Note: Intro -- Series Page -- Title Page -- Copyright -- Table of Contents -- eMagRes -- International Advisory Board -- Contributors -- Series Preface -- Preface -- Abbreviations and Acronyms -- Part A: Introduction -- Chapter 1: Drug Discovery and Development: The Role of NMR -- 1.1 Introduction to Drug Discovery and Development and the Role of NMR -- 1.2 NMR Spectroscopy in Drug Discovery and Development -- 1.3 New Applications of NMR Spectroscopy in Pharmaceutical R& -- D -- 1.4 In vivo MRS and MRI -- 1.5 Future Developments -- References -- Part B: NMR Theory & -- Experimental Methods -- Chapter 2: Modern NMR Pulse Sequences in Pharmaceutical R& -- D -- 2.1 Introduction -- 2.2 Initial Sample Adjustments -- 2.3 One-dimensional Methods -- 2.4 Pulse Sequences for 2D NMR Spectroscopy -- 2.5 Conclusions -- Related Articles in eMagRes -- References -- Further Reading -- Chapter 3: NMR Theory & -- Experimental MethodsExperimental NMR Methods for Pharmaceutical Research and Development -- 3.1 Introduction -- 3.2 NMR Hardware, Analytical Conditions -- 3.3 NMR-related Workflows -- 3.4 Quality Control -- 3.5 Conclusions -- Related Articles in eMagRes -- References -- Chapter 4: 19F NMR Spectroscopy: Applications in Pharmaceutical Studies -- 4.1 Introduction -- 4.2 Practical Aspects of 19F NMR Spectroscopy -- 4.3 Small Molecule Studies of Pharmaceutical Interest -- 4.4 Application to Fluorine-Labeled Macromolecules -- 4.5 Drug Screening Activities -- 4.6 Applications in Drug Metabolism Studies -- 4.7 19F NMR Spectroscopy In Vivo -- Related Articles in eMagRes -- References -- Chapter 5: Quantitative NMR Spectroscopy in Pharmaceutical R& -- D -- 5.1 Introduction -- 5.2 Basic Principles of qNMR -- 5.3 Signal Separation/Overlap -- 5.4 Quantification Methods -- 5.5 Applications -- 5.6 Conclusion -- Acknowledgments -- References. , Chapter 6: High-throughput NMR in Pharmaceutical R& -- D -- 6.1 Introduction -- 6.2 Overall Process View -- 6.3 Workflow - Purity and Identity of Solid Samples -- 6.4 Workflow - Purity and Identity of Screening Solutions -- 6.5 Workflow - Fragment-based Drug Discovery -- 6.6 Common Themes -- 6.7 Getting Faster -- 6.8 Summary -- References -- Chapter 7: Multivariate Data Analysis Methods for NMR-based Metabolic Phenotyping in Pharmaceutical and Clinical Research -- 7.1 Introduction -- 7.2 Raw Analytical Signal Processing -- 7.3 Exploratory Analysis of H NMR-based Metabolic Phenotypes -- 7.4 Predictive Analysis of H NMR-based Metabolic Phenotypes -- 7.5 Time-course Analysis of NMR-based Metabolic Phenotypes -- 7.6 Conclusions -- Related Articles in eMagRes -- References -- Part C: Idea to Lead -- Chapter 8: The Role of NMR in Target Identification and Validation for Pharmaceutical R& -- D -- 8.1 Introduction: What is Drug Discovery? -- 8.2 Drug Targets -- 8.3 Target Identification and Validation -- 8.4 Application of NMR in Target Identification and Validation -- Acknowledgments -- References -- Chapter 9: High-resolution MAS NMR of Tissues and Cells -- 9.1 Introduction -- 9.2 The Developments -- 9.3 Applications -- 9.4 Conclusions -- Related Articles in eMagRes -- References -- Chapter 10: NMR Studies of Inborn Errors of Metabolism -- 10.1 Introduction -- 10.2 Body Fluid NMR -- 10.3 Applications of NMR in IEM Diagnosis -- Related Articles in eMagRes -- References -- Chapter 11: NMR-based Structure Confirmation of Hits and Leads in Pharmaceutical R& -- D -- 11.1 Introduction -- 11.2 Why Is It Necessary? -- 11.3 When Should the Structure Confirmation Be Carried Out? -- 11.4 What Are the Benefits? -- 11.5 How Is Structure Confirmation Carried Out? -- 11.6 How Bad Can It Get? -- 11.7 Conclusion -- Related Articles in eMagRes -- References. , Chapter 12: Fragment-based Drug Design Using NMR Methods -- 12.1 Introduction -- 12.2 Fragment-based Drug Design vs High-throughput Screening -- 12.3 FBDD Approaches -- 12.4 Fragment Library -- 12.5 Target Druggability -- 12.6 Target-based vs Ligand-based FBDD NMR Methods -- 12.7 Protein Target Production -- 12.8 NMR-based Screening Experiments -- 12.9 19F NMR Screening -- 12.10 Hit Validation by NMR and Validation of NMR Fragment Hits -- 12.11 Nonspecific Binding -- 12.12 Fragment Prioritization -- 12.13 Hit-to-Lead -- 12.14 Linker Design -- 12.15 Protein-Ligand Affinities -- 12.16 Protein-Ligand Structure Determination -- 12.17 Clinical Candidates Originating from FBDD -- Related Articles in eMagRes -- References -- Chapter 13: Hit Discovery from Natural Products in Pharmaceutical R& -- D -- 13.1 Introduction -- 13.2 Practical Aspects of NMR Spectroscopic Experiments on Natural Products -- 13.3 Advances in NMR Acquisition and Data Processing -- 13.4 