3 Why Use Biomimetic Design of Advanced Engineering Materials? 4 1.2.4 Classification of Biomimetic Materials 7 1.3 Strategies, Methods, and Approaches for the Biomimetic Design of Engineering Materials 7 1.3.1 General Approaches for Biomimetic Engineering Materials 9 1.3.2 Special Approaches for Biomimetic Engineering Materials 10 References 11 Part I Biomimetic Structural Materials and Processing 13 2 Strong, Tough, and Lightweight Materials 15 2.1 Introduction 15 2.2 Strengthening and Toughening Principles in Soft Tissues 16 2.2.1 Overview of Spider Silk 16 2.2.2 Microstructure of Spider Silk 17 2.2.3 Mechanical Properties of Spider Silk 19 2.2.4 Strengthening and Toughening Mechanisms of Spider Silk 20 2.3 Strong and Tough Engineering Materials and Processes Mimicking Spider Silk 23 2.3.1 Biomimetic Design Principles for Strong and Tough Materials 23 2.3.2 Bioinspired Carbon Nanotube Yarns Mimicking Spider Silk Structure 24 2.4 Strengthening and Toughening Mechanisms in Hard Tissues 25 2.4.1 Nacre Microstructure 25 2.4.2 Deformation and Fracture Behavior of Nacre 27 2.4.3 Strengthening Mechanism in Nacre 29 2.4.4 Toughening Mechanisms in Nacre 31 2.4.5 Strengthening/Toughening Mechanisms in Other Hard Tissues 34 2.5 Biomimetic Design and Processes for Strong and Tough Ceramic Composites 37 2.5.1 Biomimetic Design Principles for Strong and Tough Materials 37 2.5.2 Layered Ceramic/Polymer Composites 39 2.5.3 Layered Ceramic/Metal Composites 43 2.5.4 Ceramic/Ceramic Laminate Composites 43 References 46 3 Wear-resistant and Impact-resistant Materials 49 3.1 Introduction 49 3.2 Hard Tissues with High Wear Resistance 50 3.2.1 Teeth: A Masterpiece of Biological Wear-resistance Materials 50 3.2.2 Microstructures of Enamel, Dentin, and Dentin-enamel Junction 51 3.2.3 Mechanical Properties of Dental Structures 54 3.2.4 Anti-wear Mechanisms of Enamel 56 3.2.5 Toughening Mechanisms of the DEJ 58 3.3 Biomimetic Designs and Processes of Materials for Wear-resistant Materials 59 3.3.1 Bioinspired Design Strategies for Wear-resistant Materials 59 3.3.2 Enamel-mimicking Wear-resistant Restorative Materials 61 3.3.3 Biomimetic Cutting Tools Based on the Sharpening Mechanism of Rat Teeth 62 3.3.4 DEJ-mimicking Functionally Graded Materials 64 3.4 Biological Composites with High Impact and Energy Absorbance 66 3.4.1 Mineral-based Biocomposites: Dactyl Club 67 3.4.2 Protein-based Biocomposites: Horns and Hooves 69 3.4.3 Bioinspired Design Strategies for Highly Impact-resistant Materials 72 3.5 Biomimetic Impact-resistant Materials and Processes 73 3.5.1 Dactyl Club-Biomimicking Highly Impact-resistant Composites 73 3.5.2 Damage-tolerant CNT-reinforced Nanocomposites Mimicking Hooves 74 References 76 4 Adaptive and Self-shaping Materials 79 4.1 Introduction 79 4.2 The Biological Models for Adapting and Morphing Materials 80 4.2.1 Reversible Stiffness Change of Sea Cucumber via Switchable Fiber Interactions 80 4.2.2 Gradient Stiffness of Squid Beak via Gradient Fiber Interactions 82 4.2.3 Shape Change in Plant Growth via Controlled Reinforcement Redistribution 84 4.2.4 Self-shaping by Pre-programed Reinforcement Architectures 86 4.2.5 Biomimetic Design Strategies for Morphing and Adapting 88 4.3 Biomimetic Synthetic Adaptive Materials and Processes 90 4.3.1 Adaptive Nanocomposites with Reversible Stiffness Change Capability 90 4.3.2 Squid-beak-inspired Mechanical Gradient Nanocomposites