Chemical biology Books

Book SynopsisEcotoxicology offers a comprehensive overview of the science underpinning the recognition and management of environmental contamination. It describes the toxicology of environmental contaminants, the methods used for assessing their toxicity and ecological impacts, and approaches employed to mitigate pollution and ecological health risks globally. Chapters cover the latest advances in research, including genomics, natural toxins, endocrine disruption and the toxicology of radioactive substances. The second half of the book focuses on applications, such as cradle-to-grave effects of selected industries, legal and economic approaches to environmental regulation, ecological risk assessment, and contaminated site remediation. With short capsules written by invited experts, numerous case studies from around the world and further reading lists, this textbook is designed for advanced undergraduate and graduate one-semester courses. It is also a valuable reference for graduate students and professionals. Online resources for instructors and students are also available.Table of ContentsPreamble; Preface; Part I. Approaches and Methods: 1. The history and emergence of ecotoxicology as a science Pamela Welbourn and Peter V. Hodson; 2. Measuring toxicity Peter V. Hodson and David A. Wright; 3. Contaminant uptake and bioaccumulation: mechanisms, kinetics and modelling Peter G. C. Campbell, Peter V. Hodson, Pamela M. Welbourn, David A. Wright; 4. Methods in ecotoxicology Peter. V. Hodson and David W. Wright; 5 Ecotoxicogenomics Valérie S. Langlois and Christopher J. Martyniuk; Part II. Toxicology of Individual Substances: 6. Metals and metalloids Peter G. C. Campbell, Pamela M. Welbourn and Christopher D. Metcalfe; 7. Organic compounds Christopher D. Metcalfe, David A. Wright, Peter V. Hodson; 8. Endocrine disrupting chemicals Christopher D. Metcalfe, Christopher J. Martyniuk, Valérie S. Langlois, and David A. Wright; 9. Natural toxins David A. Wright and Pamela M. Welbourn; 10. Ionising radiation Louise Winn; Part III. Complex Issues: 11. Complex issues, multiple stressors and lessons learned Pamela M. Welbourn, Peter G. C. Campbell, Peter V. Hodson and Christopher D. Metcalfe) 12. Regulatory toxicology and ecological risk assessment Peter V. Hodson, Pamela Welbourn and Peter G. C. Campbell; 13. Recovery of contaminated sites Pamela M. Welbourn and Peter V. Hodson; 14. Emerging concerns and future visions David A. Wright and Peter G. C. Campbell; Index.

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Book SynopsisSynthetic biology is the technique that enables us not just to read and edit but also write DNA to program living biological structures as though they were tiny computers. Unlike cloning Dolly the sheep-which cut and copied existing genetic material-the future of synthetic biology might be something like an app store, where you could download and add new capabilities into any cell, microbe, plant, or animal.This breakthrough science has the potential to mitigate, perhaps solve, humanity's immediate and longer-term existential challenges: climate change; the feeding, clothing, housing, and caring for billions of humans; fighting the next viral outbreak before it becomes a global pandemic; old age as a treatable pathology; bringing back extinct animals.It could also be anarchic and socially destructive. With our governing structures created in an era before startling advances in technology, we are not prepared for a future in which life could be manipulated or programmed.As futurist Amy Webb and synthetic biologist Andrew Hessel show in this book, within the next decade, we will need to make important decisions: whether to program novel viruses to fight diseases, what genetic privacy will look like, who will "own" living organisms, how companies should earn revenue from engineered cells, and how to contain a synthetic organism in a lab. The Genesis Machine? provides the background for us to understand and grapple with these issues, and think through the religious, philosophical, and ethical implications for the future.

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Book SynopsisAuthored by leading experts in the enzymology of natural product biosynthesis, this completely revised and updated edition provides a description of the types of natural products, the biosynthetic pathways that enable the production of these molecules, and an update on the discovery of novel products in the post-genomic era. Although some 500 000 – 600 000 natural products have been isolated and characterized over the past two centuries, there may be a 10-fold greater inventory awaiting immediate exploration based on biosynthetic gene cluster predictions. The approach of this book is to codify the chemical logic that underlies each natural product structural class as they are assembled from building blocks of primary metabolism. This second edition integrates many new findings into the sets of principles of the first edition that parsed categories of natural product chemistries into the underlying enzymatic mechanisms and the catalytic machinery for building the varied and complex end product metabolites. New chapters include evaluation of a core set of thermodynamically activated but kinetically stable metabolites that power both primary and secondary metabolic pathways. Also, after decades of uncertainty about the existence of various pericyclase classes, a series of genome mining, heterologous expression, and enzymatic activity characterization have validated a plethora of pericyclases over the past decade. The several types of pericyclases are involved in biosynthetic complexity generation of almost every major category of natural products. This text will serve as a reference point for chemists of every subdiscipline, including synthetic organic chemists and medicinal chemists. It will also be valuable to bioinformatic and computational biologists, pharmacognocists and chemical ecologists, and bioengineers and synthetic biologists.Table of ContentsMajor Classes of Natural Product Scaffolds and Enzymatic Biosynthetic Machinery; The Chemical Logic for Major Reaction Types; Polyketide Natural Products; Peptide Natural Products I: RiPPs; Peptide Natural Products II: Nonribosomal Peptides; Isoprenoids/Terpenes; Alkaloids I; Purine- and Pyrimidine-derived Natural Products; Phenylpropanoid Natural Product Biosynthesis; Alkaloids II: Indole Terpenes; Natural Product Oligosaccharides and Glycosides; Oxygenases, Thwarted Oxygenases, and Oxygen-dependent Halogenases; S-Adenosylmethionine; Pericyclases in Natural Product Biosynthesis; Natural Products Isolation and Characterization: Gene-independent Approaches; Natural Products in the Post Genomic Era

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Book SynopsisA balanced presentation of the concepts of physical chemistry, and their applications to biology and biochemistry. Written to straddle the worlds of physical chemistry and the life sciences, it shows how the tools of physical chemistry can elucidate biological questions.Table of ContentsFocus 1: Biochemical Thermodynamics: The First Law Focus 2: Biochemical Thermodynamics: The Second Law Focus 3: Water and Aqueous solutions Focus 4: Chemical equilibrium Focus 5: Ion and Electron Transport Focus 6: The Rates of Reactions Focus 7: Biochemical kinetics Focus 8: Atoms Focus 9: Molecules Focus 10: Macromolecules and self-assembly Focus 11: Biochemical spectroscopy Focus 12: Scattering techniques Focus 13: Gravimetric methods

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Book SynopsisThis collection explores the latest advances in riboregulators, such as RNA-only systems and ribonucleoprotein systems, and provides detailed techniques to study, evolve, and design them. Beginning with a set of chapters focused on the design and application of small RNA (sRNA) regulator systems, the book continues with sections on techniques to create switchable riboregulator systems known as riboswitches, technologies that leverage RNA-guided CRISPR-Cas systems to edit the epigenome, control gene expression, and create diagnostics, as well as computational and experimental techniques to investigate the sequence-structure-function relationship of RNA systems that can both advance fundamental understanding and rational design of riboregulators. 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 Table of Contents1. RNP-Based Control Systems for Genetic Circuits in Synthetic Biology Beyond CRISPR Trevor. R Simmons, Andrew D. Ellington, and Lydia M. Contreras 2. Computational Design of RNA Toehold-Mediated Translation Activators Kaiyue Wu, Zhaoqing Yan, and Alexander A. Green 3. Design of RNA-Based Translational Repressors Seongho Hong, Dongwon Park, Soma Chaudhary, Griffin McCutcheon, Alexander A. Green, and Jongmin Kim 4. Design of Ribocomputing Devices for Complex Cellular Logic Griffin McCutcheon, Soma Chaudhary, Seongho Hong, Dongwon Park, Jongmin Kim, and Alexander A. Green 5. Computational Design of Small Transcription Activating RNAs (STARs) Baiyang Liu and James Chappell 6. Design and Assembly of Multi-Level Transcriptional and Translational Regulators for Stringent Control of Gene Expression F. Veronica Greco, Thea Irvine, Claire S. Grierson, and Thomas E. Gorochowski 7. Model-Based Design of Synthetic Antisense RNA for Predictable Gene Repression Tae Seok Moon 8. Design of a Toolbox of RNA Thermometers Shaunak Sen, Abhilash Patel, and Krishan Kumar Gola 9. Development of Synthetic Riboswitches to Guide the Evolution of Metabolite Production in Microorganisms Minsun Kim, Sungho Jang, and Gyoo Yeol Jung 10. Efficient Method to Identify Synthetic Riboswitches Using RNA-Based Capture-SELEX Combined with In Vivo Screening Janice Kramat and Beatrix Suess 11. RNA Design Principles for Riboswitches that Regulate RNase P-Mediated tRNA Processing Anna Ender, Peter Stadler, Mario Mörl, and Sven Findeiß 12. Design, Characterization, and Application of Targeted Gene Activation in Bacteria Using a Modular CRISPRa System Maria Claudia Villegas Kcam and James Chappell 13. Reprogramming TracrRNAs for In Vitro RNA Detection and In Vivo Transcriptional Recording Chunlei Jiao and Chase L. Beisel 14. Harnessing CRISPR-Cas9 for Epigenetic Engineering Rosa S. Guerra-Resendez and Isaac B. Hilton 15. RNA Structure Prediction, Analysis, and Design: An Introduction to Web-Based Tools Raphael Angelo I. Zambrano, Carmen Hernandez-Perez, and Melissa K. Takahashi 16. Single-Molecule FRET Studies of RNA Structural Rearrangements and RNA-RNA Interactions Ewelina M. Małecka, Boyang Hua, and Sarah A. Woodson 17. Cotranscriptional RNA Chemical Probing Courtney E. Szyjka and Eric J. Strobel