1H NMR Spectroscopic Screening of Natural Product Extracts -- 13.5 Micro NMR Spectroscopy and Cryogenic NMR Probes -- 13.6 NMR Spectroscopy of Natural Products Following Chromatography -- 13.7 Dereplication and Natural Product NMR Databases -- 13.8 Conclusions -- Related Articles in eMagRes -- References -- Part D: Lead to Drug Candidate -- Chapter 14: NMR-based Structure Determination of Drug Leads and Candidates -- 14.1 Introduction -- 14.2 Background to Structure Determination by NMR in the Pharmaceutical Industry -- 14.3 Information from NMR Experiments for Structure Determination -- 14.4 Constitution. Use of C NMR Chemical Shift Predictions and H-C Chemical Shift Correlations from HSQC and HMBC Spectra -- 14.5 Stereochemistry Problems. Proton-Proton Through-space Correlations -- 14.6 Use of the N Isotope -- 14.7 Examples Where H NMR Spectra are Broad or Contain More than One Species in Solution. , 14.8 Conclusions -- References -- Chapter 15: Mixture Analysis in Pharmaceutical R& -- D Using Hyphenated NMR Techniques -- 15.1 Introduction -- 15.2 Practical and Technical Considerations in LC-NMR -- 15.3 High-performance Liquid Chromatography-Nuclear Magnetic Resonance-Mass Spectrometry (HPLC-NMR-MS) -- 15.4 Applications of LC-NMR -- 15.5 Conclusions -- Related Articles in eMagRes -- References -- Chapter 16: Conformation and Stereochemical Analysis of Drug Molecules -- 16.1 Introduction -- 16.2 Experimental Techniques -- 16.3 Analysis of NMR Results -- 16.4 Applications of Stereochemical and Conformational Studies in the Pharmaceutical Industry -- 16.5 Conclusions -- Acknowledgments -- Related Articles in eMagRes -- References -- Chapter 17: NMR Methods for the Assignment of Absolute Stereochemistry of Bioactive Compounds -- 17.1 Introduction -- 17.2 The Absolute Configuration and NMR Spectra -- 17.3 CDAs and Substrates -- 17.4 The Use of 13C NMR for Assignment -- 17.5 The Assignment of Absolute Configuration of Monofunctional Compounds by Double Derivatization -- 17.6 Single Derivatization Methods for Alcohols and Amines -- 17.7 The Assignment of Polyfunctional Compounds -- Related Articles in eMagRes -- References -- Chapter 18: Applications of Preclinical MRI/MRS in the Evaluation of Drug Efficacy and Safety -- 18.1 Introduction -- 18.2 Review of MRI/MRS Methods -- 18.3 Applications of MRI/MRS in Drug Discovery -- 18.4 Conclusions -- 18.5 Disclaimer -- 18.6 Conflict of Interests -- Acknowledgment -- Related Articles in eMagRes -- References -- Chapter 19: Practical Applications of NMR Spectroscopy in Preclinical Drug Metabolism Studies -- 19.1 Introduction -- 19.2 NMR in the Realm of ADME Discovery -- 19.3 Metabolite Concentrations versus Instrument Sensitivity -- 19.4 Sample Isolation -- 19.5 Quantitative NMR (qNMR) Spectroscopy. , 19.6 Discussion -- References -- Chapter 20: Preclinical Drug Efficacy and Safety Using NMR Spectroscopy -- 20.1 Introduction -- 20.2 Sample Types -- 20.3 Statistical Analysis of Metabonomic Data -- 20.4 Organ-specific Toxicities by NMR Spectroscopy-based Metabonomics -- 20.5 The COMET Consortium Project -- 20.6 Toxico/pharmacometabonomics -- 20.7 Conclusions -- References -- Chapter 21: Characterization of Pharmaceutical Compounds by Solid-state NMR -- 21.1 Introduction -- 21.2 Basic Experimental Methods -- 21.3 Emerging Experimental Methods -- 21.4 Crystalline Phases of Drug Substances and Excipients -- 21.5 Amorphous Phases of Drug Substances and Excipients -- 21.6 Drug Products -- 21.7 Conclusion -- Acknowledgments -- Related Articles in eMagRes -- References -- Chapter 22: Structure-based Drug Design Using NMR -- 22.1 Introduction -- 22.2 Protein Kinases -- 22.3 Protein Tyrosine Phosphatase 1B (PTP1B) -- 22.4 Ras Superfamily -- 22.5 Conclusions -- Acknowledgments -- References -- Chapter 23: Pharmaceutical Technology Studied by MRI -- 23.1 Introduction -- 23.2 Practicalities -- 23.3 Applications -- 23.4 Future Developments -- 23.5 End Note -- Acknowledgments -- References -- Further Reading -- Part E: Clinical Development -- Chapter 24: NMR-based Metabolic Phenotyping for Disease Diagnosis and Stratification -- 24.1 Introduction -- 24.2 NMR Spectroscopy and Metabolic Phenotyping -- 24.3 Conclusion -- Acknowledgments -- References -- Chapter 25: NMR-based Pharmacometabonomics: A New Approach to Personalized Medicine -- 25.1 Introduction to Personalized Medicine -- 25.2 Introduction to Metabonomics and Pharmacometabonomics -- 25.3 The First Demonstrations of Pharmacometabonomics -- 25.4 The Current Status of Pharmacometabonomics -- 25.5 Future Developments and Predictive Metabonomics -- References. , Chapter 26: Clinical MRI Studies of Drug Efficacy and Safety.