and Fabrication 93 4.3.3 Biomimetic Helical Fibers and Fabrication 94 4.3.4 Water-activated Self-shaping Materials and Fabrication 95 References 99 5 Materials with Controllable Friction and Reversible Adhesion 101 5.1 Introduction 101 5.2 Dry Adhesion: Biological Reversible Adhesive Systems Based on Fibrillar Structures 102 5.2.1 Gecko and Insect Adhesive Systems 102 5.2.2 Hierarchical Fibrillar Structure of Gecko Toe Pads 103 5.2.3 Adhesive Properties of Gecko Toe Pads 104 5.2.4 Mechanics of Fibrillar Adhesion 107 5.2.5 Bioinspired Strategies for Reversible Dry Adhesion 112 5.3 Gecko-mimicking Design of Fibrillar Dry Adhesives and Processes 112 5.3.1 Biomimetic Design Based on Geometric Replications of the Gecko Adhesive System 115 5.3.2 Biomimetic Design of Hybrid/Smart Fibrillar Adhesives 118 5.4 Wet Adhesion: Biological Reversible Adhesive Systems Based on Soft Film 121 5.4.1 Tree Frog Adhesive System 121 5.4.2 Adhesive Mechanism of Tree Frog Toe Pads 122 5.5 Artificial Adhesive Systems Inspired by Tree Frogs 123 5.6 Slippery Surfaces and Friction/Drag Reduction 125 5.6.1 Pitcher Plant: A Biological Model of a Slippery Surface 125 5.6.2 Shark Skin: A Biological Model for Drag Reduction 126 5.7 Biomimetic Designs and Processes of Slippery Surfaces 128 5.7.1 Pitcher-inspired Design of a Slippery Surface 128 5.7.2 Shark Skin-inspired Design for Drag Reduction 130 References 132 6 Self-healing Materials 135 6.1 Introduction 135 6.2 Wound Healing in Biological Systems 136 6.2.1 Self-healing via Microvascular Networks 136 6.2.2 Self-healing with Microencapsulation/Micropipe Systems in Plants 138 6.2.3 Skeleton/Bone Healing Mechanism 140 6.2.4 Tree Bark Healing Mechanism 141 6.2.5 Bioinspired Self-healing Strategies 142 6.3 Bioinspired Self-healing Materials 144 6.3.1 Self-healing Materials with Vascular Networks 144 6.3.2 Biomimetic Self-healing with Microencapsulation Systems 146 6.3.3 Biomimetic Self-healing with Hollow Fiber Systems 148 6.3.4 Self-healing Brittle Materials Mimicking Bone and Tree Bark Healing 149 6.3.5 Bacteria-mediated Self-healing Concretes 151 References 152 Part II Biomimetic Functional Materials and Processing 155 7 Self-cleaning Materials and Surfaces 157 7.1 Introduction 157 7.2 Fundamentals of Wettability and Self-cleaning 158 7.3 Self-cleaning in Nature 160 7.3.1 Lotus Effect: Superhydrophobicity-induced Self-cleaning 160 7.3.2 Slippery Surfaces: Superhydrophilicity-induced Self-cleaning 162 7.3.3 Self-cleaning in Fibrillar Adhesive Systems 164 7.3.4 Self-cleaning in Soft Film Adhesive Systems 168 7.3.5 Underwater Organisms: Self-cleaning Surfaces 169 7.3.6 Biomimetic Strategies for Self-cleaning 171 7.4 Engineering Self-cleaning Materials and Processes via Bioinspiration 173 7.4.1 Lotus Effect–inspired Self-cleaning Surfaces and Fabrication 174 7.4.2 Superhydrophilically-based Self-cleaning Surfaces and Fabrication 178 7.4.3 Gecko-inspired Self-cleaning Dry Adhesives and Fabrication 180 7.4.4 Underwater Organisms–inspired Self-cleaning Surfaces and Fabrication 183 References 185 8 Stimuli-responsive Materials 188 8.1 Introduction 188 8.2 The Biological Models for Stimuli-responsive Materials 189 8.2.1 Actuation Mechanism in Muscles 189 8.2.2 Mechanically Stimulated Morphing Structures of Venus Flytraps 191 8.2.3 Sun Tracking: Heliotropic Plant Movements Induced by Photo Stimuli 194 8.2.4 Biomimetic Design Strategies for Stimuli-responsive