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Book SynopsisMultiblock Data Fusion in Statistics and Machine Learning Explore the advantages and shortcomings of various forms of multiblock analysis, and the relationships between them, with this expert guide Arising out of fusion problems that exist in a variety of fields in the natural and life sciences, the methods available to fuse multiple data sets have expanded dramatically in recent years. Older methods, rooted in psychometrics and chemometrics, also exist. Multiblock Data Fusion in Statistics and Machine Learning: Applications in the Natural and Life Sciences is a detailed overview of all relevant multiblock data analysis methods for fusing multiple data sets. It focuses on methods based on components and latent variables, including both well-known and lesser-known methods with potential applications in different types of problems. Many of the included methods are illustrated by practical examples and are accompanied by a freely available R-package. TTable of ContentsForeword xiii Preface xv List of Figures xvii List of Tables xxxi Part I Introductory Concepts and Theory 1 1 Introduction 3 1.1 Scope of the Book 3 1.2 Potential Audience 4 1.3 Types of Data and Analyses 5 1.3.1 Supervised and Unsupervised Analyses 5 1.3.2 High-, Mid- and Low-level Fusion 5 1.3.3 Dimension Reduction 7 1.3.4 Indirect Versus Direct Data 8 1.3.5 Heterogeneous Fusion 8 1.4 Examples 8 1.4.1 Metabolomics 8 1.4.2 Genomics 11 1.4.3 Systems Biology 13 1.4.4 Chemistry 13 1.4.5 Sensory Science 15 1.5 Goals of Analyses 16 1.6 Some History 17 1.7 Fundamental Choices 17 1.8 Common and Distinct Components 19 1.9 Overview and Links 20 1.10 Notation and Terminology 21 1.11 Abbreviations 22 2 Basic Theory and Concepts 25 2.i General Introduction 25 2.1 Component Models 25 2.1.1 General Idea of Component Models 25 2.1.2 Principal Component Analysis 26 2.1.3 Sparse PCA 30 2.1.4 Principal Component Regression 31 2.1.5 Partial Least Squares 32 2.1.6 Sparse PLS 36 2.1.7 Principal Covariates Regression 37 2.1.8 Redundancy Analysis 38 2.1.9 Comparing PLS, PCovR and RDA 38 2.1.10 Generalised Canonical Correlation Analysis 38 2.1.11 Simultaneous Component Analysis 39 2.2 Properties of Data 39 2.2.1 Data Theory 39 2.2.2 Scale-types 42 2.3 Estimation Methods 44 2.3.1 Least-squares Estimation 44 2.3.2 Maximum-likelihood Estimation 45 2.3.3 Eigenvalue Decomposition-based Methods 47 2.3.4 Covariance or Correlation-based Estimation Methods 47 2.3.5 Sequential Versus Simultaneous Methods 48 2.3.6 Homogeneous Versus Heterogeneous Fusion 50 2.4 Within- and Between-block Variation 52 2.4.1 Definition and Example 52 2.4.2 MAXBET Solution 54 2.4.3 MAXNEAR Solution 54 2.4.4 PLS2 Solution 55 2.4.5 CCA Solution 55 2.4.6 Comparing the Solutions 56 2.4.7 PLS, RDA and CCA Revisited 56 2.5 Framework for Common and Distinct Components 60 2.6 Preprocessing 63 2.7 Validation 64 2.7.1 Outliers 64 2.7.1.1 Residuals 64 2.7.1.2 Leverage 66 2.7.2 Model Fit 67 2.7.3 Bias-variance Trade-off 69 2.7.4 Test Set Validation 70 2.7.5 Cross-validation 72 2.7.6 Permutation Testing 75 2.7.7 Jackknife and Bootstrap 76 2.7.8 Hyper-parameters and Penalties 77 2.8 Appendix 78 3 Structure of Multiblock Data 87 3.i General Introduction 87 3.1 Taxonomy 87 3.2 Skeleton of a Multiblock Data Set 87 3.2.1 Shared Sample Mode 88 3.2.2 Shared Variable Mode 88 3.2.3 Shared Variable or Sample Mode 88 3.2.4 Shared Variable and Sample Mode 89 3.3 Topology of a Multiblock Data Set 90 3.3.1 Unsupervised Analysis 90 3.3.2 Supervised Analysis 93 3.4 Linking Structures 95 3.4.1 Linking Structure for Unsupervised Analysis 95 3.4.2 Linking Structures for Supervised Analysis 96 3.5 Summary 98 4 Matrix Correlations 99 4.i General Introduction 99 4.1 Definition 99 4.2 Most Used Matrix Correlations 101 4.2.1 Inner Product Correlation 101 4.2.2 GCD coefficient 101 4.2.3 RV-coefficient 102 4.2.4 SMI-coefficient 102 4.3 Generic Framework of Matrix Correlations 104 4.4 Generalised Matrix Correlations 105 4.4.1 Generalised RV-coefficient 105 4.4.2 Generalised Association Coefficient 106 4.5 Partial Matrix Correlations 108 4.6 Conclusions and Recommendations 110 4.7 Open Issues 111 Part II Selected Methods for Unsupervised and Supervised Topologies 113 5 Unsupervised Methods 115 5.i General Introduction 115 5.ii Relations to the General Framework 115 5.1 Shared Variable Mode 117 5.1.1 Only Common Variation 117 5.1.1.1 Simultaneous Component Analysis 117 5.1.1.2 Clustering and SCA 123 5.1.1.3 Multigroup Data Analysis 125 5.1.2 Common, Local, and Distinct Variation 126 5.1.2.1 Distinct and Common Components 127 5.1.2.2 Multivariate Curve Resolution 130 5.2 Shared Sample Mode 133 5.2.1 Only Common Variation 133 5.2.1.1 SUM-PCA 133 5.2.1.2 Multiple Factor Analysis and STATIS 135 5.2.1.3 Generalised Canonical Analysis 136 5.2.1.4 Regularised Generalised Canonical Correlation Analysis 139 5.2.1.5 Exponential Family SCA 140 5.2.1.6 Optimal-scaling 143 5.2.2 Common, Local, and Distinct Variation 146 5.2.2.1 Joint and Individual Variation Explained 146 5.2.2.2 Distinct and Common Components 147 5.2.2.3 PCA-GCA 148 5.2.2.4 Advanced Coupled Matrix and Tensor Factorisation 153 5.2.2.5 Penalised-ESCA 156 5.2.2.6 Multivariate Curve Resolution 158 5.3 Generic Framework 159 5.3.1 Framework for Simultaneous Unsupervised Methods 159 5.3.1.1 Description of the Framework 159 5.3.1.2 Framework Applied to Simultaneous Unsupervised Data Analysis Methods 161 5.3.1.3 Framework of Common/Distinct Applied to Simultaneous Unsupervised Multiblock Data Analysis Methods 161 5.4 Conclusions and Recommendations 162 5.5 Open Issues 164 6 ASCA and Extensions 167 6.i General Introduction 167 6.ii Relations to the General Framework 167 6.1 ANOVA-Simultaneous Component Analysis 168 6.1.1 The ASCA Method 168 6.1.2 Validation of ASCA 176 6.1.2.1 Permutation Testing 176 6.1.2.2 Back-projection 178 6.1.2.3 Confidence Ellipsoids 178 6.1.3 The ASCA+ and LiMM-PCA Methods 181 6.2 Multilevel-SCA 182 6.3 Penalised-ASCA 183 6.4 Conclusions and Recommendations 185 6.5 Open Issues 186 7 Supervised Methods 187 7.i General Introduction 187 7.ii Relations to the General Framework 187 7.1 Multiblock Regression: General Perspectives 188 7.1.1 Model and Assumptions 188 7.1.2 Different Challenges and Aims 188 7.2 Multiblock PLS Regression 190 7.2.1 Standard Multiblock PLS Regression 190 7.2.2 MB-PLS Used for Classification 194 7.2.3 Sparse Multiblock PLS Regression (sMB-PLS) 196 7.3 The Family of SO-PLS Regression Methods (Sequential and Orthogonalised PLS Regression) 199 7.3.1 The SO-PLS Method 199 7.3.2 Order of Blocks 202 7.3.3 Interpretation Tools 202 7.3.4 Restricted PLS Components and their Application in SO-PLS 203 7.3.5 Validation and Component Selection 204 7.3.6 Relations to ANOVA 205 7.3.7 Extensions of SO-PLS to Handle Interactions Between Blocks 212 7.3.8 Further Applications of SO-PLS 215 7.3.9 Relations Between SO-PLS and ASCA 215 7.4 Parallel and Orthogonalised PLS (PO-PLS) Regression 217 7.5 Response Oriented Sequential Alternation 222 7.5.1 The ROSA Method 222 7.5.2 Validation 225 7.5.3 Interpretation 225 7.6 Conclusions and Recommendations 228 7.7 Open Issues 229 Part III Methods for Complex Multiblock Structures 231 8 Complex Block Structures; with Focus on L-Shape Relations 233 8.i General Introduction 233 8.ii Relations to the General Framework 234 8.1 Analysis of L-shape Data: General Perspectives 235 8.2 Sequential Procedures for L-shape Data Based on PLS/PCR and ANOVA 236 8.2.1 Interpretation of X1, Quantitative X2-data, Horizontal Axis First 236 8.2.2 Interpretation of X1, Categorical X2-data, Horizontal Axis First 238 8.2.3 Analysis of Segments/Clusters of X1 Data 240 8.3 The L-PLS Method for Joint Estimation of Blocks in L-shape Data 246 8.3.1 The Original L-PLS Method, Endo-L-PLS 247 8.3.2 Exo- Versus Endo-L-PLS 250 8.4 Modifications of the Original L-PLS Idea 252 8.4.1 Weighting Information from X3 and X1 in L-PLS Using a Parameter α252 8.4.2 Three-blocks Bifocal PLS 253 8.5 Alternative L-shape Data Analysis Methods 254 8.5.1 Principal Component Analysis with External Information 254 8.5.2 A Simple PCA Based Procedure for Using Unlabelled Data in Calibration 255 8.5.3 Multivariate Curve Resolution for Incomplete Data 256 8.5.4 An Alternative Approach in Consumer Science Based on Correlations Between X3 and X1 257 8.6 Domino PLS and More Complex Data Structures 258 8.7 Conclusions and Recommendations 258 8.8 Open Issues 260 Part IV Alternative Methods for Unsupervised and Supervised Topologies 261 9 Alternative Unsupervised Methods 263 9.i General Introduction 263 9.ii Relationship to the General Framework 263 9.1 Shared Variable Mode 263 9.2 Shared Sample Mode 265 9.2.1 Only Common Variation 265 9.2.1.1 DIABLO 265 9.2.1.2 Generalised Coupled Tensor Factorisation 266 9.2.1.3 Representation Matrices 267 9.2.1.4 Extended PCA 272 9.2.2 Common, Local, and Distinct Variation 273 9.2.2.1 Generalised SVD 273 9.2.2.2 Structural Learning and Integrative Decomposition 273 9.2.2.3 Bayesian Inter-battery Factor Analysis 275 9.2.2.4 Group Factor Analysis 276 9.2.2.5 OnPLS 277 9.2.2.6 Generalised Association Study 278 9.2.2.7 Multi-Omics Factor Analysis 278 9.3 Two Shared Modes and Only Common Variation 281 9.3.1 Generalised Procrustes Analysis 282 9.3.2 Three-way Methods 282 9.4 Conclusions and Recommendations 283 9.4.1 Open Issues 284 10 Alternative Supervised Methods 287 10.i General Introduction 287 10.ii Relations to the General Framework 287 10.1 Model and Focus 288 10.2 Extension of PCovR 288 10.2.1 Sparse Multiblock Principal Covariates Regression, Sparse PCovR 288 10.2.2 Multiway Multiblock Covariates Regression 289 10.3 Multiblock Redundancy Analysis 292 10.3.1 Standard Multiblock Redundancy Analysis 292 10.3.2 Sparse Multiblock Redundancy Analysis 294 10.4 Miscellaneous Multiblock Regression Methods 295 10.4.1 Multiblock Variance Partitioning 296 10.4.2 Network Induced Supervised Learning 296 10.4.3 Common Dimensions for Multiblock Regression 298 10.5 Modifications and Extensions of the SO-PLS Method 298 10.5.1 Extensions of SO-PLS to Three-Way Data 298 10.5.2 Variable Selection for SO-PLS 299 10.5.3 More Complicated Error Structure for SO-PLS 299 10.5.4 SO-PLS Used for Path Modelling 300 10.6 Methods for Data Sets Split Along the Sample Mode, Multigroup Methods 304 10.6.1 Multigroup PLS Regression 304 10.6.2 Clustering of Observations in Multiblock Regression 306 10.6.3 Domain-Invariant PLS, DI-PLS 307 10.7 Conclusions and Recommendations 308 10.8 Open Issues 309 Part V Software 311 11 Algorithms and Software 313 11.1 Multiblock Software 313 11.2 R package multiblock 313 11.3 Installing and Starting the Package 314 11.4 Data Handling 314 11.4.1 Read From File 314 11.4.2 Data Pre-processing 315 11.4.3 Re-coding Categorical Data 316 11.4.4 Data Structures for Multiblock Analysis 317 11.4.4.1 Create List of Blocks 317 11.4.4.2 Create data.frame of Blocks 317 11.5 Basic Methods 318 11.5.1 Prepare Data 319 11.5.2 Modelling 319 11.5.3 Common Output Elements Across Methods 319 11.5.4 Scores and Loadings 320 11.6 Unsupervised Methods 321 11.6.1 Formatting Data for Unsupervised Data Analysis 321 11.6.2 Method Interfaces 322 11.6.3 Shared Sample Mode Analyses 322 11.6.4 Shared Variable Mode 322 11.6.5 Common Output Elements Across Methods 323 11.6.6 Scores and Loadings 324 11.6.7 Plot From Imported Package 325 11.7 ANOVA Simultaneous Component Analysis 325 11.7.1 Formula Interface 325 11.7.2 Simulated Data 325 11.7.3 ASCA Modelling 325 11.7.4 ASCA Scores 326 11.7.5 ASCA Loadings 326 11.8 Supervised Methods 327 11.8.1 Formatting Data for Supervised Analyses 327 11.8.2 Multiblock Partial Least Squares 328 11.8.2.1 MB-PLS Modelling 328 11.8.2.2 MB-PLS Summaries and Plotting 328 11.8.3 Sparse Multiblock Partial Least Squares 328 11.8.3.1 Sparse MB-PLS Modelling 328 11.8.3.2 Sparse MB-PLS Plotting 329 11.8.4 Sequential and Orthogonalised Partial Least Squares 330 11.8.4.1 SO-PLS Modelling 330 11.8.4.2 Måge Plot 331 11.8.4.3 SO-PLS Loadings 332 11.8.4.4 SO-PLS Scores 333 11.8.4.5 SO-PLS Prediction 334 11.8.4.6 SO-PLS Validation 334 11.8.4.7 Principal Components of Predictions 336 11.8.4.8 CVANOVA 336 11.8.5 Parallel and Orthogonalised Partial Least Squares 337 11.8.5.1 PO-PLS Modelling 337 11.8.5.2 PO-PLS Scores and Loadings 338 11.8.6 Response Optimal Sequential Alternation 339 11.8.6.1 ROSA Modelling 339 11.8.6.2 ROSA Loadings 340 11.8.6.3 ROSA Scores 340 11.8.6.4 ROSA Prediction 340 11.8.6.5 ROSA Validation 341 11.8.6.6 ROSA Image Plots 342 11.8.7 Multiblock Redundancy Analysis 343 11.8.7.1 MB-RDA Modelling 343 11.8.7.2 MB-RDA Loadings and Scores 343 11.9 Complex Data Structures 344 11.9.1 L-PLS 344 11.9.1.1 Simulated L-shaped Data 344 11.9.1.2 Exo-L-PLS 344 11.9.1.3 Endo-L-PLS 344 11.9.1.4 L-PLS Cross-validation 345 11.9.2 SO-PLS-PM 345 11.9.2.1 Single SO-PLS-PM Model 346 11.9.2.2 Multiple Paths in an SO-PLS-PM Model 346 11.10 Software Packages 347 11.10.1 R Packages 347 11.10.2 MATLAB Toolboxes 348 11.10.3 Python 349 11.10.4 Commercial Software 349 References 351 Index 373

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Book SynopsisUnderstand new modes of analysing metabolomic data Metabolomics is the study of metabolites, small molecules and chemical substrates within cells or larger structures which collectively make up the metabolome. The field of metabolomics stands to benefit enormously from chemometrics, an approach which brings advanced statistical techniques to bear on data of this kind. Data Analysis and Chemometrics for Metabolomics constitutes an accessible introduction to chemometric techniques and their applications in the field of metabolomics. Thoroughly and accessibly written by a leading expert in chemometrics, and printed in full-colour, it brings robust data analysis into conversation with the metabolomic field to the immense benefit of practitioners. Data Analysis and Chemometrics for Metabolomics readers will also find: Statistical insights into the nature of metabolomic hypothesis testing, validation, and more All metabolomics data sets from the book on a companion website Case studies from