Note: 9780128032251_WEB1 -- Front Cover -- Encyclopedia of Spectroscopy and Spectrometry -- Copyright -- Editor Biographies -- Contributors -- Thematic Contents List -- Atomic Spectroscopy -- Electronic Spectroscopy -- Fundamentals of Spectroscopy -- High Energy Spectroscopy -- Magnetic Resonance -- Mass Spectrometry -- Spatially Resolved Methods -- Vibrational, Rotational and Raman Spectroscopies -- Contents of All Volumes -- Volume 1 -- Volume 2 -- Volume 3 -- Volume 4 -- Guide to Using the Encyclopedia -- Structure of the Encyclopedia -- Alphabetical Contents List -- Cross-references -- Example -- Index -- Contributors -- Preface to the Third Edition -- Permission Acknowledgments -- A -- Absolute Stereochemistry by NMR Spectroscopy -- Introduction -- The Foundations of the Method -- The Practice of Configurational Assignment -- Monofunctional Compounds -- Polyfunctional Compounds -- Simplified Procedures -- The Use of a Single Derivative -- Secondary alcohols: esterification shifts -- Secondary alcohols: low-temperature shifts -- Secondary alcohols and α-chiral primary amines: complexation shifts -- Polyfunctional compound: low-temperature shifts -- The Mix and Shake Method: Resin-Bound AMAAs -- Working with Mixtures of Enantiomers: HPLC-NMR -- The Use of 13C-NMR Spectroscopy for Assignment -- Further Reading -- Accelerator Mass Spectrometry (AMS) -- Introduction -- Instrumentation -- Sample Preparation/Presentation -- AMS Applications -- Further Reading -- AFM and Raman Spectroscopy, Applications in Cellular Imaging and Assays -- Introduction -- Raman-AFM Application in Monitoring Embryonic Stem Cell Growth and Differentiation -- Raman-AFM Applications on the Detection of Fatty Acid-Responsive Receptors on Single Cells -- Raman-AFM Applications on Cellular Assay in Microfluidics -- Acknowledgment -- References. , Analytical Methodology Standards for Metabolomics -- Introduction: The Need for Standardization -- Minimum Information about a Proteomic Experiment (MIAPE) -- The Metabolomics Standards Initiative (MSI) -- Future Developments in Global Standardization -- Further Reading -- Atmospheric Pressure Ionization in Mass Spectrometry -- Introduction -- API Ion Source Design -- Ion Sampling Aperture and Ion Transfer System -- Sample Introduction Devices -- Ionization in API Conditions -- Gas-Phase Ionization -- Liquid-Based Ionization -- Plasma-Based Ionization -- Applications -- Gas Analysis -- LC-MS -- ICP-MS -- Further Reading -- Atomic Absorption, Methods and Instrumentation -- Introduction -- Instrumentation -- Light Source -- Background Correction Systems -- Single-Beam and Double-Beam Instruments -- Line Isolation Devices -- Detection Systems -- Instrument Control and Output Devices -- Sample Introduction and Atom Cells -- Interferences -- Methods -- Conclusions -- Further Reading -- Atomic Absorption, Theory -- Atom Production -- Flame Atomization -- Electrothermal Atomization -- Atomic Absorption -- Emission and Absorption Line Profiles -- Calibration Curve Shapes -- Interferences -- Further Reading -- Atomic Emission and Fluorescence Theory -- Atomic Emission -- Excited State Population -- Line Widths -- Calibration Curves -- Atomic Fluorescence -- Excited State Population -- Line Widths -- Calibration Curves -- Further Reading -- Relevant Website -- Atomic Emission, Methods and Instrumentation -- Atomic Emission Sources -- Inductively Coupled Plasmas -- Direct Current Plasmas -- Microwave-Induced Plasmas -- Capacitively Coupled Microwave Plasmas -- Spectrometers -- Monochromators -- Polychromators -- Detectors -- Photomultiplier Tubes -- Charge-Coupled and Charge-Injection Devices -- Methods -- Sample Introduction -- Torches -- Nebulizers. , Concentric Nebulizers -- Cross-flow Nebulizers -- Babington-type Nebulizer -- Frit-type Nebulizer -- Ultrasonic Nebulizer -- Electrothermal Vaporization -- Hydride Generation -- Direct Solids Introduction -- Line Selection -- Spectral Interferences and Correction Techniques -- Further Reading -- Atomic Fluorescence, Methods and Instrumentation -- Introduction -- Light Sources -- Atom Cell -- Line Isolation Devices -- Detectors -- Readout and Data-Handling Systems -- Applications -- Interferences -- Detection Limits -- Conclusions -- Further Reading -- Atomic Force Microscopy: Methods and Applications -- Introduction -- Methods and Instrumentation -- Contact Mode -- Tapping Mode -- Noncontact Mode -- Force Spectroscopy -- Applications of Atomic Force Microscopy -- Atomic-Resolution Force Spectroscopy in Three Dimensions -- Biological Research With the AFM -- Nanotribology Studies With the AFM -- AFM for Catalysis Research -- Outlook on Emerging Aspects and Future Prospects of Atomic Force Microscopy -- Further Reading -- Atomic Spectroscopy, Biomedical Applications -- Introduction -- Atomic Spectroscopy -- Samples and Sample Preparation -- Applications -- Diagnosis of Deficiency and Toxicity -- Basic Physiology and Biochemistry -- Miscellaneous Applications -- Interferences Seen in the Analysis of Biomedical Sciences by Atomic Spectroscopy -- Further Reading -- Atomic Spectroscopy, Electronic Components Applications -- Further Reading -- Atomic Spectroscopy, Food and Dairy Products Applications of -- Sampling (Sample Collection and Processing) -- Sample Preparation (Reagents and Ashing Methods) -- Method Selection and Method Validation -- Instrumentation and Applications -- FAAS and GFAAS -- ICP-AES and ICP-MS -- Acknowledgements -- Further Reading -- Atomic Spectroscopy, Forensic Science Applications -- Introduction. , Multielement and Isotopic Fingerprinting -- Glass Analysis -- Bullet Lead Analysis -- Nuclear Materials Analyses -- Conclusion -- Further Reading -- Atomic Spectroscopy, Forestry and Wood Products Applications -- Introduction -- Atomic