Materials 196 8.3 Biomimetic Synthetic Stimuli-responsive Materials and Processes 198 8.3.1 Motor Molecules as Artificial Muscle: Bottom-up Approach 198 8.3.2 Electroactive Polymers as Artificial Muscle: Top-down Approach 199 8.3.3 Venus Flytrap Mimicking Nastic Materials 202 8.3.4 Biomimetic Light-tracking Materials 203 References 207 9 Photonic Materials 210 9.1 Introduction 210 9.2 Structural Colors in Nature 211 9.2.1 One-dimensional Diffraction Gratings 213 9.2.2 Multilayer Reflectors 214 9.2.3 Two-dimensional Photonic Materials 215 9.2.4 Three-dimensional Photonic Crystals 217 9.2.5 Tunable Structural Color in Organisms 218 9.3 Natural Antireflective Structures and Microlenses 220 9.3.1 Moth-eye Antireflective Structures 220 9.3.2 Brittlestar Microlens with Double-facet Lens 222 9.3.3 Biomimetic Strategies for Structural Colors and Antireflection 224 9.4 Bioinspired Structural Coloring Materials and Processes 224 9.4.1 Grating Nanostructures: Lamellar Ridge Arrays 227 9.4.2 Multilayer Photonic Nanostructures and Fabrication Approaches 229 9.4.3 Three-dimensional Photonic Crystals and Fabrication 230 9.4.4 Tunable Structural Colors of Bioinspired Photonic Materials 232 9.4.5 Electrically and Mechanically Tunable Opals 233 9.5 Bioinspired Antireflective Surfaces and Microlenses 233 References 236 10 Catalysts for Renewable Energy 240 10.1 Introduction 240 10.2 Catalysts for Energy Conversion in Biological Systems 242 10.2.1 Biological Catalysts in Biological “Fuel Cells” 242 10.2.2 Oxygen Evolution Catalyzed by Water-oxidizing Complex 242 10.2.3 Biological Hydrogen Production with Hydrogenase Enzymes 245 10.2.4 Natural Photosynthesis and Enzymes 245 10.2.5 Biomimetic Design Principles for Efficient Catalytic Materials 247 10.3 Bioinspired Catalytic Materials and Processes 248 10.3.1 Bioinspired Catalyst for Hydrogen Fuel Cells 249 10.3.2 WOC-biomimetic Catalysts for Oxygen Evalution Reactions in Water Splitting 255 10.3.3 Hydrogenase-biomimetic Catalysts for Hydrogen Generation 259 10.3.4 Artificial Photosynthesis 261 References 266 Part III Biomimetic Processing 271 11 Biomineralization and Biomimetic Materials Processing 273 11.1 Introduction 273 11.2 Materials Processing in Biological Systems 274 11.2.1 Biomineralization 274 11.2.2 Surface-directed Biomineralization 277 11.2.3 Enzymatic Biomineralization 278 11.2.4 Organic Matrix-templated Biomineralization 279 11.2.5 Homeostasis and Storage of Metallic Nanoparticles 282 11.2.6 Bioinspired Strategies for Synthesizing Processes 282 11.3 Biomimetic Materials Processes 284 11.3.1 Synthesis of Mineralized Collagen Fibrils with Macromolecular Templates 284 11.3.2 Synthesis of Nanoparticles and Films Catalyzed with Silicatein 286 11.3.3 Synthesis of Magnetite using Natural and Synthetic Proteins 288 11.3.4 Nanofabrication of Barium Titanate using Artificial Proteins 290 11.3.5 Protein-assisted Nanofabrication of Metal Nanoparticles 292 References 294 Index 298