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Book SynopsisDNA ORIGAMI Discover the impact and multidisciplinary applications of this subfield of DNA nanotechnology DNA origami refers to the technique of assembling single-stranded DNA template molecules into target two- and three-dimensional shapes at the nanoscale. This is accomplished by annealing templates with hundreds of DNA strands and then binding them through the specific base-pairing of complementary bases. The inherent properties of these DNA moleculesmolecular recognition, self-assembly, programmability, and structural predictabilityhas given rise to intriguing applications from drug delivery systems to uses in circuitry in plasmonic devices. The first book to examine this important subfield, DNA Origami brings together leading experts from all fields to explain the current state and future directions of this cutting-edge avenue of study. The book begins by providing a detailed examination of structural design and assembly systems and their applicatioTable of ContentsList of Contributors xiii Preface xvii 1 DNA Origami Technology: Achievements in the Initial 10 Years 1 Masayuki Endo 1.1 Introduction 1 1.1.1 DNA Nanotechnology Before the Emergence of DNA Origami 3 1.2 Two- Dimensional DNA Origami 3 1.3 Programmed Arrangement of Multiple DNA Origami Components 6 1.4 Three- Dimensional DNA Origami Structures 9 1.5 Modification and Functionalization of 2D DNA Origami Structures 11 1.5.1 Selective Placement of Functional Nanomaterials 11 1.5.2 Selective Placement of Functional Molecules and Proteins via Ligands 13 1.5.3 Distance- Controlled Enzyme Reactions and Photoreactions 13 1.6 Single- Molecule Detection and Sensing using DNA Origami Structures 14 1.6.1 Single- Molecule RNA Detection 14 1.6.2 Single- Molecule Detection of Chemical Reactions 14 1.6.3 Single- Molecule Detection using Mechanical DNA Origami 14 1.6.4 Single- Molecule Sensing using Mechanical DNA Origami 14 1.7 Application to Single Biomolecule AFM Imaging 16 1.7.1 High- Speed AFM- Based Observation of Biomolecules 16 1.7.2 Visualization of DNA Structural Changes in the DNA Nanospace 18 1.7.3 Visualization of the Reaction Events of Enzymes and Proteins in the DNA Nanospace 18 1.8 Single- Molecule Fluorescence Studies 19 1.8.1 Nanoscopic Ruler for Single- Molecule Imaging 19 1.8.2 Kinetics of Binding and Unbinding Events and DNA- PAINT 21 1.8.3 DNA Barcode Imaged by DNA- PAINT 21 1.9 DNA Molecular Machines 22 1.9.1 DNA Assembly Line Constructed on the DNA Origami 22 1.9.2 DNA Spider System Constructed on the DNA Origami 22 1.9.3 DNA Motor System Constructed on the DNA Origami 24 1.10 Selective Incorporation of Nanomaterials and the Applications 24 1.10.1 DNA Origami Plasmonic Structure with Chirality 24 1.10.2 Surface- Enhanced Fluorescence by Gold Nanoparticles and DNA Origami Structure 26 1.10.3 Placement of DNA Origami onto a Fabricated Solid Surface 26 1.11 Dynamic DNA Origami Structures Responsive to External Stimuli 27 1.11.1 DNA Origami Structures Responsive to External Stimuli 27 1.11.2 Stimuli- Responsive DNA Origami Plasmonic Structures 27 1.11.3 Photo- Controlled DNA Origami Plasmonic Structures 27 1.12 Conjugation of DNA Origami to Lipid 29 1.12.1 DNA Origami Channel with Gating 29 1.12.2 DNA Origami Templated Synthesis of Liposomes 29 1.13 DNA Origami for Biological Applications 29 1.13.1 Introduction of DNA Origami into Cells and Functional Expression 29 1.13.2 Drug Release Using the Properties Characteristic for DNA Origami 31 1.13.3 DNA Origami Structures Coated with Lipids and Polymers 32 1.13.4 Nanorobot with Dynamic Mechanism 32 1.13.5 Nanorobot Targeting Tumor In Vivo 32 1.14 Conclusions 33 References 34 2 Wireframe DNA Origami and Its Application as Tools for Molecular Force Generation 41 Marco Lolaico and Björn Högberg 2.1 Introduction 41 2.2 Pre- Origami Wireframe DNA Nanostructures 42 2.3 Hierarchical DNA Origami Wireframe 43 2.4 Entire DNA Origami Design 45 2.5 DNA Origami Wireframe as Tools for Molecular Force Application 50 2.5.1 Introduction 50 2.5.2 Results and Discussion 51 2.6 Conclusions 54 2.6.1 Materials and Methods 54 References 55 3 Capturing Structural Switching and Self- Assembly Events Using High- Speed Atomic Force Microscopy 59 Yuki Suzuki 3.1 Introduction 59 3.2 DNA Origami Nanomachines 60 3.3 Ion- Responsive Mechanical DNA Origami Devices 60 3.4 Photoresponsive Devices 62 3.5 Two- Dimensional Self- Assembly Processes 64 3.6 Sequential Self- Assembly 66 3.7 Photostimulated Assembly and Disassembly 67 3.8 Conclusions and Perspectives 69 References 69 4 Advancement of Computer- Aided Design Software and Simulation Tools for Nucleic Acid Nanostructures and DNA Origami 75 Ibuki Kawamata 4.1 Introduction 75 4.2 General- Purpose Software 76 4.3 Software for Designing Small DNA Nanostructures 78 4.4 Software for Designing DNA Origami 81 4.5 Software for Designing RNA Nanostructures 84 4.6 Software for Designing Base Sequence 84 4.7 Software for Simulating Nucleic Acid Nanostructures 85 4.8 Summary and Future Perspective 86 References 87 5 Dynamic and Mechanical Applications of DNA Nanostructures in Biophysics 101 Melika Shahhosseini, Anjelica Kucinic, Peter Beshay, Wolfgang Pfeifer, and Carlos Castro 5.1 Introduction 101 5.1.1 What Makes DNA a Good Material for Dynamic Applications 101 5.1.2 Rupture Forces 103 5.2 Applications 105 5.2.1 Force Spectroscopy 105 5.2.1.1 Utilizing the Stiffness of DNA for Force Spectroscopy 105 5.2.1.2 Applications that Utilize Rupture Forces 107 5.2.2 DNA Devices that Probe and Control DNA–DNA Interactions 108 5.2.2.1 Detection 108 5.2.2.2 Modulation 111 5.2.3 DNA Devices that Respond to Biomolecules 111 5.2.4 DNA Devices to Study Biological Molecular Motors 116 5.2.5 DNA Walkers 116 5.2.6 DNA Computing 119 5.3 Tools for Quantifying DNA Devices and their Functions 120 5.4 Modeling and Analysis 123 5.5 Conclusion 124 References 124 6 Plasmonic Nanostructures Assembled by DNA Origami 135 Sergio Kogikoski, Jr, Anushree Dutta, and Ilko Bald 6.1 Introduction 135 6.2 Optical Properties of the DNA Origami- Based Plasmonic Nanostructures 135 6.3 Nanoparticle Functionalization with DNA 138 6.4 DNA Origami- Based Plasmonic Assemblies 140 6.5 Surface- Enhanced Raman Scattering (SERS) and Other Plasmonic Effects 143 6.6 Conclusion 152 Acknowledgments 152 References 152 7 Assembly of Nanoparticle Superlattices Using DNA Origami as a Template 155 Sofia Julin, Petteri Piskunen, Mauri A. Kostiainen, and Veikko Linko 7.1 Introduction 155 7.2 Gold Nanoparticles 156 7.2.1 Oligonucleotide- Modified AuNPs 156 7.2.2 Cationic AuNPs 158 7.3 Formation of DNA Origami- Assisted Superlattices 158 7.3.1 Superlattices Formed by Oligonucleotide- Functionalized AuNPs 159 7.3.2 Superlattice Formed by Cationic AuNPs 160 7.4 Characterization of Assemblies 160 7.4.1 Electron Microscopy 161 7.4.2 Small- Angle X- ray Scattering 161 7.5 Conclusions and Future Perspectives 162 Acknowledgments 164 References 164 8 Mechanics of DNA Origami Nanoassemblies 167 Deepak Karna, Jiahao Ji, and Hanbin Mao 8.1 Introduction 167 8.2 Analytical Tools to Investigate Mechanical Properties of Nanoassemblies 168 8.2.1 Optical Tweezers 168 8.2.2 Magnetic Tweezers 169 8.2.3 Atomic Force Microscopy (AFM) 169 8.3 Mechanical Strength of DNA Origami Structures 171 8.4 Applications of Origami Nanostructures by Exploiting their Mechanical Strength 173 8.5 Mechanochemical Properties of DNA Origami 175 8.6 Conclusions 177 References 177 9 3D DNA Origami as Single- Molecule Biophysical Tools for Dissecting Molecular Motor Functions 181 Mitsuhiro Iwaki 9.1 Introduction 181 9.2 DNA Origami Nanospring 181 9.2.1 Design of DNA Origami Nanospring 181 9.2.2 Nanospring Mechanical Properties 182 9.2.3 Application to a Myosin VI Processive Motor 183 9.3 DNA Origami Thick Filament Mimicking Muscle Structure 187 9.3.1 Mystery of Muscle Contraction 187 9.3.2 Design of a DNA Origami- Based Thick Filament 188 9.3.3 High- speed AFM Observation of Force Generation by Myosin 189 9.3.4 High- Speed Darkfield Imaging of Force Generation by Myosin 189 9.4 Perspective 193 References 193 10 Switchable DNA Origami Nanostructures and Their Applications 197 Jianbang Wang, Michael P. O’Hagan, Verena Wulf, and Itamar Willner 10.1 Introduction 197 10.2 Switchable Machines Constructed from DNA Origami Scaffolds 198 10.2.1 Chemical Triggers for Origami Scaffolds 198 10.2.1.1 Triggering Origami Devices with Strand Displacement Reactions 198 10.2.1.2 Triggering Origami with Ion Concentration 200 10.2.1.3 Triggering Origami with Molecular Species 202 10.2.2 Physical Triggers for Origami Scaffolds 204 10.2.2.1 Triggering Origami with Temperature 204 10.2.2.2 Triggering Origami with Electric Fields 206 10.2.2.3 Triggering Origami with Magnetic Fields 206 10.2.2.4 Triggering Origami with Light 208 10.3 DNA Origami Scaffolds for Defined Mechanical Operations 210 10.3.1 Origami Scaffolds that Dictate the Motility of Elements 212 10.3.2 Engineering Mechanical Functions of Origami Tiles 218 10.4 Switchable Interconnected 2D Origami Assemblies 218 10.5 Dynamic Triggered Switching of Origami for Controlled Release 223 10.6 Switchable Plasmonic Phenomena with DNA Origami Scaffolds 227 10.7 Origami- Guided Organization of Nanoparticles and Proteins 234 10.8 Conclusions and Perspectives 238 References 239 11 The Effect of DNA Boundaries on Enzymatic Reactions 241 Richard Kosinski and Barbara Saccà 11.1 Introduction 241 11.2 DNA- Scaffolded Single Enzymes 242 11.3 DNA- Scaffolded Enzyme Cascades 247 11.4 On the Proximity Model and Other Hypotheses 250 11.5 Conclusions 254 Acknowledgments 256 References 256 12 The Methods to Assemble Functional Proteins on DNA Scaffold and their Applications 261 Eiji Nakata, Shiwei Zhang, Huyen Dinh, Peng Lin, and Takashi Morii 12.1 Introduction 261 12.2 Overview of the Methods for Arranging Proteins on DNA Scaffolds 262 12.2.1 Reversible Conjugation between Protein and DNA 263 12.2.1.1 Biotin- Avidin 264 12.2.1.2 Antibody- Antigen 264 12.2.1.3 Ni- NTA- Hexahistidine 266 12.2.1.4 Aptamers 266 12.2.1.5 Apo- Protein Reconstitution by the Prosthetic Group 266 12.2.2 Irreversible Conjugation between Protein and DNA 266 12.2.2.1 Chemical Crosslinking of Protein and DNA via Cross- Linker 267 12.2.2.2 Crosslinking of Genetically Fused Protein with Chemically Modified DNA 267 12.2.2.3 Covalent Conjugation of Genetically Modified Proteins to Unmodified DNA 269 12.2.2.4 Applications of the Enzyme Assembled DNA Scaffolds 269 12.3 DNA- Binding Adaptor for Assembling Proteins on DNA Scaffold and its Application 270 12.3.1 DNA- Binding Adaptor for Reversible Assembly of Proteins via Noncovalent Interactions 270 12.3.2 Modular Adaptors for Covalent Conjugation of Genetically Modified Proteins to Chemically Modified DNA 272 12.3.3 Application of DNA- Binding Adaptors for Assembling Proteins on DNA Scaffolds 275 12.3.3.1 Assembling Protein of Interest on DNA Scaffold in Cell 275 12.3.3.2 Enzymatic Reaction System on a DNA Scaffold 275 12.4 Summary 278 References 278 13 DNA Origami for Synthetic Biology: An Integrated Gene Logic- Chip 281 Hisashi Tadakuma 13.1 Introduction 281 13.2 Biomolecule Integration on DNA Nanostructure 281 13.2.1 Nature Uses “Reaction Field” to Overcome the Cross- Talk Problem 281 13.2.2 Synthetic Biology Approach 282 13.2.3 DNA–Protein Complex 282 13.2.4 Enzymatic Reaction on DNA Origami for Low- Molecular- Weight Substrate 284 13.3 Gene Expression Control Using DNA Nanostructure 285 13.3.1 Enzymatic Reaction on DNA Origami for High- Molecular- Weight Substrate 285 13.3.2 Resolving Synthetic Biology Limitation by DNA Origami- Based Nano- Chip 286 13.3.3 Unique Characters of the Nano- Chip 288 13.3.4 Limitation of the Nano- Chip 292 13.4 Summary and Perspective 292 Acknowledgments 293 References 293 14 DNA Origami for Molecular Robotics 297 Akinori Kuzuya 14.1 DNA Origami as a Stage for DNA Walkers and Robotic Arms 297 14.2 Nanomechanical DNA Origami 298 14.3 DNA Origami Used in Combination with Molecular Motors 300 14.4 Future Perspective 301 References 303 15 DNA origami Nanotechnology for the Visualization, Analysis, and Control of Molecular Events with Nanoscale Precision 305 Xiwen Xing and Masayuki Endo 15.1 Introduction 305 15.2 Designing of DNA Origami Frames for the Direct Observation of DNA Conformational Changes 308 15.3 Direct Observation of DNA Structural Changes in the DNA Origami Frame 308 15.3.1 G- Quadruplex Formation and Disruption 308 15.3.2 G- Quadruplex Formation by the Assembly of Four DNA Strands 309 15.3.3 Light- Induced Hybridization and Dehybridization of the Photoswitchable DNA Strands 309 15.3.4 Direct Observation of B–Z Transition in the Equilibrium State 312 15.3.5 Topological Control of G- Quadruplex and I- Motif Formation in the dsDNA 314 15.4 Direct Observation and Regulation of Enzyme Reactions in the DNA Origami Frame 315 15.4.1 Direct Observation and Regulation of Cre- Mediated DNA Recombination in the DNA Origami Frame 315 15.4.2 Holiday- Junction Resolution Mediated by DNA Resolvase 317 15.4.3 DNA Oxidation in the DNA Demethylation Process Mediated by TET Enzyme 317 15.4.4 Searching and Recognition of Target Sites by using Photoresponsive Transcription Factor GAL 4 319 15.5 Direct Observation of a Mobile DNA Nanomachine using DNA Origami 321 15.5.1 A DNA Linear Motor System Created on a DNA Origami System 321 15.5.2 Single- Molecule Operation of DNA Motor by using Programmed Instructions 321 15.5.3 Photo- Controlled DNA Motor System Constructed on DNA Origami 324 15.5.4 Photo- Controlled DNA Rotator System Constructed on DNA Origami 324 15.6 Limitations of AFM Imaging and Comparison with other Imaging Techniques 326 15.7 Conclusions and Perspectives 326 References 327 16 Stability and Stabilization of DNA Nanostructures in Biomedical Applications 333 Soumya Chandrasekhar, Praneetha Sundar Prakash, and Thorsten- Lars Schmidt 16.1 Threats for DNA Nanostructures 333 16.1.1 Errors from Nanostructure Synthesis 334 16.1.1.1 Missing Strands 334 16.1.1.2 Oligonucleotide Synthesis Errors 335 16.1.2 Denaturation of DNA Duplexes 336 16.1.2.1 Melting 336 16.1.2.2 The Role of Cations 336 16.1.2.3 Influence of pH on Duplex Stability 337 16.1.3 Backbone Cleavage 337 16.1.3.1 Acid- Induced Depurination 337 16.1.3.2 Base- Induced Cleavage of RNA 338 16.1.3.3 Enzymatic Digest 338 16.1.4 Chemical Damage at the Nucleobases 339 16.1.4.1 Ultraviolet Radiation 339 16.1.4.2 Radiative and Oxidative DNA Damage 340 16.1.4.3 Deamination 340 16.1.5 DNA Structures for Biological Applications 341 16.1.5.1 Bioimaging 341 16.1.5.2 Biosensing 341 16.1.5.3 Computing 341 16.1.5.4 Single- Molecule Biophysics and Mechanobiology 343 16.1.5.5 Drug Delivery and Gene Therapy 343 16.1.6 In vitro and In vivo Degradation and Clearance of DNA Structures 343 16.1.6.1 Common in vitro and in vivo Stability Assays 344 16.1.6.2 Degradation of DN in in vitro and in vivo 344 16.1.6.3 Low Mg2+ Conditions 346 16.1.6.4 Presence of Nucleases 346 16.1.6.5 Cellular Uptake and Clearance of DNs 347 16.1.6.6 Immune Response 348 16.2 Strategies to Protect DNA Origami Structures 349 16.2.1 Stabilization by Design 349 16.2.2 Stabilization by Covalent Strategies 351 16.2.2.1 Enzymatic Ligation 351 16.2.2.2 Chemical Crosslinking 352 16.2.2.3 Photo Crosslinking 354 16.2.2.4 Base Analogues and Backbone Modification 356 16.2.3 Stabilization by Non- Covalent Strategies and Additives 356 16.2.3.1 Inorganic Materials 356 16.2.3.2 Proteins 358 16.2.3.3 Polymer, Peptides, and Polycation Coatings 358 References 362 17 DNA Nanostructures for Cancer Diagnosis and Therapy 379 Zhe Li and Yonggang Ke 17.1 Introduction 379 17.2 DNA Nanostructure- Based Diagnostics 380 17.2.1 Nucleic Acid Detection 380 17.2.2 Protein and Exosome Detection 382 17.2.3 Tumor Cell Detection 384 17.2.4 Imaging 385 17.3 DNA Nanostructure- Based Drug Delivery 386 17.3.1 Small Molecules 386 17.3.1.1 Doxorubicin 386 17.3.1.2 Platinum- Based Drugs 387 17.3.2 Biologics 389 17.3.2.1 CpG 389 17.3.2.2 RNA 390 17.3.2.3 Protein 392 17.3.3 Inorganic Nanoparticles 393 17.4 Challenges and Prospects 394 17.4.1 Stability 394 17.4.1.1 Nucleases 395 17.4.1.2 Mg2+ 395 17.4.1.3 Shape and Superstructure of DNA Nanostructures 396 17.4.2 Drug Loading Efficiency 396 17.4.3 Drug releasing efficiency 397 17.4.4 Cell Internalization 398 References 400 Index 411