Spectroscopic Techniques in Use -- Forestry -- Wood and Wood Products -- Wood Preservatives -- Preservative Penetration and Retention -- Naturally Occurring Levels of Elements -- General Instrument Settings -- Analytical Procedures -- General Comments -- Applications of Atomic Spectroscopy in Forestry and Wood Products -- Fine Estuarine Sediments -- Algae and Animal Tissues -- Trees and Herbaceous Plant Material -- Forest Soils -- Solid Wood -- Water -- Air -- Future developments -- Further Reading -- Atomic Spectroscopy, Forestry and Wood Products Applications -- Introduction -- Atomic Spectroscopic Techniques in Use -- Forestry -- Wood and Wood Products -- Wood Preservatives -- Preservative Penetration and Retention -- Naturally Occurring Levels of Elements -- General Instrument Settings -- Analytical Procedures -- General Comments -- Applications of Atomic Spectroscopy in Forestry and Wood Products -- Fine Estuarine Sediments -- Algae and Animal Tissues -- Trees and Herbaceous Plant Material -- Forest Soils -- Solid Wood -- Water -- Air -- Future developments -- Further Reading -- Atomic Spectroscopy, Historical Perspective -- Further Reading -- Atomic Spectroscopy, Pharmaceutical Applications -- Introduction -- Techniques of Interest in the Analysis of Pharmaceutical Products -- How Is an Analytical Technique Selected in a Pharmaceutical Laboratory? -- The Stages of the Drug Development Process - Some Background -- Preclinical (Discovery) Testing -- Clinical (IND) Phase -- NDA Phase (Phase IV) -- Further Reading -- ATR and Reflectance IR Spectroscopy, Applications -- Introduction. , Theory of Reflectance Spectroscopy -- Fresnel's Equations -- Energy Flux Density -- The Kramers-Kronig Relations -- Internal Reflection Spectroscopy (ATR) -- Applications -- Diffuse Reflectance -- Specular Reflection Spectroscopy -- Reflection Absorption Spectroscopy -- Reflection Absorption Spectroscopy (RAS) at Near-normal Incidence -- RAS at Grazing Angle -- Polarization Modulation RAS -- ATR Spectroscopy -- Quantitative Analysis of ATR Spectra -- The Concept of Effective Thickness -- Relative Electric Field Components -- Validity of the Effective Thickness Concept -- Quantitative Analysis Taking Sample Absorption and Thickness into Account -- Orientation Measurements -- Determination of Surface Concentration -- Special Experimental ATR Techniques -- SBSR Technique -- Modulated Excitation ME Spectroscopy and 2D IR Spectroscopy -- 2D FTIR Spectroscopy -- Sensitivity of ATR Spectroscopy -- Sensitivity of Stationary ATR Measurements -- Quantitative Analysis of Stationary ATR Spectra -- Dichroic Ratio of Symmetric CH2 Stretching -- Mean Orientation of Hydrocarbon Chains -- Mean Order Parameter of CH2 Groups -- Surface Concentration and Area per Molecule -- Conclusions -- Sensitivity of ME ATR Spectroscopy -- Sensitivity of ME-Spectroscopy -- Selectivity of pH ME -- Manufacturers of Reflection Accessories -- Standard Equipment for Reflection Spectroscopy -- Special Equipment for SBSR-ATR and ME-ATR Spectroscopy -- Further Reading -- B -- Biofluids Studied by NMR Spectroscopy -- Introduction -- Resonance Assignment in NMR Spectra of Biofluids -- NMR Studies of Dynamic Interactions -- NMR Spectroscopy of Blood Plasma and Whole Blood -- NMR Peak Assignments -- 1H NMR Spectroscopy of Whole Blood and Red Blood Cells -- NMR Spectroscopy of Human and Animal Urine -- Sample Preparation and NMR Assignments -- NMR Spectra of Urine in Disease. , Evaluation of Toxic Effects of Xenobiotics Using NMR Spectroscopy of Urine.

Note: Front Cover -- The Handbook of Metabonomics and Metabolomics -- Copyright Page -- Table of Contents -- Foreword -- Preface -- Chapter 1 Metabonomics and Metabolomics Techniques and Their Applications in Mammalian Systems -- 1.1. Metabonomics and metabolomics in relation to other "omics" approaches -- 1.2. The concept of global systems biology -- 1.3. Interactions between host and other genomes -- 1.4. Time-scales of "-omics" events -- 1.5. Samples for metabonomics and metabolomics -- 1.6. Analytical technologies -- 1.7. Chemometric methods -- 1.8. New approaches to biomarker identification using chemometrics -- 1.9. Standardisation of metabolic experiments and their reporting -- 1.10. Overview of applications of metabonomics and metabolomics to mammalian systems -- 1.11. Concluding remarks -- References -- Chapter 2 Cellular Metabolomics: The Quest for Pathway Structure -- 2.1. Introduction -- 2.2. How large is the metabolome? -- 2.3. Metabolite identification -- 2.4. Pathway identification -- 2.5. "Omics" data integration -- 2.6. Metabolic fluxes -- 2.7. Metabolic networks -- Acknowledgments -- References -- Chapter 3 NMR Spectroscopy Techniques for Application to Metabonomics -- 3.1. Introduction -- 3.2. Principles of NMR -- 3.3. Hardware requirements and automation -- 3.4. Sample handling -- 3.5. NMR Experiments and their processing -- 3.6. Data pre-processing -- 3.7. Outlook -- References -- Chapter 4 High-Resolution Magic Angle Spinning NMR Spectroscopy -- 4.1. Introduction -- 4.2. Nuclear spin Hamiltonian -- 4.3. Coherence averaging by magic angle spinning -- 4.4. MAS NMR experiments -- 4.5. Pulse sequences -- 4.6. Applications -- Acknowledgements -- References -- Chapter 5 Chromatographic and Electrophoretic Separations Combined with Mass Spectrometry for Metabonomics -- Abstract -- 5.1. Introduction. , 5.2. Gas Chromatography-Mass Spectrometry -- 5.3. Liquid Chromatography-Mass Spectrometry -- 5.4. HPLC-MS for metabonomics -- 5.5. Capillary LC-MS -- 5.6. Ultra performance Liquid Chromatography-Mass Spectrometry -- 5.7. Capillary zone electrophoresis-Mass Spectrometry -- 5.8. GC-, LC- and CE-MS for metabonomics: A perspective -- 5.9. Conclusions -- References -- Chapter 6 Chemometrics Techniques for Metabonomics -- 