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Table of ContentsList of Contributors xiii Foreword xvii Preface xix 1 Contemporary Protein Analysis by Ion Mobility Mass Spectrometry 1Johannes P.C. Vissers and James I. Langridge 1.1 Introduction 1 1.2 Traveling-Wave Ion Mobility Mass Spectrometry 1 1.3 IM–MS and LC–IM–MS Analysis of Simple and Complex Mixtures 2 1.4 Outlook 7 Acknowledgment 8 References 8 2 High-Resolution Accurate Mass Orbitrap and Its Application in Protein Therapeutics Bioanalysis 11Hongxia Wang and Patrick Bennett 2.1 Introduction 11 2.2 Triple Quadrupole Mass Spectrometer and Its Challenges 11 2.3 High-Resolution Mass Spectrometers 12 2.4 Quantitation Modes on Q Exactive Hybrid Quadrupole Orbitrap 13 2.5 Protein Quantitation Approaches Using Q Exactive Hybrid Quadrupole Orbitrap 14 2.6 Data Processing 16 2.7 Other Factors That Impact LC–MS-based Quantitation 16 2.8 Conclusion and Perspectives of LC–HRMS in Regulated Bioanalysis 18 References 18 3 Current Methods for the Characterization of Posttranslational Modifications in Therapeutic Proteins Using Orbitrap Mass Spectrometry 21Zhiqi Hao, Qiuting Hong, Fan Zhang, Shiaw-Lin Wu, and Patrick Bennett 3.1 Introduction 21 3.2 Characterization of PTMs Using Higher-Energy Collision Dissociation 23 3.3 Application of Electron Transfer Dissociation to the Characterization of Labile PTMs 26 3.4 Conclusion 31 Acknowledgment 32 References 32 4 Macro- to Micromolecular Quantitation of Proteins and Peptides by Mass Spectrometry 35Suma Ramagiri, Brigitte Simons, and Laura Baker 4.1 Introduction 35 4.2 Key Challenges of Peptide Bioanalysis 36 4.3 Key Features of LC/MS/MS-Based Peptide Quantitation 38 4.4 Advantages of the Diversity of Mass Spectrometry Systems 41 4.5 Perspectives for the Future 41 References 42 5 Peptide and Protein Bioanalysis Using Integrated Column-to-Source Technology for High-Flow Nanospray 45Shane R. Needham and Gary A. Valaskovic 5.1 Introduction – LC–MS Has Enabled the Field of Protein Biomarker Discovery 45 5.2 Integration of Miniaturized LC with Nanospray ESI-MS Is a Key for Success 46 5.3 Micro- and Nano-LC Are Well Suited for Quantitative Bioanalysis 47 5.4 Demonstrating Packed-Emitter Columns Are Suitable for Bioanalysis 49 5.5 Future Outlook 51 References 52 6 Targeting the Right Protein Isoform: Mass Spectrometry-Based Proteomic Characterization of Alternative Splice Variants 55Jiang Wu 6.1 Introduction 55 6.2 Alternative Splicing and Human Diseases 55 6.3 Identification of Splice Variant Proteins 56 6.4 Conclusion 64 References 64 7 The Application of Immunoaffinity-Based Mass Spectrometry to Characterize Protein Biomarkers and Biotherapeutics 67Bradley L. Ackermann and Michael J. Berna 7.1 Introduction 67 7.2 Overview of IA-MS Methods 69 7.3 IA-MS Applications – Biomarkers 74 7.3.1 Peptide Biomarkers 74 7.4 IA-MS Applications – Biotherapeutics 81 7.5 Future Direction 84 References 85 8 Semiquantification and Isotyping of Antidrug Antibodies by Immunocapture-LC/MS for Immunogenicity Assessment 91Jianing Zeng, Hao Jiang, and Linlin Luo 8.1 Introduction 91 8.2 Multiplexing Direct Measurement of ADAs by Immunocapture-LC/MS for Immunogenicity Screening, Titering, and Isotyping 93 8.3 Indirect Measurement of ADAs by Quantifying ADA Binding Components 95 8.4 Use of LC–MS to Assist in Method Development of Cell-Based Neutralizing Antibody Assays 96 8.5 Conclusion and Future Perspectives 97 References 97 9 Mass Spectrometry-Based Assay for High-Throughput and High-Sensitivity Biomarker Verification 99Xuejiang Guo and Keqi Tang 9.1 Background 99 9.2 Sample Processing Strategies 100 9.3 Advanced Electrospray Ionization Mass Spectrometry Instrumentation 102 9.4 Conclusion 105 References 105 10 Monitoring Quality of Critical Reagents Used in Ligand Binding Assays with Liquid Chromatography Mass Spectrometry (LC–MS) 107Brian Geist, Adrienne