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Book SynopsisTable of ContentsPREFACE xxix ABOUT THE AUTHORS xxxi 1 The Drug Development Process and The Global Pharmaceutical Marketplace 1 2 Regulation of Human Pharmaceutical Safety: Routes To Human Use and Market 19 3 Data Mining: Sources of Information For Consideration In Study And Program Design and In Safety Evaluation 67 4 Electronic Records, Reporting, and Submission: eCTD and Send 75 5 Screens in Safety and Hazard Assessment 83 6 Formulations, Routes, and Dosage Regimens 95 7 Mechanisms And End Points Of Drug Toxicity 131 8 Pilot Toxicity Testing In Drug Safety Evaluation: MTD and DRF 143 9 Repeat-Dose Toxicity Studies 173 10 Genotoxicity 183 11 QSAR Tools For Drug Safety 223 12 Toxicogenomics 241 13 Immunotoxicology In Drug Development 247 14 Nonrodent Animal Studies 293 15 Developmental And Reproductive Toxicity Testing 331 16 Carcinogenicity Studies 363 17 Histopathology and Clinical Pathology In Nonclinical Pharmaceutical Safety Assessment 395 18 Irritation And Local Tissue Tolerance In Pharmaceutical Safety Assessment 403 19 Pharmacokinetics And Toxicokinetics In Drug Safety Evaluation 425 20 Safety Pharmacology 457 21 Special Concerns For The Preclinical Evaluation Of Biotechnology Products 477 22 Safety Assessment of Inhalant Drugs And Dermal Route Drugs 507 23 Special Case Products: Imaging Agents 529 24 Special Case Products: Drugs For Treatment Of Cancer 535 25 Pediatric Product Safety Assessment (2006 Guidance, Including Juvenile And Pediatric Toxicology) 543 26 Use Of Imaging, Imaging Agents, And Radiopharmaceuticals In Nonclinical Toxicology 551 27 Occupational Toxicology In The Pharmaceutical Industry 571 28 Strategy and Phasing For Nonclinical Drug Safety EvaluationIn The Discovery and Development of Pharmaceuticals 585 29 The Application of In Vitro Techniques In Drug Safety Assessment 603 30 Evaluation Of Human Tolerance And Safety In Clinical Trials: Phase I And Beyond 635 31 Postmarketing Safety Evaluation: Monitoring, Assessing, And Reporting of Adverse Drug Responses (ADRs) 683 32 Statistics In Pharmaceutical Safety Assessment 707 33 Combination Products: Drugs and Devices 767 34 Qualification Of Impurities, Degradants, Residual Solvents, Metals, and Leachables in Pharmaceuticals 777 35 Tissue, Cell, and Gene Therapy 789 36 Adverse Outcome Pathways in Drug Safety Assessment 801 Appendix A: Selected Regulatory and Toxicological Acronyms 805 Appendix B: Definition Of Terms And Lexicon of "Clinical" Observations in Nonclinical (Animal) Studies 807 Appendix C: Notable Regulatory Internet Addresses 811 Appendix D: Glossary Of Terms Used in The Clinical Evaluation of Therapeutic Agents 817 Appendix E: Common Vehicles For The Nonclinical Evaluation of Therapeutic Agents 821 Appendix F: Global Directory of Contract Toxicology Labs 919 INDEX 945

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Book SynopsisProtein Homeostasis in Drug Discovery Comprehensive resource on all aspects of protein homeostasis, covering both historical perspectives and emerging technologies that are revolutionizing the field Protein Homeostasis in Drug Discovery highlights drug discovery and development efforts targeting protein homeostasis and considers the emerging appreciation that a protein's activity may not be the only factor to consider when developing therapeutic agents. The chapters cover various aspects of protein homeostasis such as cellular localization, abundance, interactions, and more. Moreover, the text contains up-to-date information regarding targeted protein degradation, an emerging drug discovery modality. Readers interested in targeting different regulatory events that control protein homeostasis or modulating protein abundance will find this book an excellent resource. Furthermore, those interested in the link between biological function and regulating prTable of ContentsList of Contributors ix Preface xv Section I Protein Folding and Quality Control in Drug Discovery 1 1 Epichaperomes as a Gateway to Understanding, Diagnosing, and Treating Disease Through Rebalancing Protein–Protein Interaction Networks 3Chander S. Digwal, Sahil Sharma, Anand R. Santhaseela, Stephen D. Ginsberg, and Gabriela Chiosis 2 Stability of Steroid Hormone Receptors: The Intersection of Proteostasis and Selective Degradation 27Zachary J. Gale-Day and Jason E. Gestwicki 3 Pharmacological Chaperones: Therapeutic Potential for Diseases Resulting from GPCR Misfolding 65Suli-Anne Laurin, Sajjad Ahrari, and Michel Bouvier Section II Protein Degradation and Clearance as Drug Targeting Opportunities 135 4 Exploiting the Proteasome for Disease Treatment: From Dynamic Architecture to Vast Functions 137Gwen R. Buel, Xiuxiu Lu, and Kylie J. Walters 5 Targeting the Ubiquitination Cascade for Drug Discovery 179Qi Liu, Gabriel LaPlante, and Wei Zhang 6 Understanding, Targeting, and Hijacking Autophagy 227Hongguang Xia, Xiaoyan Xu, Mengxin Zhou, Manke Zhang, and Lingzhi Ye 7 Deubiquitinating Enzymes: From Undruggable Targets to Emerging Opportunities 249Xiaoxi Liu, Laura Doherty, Alejandra Felix, and Sara Buhrlage Section III Redirecting Protein Degradation Processes for Drug Development 283 8 History of IMiDs and Protein Degradation as a Pharmacological Modality 285Junichi Yamamoto, Tomoko Asatsuma-Okumura, Takumi Ito, Yuki Yamaguchi, and Hiroshi Handa 9 PROTAC Degraders: Mechanism, Recent Advances, and Future Challenges 317Alessio Ciulli and Oliver Hsia 10 Biochemical Principles of Targeted Protein Degradation 357Roman V. Agafonov, Richard W. Deibler, William A. Elam, Joe S. Patel, and Stewart L. Fisher 11 Pharmacology of PROTAC Degrader Molecules: Optimizing for In Vivo Performance 385Andy Pike, Sofia Guzzetti, Pablo M. Morentin Gutierrez, and James S. Scott Section IV Emerging Technologies and Future Opportunities 419 12 Proximity-Inducing Bifunctional Molecules Beyond PROTACs 421Sophia Lai, Ashley E. Modell, and Amit Choudhary 13 Strategies for Tag-Based Protein Control 447Behnam Nabet, Nathanael S. Gray, and Fleur M. Ferguson 14 Targeted Protein Degradation in Antiviral Drug Discovery 465Mélissanne de Wispelaere and Priscilla L. Yang 15 Beyond Inhibition: Ligand-Based Pharmacological Exploration as a Strategy Toward New Targets and Modalities 491Milka Kostic and Lyn H. Jones Index 519

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Book SynopsisTable of ContentsAbout the editors, xiii About the contributors, xv Foreword, xix Preface, xxiii Series preface, xxvii Acknowledgments, xxix 1 The anthropology of violent death and the treatment of the bodies: an introduction, 1Roberto C. Parra and Douglas H. Ubelaker 2 The posthumous dignity of dead persons, 1Antoon De Baets 2.1 Introduction: generations and posthumous dignity, 15 2.2 The dead and posthumous dignity, 17 2.3 Evidence for posthumous dignity, 18 2.4 Duties flowing from posthumous dignity, 19 2.5 The nature of posthumous dignity, 23 2.6 Semantic debates about posthumous dignity, 25 2.7 Breaches of posthumous dignity, 26 2.8 Restoration of posthumous dignity, 28 2.9 Conclusion: the impact of posthumous dignity, 31 3 Continuing bonds and social memory: absence--presence, 39Avril Maddrell 3.1 What are continuing bonds and how are they experienced and expressed?, 39 3.2 Continuing bonds and the well-being of mourners, 43 3.3 Implications for professional service providers, 46 4 The archaeology of disappearance, 49Alfredo González-Ruibal 4.1 Introduction, 49 4.2 Disappearance and power: concealment, dispersal, and virtualization, 51 4.3 Material disappearance, human disappearance, 55 4.4 The disappearance of disappearance, 58 4.5 Concluding Remarks, 62 5 Bioarchaeology of violent death, 67Anna Osterholtz, Debra Martin and Ryan Harrod 5.1 Introduction and background, 67 5.2 Categories of group-level violent death, 70 5.2.1 Bioarchaeology of Massacres, 70 5.3 Case studies illustrating integrative approaches to massacres in the past, 70 5.4 Differentiating between kratophanous violence and ritualized death, 77 5.5 Conclusions, 81 6 Destruction, mass violence, and human remains: Dealing with dead bodies as a "total social phenomenon", 91Élisabeth Anstett 6.1 Introduction, 91 6.2 Understanding the forms taken by the Forensic Turn, and its effects, 93 6.3 Understanding the genealogy of professional practices of disinterment, 98 6.4 The blind spots of a total social phenomenon of great complexity, 102 6.5 Conclusion, 103 7 Kill, kill again and destroy: when death is not enough, 109Roberto C. Parra, Digna M. Vigo-Corea and Pierre Perich 7.1 Introduction, 109 7.2 Dehumanizing, 111 7.3 When death is not enough, 114 7.4 Dismembering/mutilating: the perspective from culture, 121 7.5 Conclusions, 126 8 Mourning violent deaths and disappearances, 133Antonius C. G. M. Robben 8.1 Introduction, 133 8.2 The conflictive mourning of the dead and missing after the First World War, 134 8.3 Enduring bonds of the living, the dead, and the disappeared in Argentina, 138 8.4 Oscillatory mourning of the dead and the disappeared by the bereaved, 142 8.5 Conclusion, 147 9 Whose humanitarianism, whose forensic anthropology?, 153Jaymelee J. Kim and Adam Rosenblatt 9.1 Introduction, 153 9.2 Positionality of the authors, 155 9.3 Reconceptualizing violent deaths, 156 9.4 The dead as articipants in forensic anthropology, 158 9.5 What's missing from human rights, 166 9.6 The continued expansion of forensic anthropology, 169 10 Battlefields and killed in action: tombs of the unknown soldier and commemoration, 177Laura Wittman 10.1 Introduction, 177 10.2 Tomb of the unknown soldier, 178 10.3 Mutilated victory, 182 10.4 As an Epilogue, 190 11 Mass grave protection and missing persons, 197Melanie Klinkner 11.1 Introduction, 197 11.2 Missing persons in mass graves: a worldwide phenomenon, 198 11.3 The legal framework for mass grave protection, 201 11.4 Practicalities of protection, 208 11.5 Protection on a global scale, 210 11.6 Conclusion: the need to do better, 213 12 Respect for the dead under international law and Islamic law in armed conflicts, 219Ahmed Al-Dawoody and Alexandra Ortiz Signoret 12.1 Introduction, 219 12.2 The Legal Framework, 220 12.3 Search for, Collect, and Evacuate the Dead without Adverse Distinction, 221 12.4 Identification and Recording of Information on the Dead, 224 12.5 Respecting the Dead and Dignified Treatment, 226 12.6 Respectful Disposal of the Dead, 229 12.7 Gravesites and Other Locations of Mortal Remains, 233 12.8 Exhumations, 234 12.9 Return of Human Remains and Personal Effects of the Dead, 236 12.10 Conclusion, 239 13 Unmaking forgotten mass graves and honorable burial: engaging with the spanish civil war legacy, 251Francisco Ferrándiz 13.1 Overture, 251 13.2 On Funerary Militarism, 252 13.3 Franco's Militarist Imprint Under Siege, 256 13.4 Unmaking the Generalissimo's Burial, 262 13.5 Military disassemblage, 269 14 Dealing with bad death in post-conflict societies: forensic devices, burials of exhumed remains, and mourning processes in Peru, 277Valérie Robin-Azevedo 14.1 Models for dealing with death: morphologies of "good death" and "bad death", 277 14.2 Contexts of mass violence through the lens of bad death, 278 14.3 Transitional justice, the forensic turn, and the "dignified burial": can we reverse bad death?, 280 14.4 From the necropolitics to the necrogovernamentality of the Peruvian state, 281 14.5 Exhumation of mass graves and the reactivation of bad death in the Andes, 284 14.6 The task of identification or the process of rehumanization of ill-treated bodies, 287 14.7 The uncertain dates and stretched time of bad death, 291 14.8 Body substitutes in the absence of any trace of remains, 293 14.9 Conclusion, 295 15 Migrant death and the ethics of visual documentation in forensic anthropology, 303Krista E. Latham, Alyson J. O'Daniel and Tanya Ramos 15.1 Introduction, 303 15.2 Disciplinary ethics and social change: contextualizingforensic anthropology practices, 304 15.3 Methods and scope, 309 15.4 Making the case for a more socially aware practice of forensic anthropology, 318 15.5 Closing, 320 16 Bedeviling binaries: an integrated and dialectical approach to forensicanthropology in northern Uganda, 327Tricia Redeker Hepner and Dawnie W. Steadman 16.1 Introduction, 327 16.2 Restless spirits and human remains in Acholiland, Uganda, 329 16.3 The integrated approach, 336 16.4 To excavate or not to excavate?, 340 16.5 Conclusion: from binary to dialectical relationships, 344 17 Guiding principles for the dignified management of the dead in humanitarian emergencies and to prevent them from becoming missing persons, 351Stephen Cordner and Morris Tidball-Binz 17.1 Why the need for these principles?, 351 17.2 To whom are the guiding principles addressed?, 354 17.3 Setting the scene, 355 17.4 The preamble to the Guiding Principles, 360 17.5 The Guiding Principles, 362 17.6 The process of producing the Guiding Principles, 369 17.7 Conclusions, 369 18 Epilog: Anthropology of violent death and forensic humanitarian action, 375Douglas H. Ubelaker and Roberto C. Parra 18.1 Humanity and its less violent reactions?, 375 18.2 Anthropology applied to forensic sciences and the notion of anthropology of violent death in the humanitarian context, 377 Note 382 References 383 Index, 385