6.1. Introduction -- 6.2. Chemometric approaches to metabonomic studies -- 6.3. Summary -- 6.4. Extensions and future outlook -- References -- Chapter 7 Non-linear Methods for the Analysis of Metabolic Profiles -- 7.1. Introduction -- 7.2. Unsupervised methods -- 7.3. Supervised methods -- 7.4. Other methods -- 7.5. Conclusions -- Acknowledgements -- References -- Chapter 8 Databases and Standardisation of Reporting Methods for Metabolic Studies -- 8.1. Introduction: The challenges -- 8.2. Tackling the challenges -- 8.3. Standards in action - a working example -- 8.4. Final remarks -- References -- Chapter 9 Metabonomics in Preclinical Pharmaceutical Discovery and Development -- 9.1. Introduction -- 9.2. Background -- 9.3. Methods -- 9.4. Preclinical efficacy -- 9.5. Preclinical toxicity -- 9.6. Conclusions -- References -- Chapter 10 Applications of Metabonomics in Clinical Pharmaceutical R& -- D -- 10.1. Introduction -- 10.2. Clinical applications of metabonomics in pharmaceutical R& -- D to establish Confidence in Rationale and Confidence in Safety -- 10.3. Summary and future outlook -- References -- Chapter 11 Exploiting the Potential of Metabonomics in Large Population Studies: Three Venues -- 11.1. Introduction -- 11.2. Disease risk and pathogenesis -- 11.3. Metabolic signatures of physical and psychosocial experience -- 11.4. Metabolic distinctions in populations studies -- 11.5. Summary and discussion -- Acknowledgments. , References -- Chapter 12 Metabolite Profiling and Cardiovascular Disease -- 12.1. Introduction -- 12.2. Current approaches to molecular fingerprinting -- 12.3. Profiling diagnostics for coronary heart disease -- 12.4. Metabonomics of coronary heart disease -- 12.5. The next steps -- References -- Chapter 13 The Role of NMR-based Metabolomics in Cancer -- 13.1. In the era of "-omics" -- 13.2. Current metabolomics -- 13.3. Current oncology -- 13.4. From histological to molecular pathology -- 13.5. Chemical detection of cancer -- 13.6. Magnetic resonance spectroscopy and cancer -- 13.7. Development of intact tissue MRS -- 13.8. From tissue MR spectra to cancer metabolomics -- 13.9. Future directions and implications -- References -- Chapter 14 NMR Spectroscopy of Body Fluids as a Metabolomics Approach to Inborn Errors of Metabolism -- 14.1. Introduction -- 14.2. Methods -- 14.3. NMR spectra of body fluids -- 14.4. Future perspectives -- References -- Chapter 15 A Survey of Metabonomics Approaches for Disease Characterisation -- 15.1. Introduction -- 15.2. Healthy individuals -- 15.3. Effects of nutrition supplements and natural remedies -- 15.4. Genetically modified animal models of disease and genetic disorders -- 15.5. Metabonomics in disease studies -- 15.6. Concluding remarks -- References -- Chapter 16 Metabolic Profiling: Applications in Plant Science -- 16.1. Introduction -- 16.2. The plant metabolome -- 16.3. Metabolite profiling technologies -- 16.4. Agrochemical development -- 16.5. Metabolite engineering in plants -- 16.6. Plant secondary metabolism -- 16.7. Complex problems in plant science -- 16.8. Plant functional genomics -- 16.9. Breeding -- 16.10. Nutrition and medicine -- 16.11. Outlook to systems biology -- 16.12. Summary and outlook -- References -- Chapter 17 In vivo NMR Applications of Metabonomics -- 17.1. Introduction. , 17.2. In situ NMR Assignments of body fluid metabolites -- 17.3. In vivo NMR Spectroscopy -- 17.4. Conclusions -- References -- Chapter 18 Applications of Metabonomics Within Environmental Toxicology -- 18.1. Introduction -- 18.2. Examining the impact of environmental toxins on mammalian species using laboratory models -- 18.3. Examining the impact of environmental toxins on wild mammal species -- 18.4. Use of high resolution Magic Angle Spinning NMR spectroscopy in studies on the effects of environmental contaminants on mammals -- 18.5. Examining the impact of environmental toxins on fish -- 18.6. Examining the impact of environmental toxins on invertebrates -- 18.7. Future directions and conclusions -- References -- Chapter 19 Global Systems Biology Through Integration of "Omics" Results -- 19.1. Introduction -- 19.2. Integration and correlation of metabonomic and metabolomic analytical data -- 19.3. Integration of metabolomic and metabonomic data from different types of sample -- 19.4. Integration of data from different omics approaches -- 19.5. Future requirements for modelling hyper-complex biological systems -- References -- Index.

Note: Front Cover -- The Handbook of Metabolic Phenotyping -- Copyright -- Contents -- Contributors -- Foreword -- Preface -- Chapter 1: An Overview of Metabolic Phenotyping and Its Role in Systems Biology -- 1. The History and Evolution of Metabolic Profiling -- 1.1. The Early Years -- 1.2. Modern Metabolic Profiling Using NMR Spectroscopy -- 1.3. Modern Metabolic Profiling Using Mass Spectrometry -- 1.4. Definition of the Field and Efforts in Standardization -- 1.5. Development of Computational Technologies -- 1.5.1. Multivariate Statistics -- 1.5.2. Statistical Spectroscopy -- 1.5.3. Databases -- 2. Application Areas -- 2.1. Drug Metabolism and Toxicology -- 2.2. Plant-Based Metabolomics -- 2.3. Human Disease -- 2.3.1. Hepatology and Gastroenterology -- 2.3.2. Neuropathologies -- 2.3.3. Cancer -- 2.3.4. Cardiometabolic Disease -- 2.3.5. Organ Transplantation -- 2.3.6. Renal Diseases -- 2.3.7. Infectious Diseases -- 2.3.8. Epidemiology & -- MWAS -- 2.3.9. Nutrition -- 2.4. Mechanistic Studies of Disease Models -- 2.4.1. In Vivo Models -- 2.4.2. In Vitro Models -- 2.5. Predictive Metabolic Phenotyping (Pharmacometabonomics) -- 2.6. Emerging Metabolic Profiling Technologies -- 3. Concluding Remarks -- References -- Chapter 2: NMR Spectroscopy Methods in Metabolic Phenotyping -- 1. The Nature of NMR Spectroscopy -- 2. NMR and the Complex Mixture Problem -- 3. NMR Sample Storage and Preparation -- 4. Initial 1H NMR Analysis, High-Throughput Screening, and Basic Editing Techniques -- 4.1. Solvent Signal Suppression -- 4.2. Editing of Basic 1D 1H NMR Spectra -- 5. Higher Dimensional NMR: The Quest for Resolution, Correlation, and Component Identity -- 5.1. ``Go-to´´ Techniques: Basic 2D NMR Methods -- 5.1.1. Heteronuclear Single Quantum Coherence -- 5.1.2. HSQC-TOCSY -- 5.1.3. TOCSY -- 5.1.4. J-Resolved. , 5.2. Diffusion-Ordered Methods for Self-Diffusion Coefficient Measurement -- 5.2.1. 