Clements-Egan, and Tong-Yuan Yang 10.1 Introduction 107 10.2 Case Study Examples 114 10.3 Discussion 122 Acknowledgment 126 References 126 11 Application of Liquid Chromatography-High Resolution Mass Spectrometry in the Quantification of Intact Proteins in Biological Fluids 129Stanley (Weihua) Zhang, Jonathan Crowther, and Wenying Jian 11.1 Introduction 129 11.2 Workflows for Quantification of Proteins Using Full-Scan LC-HRMS 131 11.3 Internal Standard Strategy 133 11.4 Calibration and Quality Control (QC) Sample Strategy 135 11.5 Common Issues in Quantification of Proteins Using LC-HRMS 135 11.6 Examples of LC-HRMS-Based Intact Protein Quantification 137 11.7 Conclusion and Future Perspectives 138 Acknowledgment 140 References 140 12 LC–MS/MS Bioanalytical Method Development Strategy for Therapeutic Monoclonal Antibodies in Preclinical Studies 145Hongyan Li, Timothy Heath, and Christopher A. James 12.1 Introduction: LC-MS/MS Bioanalysis of Therapeutic Monoclonal Antibodies 145 12.2 Highlights of Recent Method Development Strategies 146 12.3 Case Studies of Preclinical Applications of LC–MS/MS for Monoclonal Antibody Bioanalysis 154 12.4 Conclusion and Future Perspectives 156 References 158 13 Generic Peptide Strategies for LC–MS/MS Bioanalysis of Human Monoclonal Antibody Drugs and Drug Candidates 161Michael T. Furlong 13.1 Introduction 161 13.2 A Universal Peptide LC–MS/MS Assay for Bioanalysis of a Diversity of Human Monoclonal Antibodies and Fc Fusion Proteins in Animal Studies 161 13.3 An Improved “Dual” Universal Peptide LC–MS/MS Assay for Bioanalysis of Human mAb Drug Candidates in Animal Studies 165 13.4 Extending the Universal Peptide Assay Concept to Human mAb Bioanalysis in Human Studies 170 13.5 Internal Standard Options for Generic Peptide LC–MS/MS Assays 173 13.6 Sample Preparation Strategies for Generic Peptide LC–MS/MS Assays 175 13.7 Limitations of Generic Peptide LC–MS/MS Assays 177 13.8 Conclusion 178 Acknowledgments 178 References 178 14 Mass Spectrometry-Based Methodologies for Pharmacokinetic Characterization of Antibody Drug Conjugate Candidates During Drug Development 183Yongjun Xue, Priya Sriraman, Matthew V. Myers, Xiaomin Wang, Jian Chen, Brian Melo, Martha Vallejo, Stephen E. Maxwell, and Sekhar Surapaneni 14.1 Introduction 183 14.2 Mechanism of Action 183 14.3 Mass Spectrometry Measurement for DAR Distribution of Circulating ADCs 186 14.4 Total Antibody Quantitation by Ligand Binding or LC–MS/MS 189 14.5 Total Conjugated Drug Quantitation by Ligand Binding or LC–MS/MS 193 14.6 Catabolite Quantitation by LC–MS/MS 196 14.7 Preclinical and Clinical Pharmacokinetic Support 197 14.8 Conclusion and Future Perspectives 198 References 198 15 Sample Preparation Strategies for LC–MS Bioanalysis of Proteins 203Long Yuan and Qin C. Ji 15.1 Introduction 203 15.2 Sample Preparation Strategies to Improve Assay Sensitivity 205 15.3 Sample Preparation Strategies to Differentiate Free, Total, and ADA-Bound Proteins 213 15.4 Sample Preparation Strategies to Overcome Interference from Antidrug Antibodies or Soluble Target 214 15.5 Protein Digestion Strategies 214 15.6. Conclusion 215 Acknowledgment 216 References 216 16 Characterization of Protein Therapeutics by Mass Spectrometry 221Wei Wu, Hangtian Song, Thomas Slaney, Richard Ludwig, Li Tao, and Tapan Das 16.1 Introduction 221 16.2 Variants Associated with Cysteine/Disulfide Bonds in Protein Therapeutics 221 16.3 N–C-Terminal Variants 225 16.4 Glycation 226 16.5 Oxidation 226 16.6 Discoloration 228 16.7 Sequence Variants 230 16.8 Glycosylation 232 16.9 Conclusion 240 References 240 Index 251