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Book SynopsisGenomic and Epigenomic Biomarkers of Toxicology and Disease The latest developments in biomarker research applicable to toxicology and medicine Research on genomic and epigenomic biomarkers is developing rapidly with cutting-edge studies scattered throughout the academic literature, making the status of ongoing scientific activity in this area difficult to ascertain. Genomic and Epigenomic Biomarkers of Toxicology and Disease: Clinical and Therapeutic Actions delivers a comprehensive and authoritative compilation of up-to-date developments in the application of genomic and epigenomic biomarkers to toxicology, disease prevention, cancer detection, therapeutics, gene therapy, and other areas. With contributions from a collection of internationally recognized investigators, this edited volume offers unique insights into current trends and future directions of research in the discussed areas. Combining state-of-the-art information on genomic and epigenomTable of ContentsDedication ix Preface xi Acknowledgements xiii List of Contributors xv 1 Genomic and Epigenomic Biomarkers for Predictive Toxicity and Disease 1 Saura C. Sahu 2 MicroRNAs as Non-invasive Biomarkers of Toxicity and Chemical Hazard: Genomic and Epigenomic Biomarkers of Toxicology and Disease 7 Gail M. Nelson and Brian N. Chorley 3 EV (Extracellular Vesicle)-associated miRNAs as Biomarkers of Toxicity 37 Ryuichi Ono, Yusuke Yoshioka, Yusuke Furukawa, Mie Naruse, Makiko Kuwagata, Takahiro Ochiya, Satoshi Kitajima, and Yoko Hirabayashi 4 Circulating miRNAs as Biomarkers of Toxic Heavy Metal Exposure 63 Alexandra N. Nail, Ana P. Ferragut Cardoso, Mayukh Banerjee, and J. Christopher States 5 MicroRNA Biomarkers of Malignant Mesothelioma 89 Lijin Zhu, Fangfang Zhang, Min Zhang, Hailing Xia, Xiuyuan Yuan, and Yanan Gao 6 Role of Non-coding RNAs in Innate Immune Responses Perturbed by Environmental Arsenic Exposure 101 Liz Saavedra Perez and Benjamin L. King 7 Transcriptomics: Applications in Toxicology and Medicine 133 Pius Joseph Copyrighted Material 8 Network Biology for Biomarker Discovery and Therapy in Cancer 163 Asim Bikas Das 9 Epigenetic Biomarkers: Link to Maternal Exposure and Offspring Health Outcomes 185 Jairus Pulczinski, Moira Mccormick, Yuchen Sun, Musa Watfa, Robert YS Cheng, and Wan-Yee Tang 10 The Role of Dynamic Epigenetic Changes in Modulating Homeostasis after Exposure to Low-dose Environmental Chemicals 213 Chongli Yuan, Jennifer L. Freeman, Junkai Xie, and Han Zhao 11 Emerging Non-invasive Molecular Biomarkers for Early Cancer Detection 229 Jacob Sobota, Yingxue Zhang, Eid Alshammari,and Zhe Yang 12 Aberrant DNA Methylation of Tumor Suppressor Genes and Oncogenes as Cancer Biomarkers 251 Eid Alshammari, Yingxue Zhang, Jacob Sobota, and Zhe Yang 13 SMYD Protein Family as Promising Biomarkers for Cancer Diagnosis and Prognosis 273 Yingxue Zhang, Eid Alshammari, Jacob Sobota, and Zhe Yang 14 Toward Precision Medicine: Epigenetic Alterations in Human Melanoma 309 Carmen Elena Condrat, Elena Codruta Dobrica, Sanda Maria Cretoiu, and Dragos Cretoiu 15 Currents Trends and Future Perspectives in Our Epigenetic Signatures: What a Diet Can Trigger 333 Elena-Codruța Dobrică, Mihnea-Alexandru Găman, Matei-Alexandru Cozma, and Sanda Maria Cretoiu 16 Genetic and Epigenetic Biomarkers of Organophosphate Compounds, Dialkyl Phosphate Exposure, and Their Relation to Biological Effects 363 David S. Hernández-Toledano and Libia Vega 17 Genetic, Epigenetic, and Anatomical Factors in Agenesis and Development of Female Reproductive Tract 383 Tadaaki Nakajima, Tomomi Sato, and Taisen Iguchi 18 Cause or Consequence: Epigenomic DNA Methylation Changes in Arsenic- Mediated in Vitro Transformation of Human Prostate Cells 395 B. Alex Merrick, Dhiral P. Phadke, Ruchir R. Shah, Deepak Mav, and Erik J. Tokar 19 Epigenetic Regulation of Sex Determination and Toxicity in Nonmammalian Vertebrates 415 Genki Yamagishi, Taisen Iguchi, and Shinichi Miyagawa 20 Characterization of Genomic and Epigenomic Biomarkers of Nanoparticle Toxicity Using the Zebrafish Model System 449 Athira Sairanthry Suku, Parayanthala Valappil Mohanan, and Jennifer L. Freeman Index 477

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Book SynopsisTable of ContentsPreface xvii About the Authors xix Part I Introduction to Viruses 1 1 Overview of Molecular Biology 3 Contributing Author: Sarah Forster 1.1 Cell Basics 4 1.1.1 Cytoplasm 5 1.1.2 Ribosomes 5 1.1.3 Nucleus 6 1.2 Cell Replication 6 1.2.1 Nucleic Acids 6 1.2.2 DNA Replication 7 1.2.3 RNA Structure and Role 9 1.2.4 Protein Synthesis 9 1.3 Cellular Transport 11 1.3.1 Plasma Membrane 11 1.3.2 Cell Signaling 11 1.4 Immune Defense 12 1.4.1 Innate Immunity 12 1.4.2 Adaptive Immunity 13 1.4.2.1 Humoral Immunity 13 1.4.2.2 Cellular Immunity 14 1.5 Applications 14 1.6 Chapter Summary 16 1.7 Problems 16 References 16 2 Basics of Virology 19 2.1 Viral Basics and Terminology 19 2.2 Viral Life Cycle 21 2.2.1 Attachment (Connection) 21 2.2.2 Penetration (Entry) 22 2.2.3 Uncoating 22 2.2.4 Replication 23 2.2.5 Assembly 23 2.2.6 Maturation and Release 23 2.3 Virus Structure and Classification 24 2.3.1 DNA Viruses 25 2.3.2 RNA Viruses 25 2.3.3 Reverse Transcription Viruses (Retroviruses) 27 2.4 Viruses in Context of the Tree of Life 27 2.5 Viral Genetics 28 2.5.1 Antigenic Shift 28 2.5.2 Antigenic Drift 29 2.5.3 Phenotypic Mixing 29 2.5.4 Complementation 29 2.6 Applications 29 2.7 Chapter Summary 31 2.8 Problems 31 References 32 3 Pandemics, Epidemics, and Outbreaks 33 3.1 Human Viral Diseases 34 3.2 Ebola and Marburg Viruses 35 3.2.1 Symptoms 36 3.2.2 Diagnosis 37 3.2.3 Prevention and Treatment 37 3.3 Human Immunodeficiency Disease (HIV) 38 3.3.1 HIV Symptoms 39 3.3.1.1 Stage 1: Acute Infection 39 3.3.1.2 Stage 2: Chronic HIV Infection (Latent Phase) 39 3.3.1.3 Stage 3: Acquired Immunodeficiency Syndrome (AIDS) 39 3.3.2 Diagnosis 40 3.3.3 HIV Prevention and Treatment 40 3.4 Influenza 41 3.4.1 Influenza Symptoms 41 3.4.2 Influenza Diagnosis 42 3.4.3 Influenza Prevention and Treatment 42 3.4.4 Influenza Pandemics 43 3.5 Coronaviruses 44 3.5.1 Symptoms 45 3.5.1.1 Typical Acute Symptoms 45 3.5.1.2 Post-COVID Conditions 46 3.5.1.3 COVID-19 Multiorgan System Effects (MIS) 46 3.5.2 COVID-19 Diagnosis 47 3.5.3 COVID-19 Prevention and treatment 48 3.6 Current and Emerging Viral Threats 48 3.7 Applications 51 3.8 Chapter Summary 52 3.9 Problems 53 References 53 4 Virus Prevention, Diagnosis, and Treatment 57 4.1 Vaccination Successes and Challenges 58 4.2 Current Vaccine Technology 59 4.2.1 Live-attenuated vaccines 60 4.2.2 Inactivated vaccines 61 4.2.3 Recombinant Subunit Vaccines 61 4.2.4 Viral Vector Vaccines 62 4.2.5 Messenger RNA (mRNA) Vaccines 62 4.3 U.S.-Approved Vaccines and Requirements 63 4.3.1 Commercially Available Viral Vaccines 63 4.3.2 Vaccination Requirements 63 4.4 Viral Testing and Diagnosis 64 4.4.1 Viral Testing 65 4.4.2 Antibody Testing 66 4.5 Antiviral Treatment Options 66 4.5.1 HIV 67 4.5.1.1 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) 67 4.5.1.2 Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 67 4.5.1.3 Protease Inhibitors (PIs) 67 4.5.1.4 Fusion Inhibitors (FIs) 67 4.5.1.5 Integrase Strand Transfer Inhibitors (INSTIs) 67 4.5.1.6 CCR5 Antagonists 67 4.5.1.7 Attachment Inhibitors 68 4.5.1.8 Post-Attachment Inhibitors 68 4.5.1.9 Pharmacokinetic Enhancers 68 4.5.2 Influenza 68 4.5.3 Hepatitis C virus (HCV) 68 4.5.4 Other Treatment Options 69 4.6 Applications 70 4.7 Chapter Summary 71 4.8 Problems 72 References 72 5 Safety Protocols and Personal Protection Equipment 75 Contributing Author: Emma Parente 5.1 Regulations and Oversight of Safety Protocols 76 5.2 Protective and Safety Systems 76 5.2.1 Personal Protective Devices and Practices 76 5.2.2 Antimicrobial Suppression And Eradication 77 5.3 Disinfection Categories and Procedures 78 5.4 Occupational Health and Safety Administration Hazmat Regulations 79 5.4.1 HAZMAT Level A Protection 80 5.4.2 HAZMAT Level B Protection 81 5.4.3 Level C Protection 82 5.4.4 Level D Protection 83 5.5 Bio Level Safety and Security 83 5.6 COVID-Related Safety Precautions 84 5.6.1 Personal Protective Equipment 84 5.6.2 Transmission Control 85 5.7 Applications 85 5.8 Summary 87 5.9 Problems 87 References 88 6 Epidemiology and Virus Transmission 91 6.1 Overview of Epidemiology 92 6.2 Government Agencies’ Contributions to Public Health 94 6.2.1 The Role of the Centers for Disease Control and Prevention (CDC) 94 6.2.2 The World Health Organization (WHO): Successes and Challenges 95 6.3 Epidemiologic Study Design 96 6.3.1 Outbreak Case Example 98 6.3.2 Clinical Trials 99 6.4 Virus Transmission 100 6.4.1 Modes of Transmission 101 6.5 Applications 102 6.6 Chapter Summary 104 6.7 Problems 105 References 105 Part II Practical and Technical Considerations 109 7 Engineering Principles and Fundamentals 111 Contributing Author: Vishal Bhatty 7.1 History of Engineering 112 7.2 Problem Solving: The Engineering Approach 113 7.2.1 Problem-Solving Methodology 114 7.2.2 Engineering and Scientific Sources 115 7.3 Units and Conversion Constants 115 7.3.1 The Metric System 115 7.3.2 The SI System 117 7.4 Dimensional Analysis 117 7.5 Process Variables 119 7.6 The Conservation Laws 121 7.7 Thermodynamics and Kinetics 125 7.8 Applications 126 7.9 Chapter Summary 130 7.10 Problems 130 References 131 8 Legal and Regulatory Considerations 133 8.1 The Regulatory System 134 8.1.1 Laws, Regulations, Plans and policy: The Differences 135 8.1.2 Policies and Plans 137 8.2 The Role of Individual States 138 8.3 Key Government Agencies 140 8.3.1 Environmental Protection Agency (EPA) 140 8.3.2 Centers for Disease Control and Prevention (CDC) 141 8.3.3 Food and Drug Administration (FDA) 141 8.3.4 Occupational Health and Safety Administration (OSHA) 141 8.3.5 Legal Considerations during a Public Health Crisis 142 8.4 Public Health Emergency Declarations 143 8.5 Key Environmental Acts 145 8.6 The Clean Air Act 145 8.7 Regulation of Toxic Substances 147 8.7.1 Toxic Water Pollutants: Control and Classification 150 8.7.2 Drinking Water 150 8.7.3 Surface Water Treatment Rules (SWTR) 151 8.8 Regulations Governing Infectious Diseases 153 8.8.1 Vaccination Laws 155 8.8.2 State Healthcare Worker and Patient Vaccination Laws 155 8.8.3 State-Mandated Childhood Vaccinations 155 8.9 Applications 155 8.10 Chapter Summary 159 8.11 Problems 159 References 160 9 Emergency Planning and Response 163 9.1 The Importance of Emergency Planning and Response 164 9.2 Planning for Emergencies 166 9.2.1 Preparedness Training 166 9.3 Plan Implementation 167 9.3.1 Notification of Public and Regulatory Officials 168 9.4 EP&R for Epidemics and Pandemics 169 9.4.1 Federal Public Health and Medical Emergency Preparedness 170 9.4.2 Emergency Operations Center 170 9.4.3 Disease Containment 172 9.4.4 Public Notification of Pandemic Quarantines and Lockdowns 173 9.4.5 The National Strategy for Pandemic Influenza (NSPI) 173 9.5 EP&R for Industrial Accidents 174 9.5.1 Emergency Planning and Community Right-to-Know Act (epcra) 175 9.5.2 The Planning Committee 177 9.6 EP&R for Natural Disasters 179 9.7 Current and Future Trends 181 9.8 Applications 181 9.9 Chapter Summary 184 9.10 Problems 184 References 185 10 Ethical Considerations within Virology 189 Contributing Author: Paul DiGaetano, Jr. 10.1 Core Ethics Principles 190 10.2 Important Tenets of Ethical Research 191 10.2.1 Conducting Research During a Health Crisis 192 10.2.2 Scientific Cooperation During a Health Crisis 192 10.2.3 Fair and Ethical Study Design and Implementation 193 10.3 Ethical Dilemmas in Public Health 193 10.3.1 Public Health Surveillance 193 10.3.2 Ethical Evaluation of Nonpharmaceutical Interventions 195 10.3.3 Ethical Consideration Involving Restrictions of Movement 197 10.4 Ethical Considerations Regarding Medical Interventions 199 10.4.1 Emergency Use Of Medical Interventions 200 10.5 Applications 201 10.6 Chapter Summary 202 10.7 Problems 203 References 203 11 Health and Hazard Risk Assessment 205 11.1 Introduction to Risk Assessment 207 11.2 The Health Risk Assessment Process 209 11.3 Dose–Response Assessment 211 11.4 The Hazard Risk Assessment Process 213 11.5 Hazard Risk Versus Health Risk 214 11.5.1 Health Risk Assessment (HRA) Example 215 11.5.2 Hazard Risk Assessment (HRZA) Example 215 11.6 COVID-19 Pandemic Hazard Risk 216 11.7 The Uncertainty Factor 217 11.8 Applications 218 11.9 Chapter Summary 220 11.10 Problems 220 References 221 Part III Engineering Considerations 223 12 Introduction to Mathematical Methods 225 Contributing Author: Julian Theodore 12.1 Differentiation 226 12.2 Integration 228 12.2.1 The Trapezoidal Rule 228 12.2.2 Simpson’s Rule 229 12.3 Simultaneous Linear Algebraic Equations 230 12.3.1 Gauss–Jordan Reduction 231 12.3.2 Gauss Elimination 232 12.3.3 Gauss–Seidel Approach 232 12.4 Nonlinear Algebraic Equations 233 12.5 Ordinary Differential Equations 234 12.6 Partial Differential Equations 237 12.7 Applications 237 12.8 Chapter Summary 240 12.9 Problems 240 References 241 13 Probability and Statistical Principles 243 13.1 Probability Definitions and Interpretations 244 13.2 Introduction to Probability Distributions 246 13.3 Discrete Probability Distributions 247 13.3.1 The Binomial Distribution 248 13.3.2 Multinomial Distribution 248 13.3.3 Hypergeometric Distribution 249 13.3.4 Poisson Distribution 250 13.4 Continuous Probability Distributions 250 13.4.1 Measures of Central Tendency and Scatter 251 13.4.2 The Normal Distribution 252 13.4.3 The Lognormal Distribution 256 13.4.4 The Exponential Distribution 257 13.4.5 The Weibull Distribution 258 13.5 Contemporary Statistics 259 13.5.1 Confidence Intervals for Means 260 13.5.2 Confidence Intervals for Proportions 260 13.5.3 Hypothesis Testing 261 13.5.4 Hypothesis Test for Means and Proportions 261 13.5.5 The F Distribution 262 13.5.6 Analysis of Variance (ANOVA) 262 13.5.7 Nonparametric Tests 264 13.6 Applications 264 13.7 Chapter Summary 268 13.8 Problems 268 References 269 14 Linear Regression 271 14.1 Rectangular Coordinates 272 14.2 Logarithmic Coordinates 273 14.3 Methods of Plotting Data 275 14.4 Scatter Diagrams 275 14.5 Curve Fitting 278 14.6 Method of Least Squares 280 14.7 Applications 284 14.8 Chapter Summary 287 14.9 Problems 288 References 288 15 Ventilation 289 15.1 Introduction to Industrial Ventilation Systems 290 15.2 Components of Ventilation Systems 291 15.3 Fans, Valves and Fittings, and Ductwork 293 15.3.1 Fans 293 15.3.2 Valves and Fittings 295 15.4 Selecting Ventilation Systems 296 15.5 Key Process Equations 298 15.5.1 Regarding Friction Losses 299 15.6 Ventilation Models 300 15.7 Model Limitations 302 15.8 Infection Control Implications 303 15.9 Applications 305 15.10 Chapter Summary 309 15.11 Problems 310 References 310 16 Pandemic Health Data Modeling 313 16.1 COVID-19: A Rude Awakening 315 16.2 Earlier Work 316 16.3 Planning for Pandemics 318 16.4 Generating Mathematical Models 319 16.5 Pandemic Health Data Models 324 16.6 In Review 329 16.7 Applications 331 16.8 Chapter Summary 338 16.9 Problems 338 References 339 17 Optimization Procedures 341 17.1 The History of Optimization 342 17.2 The Scope of Optimization 344 17.3 Conventional Optimization Procedures 346 17.4 Analytical Fomulation of the Optimum 347 17.5 Contemporary Optimization: Concepts in Linear Programming 350 17.6 Applied Concepts in Linear Programming 351 17.7 Applications 355 17.8 Chapter Summary 357 17.9 Problems 358 References 359 Index 361