2D Correlations With Diffusion Encoding by 3D NMR -- 5.2.2. Pureshift and Diffusion Encoding: A Resolution Revolution -- 6. Improving 2D Resolution Without Cost: Experimental Methods and Data Treatments -- 6.1. PSYCHE-Based 2D Correlations With Covariance Processing -- 6.2. Pure Shift 2D Heteronuclear Correlations -- 6.3. Nonuniform Sampling -- 7. Substantially Boosting Signal Sensitivity -- 7.1. Dissolution Dynamic Nuclear Polarization -- 7.2. Signal Amplification by Reversible Exchange -- 8. Quantitation -- 8.1. HSQC0 -- 9. Preparation of Data for Chemometric Analysis -- 10. Conclusion, Perspective, and Outlook -- References -- Chapter 3: The Role of Ultra Performance Liquid Chromatography-Mass Spectrometry in Metabolic Phenotyping -- 1. Introduction -- 2. The Emergence and Requirements of Ultra Performance Liquid Chromatography for Metabolic Phenotyping -- 3. The Requirements of Mass Spectrometers for Metabolic Phenotyping -- 4. Types of Data Acquired in UPLC-MS Studies -- 5. Quality Assurance and Quality Control in UPLC-MS-Based Metabolic Phenotyping -- 5.1. System Suitability Test Solution [10, 35] -- 5.2. Isotopically Labeled Internal Standards [10, 17, 80] -- 5.3. Within-Study Pooled Quality Control Sample [10, 17, 82] -- 5.4. Long-Term Reference Material [17, 85] -- 5.5. Extraction Blank Samples -- 6. Analytical Robustness for Small-Scale and Large-Scale Studies -- 7. Data Processing -- 8. Metabolite Annotation and Identification -- 9. Exemplar Applications -- Acknowledgments -- References -- Chapter 4: GC-MS-Based Metabolic Phenotyping -- 1. Introduction -- 2. GC-MS as an Analytical Technique -- 3. GC-MS Metabolic Phenotyping Workflow -- 4. Sample Preparation for GC-MS-Based Metabolic Phenotyping -- 5. Data Processing -- 6. Statistical Evaluation. , 7. Biochemical Interpretation -- 8. GC-MS Troubleshooting -- 9. Clinical Applications -- 10. Conclusion -- References -- Chapter 5: Metabolic Phenotyping Using Capillary Electrophoresis Mass Spectrometry -- 1. Introduction -- 1.1. Instrumentation -- 1.2. Principles of Capillary Zone Electrophoresis -- 1.3. Conditions That Can Be Modified to Optimize the Separation and Limitations When Coupled to MS -- 1.4. Strengths -- 1.5. Weaknesses -- 1.6. Coupling to MS -- 2. Workflow -- 2.1. Design -- 2.2. Sample -- 2.3. Separation and Detection -- 2.3.1. Materials -- 2.3.2. Capillary Preparation -- 2.3.3. CE-MS Method -- 2.4. Data -- 2.5. Statistics -- 2.6. Identification -- 2.7. Meaning -- 3. Applications -- 3.1. Cancer -- 3.2. Metabolic Disorders -- 3.3. Neurodegenerative Diseases and Brain Disorders -- 3.4. Others -- 3.4.1. Infectious Diseases -- 3.4.2. Alcohol Abuse -- 3.4.3. Clinical Approaches -- 4. Conclusions and Future Trends -- References -- Chapter 6: Supercritical Fluid Chromatography for Metabolic Phenotyping: Potential and Applications -- 1. Introduction -- 2. Application of SFC to Nonpolar Metabolite Analysis -- 2.1. Lipids -- 2.2. Bile and Bile Acids -- 2.3. Applications of SFC to Polar Metabolite Analysis -- 3. Conclusion -- References -- Chapter 7: The iKnife: Development and Clinical Applications of Rapid Evaporative Ionization Mass Spectrometry -- Abbreviations -- 1. Introduction -- 2. Basic Principles of Mass Spectrometry -- 3. Nonambient and Ambient Mass Spectrometry -- 4. Development of Rapid Evaporative Ionization Mass Spectrometry (REIMS) (the iKnife) -- 5. Model Generation: The Concept of Profiling -- 6. Clinical Applications -- 6.1. Oncological Surgery: Introduction -- 6.2. Breast Cancer: The iKnife as a Diagnostic and Margin Assessment Tool -- 6.3. Brain Tumors: The iKnife as a Diagnostic and Extent of Resection Assessment Tool. , 6.4. Gastroenterology: The iEndoscope -- 7. Microbiology Applications -- 8. Conclusions -- References -- Chapter 8: Univariate Statistical Modeling, Multiple Testing Correction, and Visualization in Metabolome-Wide Association ... -- 1. Metabolic Phenotyping: Opportunities and Challenges -- 1.1. Application to Public Health Studies -- 1.2. Overview of the Analytical Pipeline in Metabolic Phenotyping -- 2. Metabolome-Wide Association Study: Univariate Approaches -- 2.1. Imputation and Normalization -- 2.2. Statistical Analyses Using Univariate Approaches -- 2.3. Linear and Generalized Linear Models -- 2.4. (Generalized) Linear Mixed Models -- 2.5. Meta-Analyses -- 3. Metabolome-Wide Significance Level -- 3.1. FWER and FDR Control -- 3.2. Defining the Metabolome-Wide Significance Level -- 4. Results Prioritization and Visualization -- 5. Conclusions -- Acknowledgment -- References -- Chapter 9: Multivariate Statistical Methods for Metabolic Phenotyping -- 1. Introduction -- 1.1. Mathematical Notations -- 1.2. Data Transformations -- 1.2.1. Mean Centering -- 1.2.2. Autoscaling -- 1.2.3. Generalized Equation for Scaling -- 1.3. Data Set Partitioning -- 2. Unsupervised Pattern Recognition -- 2.1. Unsupervised Methods for Dimension Reduction and Multivariate Projections -- 2.1.1. Principal Component Analysis -- 2.1.2. Projection Pursuit and Independent Component Analysis -- 2.1.3. Kernel Principal Component Analysis -- 2.1.4. Sparse Principal Component Analysis -- 2.2. Outlier Detection -- 2.2.1. Hotelling's T2 -- 2.2.2. Quality Control