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Book SynopsisFeatures a solid foundation of mathematical and computational tools to formulate and solve real-world PDE problems across various fields With a step-by-step approach to solving partial differential equations (PDEs), Differential Equation Analysis in Biomedical Science and Engineering: Partial Differential Equation Applications with R successfully applies computational techniques for solving real-world PDE problems that are found in a variety of fields, including chemistry, physics, biology, and physiology. The book provides readers with the necessary knowledge to reproduce and extend the computed numerical solutions and is a valuable resource for dealing with a broad class of linear and nonlinear partial differential equations. The author's primary focus is on models expressed as systems of PDEs, which generally result from including spatial effects so that the PDE dependent variables are functions of both space and time, unlike ordinary differential equaTable of ContentsPreface ix 1. Introduction to Partial Differentiation Equation Analysis: Chemotaxis 1 2. Pattern Formation 43 3. Belousov–Zhabotinskii Reaction System 103 4. Hodgkin–Huxley and Fitzhugh–Nagumo Models 127 5. Anesthesia Spatiotemporal Distribution 163 6. Influenza with Vaccination and Diffusion 207 7. Drug Release Tracking 243 8. Temperature Distributions in Cryosurgery 287 Index 323

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Book SynopsisEssentials of Machine Olfaction and Taste This book provides a valuable information source for olfaction and taste which includes a comprehensive and timely overview of the current state of knowledge of use for olfaction and taste machines Presents original, latest research in the field, with an emphasis on the recent development of human interfacingCovers the full range of artificial chemical senses including olfaction and taste, from basic through to advanced levelTimely project in that mobile robots, olfactory displays and odour recorders are currently under research, driven by commercial demandTable of ContentsPreface xi About the Contributors xiii 1 Introduction to Essentials of Machine Olfaction and Tastes 1Takamichi Nakamoto 2 Physiology of Chemical Sense and its Biosensor Application 3Ryohei Kanzaki, Kei Nakatani, Takeshi Sakurai, Nobuo Misawa and Hidefumi Mitsuno 2.1 Introduction 3 2.2 Olfaction and Taste of Insects 4 2.2.1 Olfaction 4 2.2.1.1 Anatomy of Olfaction 4 2.2.1.2 Signal Transduction of Odor Signals 6 2.2.1.3 Molecular Biology of Olfaction 7 2.2.2 Taste 8 2.2.2.1 Anatomy of Taste 8 2.2.2.2 Molecular Biology and Signal Transduction of Taste 9 2.3 Olfaction and Taste of Vertebrate 11 2.3.1 Olfaction 11 2.3.1.1 Anatomy of Olfaction 11 2.3.1.2 Transduction of Odor Signals 12 2.3.1.3 Molecular Biology of Olfaction 15 2.3.2 Taste 17 2.3.2.1 Anatomy of Taste 17 2.3.2.2 Transduction of Taste Signals 18 2.3.2.3 Molecular Biology of Taste 20 2.4 Cell‐Based Sensors and Receptor‐Based Sensors 21 2.4.1 Tissue‐Based Sensors 23 2.4.2 Cell‐Based Sensors 26 2.4.3 Receptor‐Based Sensors 30 2.4.3.1 Production of Odorant Receptors 34 2.4.3.2 Immobilization of Odorant Receptors 35 2.4.3.3 Measurement