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Book SynopsisParasitic Infections Understand and defeat a scourge of public health with this cutting-edge guide Parasitic diseases are considered as an important public health problem due to the high morbidity and mortality rates, particularly in countries where climate and level of economic development create serious challenges to the creation of public health infrastructure, thus can make parasitic infections both graver and more difficult to contain. As we come to understand the global ramifications of public health, there has never been a more crucial time to understand these infections and the processes by which they can be managed and defeated. Parasitic Infections is a comprehensive overview of parasitic immunopathology, including the fundamentals of parasite biology, mechanisms and processes of infection, and the key steps of drug discovery and treatment. In addition to detailed coverage of the most commonly encountered infectious parasites, analysis of the immTable of ContentsList of Contributors ix Preface xv Acknowledgments xviii 1 Introduction: Back to the Future ‒ Solutions for Parasitic Problems 1 Rahime Şimşek, Aqsa Farooqui, Salah-Ud-Din Khan, and Shahanavaj Khan 2 Induction of Immune Responses and Inflammation to Parasitic Infections 47 Gurdeep Singh, Abhishek Tiwari, Varsha Tiwari, and Mukesh Kr Singh 3 Animal Parasites: Insight into Natural Resistance 60 Nasib Zaman, Muhammad Rizwan, Kishawar Sultana, Abdur Rauf, Yahya S. Al-Awthan, and Omar Bahattab 4 Immune Response against Protozoan Parasites 73 Ahmed Olatunde, Olalekan Ogunro, Habibu Tijjani, Shakir Mayowa Obidola, Mustapha Abdullahi Akpaki, Archana Yadav, Manisha Nigam, and Abhay Prakash Mishra 5 Immune Response against Helminths 100 Varsha Tiwari, Abhishek Tiwari, Gurdeep Singh, and Mukesh Kr Singh 6 Ectoparasites Host Resistance and Tolerance 124 Jacob Kehinde Akintunde and Ayodeji Mathias Adegoke 7 Microorganisms as Drivers of Host‒Parasite Interactions 141 Rahul Negi, Munni Bhandari, Rahul Kunwar Singh, and Tribhuvan Mohan Mohapatra 8 Neglected Parasitic Infections: History to Current Status 156 Sarmistha Debbarma, Jupi Talukdar, Prabhakar Maurya, Luit Moni Barkalita, and Anupam Brahma 9 Molecular Techniques for the Study and Diagnosis of Parasite Infection 176 Syed Muhammad Mukarram Shah, Saira, and Fida Hussain 10 Drugs for the Control of Parasitic Diseases: Current Status and Case Studies 205 Pratichi Singh, Swetanshu, Shikha Yadav, Adeline Lum Nde, and Vijay Jyoti Kumar 11 Opportunities and Challenges in the Development of Antiparasitic Drugs 227 Maryam Bello-Akinosho, Kayode Olayinka Afolabi, Harish Chandra, Dearikha Karina Mayashinta, Yulia Dwi Setia, and Carolina Pohl-Albertyn 12 Phytopharmaceuticals as an Alternative Treatment against Parasites 251 Rajesh Kumar, Seetha Harilal, Arti Gautam, Manisha Nigam, and Abhay Prakash Mishra 13 Nanoparticles for Antiparasitic Drug Delivery 303 Abdulkadir Mohammed Danyaro, Habibu Tijjani, Swinder Jeet Singh Kalra, and Ahmed Olatunde 14 Vaccination Against Parasitic Infection: From Past to Current Approaches in the Development of a Vaccine 328 Mukesh Kr Singh, Gurdeep Singh, Varsha Tiwari, and Abhishek Tiwari 15 Current Trends in Parasitic Diseases and Precautionary Measures 356 Nisha Singh Index 382

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Book SynopsisTable of ContentsForeword xii Preface xiv Symbols and Abbreviations xvi 1 History and Context 1 1.1 From Cells to Their Nuclei 1 1.1.1 The Cell Theory 2 1.1.2 Mitosis 3 1.1.3 The Chromosome Theory of Heredity 6 1.1.4 Deoxyribonucleic Acid (DNA) 9 1.1.5 Cell Cycles Come in Many Flavors 12 2 Cell Growth and Division 17 2.1 Balanced Growth and Cell Proliferation 17 2.2 Measures of Cell Growth 21 2.3 The Relationship Between Cell Growth and Division 24 2.4 Patterns of Growth in the Cell Cycle 27 2.4.1 Amoeba Cell Growth 28 2.4.2 Fission Yeast Growth 29 2.4.3 Budding Yeast Growth 30 2.4.4 Mammalian Cell Growth 31 2.5 Sizers vs Adders 32 3 Assaying Cell Cycle Progression 39 3.1 Measuring Cell Cycle Phases 39 3.1.1 Single- Cell Imaging 39 3.1.2 Labeled Mitoses 41 3.1.3 Frequency Distributions 43 3.2 Growth Limitations and Variations in the Duration of Cell Cycle Phases 46 3.3 Synchronous Cultures 49 3.3.1 How can One Induce Synchrony? 49 3.3.2 Selecting for Synchrony 52 3.3.2.1 Elutriation: The Mother of all Synchrony Selections 53 4 The Master Switch 57 4.1 Genetic Analyses Leading the Way 59 4.1.1 The cdc28 Mutant of Budding Yeast 59 4.1.2 From the wee1 to the cdc2 Mutant of Fission Yeast 63 4.1.3 What is True for One is True for All 66 4.2 All Roads Lead to the Same Control System 67 4.2.1 Cyclins 67 4.2.2 Maturation Promoting Factor (MPF) 70 4.3 Making Sense of it All 75 4.3.1 Cyclins Galore in Budding Yeast 76 4.3.1.1 G1 Cyclins 77 4.3.2 Back to wee1 78 5 Controlling the Master Switch 80 5.1 Cyclins in Cdk Complexes 81 5.2 Cdk as a Target of Phosphorylations 84 5.2.1 Activating Phosphorylation 84 5.2.2 Inhibitory Phosphorylation 85 5.3 Other Proteins in Cyclin/Cdk Complexes 86 5.3.1 Cdk Inhibitors 86 5.3.1.1 Cip/Kip Proteins 88 5.3.1.2 INK4 Proteins 88 5.3.2 Cks1 89 5.4 What Are Its Targets and How Cdk Phosphorylates Them 89 5.4.1 Defining the Cdk Substrate Universe 89 5.4.2 Cyclin the Recruiter 91 5.4.3 Here Comes Cks1 92 5.5 Ordering Cdk Phosphorylation in the Cell Cycle 94 5.5.1 Order from Intrinsic Cdk Activity 94 5.5.2 Precision from Specificity 96 6 A Full Circle of the Switch 99 6.1 Modeling a Cell Cycle Oscillator 99 6.2 The M- Cdk Switch 103 6.2.1 Exit from Interphase into Mitosis 103 6.2.2 The Anaphase Promoting Complex (apc) 104 6.2.3 From Metaphase to Anaphase 105 6.2.4 Flipping the M- Cdk Switch Off 106 6.2.5 Unsolved Problem: “Sizing” the M-.Cdk Switch 109 6.3 The G1/S Cdk Switch 110 6.3.1 G1- Cdk Activates G1/S Transcription 111 6.3.1.1 Doing Away with Transcriptional Inhibitors 111 6.3.2 Positive Feedback at the G1/S Switch 114 6.3.3 Negative Feedback at the G1/S Switch 115 6.3.4 Physiological Relevance of G1/S Switch in Cancer 116 6.4 Transcriptional Waves Until the End of the Cell Cycle 117 6.5 Comments on Overall Gene Expression in the Cell Cycle 119 7 Duplicating the Genome 121 7.1 DNA Replication 121 7.1.1 Setting the Stage 122 7.1.2 Origin Firing 126 7.1.3 Chromatin 128 7.1.4 Sisters Stay Together 129 7.2 Checkpoints 132 7.2.1 The General Concept 132 7.2.2 DNA Damage Checkpoint 134 8 Segregating the Chromosomes 138 8.1 Blind Men’s Riddle 138 8.2 The Mitotic Spindle 139 8.2.1 Tubulin 140 8.2.2 MTs are Dynamic 142 8.2.3 Scaling the Spindle 146 8.3 The MT Organizing Centers (MTOCs) 147 8.4 The Kinetochore 152 8.4.1 Kinetochore- MT Attachment: Stochastic or Deterministic? 154 8.4.2 May the Force Be With You 156 8.5 The Spindle Assembly Checkpoint (SAC) 159 9 Segregating Organelles and the Cytoplasm 162 9.1 The Golgi 164 9.2 Mitochondria 166 9.3 Lysosomes and Vacuoles 169 9.4 Mitotic Fragmentation of the Nuclear Envelope 170 9.5 Cytokinesis: Two from One 172 9.5.1 Position 172 9.5.2 Assemble 176 9.5.3 Contract 179 References 189 Index 209

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Book SynopsisThe given compilation is devoted to the anniversary of Professor Gennady E Zaikov. The compilation itself has been prepared by those scientists with whom G. E. Zaikov has worked during more than half a century of his scientific career.