Samples -- 2.2.3. Robust Principal Component Analysis -- 2.3. Other Data Exploration Approaches for Specific Experimental Designs and Multiway Analysis -- 2.3.1. Multiway Methods -- 2.3.2. Multivariate Curve Resolution -- 2.3.3. Nonnegative Principal Component Analysis and Nonnegative Matrix Factorization. , 3. Supervised Pattern Recognition and Multivariate Regression -- 3.1. Discriminant and Cluster Analysis -- 3.1.1. Linear Discriminant Analysis -- 3.1.2. Quadratic Discriminant Analysis -- 3.1.3. k-Nearest Neighbors -- 3.1.4. k-Means, k-Medoids, and Fuzzy Alternatives -- 3.2. Multivariate Regression -- 3.2.1. Multiple Linear Regression -- 3.2.2. Principal Component Regression -- 3.2.3. Partial Least Squares -- 3.2.4. Kernel Partial Least Squares -- 3.2.5. Orthogonal Signal Correction-Filtered Partial Least Squares and Orthogonal Projections to Latent Structures -- 3.2.6. Two-Block Orthogonal Projections to Latent Structures -- 3.2.7. Kernel Orthogonal Projections to Latent Structures -- 3.3. Penalized Regression -- 3.3.1. Ridge Regression and Kernel Ridge Regression -- 3.3.2. Sparse Penalized Regression Using the Lasso -- 3.3.3. The Elastic Net, a Weighted Average of Lasso and Ridge Regression -- 3.4. Nonparametric Machine Learning and Recursive Partitioning Methods -- 3.4.1. Support Vector Machines -- 3.4.2. Variable Importance in Linear Support Vector Machines -- 3.4.3. Uncovering Variable Importance for Nonlinear Kernel-Based Models -- 3.4.4. Decision Trees for Classification -- 3.4.5. Random Forests -- 3.5. Prediction Error Rates and Model Fits -- 3.6. Other Supervised Methods and Those for Specific Experimental Designs -- 3.6.1. ANOVA-Based Decompositions -- 3.6.2. Bayesian Approaches -- 3.6.3. Deep Learning Algorithms -- 4. Statistical Approaches for Biomarker Identification -- 4.1. Statistical Total Correlation Spectroscopy -- 4.2. Correlation Networks of Biological Coregulation -- 4.3. Subset Optimization by Reference Matching and the Statistical Use of Second Dimension Data -- 4.4. Statistical Hetero Spectroscopy and Data Fusion -- 5. Conclusion -- References -- Chapter 10: Data-Driven Visualizations in Metabolic Phenotyping. , 1. Visualizing Metabolic Phenotyping Data and Analysis.

Note: Vol1 -- 001-v01-i-iv-9780123744173 -- 002-v01-v-v-9780123744173 -- Editors Affiliations -- 003-v01-vii-viii-9780123744173 -- 004-v01-ix-x-9780123744173 -- Preface to 1st Edition -- 005-v01-xi-xi-9780123744173 -- Preface to 2nd Edition -- 006-v01-xiii-xiii-9780123744173 -- Acknowledgements -- 007-v01-xiv-xiv-9780123744173 -- Disclaimer -- 008-v01-xv-xv-9780123744173 -- Guide to Use of the Encyclopedia -- Structure of the Encyclopedia -- Alphabetical Contents List -- Cross-references -- Example -- Index -- ‡Contributors -- 009-v01-xvii-xx-9780123744173 -- 010-v01-xxi-xxxii-9780123744173 -- 011-v01-xxxiii-xxxvii-9780123744173 -- Subject Classifications -- Atomic Spectroscopy -- Historical Overview -- Theory -- Methods and Instrumentation -- Applications -- Electronic Spectroscopy -- Theory -- Methods and Instrumentation -- Applications -- Fundamentals of Spectroscopy -- Theory -- Methods and Instrumentation -- Applications -- High Energy Spectroscopy -- Theory -- Methods and Instrumentation -- Applications -- Magnetic Resonance -- Historical Overview -- Theory -- Methods and Instrumentation -- Applications -- Mass Spectrometry -- Historical Overview -- Theory -- Methods and Instrumentation -- Applications -- Spatially Resolved (and other Structural) Methods -- Theory -- Methods and Instrumentation -- Applications -- Vibrational, Rotational and Raman Spectroscopies -- Historical Overview -- Theory -- Methods and Instrumentation -- Applications -- 012-v01-1-3-9780123744173 -- Accelerator Mass Spectrometry (AMS) -- Introduction -- Instrumentation -- Sample Preparation/Presentation -- AMS Applications -- Further Reading -- 013-v01-4-8-9780123744173 -- Analytical Methodology Standards for Metabolomics -- Introduction: The Need for Standardization -- Minimum Information about a Proteomic Experiment (MIAPE) -- The Metabolomics Standards Initiative (MSI). , Future Developments in Global Standardization -- Further Reading -- 014-v01-9-14-9780123744173 -- Applications of Circular Dichroism -- 015-v01-15-22-9780123744173 -- Applications of Single Photon Imaging -- Introduction -- Clinical Imaging Protocols -- Radiotracers -- Clinical Single-Photon Imaging Studies -- Cardiac Imaging -- Bone Scans -- Lung Scans -- Imaging of Kidneys and Renal Function -- Other Clinical NM Studies -- Molecular Imaging -- Further Reading -- 016-v01-23-38-9780123744173 -- Art Works Studied Using IR and Raman Spectroscopy -- Introduction -- Comparison of Infrared and Raman Spectroscopies -- Applications of IR and Raman Spectroscopies -- Plastics -- Glass -- Faience -- Biomaterials -- Paintings -- Medieval Manuscripts -- Wall Paintings -- Further Reading -- 017-v01-39-45-9780123744173 -- Atmospheric Pressure Ionization in Mass Spectrometry -- Introduction -- API Ion Source Design -- Ion Sampling Aperture and Ion Transfer System -- Sample Introduction Devices -- Ionization in API Conditions -- Gas-Phase Ionization -- Liquid-Based Ionization -- Plasma-Based Ionization -- Applications -- Gas Analysis -- LC-MS -- ICP-MS -- Further Reading -- 018-v01-46-53-9780123744173 -- Atomic Absorption, Methods and Instrumentation -- 019-v01-54-62-9780123744173 -- Atomic Absorption, Theory -- Atom Production -- Flame Atomization -- Electrothermal Atomization -- Atomic Absorption -- Emission and Absorption Line Profiles -- Calibration Curve Shapes -- Interferences -- Further Reading -- 020-v01-63-69-9780123744173 -- Atomic Emission and Fluorescence Theory -- Atomic Emission -- Excited State Population -- Line Widths -- Calibration Curves -- Atomic Fluorescence -- Excited