from Odorant Receptors 36 2.4.4 Summary of the Biosensors 41 2.5 Future Prospects 42 References 43 3 Large‐Scale Chemical Sensor Arrays for Machine Olfaction 49Mara Bernabei, Simone Pantalei and Krishna C. Persaud 3.1 Introduction 49 3.2 Overview of Artificial Olfactory Systems 50 3.3 Common Sensor Technologies Employed in Artificial Olfactory Systems 53 3.3.1 Metal‐Oxide Gas Sensors 53 3.3.2 Piezoelectric Sensors 54 3.3.3 Conducting Polymer Sensors 55 3.4 Typical Application of “Electronic Nose” Technologies 58 3.5 A Comparison between Artificial and the Biological Olfaction Systems 58 3.6 A Large‐Scale Sensor Array 59 3.6.1 Conducting Polymers 60 3.6.2 Sensor Interrogation Strategy 62 3.6.3 Sensor Substrate 64 3.7 Characterization of the Large‐Scale Sensor Array 68 3.7.1 Pure Analyte Study: Classification and Quantification Capability 69 3.7.2 Binary Mixture Study: Segmentation and Background Suppression Capability 75 3.7.3 Polymer Classes: Testing Broad and Overlapping Sensitivity, High Level of Redundancy 76 3.7.4 System Robustness and Long‐Term Stability 77 3.8 Conclusions 79 Acknowledgment80 References 80 4 Taste Sensor: Electronic Tongue with Global Selectivity 87Kiyoshi Toko, Yusuke Tahara, Masaaki Habara, Yoshikazu Kobayashi and Hidekazu Ikezaki 4.1 Introduction 87 4.2 Electronic Tongues 90 4.3 Taste Sensor 92 4.3.1 Introduction 92 4.3.2 Principle 93 4.3.3 Response Mechanism 93 4.3.4 Measurement Procedure 97 4.3.5 Sensor Design Techniques 98 4.3.6 Basic Characteristics 103 4.3.6.1 Threshold 106 4.3.6.2 Global Selectivity 106 4.3.6.3 High Correlation with Human Sensory Scores 108 4.3.6.4 Definition of Taste Information 109 4.3.6.5 Detection of Interactions between Taste Substances 110 4.3.7 Sample Preparation 111 4.3.8 Analysis 112 4.4 Taste Substances Adsorbed on the Membrane 116 4.5 Miniaturized Taste Sensor 117 4.6 Pungent Sensor 122 4.7 Application to Foods and Beverages 124 4.7.1 Introduction 124 4.7.2 Beer 124 4.7.3 Coffee 127 4.7.4 Meat 132 4.7.5 Combinatorial Optimization Technique for Ingredients and Qualities Using a GA 134 4.7.5.2 Ga 134 4.7.5.3 Constrained Nonlinear Optimization 137 4.7.6 For More Effective Use of “Taste Information” 137 4.7.6.1 Key Concept 138 4.7.6.2 Taste Attributes or Qualities become Understandable and Translatable When They Are Simplified 138 4.7.6.3 Simplification of Large Numbers of Molecules into a Couple of Taste Qualities Allows Mathematical Optimization 140 4.7.6.4 Summary 141 4.8 Application to Medicines 141 4.8.1 Introduction 141 4.8.2 Bitterness Evaluation of APIs and Suppression Effect of Formulations 141 4.8.3 Development of Bitterness Sensor for Pharmaceutical Formulations 143 4.8.3.1 Sensor Design 143 4.8.3.2 Prediction of Bitterness Intensity and Threshold 144 4.8.3.3 Applications to Orally Disintegrating Tablets 146 4.8.3.4 Response Mechanism to APIs 154 4.8.4 Evaluation of Poorly Water‐Soluble Drugs 156 4.9 Perspectives 160 References 163 5 Pattern Recognition 175Saverio De Vito, Matteo Falasconi and Matteo Pardo 5.1 Introduction 175 5.2 Application Frameworks and Their Challenges 176 5.2.1 Common Challenges 176 5.2.2 Static In‐Lab Applications 177 5.2.3 On‐Field Applications 178 5.3 Unsupervised Learning and Data Exploration 180 5.3.1 Feature Extraction: Static and Dynamic Characteristics 180 5.3.2 Exploratory Data Analysis 184 5.3.3 Cluster Analysis 189 5.4 Supervised Learning 190 5.4.1 Classification: Detection and Discrimination of Analytes and Mixtures of Volatiles 192 5.4.2 Regression: Machine Olfaction Quantification Problems and Solutions 196 5.4.3 Feature Selection 200 5.5 Advanced Topics 202 5.5.1 System Instability Compensation 202 5.5.2 Calibration Transfer 208 5.6 Conclusions 210 References 211 6 Using Chemical Sensors as “Noses” for Mobile Robots 219Hiroshi Ishida, Achim J. Lilienthal, Haruka Matsukura, Victor Hernandez Bennetts and Erik Schaffernicht 6.1 Introduction 219 6.2 Task Descriptions 220 6.2.1 Definitions of Tasks 220 6.2.2 Characteristics of Turbulent Chemical Plumes 222 6.3 Robots and Sensors 224 6.3.1 Sensors for Gas Detection 224 6.3.2 Airflow Sensing 225 6.3.3 Robot Platforms 226 6.4 Characterization of Environments 226 6.5 Case Studies 230 6.5.1 Chemical Trail Following 230 6.5.2 Chemotactic Search versus Anemotactic Approach 232 6.5.3 Attempts to Improve Gas Source Localization Robots 236 6.5.4 Flying, Swimming, and Burrowing Robots 238 6.5.5 Gas Distribution Mapping 239 6.6 Future Prospective 241 Acknowledgment242 References 242 7 Olfactory Display and Odor Recorder 247Takamichi Nakamoto 7.1 Introduction 247 7.2 Principle of Olfactory Display 247 7.2.1 Olfactory Display Device 248 7.2.2 Olfactory Display Related to Spatial Distribution of Odor 250 7.2.3 Temporal Intensity Change of Odor 251 7.2.3.1 Problem of Smell Persistence 251 7.2.3.2 Olfactory Display Using Inkjet Device 254 7.2.4 Multicomponent Olfactory Display 256 7.2.4.1 Mass Flow Controller 256 7.2.4.2 Automatic Sampler 256 7.2.4.3 Solenoid Valve 258 7.2.4.4 Micropumps and Surface Acoustic Wave Atomizer 260 7.2.5 Cross Modality Interaction 261 7.3 Application of Olfactory Display 263 7.3.1 Entertainment 263 7.3.2 Olfactory Art 265 7.3.3 Advertisement 266 7.3.4 Medical Field 266 7.4 Odor Recorder 267 7.4.1 Background of Odor Recorder 267 7.4.2 Principle of Odor Recorder 268 7.4.3 Mixture Quantification Method 271 7.5.1 Odor Approximation 274 7.5.2 MIMO Feedback Method 276 7.5.3 Method to Increase Number of Odor Components 278 7.5.3.1 SVD Method 278 7.5.3.2 Two‐Level Quantization Method 280 7.5.4 Dynamic Method 283 7.5.4.1 Real‐Time Reference Method 284 7.5.4.2 Concurrent Method 287 7.5.5 Mixture Quantification Using Huge Number of Odor Candidates 289 7.6 Exploration of Odor Components 292 7.6.1 Introduction of Odor Components 292 7.6.2 Procedure for Odor Approximation 293 7.6.3 Simulation of Odor Approximation 295 7.6.4 Experiment on Essential Oil Approximation 297 7.6.5 Comparison of Distance Measure 301 7.6.6 Improvement of Odor Approximation 303 7.7 Teleolfaction 305 7.7.1 Concept of Teleolfaction 305 7.7.2 Implementation of Teleolfaction System 306 7.7.3 Experiment on Teleolfaction 307 7.8 Summary 308 References 309 8 Summary and Future Perspectives 315Takamichi Nakamoto Index 317

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

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

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

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

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

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

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

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

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

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

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