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Book SynopsisBuilding upon the previous volumes, The Chemical Biology of Sulfur, The Chemical Biology of Phosphorus, and The Chemical Biology of Nitrogen, this book examines the organic chemistry of life, The Chemical Biology of Carbon. It examines chemical biology open to carbon-containing natural metabolites that allow both retrospective and predictive behaviours of both biosynthetic and degradative metabolism in primary and secondary pathways. This book also notes the centrality of a core set of heterocycles in metabolites and coenzyme forms of vitamins and how that chemistry enables life. The organic chemical fundamental considerations are always tied to specific metabolites and metabolic transformations. This context makes this volume not a classical organic or even bioorganic approach to organic chemistry in vivo but instead a unique analysis of how the rules and reactivities of organic chemistry underlie the organic chemistry of life. The Chemical Biology of Carbon is an ideal reference and guide for medicinal chemists, chemical biologists, organic chemists as well as postgraduate, graduate and advanced undergraduate students in these areas and related disciplines.Table of ContentsIntroduction to Carbon Chemical Biology; Olefin and Alkyne Functional Groups; C–O Bond Formation and Reactivity: A Family of Related Functional Groups; Carbon–Sulfur Bonds: Adding to Functional Group Inventory; Carbon–Nitrogen Functional Groups; Purines and Pyrimidines: Essential Nitrogen Heterocycles; Carbacyclic Metabolites: Alicyclic and Aromatic Rings in Chemical Biology; Heterocycles-I; Heterocycles in Chemical Biology-II: Vitamins; Routes That Make and Break C–H and C–C Bonds In Vivo I: Carbanion Generation; Routes to Make and Break C–C Bonds II: Carbon Electrophiles; Carbon Radicals; Cascades vs Concerted Reactions; Glucose Chemical Biology; C–C Bonds in Biosynthesis: Squalene and the Sterol Biosynthetic Pathway; Chemical Biology of the Nitrogen Heterocycle Porphobilinogen in Tetrapyrrole Macrocycle Biosynthesis

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Book SynopsisThe book presents recent remediation techniques for heavy metal contamination in wastewater, with a focus on recently-developed and sustainable materials such as metal oxides and their composites, two-dimensional materials, organic-inorganic ion exchange materials, nanomaterials, bagasse, and olive-oil waste chelating materials. Chapters also describe the analysis of heavy metals, membranes for water treatment, sources and impact of heavy metals and opportunities and challenges in heavy metal remediation.Table of ContentsChapter 1 Analytical methods for the determination of heavy metals in water Mauricio Llaver, María N. Oviedo, Pamela Y. Quintas, Rodolfo G. Wuilloud Chapter 2 Olive-oil waste for the removal of heavy metals from wastewater M.A. Martín-Lara, M.J. Muñoz-Batista, G. Blázquez, A. Pérez, M. Calero Chapter 3 Metal oxide composites for heavy metal ions removal Safoura Daneshfozoun, Anum Tahir, Zaman Tahir, Awais Ali Aslam, Muhammad Shahid Nazir, Mohd Azmuddin Abdullah Chapter 4 Two-dimensional materials for heavy metal removal Siyuan Luo, Hong Chen Chapter 5 Membranes for heavy metals removal Luciano Marder, Tatiane Benvenuti, Alexandre Giacobbo, Marco Antônio Siqueira Rodrigues, Jane Zoppas Ferreira, and Andréa Moura Bernardes Chapter 6 Metal oxides for removal of heavy metal ions Trishamoni Kashyap1, Biswajit Choudhury Chapter 7 Organic-Inorganic Ion Exchange Materials for Heavy Metal Removal from Water Mesut Yılmazoğlu Chapter 8 Low-cost technology for heavy metal cleaning from water Muhammad Shahid Nazir, Zaman Tahir, Masoom Fatima, Sadaful Hassan, Zulfiqar Ali, Majid Niaz Akhtar​, Mohd. Azmuddin Abdullah Chapter 9 Use of nanomaterials for heavy metal remediation Wojciech Stawiński, Katarzyna Wal, Kamila Startek Chapter 10 Ecoengineered approaches for the remediation of polluted river ecosystems Shabnam Shaikh, Kunal R. Jain, Datta Madamwar, Chirayu Desai Chapter 11 Ballast water definition, components, aquatic invasive species, control and management and treatment technologies Mohamed A. Hassaan and Ahmed El Nemr Chapter 12 Source, pollution and remediation of carcinogenic hexavalent chromium from industrial, mining effluents Aliya Naz; Abhiroop Chowdhury; Brijesh Kumar Mishra Chapter 13 Pesticides in Drinking Water and Removal Techniques Jagvir Singh and Anuradha Chapter 14 Opportunities and challenges in heavy metal removal from water Mriganka Sekhar Manna and Chanchal Bhaumik Chapter 15 Modification of Bagasse for Heavy Metal Removal form Water Radwa A. El-Salamony Chapter 16 Chelating materials for the removal of heavy metals from water Pamela Y. Quintas, Emiliano F. Fiorentini, Leticia B. Escudero Chapter 17 Sources of heavy metals pollution Vhahangwele Masindi, Philani Mkhonza, Memory Teker

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Book SynopsisAdvanced Chemical Biology The modern approach to teaching chemical biology Advanced Chemical Biology is organized around the central dogma of life, progressing from genes to proteins and higher-order cellular structures, including core application areas such as imaging, chemical genetics, activity-based protein profiling, and natural product discovery and biosynthesis. Advanced topics and applications in, e. g., microbiology, developmental biology, and neurobiology, are covered in separate sections. Every chapter is homogeneous in style and layout, consisting of a short historical introduction followed by a description of the underlying concepts and a selection of recent examples of how the concept has been turned into practice. The subdivision of the contents into core and supplemental chapters enables a flexible use in teaching, both for a one-semester and a two-semester course. Written by authors and editors coming from the leading scientific institutions that have developed the concepts and technologies for this discipline, Advanced Chemical Biology includes specific information on topics like: DNA function, synthesis and engineering, chemical approaches to genome integrity, and RNA function, synthesis, and probing Chemical approaches to transcription and RNA regulation in vivo, chemical biology of genome engineering, and peptide/protein synthesis and engineering Directed evolution for chemical biology, chemical biology of cellular metabolism, chemical biology of lipids, and protein post-translational modifications Chemical glycobiology, chemical and enzymatic modification of proteins, genetic code expansion, bio-orthogonal chemistry, and cellular imaging With its broad scope and focus on turning concepts into applications, Advanced Chemical Biology is an excellent starting point for anyone entering the field and looking for a guide to the wide range of available methods and strategies that chemical biology has to offer. With a Foreword by Nobel Laureate Carolyn Bertozzi.Trade ReviewInteressante Richtung des Lehrbuches, stärker aus chemischer Perspektive betrachtet. Erweitert dadurch den Blickwinkel aufs Fach gerade für Wissenschaftler die stärker aus der biologischen Richtung kommen. Prof. Dr. David Kostner, Hochschule München, Biotechnologie (11/2023)Table of ContentsCORE TOPICS Introduction DNA function, synthesis and engineering Chemical approaches to genome integrity and engineering RNA function, synthesis and engineering Chemical approaches to transcription and RNA regulation in vivo Peptide synthesis and engineering Protein engineering and semisynthesis Biomolecular structure determination Biomolecular structure prediction and design Directed Evolution Cellular metabolism Membrane biology and lipid signaling Posttranslational modifications Chemical glycobiology Bioconjugation Genetic code expansion Bioorthogonal chemistry Cellular imaging In vivo imaging Natural product biosynthesis Natural product discovery Activity-based protein profiling Chemical genetics Development of small molecule probes and therapeutics SUPPLEMENTAL TOPICS Metals in biology Chemical redox-biology Chemical microbiology Chemical mammalian cell biology Chemical developmental biology Chemical immunology Chemical neurobiology Chemical plant biology Chemical virology Chemical parasitology

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Book SynopsisA concise and authoritative introduction to scanning electron microscopy in the biological sciences In A Practical Guide to Scanning Electron Microscopy distinguished electron microscopist Gerhard Wanner delivers a practical handbook for biological scientists working with microbial, plant, and animal cells and tissues, enabling them to successfully apply scanning electron microscopy (SEM) to their object of study. The book begins with an introduction to the principles of electron microscopy and the operation of electron microscopes before moving on to describe the preparation and mounting of specimens. It also explores the process of recoding images and their subsequent analysis, along with a wide range of advanced microscopy techniques, including cryo-SEM, FIB-SEM tomography, and stereo-SEM. Scanning Electron Microscopy in the Biosciences contains hundreds of carefully selected microscopic images, as well as hands-on, step-by-step guidance required to perform a successful TEM experiment. Readers will also find: Thorough introductions to optics, electron microscopy, electrons, and the components of electron microscopes In-depth examinations of the preparation of biological specimens and specimen mounting for scanning electron microscopy A comparison of different SEM modes and their strengths and weaknesses An introduction to novel techniques such as correlative light and electron microscopy (CLEM), array tomography, and cryo-scanning electron microscopy Perfect for cell biologists and microbiologists, A Practical Guide to Scanning Electron Microscopy in the Biosciences also belongs in the libraries of neurobiologists and biophysicists.Table of ContentsIntroduction Optics Electron Microscopy The Electrons Components of the Electron Microscope Preparation of Biological Specimens Specimen Mounting for SEM Microscopy Resolution Analytics X-Rays FIB/SEM Serial Block Face SEM Array Tomography Cryo-SEM VP-SEM Stereo-SEM

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Book SynopsisBioactive Egg Compounds presents the latest results and concepts in the biotechnological use of egg compounds. Following an introduction to the different compounds of egg white, yolk and shell, the nutritive value of egg compounds is discussed. The text describes procedures for processing egg compounds to improve their nutritive value, including so-called enriched eggs. Also described is the isolation and application of egg compounds with special properties, such as antibiotic action.Table of ContentsComposition and Extraction of Egg Components.- Composition and Structure of Hen Egg Yolk.- Low-density Lipoproteins (LDL) or Lipovitellenin Fraction.- High-density Lipoproteins (HDL) or Lipovitellin Fraction.- Phosvitin.- Livetin Fractions (IgY).- Lysozyme.- Ovotransferrin.- Ovalbumin and Gene-Related Proteins.- Ovomucin.- Riboflavin-Binding Protein (Flavoprotein).- Avidin.- Proteases.- Antiproteases.- Minor Proteins.- Structure and Formation of the Eggshell.- Eggshell Matrix Proteins.- Function of Eggshell Matrix Proteins.- Use of Egg Compounds for Human Nutrition.- Nutritional Evaluation of Egg Compounds.- Concepts of Hypoallergenicity.- Egg Enrichment in Omega-3 Fatty Acids.- Enrichment in Vitamins.- Enrichment in Selenium and Other Trace Elements.- Use of Eggs for Human/Animal Health and Biotechnology.- Compounds with Antibacterial Activity.- Egg-Protein-Derived Peptides with Antihypertensive Activity.- Use of IgY Antibodies in Human and Veterinary Medicine.- Egg Compounds with Antioxidant and Mineral Binding Properties.- Use of Lecithin and Lecithin Fractions.- Extraction of Several Egg Compounds at a Pilot Scale.- Use of Egg Compounds for Cosmetics and Pharmaceutics.- Use of Egg Compounds for Cryoprotection of Spermatozoa.- Egg-Protein-Based Films and Coatings.- Magnetic Particles for Egg Research.- Avidin-Biotin Technology.

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Book SynopsisDas bewährte Standardwerk Bioanalytik beschreibt und erläutert alle analytischen Methoden, die heute in der Biochemie und Molekularbiologie eingesetzt werden - in fünf großen Abschnitten: Proteinanalytik, 3D-Strukturaufklärung, Spezielle Stoffgruppen, Nucleinsäureanalytik, Systematische Funktionsanalytik. Die komplett überarbeitete 3. Auflage berücksichtigt zahlreiche methodische Weiterentwicklungen und greift auch hochaktuelle Trends in der Forschung auf. Großer Wert wurde auf eine kritische, praxisbezogene Darstellung der Methoden und auf eine Vernetzung der verschiedenen Kapitel untereinander gelegt. So wird die Neuauflage dieses kompetenten und informationsreichen Lehr- und Handbuches wieder all jenen, die sich in der Vielfalt der biologisch-chemischen Labormethoden zurechtfinden müssen, als zuverlässiger Wegweiser dienen.Table of Contents1 Bioanalytik - eine eigenständige Wissenschaft.- Teil I Proteinanalytik.- 2 Proteinreinigung.- 3 Proteinbestimmungen.- 4 Enzymatische Aktivitätstests.- 5 Mikrokalorimetrie.- 6 Immunologische Techniken.- 7 Chemische Modifikation von Proteinen und Proteinkomplexen.- 8 Spektroskopie.- 9 Lichtmikroskopische Verfahren – Imaging.- 10 Spaltung von Proteinen .- 11 Chromatographische Trennmethoden.- 12 Elektrophoretische Verfahren.- 13 Kapillarelektrophorese.- 14 Aminosäureanalyse.- 15 Proteinsequenzanalyse.- 16 Massenspektrometrie.- 17 Massenspektrometriebasierte Immunassays.- 18 Bildgebende Massenspektrometrie.- 19 Protein-Protein-Wechselwirkungen.- 20 Bio- und biomimetische Sensoren.- Teil II 3D-Strukturaufklärung.- 21 Magnetische Resonanzspektroskopie von Biomolekülen.- 22 EPR-Spektroskopie an biologischen Systemen.- 23 Elektronenmikroskopie.- 24 Rasterkraftmikroskopie.- 25 Röntgenstrukturanalyse.- Teil III Spezielle Stoffgruppen.- 26 Analytik synthetischer Peptide.- 27 Kohlenhydratanalytik.- 28 Lipidanalytik.- 29 Analytik posttranslationaler Modifikationen: Phosphorylierung und oxidative Cysteinmodifikation von Proteinen.- Teil IV Nucleinsäureanalytik.- 30 Isolierung und Reinigung von Nucleinsäuren.- 31 Aufarbeitung und chemische Analytik von Nucleinsäuren.- 32 RNA-Strukturaufklärung durch chemische Modifikation.- 33 Polymerasekettenreaktion.- 34 DNA-Sequenzierung.- 35 Analyse der epigenetischen Modifikationen.- 36 Protein-Nucleinsäure-Wechselwirkungen.- Teil V Systematische Funktionsanalytik.- 37 Sequenzanalyse.- 38 Hybridisierung fluoreszenzmarkierter DNA zur Genomanalyse in der molekularen Cytogenetik.- 39 Physikalische, genetische und funktionelle Kartierung des Genoms.- 40 DNA-Microarray-Technologie.- 41 Silencing-Technologien zur Analyse von Genfunktionen.- 42 Proteomanalyse.- 43 Metabolomics- 44 Interactomics - systematische Protein-Protein-Wechselwirkungen.- 45 Chemische Biologie.- 46 Toponomanalyse.- 47 Organ-on-Chip.- 48 Systembiologie.- Anhang

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Book SynopsisThe field of plant biochemistry is of great significance in the agricultural sciences, and it is essential to have a solid understanding of the biochemical mechanisms involved in the synthesis of various plant components. This knowledge is crucial for advancements in other areas of agriculture such as plant breeding, plant protection, and plant production. In recent times, biotechnology and biochemistry have been working together to address various problems faced by humans and other living beings. This book is specifically designed to provide valuable information to graduate and post-graduate students in agriculture and biology. Additionally, it will serve as a useful reference book for researchers in plant breeding, agronomy, plant physiology, and plant protection. This book will be instrumental in solving many global problems faced by present and future generations.