State Population -- Line Widths -- Calibration Curves -- Further Reading -- Relevant Website -- 021-v01-70-77-9780123744173 -- Atomic Emission, Methods and Instrumentation. , 022-v01-78-83-9780123744173 -- Atomic Fluorescence, Methods and Instrumentation -- Introduction -- Light Sources -- Atom Cell -- Line Isolation Devices -- Detectors -- Readout and Data-Handling Systems -- Applications -- Interferences -- Detection Limits -- Conclusions -- See Also -- Further Reading -- 023-v01-84-90-9780123744173 -- Atomic Spectroscopy, Forensic Science Applications -- Introduction -- Multielement and Isotopic Fingerprinting -- Glass Analysis -- Bullet Lead Analysis -- Nuclear Materials Analyses -- Conclusion -- Further Reading -- 024-v01-91-93-9780123744173 -- Atomic Spectroscopy, Historical Perspective -- Further Reading -- 025-v01-94-109-9780123744173 -- ATR and Reflectance IR Spectroscopy, Applications -- Introduction -- Theory of Reflectance Spectroscopy -- Fresnel's Equations -- Energy Flux Density -- The Kramers-Kronig Relations -- Internal Reflection Spectroscopy (ATR) -- Applications -- Diffuse Reflectance -- Specular Reflection Spectroscopy -- Reflection Absorption Spectroscopy -- Reflection Absorption Spectroscopy (RAS) at Near-normal Incidence -- RAS at Grazing Angle -- Polarization Modulation RAS -- ATR Spectroscopy -- Quantitative Analysis of ATR Spectra -- The Concept of Effective Thickness -- Relative Electric Field Components -- Validity of the Effective Thickness Concept -- Quantitative Analysis Taking Sample Absorption and Thickness into Account -- Orientation Measurements -- Determination of Surface Concentration -- Special Experimental ATR Techniques -- SBSR Technique -- Modulated Excitation ME Spectroscopy and 2D IR Spectroscopy -- 2D FTIR Spectroscopy -- Sensitivity of ATR Spectroscopy -- Sensitivity of Stationary ATR Measurements -- Quantitative Analysis of Stationary ATR Spectra -- Dichroic Ratio of Symmetric CH2 Stretching -- Mean Orientation of Hydrocarbon Chains -- Mean Order Parameter of CH2 Groups. , Surface Concentration and Area per Molecule -- Conclusions -- Sensitivity of ME ATR Spectroscopy -- Sensitivity of ME-Spectroscopy -- Selectivity of pH ME -- Manufacturers of Reflection Accessories -- Standard Equipment for Reflection Spectroscopy -- Special Equipment for SBSR-ATR and ME-ATR Spectroscopy -- Further Reading -- 026-v01-111-117-9780123744173 -- Biochemical Applications of Fluorescence Spectroscopy -- 027-v01-118-127-9780123744173 -- Biochemical Applications of Raman Spectroscopy -- 028-v01-128-141-9780123744173 -- Biofluids Studied by NMR Spectroscopy -- Introduction -- Resonance Assignment in NMR Spectra of Biofluids -- NMR Studies of Dynamic Interactions -- NMR Spectroscopy of Blood Plasma and Whole Blood -- NMR Peak Assignments -- 1H NMR Spectroscopy of Whole Blood and Red Blood Cells -- NMR Spectroscopy of Human and Animal Urine -- Sample Preparation and NMR Assignments -- NMR Spectra of Urine in Disease -- Evaluation of Toxic Effects of Xenobiotics Using NMR Spectroscopy of Urine -- NMR Spectroscopy of Cerebrospinal Fluid -- NMR Spectroscopy of Seminal Fluids -- NMR Spectroscopy of Bile -- NMR Spectroscopy of Bile and Dynamic Interactions of Metabolites -- NMR Spectroscopy of Miscellaneous Body Fluids -- Amniotic and Follicular Fluids -- Milk -- Synovial Fluid -- Aqueous Humor and Vitreous Humor -- Saliva -- Digestive Fluids -- Pathological Cyst Fluid -- Further Reading -- Relevant Website -- 029-v01-142-152-9780123744173 -- Biological Applications of IR -- Introduction -- Microbiological Applications -- Botanical Applications -- Biomedical and Clinical Applications -- Further Reading -- 030-v01-153-165-9780123744173 -- Biomacromolecular Applications of Circular Dichroism and ORD -- Proteins and Polypeptides -- Analysis of the Secondary Structure of Proteins -- Determination of the Thermodynamics of Protein Folding. , Analysis of Conformational Transitions -- Detection of Folding Intermediates -- Determination of the kinetics of protein folding -- Analysis of Protein-Ligand Interactions -- Nucleic Acids -- Analysis of the Secondary Structure of Polynucleotides -- Homopolynucleotides -- Heteropolynucleotides -- Analysis of Conformational Transitions of Nucleic Acids -- Analysis of Ligand Binding to Nucleic Acids -- Carbohydrates -- Determination of Carbohydrate Structure and Linkages -- Analysing Conformational Transitions of Carbohydrates Using CD and ORD -- Further Reading -- 031-v01-166-173-9780123744173 -- Biomacromolecular Applications of UV-Visible Absorption Spectroscopy -- 032-v01-174-182-9780123744173 -- Biomedical Applications of Atomic Spectroscopy -- 033-v01-183-184-9780123744173 -- Biometallics/Metallomics Techniques and Applications -- Introduction -- Intrinsic Bioelement Determination (P, S, Se, I, and Other Metals) -- Extrinsic Metal Tag Determination -- Further Reading -- 034-v01-185-193-9780123744173 -- Biomolecular X-Ray Crystallography, Structure Determination Methods -- Diffraction Theory and Structure Synthesis -- Crystal Symmetry -- Space Group Symmetry -- Assigning the Space Group -- Sample Preparation and Crystallogenesis -- Data Collection -- X-ray Sources -- Detectors -- Cryo-Freezing -- Data Processing Software -- Mosflm and Scala -- XDS/XSCALE -- Phase Problem -- The Patterson Methods -- MIR Phasing -- MAD Phasing -- SAD Phasing -- Molecular Replacement -- Direct Methods -- Electron Density Improvement -- Structure Refinement -- Further Reading -- 035-v01-195-203-9780123744173 -- Calibration and Reference Systems (Regulatory Authorities) -- Overview -- Spectroscopic Coverage -- 036-v01-204-211-9780123744173 -- Carbohydrates Studied by NMR -- Introduction -- Sample Preparation -- Analysis of Carbohydrate Structure by NMR. , 1H NMR of Carbohydrates.