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Book SynopsisThis reference book, which is the second volume of Targeting Oxidative Stress in Cancer, explores oxidative stress as the potential therapeutic target for cancer therapy. The initial chapters discuss the molecular mechanisms of oxidative stress and its effects on different signaling pathways. Subsequently, the sections examine the impact of redox signaling on tumor cell proliferation and consider the therapeutic potential of dietary phytochemicals and nutraceuticals in reactive oxygen species (ROS)-induced cancer. In turn, it examines the evidence supporting the use of Vitamin C in cancer management, before presenting various synthetic and natural compounds that have therapeutic implications for oxidative stress-induced cancer. It also explores the correlation between non-coding RNA and oxidative stress. Furthermore, the book summarizes the role of stem cells in ROS-induced cancer therapy and reviews the therapeutic applications of nanoparticles to alter redox haemostasis in cancer cells. Lastly, it explores heat-shock proteins, ubiquitin ligases, and probiotics as potential therapeutic agents in ROS-mediated cancer. This book is a useful resource for basic and translational scientists as well as clinicians interested in the field of oxidative stress and cancer therapy. ​Table of ContentsSection A: Therapeutic implications of natural compounds Chapter 1 Natural dietary alkaloids and its synthetic derivatives as oxidative stress-inducing agents for cancer therapy Chapter 2. Role of antioxidants in the treatment of hepatocellular carcinoma Chapter 3. Antioxidants in cancer prevention Chapter 4. Therapeutic potential of natural agents against oxidative stress influenced colitis-associated cancer. Chapter 5. Prevention of fertility due to chemotherapy-induced ovarian failure: Role of therapeutic antioxidant Chapter 6 Human papiloma virus (HPV) related cancer, redox state and antioxidant therapy. Chapter 7. The effect of antioxidants on chemotherapy-induced apoptosis Chapter 8. Therapeutic potential of Natural antioxidants in Chemotherapeutic Agent Cyclophosphamide Associated Cardiotoxicity Chapter 9. Therapeutic implications of phytochemicals in ROS induced cancer Chapter 10. Nutraceuticals in cancer therapy: challenges and opportunities Chapter 11. Role of dietary antioxidants in chemoprevention of nitrosamines induced carcinogenesis. Chapter 12 Role of Rosmarinus officinalis (rosemary) essential oil in oxidative stress induced brain cancer Chapter 13 Therapeutic Flavonoids in cancer: ROS-mediated mechanisms Chapter 14 Protective effect of Quercetin, Luteolin, and Fisetin via stimulating the p53 mediated signaling in cancer. Section B: Therapeutic implications of synthetic compounds Chapter 15. Nitrogen- and sulfur-containing heterocycles as dual anti-oxidant and anti-cancer agents Chapter 16. Small molecule inhibitors that target signal transduction pathways involved in oxidative stress-induced cancer: current status and future directions. Chapter 17. Polyphenolic acetates as therapeutics and adjuvant in the therapy of Cancer. Chapter 18 Application of Peptides as cancer therapeutic Chapter 19 Retinoids and reactive oxygen species in cancer cell death and therapeutics. Chapter 20. Benzophenone-2 on oxidative stress induced brain cancer Chapter 21 Salubrinal promotes cisplatin resistance in human gastric cancer cells via enhabced xCT expression and glutathione biosynthesis. Chapter 22. Beyond natural antioxidants in cancer therapy: novel synthetic approaches in harnessing oxidative stress. Chapter 23. Evaluation of chalcore-linked pyrazole pyrimidines in oxidative stress induced breast cancer Chapter 24. Engineered biopolymer for post operated cancer wound healing Chapter 25. Role of TNF-α inhibitors in oxidative stress induced ovarian cancer Chapter 26. Oxidative stress induced colon cancer: effect of Tanshienone Chapter 27. PARP inhibitor olaparib in oxidative stress induced colon cancer Chapter 28. Prevention of ROS induced gastrointestinal carcinoma by synthetic compounds Section C : Radiation and photodynamic approaches in ROS induced cancer therapeutics Chapter 29 Radiotherapy and Oxidative Stress Chapter 30. Photodynamic therapy induced oxidative stress for cancer treatment. Chapter 31 Hybrid nanomaterials for photodynamic therapy Chapter 32. Cross-talk between ROS dependent apoptotic and autophagic signalling pathways in Zn(II) pththalalocyanine photodynamic therapy in melanoma Chapter 33 Elevating the reactive oxygen species in cancer cells by photodynamic therapy: Pro-oxidative approach for cancer treatment. Section D: Non-coding RNA in therapeutics of ROS induced cancer Chapter 34 Oxidative stress mediated miRNA regulation in cancer Chapter 35 Non-coding RNAs in the regulation of voltage gated anion channels: An emerging aspect of ROS induced cancer therapeutics Chapter 36. Exosomal non-coding RNAs: A future of therapeutics in regulating oxidative stress induced breast cancer. Chapter 37 Chapter miRNA and oxidative stress cross talk in cancer Chapter 38 miRNA-mediated oxidative stress induction in cancer Chapter 39. miRNA and oxidative stress cross talk in cancer Chapter 40. A Critical approach in the Analysis of lncRNA characteristics for Cancer Therapy Chapter 41. Long non coding RNA acting as therapeutic target for oxidative stress induced pancreatic cancer Chapter 42. Short non-coding RNAs: Emerging molecular players in therapeutics of ROS induced cancer Section E : Stem cells in therapeutics of ROS induced cancer Chapter 43. Colon cancer stem cells: Target for treatment of oxidative stress induced colorectal cancer Chapter 44. Therapeutic modalities regarding ROS in leukemia and hematopoietic stem/progenitor cell perspective Chapter 45.Stemness and stromal niche: Targets in oxidative stress induced oral cancer Chapter 46. Targeting developmental pathways in Stem Cell for the therapy of Cancer Chapter 47. Cancer stem cell oxidative phosphorylation: Target for cancer therapy. Chapter 48. Targeting oxidative stress specific NRF2 in pancreatic cancer stem cells Chapter 49. Stem cells in ROS induced cancer therapy. Section F: Nanotechonology based therapeutics of ROS induced cancer Chapter 50 Role of natural polyphenols against toxicity induced by oxidative stress in cancer cells.Title: The multifaceted function of nanoparticles in modulating oxidative stress for cancer therapy Chapter 51. Emerging role of redox active nanoceria in cancer therapeutics via oxidative stress Chapter 52. Nano technology in ROS induced cancer therapy. Chapter 53. Nanotechnology-based ROS triggered therapeutic strategies in cancer. Chapter 54. Nanotechnology in cancer diagnosis and therapy Chapter 55. Emerging Nano selenium: An insight to its current Status and potentials in ROS induced cancer Prevention and Therapy' Chapter 56. Oxidative Stress-dependent Anticancer Potentiality of Nano-therapeutic Zinc Oxide Section G: Bioinformatics and system biology approach for targeting ROS in cancer therapy Chapter 57 Molecular insights into the roles of E3 ligases in ROS mediated cancer from a bioinformatics perspective Chapter 58 Elucidation of possible role of heat shock protein as potent therapeutic agent in ROS mediated cancer and its assessment through computational biology methods. Chapter 59. Dynamical methods to study interaction in proteins facilitating molecular understanding of ROS induced cancer Chapter 60. Role of Meprin in therapeutics of ROS induced cancer Chapter 61. Different databases and their utilities to in analyzing ROS mediated cancer Section H: Other aspects of therapeutics of ROS induced cancer Chapter 62 A CRISPR-Cas based therapeutics in oxidative stress-induced cancer. Chapter 63. Role of hypoxia in ROS induced cancer therapy Chapter 64. Syed Ehtaishamul Haque < Chapter 65. Molecular mechanism of oxidative stress in cancer and its therapy Chapter 65. Pro-apoptotic effects of dietary flavonoids in oxidative stress-induced cancer. Chapter 66. Redox signalling: hallmarks of cancer progression and resistance to treatments Chapter 67 Mechanistic and therapeutic crosstalk of lipid peroxidation in oxidative stress and breast cancer. Chapter 68. Targeting Myeloid Leukemia via ROS and Oxidative Stress Chapter 69. Immunotherapeutic approaches for treatment of oxidative stress in haematological malignancies Chapter 70 Application of regulating ROS in overcoming cancer multidrug resistance Chapter 71. Y-Box binding protein 1: A promising therapeutic target for cancer relapses. Chapter 72. Microbes induced oxidative stress for cancer development and therapeutic role of probiotics Chapter 73. Implications of ROS in Endometriosis and Ovarian cancer: Potential avenue in cancer therapy. Chapter 74.Implications of oxidative stress in autophagy and its connection with apoptosis in carcinogenesis Chapter 75. Role of Forkhead box proteins regulating epithelial mesenchymal transition in breast cancer.

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Book SynopsisThis book discusses the novel metabolic cross-talk between immune and tumor cells in the tumor microenvironment that promotes their growth and progression. It also describes deregulated metabolism in cancer cells that promotes suppressive and cancer cell-favourable microenvironment. Further, the book provides novel insights on the metabolic changes in immune cells that promote tumor cell growth and survival. In turn, it also reviews the involvement of immuno-onco metabolic cross-talk in the development of resistance to chemo-radiation therapy (CRT) in tumor cells. Lastly, it also explores the potential of immuno-oncology metabolism as a therapeutic approach against tumor cells.Table of Contents1 Cancer Metabolism and Aggressive Tumor Behaviour.- 2 Immune Cell Metabolism and Function.- 3 Cancer Cell Metabolism Effecting Immune function.- 4 Immune Cell Metabolites as Fuel for Cancer Cells.- 5 Immuno-Onco metabolism and Resistance to Therapy.- 6 Targeting Immuno-Onco metaolism in Cancers.- 7 Timing of the major metabolic switches in immune cell activation and differentiation during cancer development.

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Book SynopsisThis book covers the basic and sustainable approach of nanofiltration membrane techniques along with their fabrication, characterization, separation mechanisms, and broad applications in the field of wastewater treatment. It provides a wide knowledge of nanofiltration technique to water purification audience concerning the recent development with various illustrations, methods and results for graduate students, scientists, academicians, researchers, and industrialists. Readers from wastewater and water purification will have a quick reference by exploring the research literature on the subject field with commercial value-added research applications of nanofiltration membrane.Table of Contents 1. Introduction and basic principle of Nanofiltration membrane Process.- 2. Synthesis and characterization of nanofiltration membrane.- 3. Pretreatments before the nanofiltration technique.- 4. Graphene oxide based nanofiltration membrane for wastewater treatment.- 5. Nano-filtration application in the textile industry for wastewater treatment.- 6. Dye removal from industrial water using nanofiltration membrane.- 7. Volatile organic compounds removal by nanofiltration from groundwater.- 8. Desalination through nanofiltration technique .- 9. Modified nanofiltration membrane for wastewater treatment.- 10. Performance of Ceramic Nanofiltration Membranes in Water Purification.- 11. Fouling Mechanisms in Nanofiltration Membranes.- 12. Nanofiltration Technology Applied for Peat and Wetland Saline Water.- 13. Removal of Pollutants from Wastewater through Nanofiltration: A review.

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Book SynopsisThe book presents a systematic and detailed introduction on starch debranching enzymes concerning the classification, biochemical properties, features on sequences and structures, enzyme engineering, production, and current applications. All relevant contents are organized to focus on characteristics, productions and industrial applications of the starch debranching enzymes. It is purposed to deepen the understandings on the pre-existing researches, developments, and bottlenecks, and also to discuss the research hotspots and application perspectives of starch debranching enzymes. The book is written for researchers, professional/practitioners and graduate students in the field of enzymology, microbiology, and food science etc.Table of ContentsChapter 1. An Overview on Starch Processing and Key Enzymes.- Chapter 2. Classification and Enzyme Properties of Starch Debranching Enzymes.- Chapter 3. Sequence, Structure, and Engineering of Microbial Starch Debranching Enzymes.- Chapter 4. Production and the Applications in Preparation of Branched Sugar Products of Starch-Debranching Enzymes.- Chapter 5. Recombinant Expression of Starch Debranching Enzymes in Escherichia coli.- Chapter 6. Production of Starch Debranching Enzymes in Bacillus Strains. Chapter 7. Applications of Starch Debranching Enzymes in Starch Processing

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Book SynopsisThis book elucidates the sustainable production of commercially important biomolecules in medicines, food, and beverage processing, through biological systems, including microorganisms, animal cells, plant cells, tissues, enzymes, and in vitro. It discusses promising technologies for the manipulation of cells including, genetic engineering, synthetic biology, genome editing, and metabolic engineering. The initial chapters of the book introduce topics on biomanufacturing, circular economy, strain design and improvement, upstream and downstream processing. The subsequent chapters cover artificial intelligence-assisted production, designer cell factories, biosensors for monitoring biomolecules, different cells factories, biosynthetic pathways, and genome editing approaches for scale-up biomanufacturing. Lastly, the book discusses the opportunities and challenges of implementing biological systems for the production of biomolecules. ​This book is a valuable source for students, researchers, scientists, clinicians, stakeholders, policymakers, and practitioners to understand biomanufacturing for the sustainable production of biomolecules.Table of ContentsChapter 1. Strain design and optimization methods for sustainable production.- Chapter 2. Designer and minimal cells for production of biomolecules.- Chapter 3. Recent advances in downstream processing deployed in the treatment of pharmaceutical effluents.- Chapter 4. Microbial conversion of waste to biomolecules.- Chapter 5. Biosensor for detecting biomolecules.- Chapter 6. Artificial Intelligence Assisted Production of Biomolecules.- Chapter 7. Escherichia coli cell factory for synthesis of biomolecules.- Chapter 8. Bacillus subtilis cell factory.- Chapter 9. Pseudomonas putida cell factory.- Chapter 10. Cyanobacteria for marine based biomolecules.- Chapter 11. Yeast cell factory for biomolecules.- Chapter 12. Plant cell factory for biomolecules.- Chapter 13. Genetic manipulation of crop for enhanced food quality and nutrition towards sustainable production.- Chapter 14. Insect cell factory for production of biomolecules.- Chapter 15. Mammalian cell factor for biomolecules.- Chapter 16. Genome editing guided production of biomolecules.- Chapter 17. Cell free protein synthesis system for sustainable production of biofuels.- Chapter 18. Challenges and opportunities in biomanufacturing.

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