Chemistry Books

Book SynopsisOSHA (29 CFR 1910.119) has recognized AIChE/DIERS two-phase flow publications as examples of good engineering practice for process safety management of highly hazardous materials. The prediction of when two-phase flow venting will occur, and the applicability of various sizing methods for two-phase vapor-liquid flashing flow, is of particular interest when designing emergency relief systems to handle runaway reactions. This comprehensive sourcebook brings together a wealth of information on methods that can be used to safely size emergency relief systems for two-phase vapor-liquid flow for flashing or frozen, viscous or nonviscous fluids. Design methodologies are illustrated by selected sample problems. Written by industrial experts in the safety field, this book will be invaluable to those charged with operating, designing, or managing today''s and tomorrow''s chemical process industry facilities.Table of ContentsPreface. Introduction. 1. Overview. 2. Design Institute for Emergency Relief Systems (DIERS). 3. A Strategy for Major Accidental Release Prevention. 4. A Strategy for Emergency Relief System Design. 5. An Approach to Emergency Relief System Design Assessment. 6. Two-Phase Vapor-Liquid Flow. 7. Two-Phase Vapor-Liquid Flow Onset and Disengagement. 8. Two-Phase Vapor-Liquid Hydrodynamics. 9. DIERS Bench-Scale Apparatus. 10. Runaway Reaction Emergency Relief System Design Computer Program. 11. References. Appendix A. DIERS Committees. Appendix B. DIERS Sponsors. Appendix C. DIERS Contractors. Chapter I. Vapor Disengagement Dynamics. 1. Overview. 1.1 Vapor Disengagement Dynamics. 1.2 Design Considerations. 2. Detailed Discussion. 2.1 Open Literature References. 2.2 Project Manual. 3. References. Appendix I-A The Coupling Equation and Flow Models. Appendix I-B Best Estimate Procedure to Calculate Two-Phase Vapor-Liquid Flow Onset/Disengagement. Appendix I-C Fluid Behavior in Venting Vessels. Appendix I-D Energy and Material Balance Derivations for Emergency Pressure Relief of Vessels. Annex I-D1 Internal Energy and Venting Calculations. Chapter II. Pressure Relief System Flow. 1. Introduction. 1.1 Scope. 1.2 Organization. 1.3 Special Terminology. 2. Recommended Design Methods. 2.1 Newtonian Flow. 2.2 Complex Fluids. 2.3 Useful Approximations. 3. Technology Base. 3.1 General Flow Equations. 3.2 Nozzle Flow Models. 3.3 Sharp Reductions. 3.4 Pressure Recovery/Expansions/Equilibrations. 3.5 Pipe Flow. 3.6 Application to Pressure Relief System Elements. 3.7 Networks. 3.8 Complex Fluids. 4. Nomenclature. 5. Acknowledgments. 6. References. Appendix II-A Thermophysical Property Requirements. Appendix II-B Equilibrium Flash Calculations. Appendix II-C Model Parameters for Pipe Entrance Sections. Appendix II-D Computer Routines in SAFIRE Program. Appendix II-E Example Problems. Appendix II-F Generalized Correlations and Design Charts. Chapter III. DIERS Phase III Large-Scale Integral Tests. 1. Summary. 2. Introduction. 2.1 Program Objectives. 2.2 Program Description. 3. Test Configurations. 4. Test Results. 4.1 Tests T1 to T8 4.2 Tests V32-W1 to V32-W8. 4.3 Tests T9, T10, T11, T14, and T15. 4.4 Tests T12 and T13. 4.5 Tests T20. 4.6 Tests T17 and T18. 4.7 Tests T21, T22, T23, and T24. 4.8 ICRE Tests 32-6 to 32-11. 4.9 ICRE Tests 2000-1 to 2000-5. 4.10 ICRE Tests 32-14, 32-15, and 32-18. 5. Acknowledgments. 6. References. Appendix III-A Test Configurations. Appendix III-B Experimental Results and Model Comparisons. Appendix III-C Kinetics Model for Styrene Polymerizations. Chapter IV. High Viscosity Flashing Two-Phase Flow. 1. Introduction. 1.1 General Discussion of High Viscosity Flow in Relief Systems. 1.2 Why High Viscosity Systems Require Special Consideration. 1.3 Necessity for Conservatism. 2. Summary of DIERS High Viscosity Relief Flow Tests. 2.1 Project Overview. 2.2 Styrene Reactive Tests. 2.3 Small-Scale Rubber Cement Bottom-Vented tests. 2.4 Large-Scale Rubber Cement Tests. 2.5 Large-Scale Polystyrene-Ethylbenzene Bottom-Vented Tests. 3. Recommended Design Practices. 3.1 Theory and Scaling for Highly Viscous Systems. 3.2 General Equations for Newtonian Fluids. 3.3 Approximate Momentum Balances for Scaling Power-Law and Newtonian Fluids. 3.4 Scaling Using Integrated Approximate Momentum Balance for Newtonian Fluids. 3.5 Scaling Using Approximate Momentum Balance for Power-Law Fluids. 4. Unanswered Questions about High Viscosity Flow. 4.1 Uncertainties. 5. References. Appendix IV-A Simplified Theory and Sample Problems. Chapter V. Containment, Disposal, and Mechanical Design. 1. Introduction. 2. Blowdown in Drum Design. 2.1 Types of Knock-Out (Blowdown) Drums and Catchtanks. 2.2 Sizing of Blowdown Drums. 3. Disposal of Vapors from Blowdown Drums. 3.1 Direct Discharge to the Atmosphere. 3.2 Discharge through a Scrubber. 3.3 Discharge through a Vent Condenser. 3.4 Discharge to a Flare Stack or Incinerator. 4. Mechanical Design. 4.1 Vent Piping Considerations. 4.2 Catchtank Mechanical Design and Safety Considerations. 4.3 Reaction Forces—General. 4.4 Reaction Forces Equations. 4.5 Reaction Forces on Safety Valve Nozzles/Piping. 4.6 Reaction Forces from Rupture Disk Discharge. 4.7 Transient Effects of Reaction Forces, Rupture Disk Discharge. 4.8 Thrust Restraint Design. 4.9 Other Blowdown Load Considerations. 5. References. Chapter VI. DIERS Bench-Scale Apparatus. 1. Background. 1.1 DIERS Requirements for a Bench-Scale Apparatus. 1.2 Limitations of Previous Test Equipment. 2. How the Test Methodology Fits into the Overall Process Safety Design. 2.1 Requests. 2.2 Worst Credible Incident Scenario. 2.3 Screening Tests. 2.4 DIERS Venting Tests and Analysis. 2.5 Recommendations. 3. Description of the DIERS Bench-Scale Apparatus. 3.1 Schematic Description of Apparatus. 3.2 Apparatus Control and Data Recording. 3.3 Test Cell Configurations. 4. Emergency Relief System (ERS) Sizing Using the DIERS Bench-Scale Apparatus. 4.1 Emergency Relief System (ERS) Overview. 4.2 Functions of the Bench-Scale Apparatus. 4.3 Onset/Disengagement Behavior Testing. 4.4 Flow Rate Calculation/Viscosity Characterization. 4.5 Characterization of Runaway Reaction Behavior. 4.6 ERS Design—Analytical Methods/FAI Nomograph. 4.7 ERS Design—Area: Charge Scaling (Top Vent Test/Top ERS Device). 4.8 ERS Design—Area: Charge Scaling/Scaling Equation Method (Bottom Vent Test/Top or Bottom ERS Devices). 4.9 Limitations on Area: Charge Scaling for ERS Design. 5. References. Appendix V1-A Experimental ERS Sizing—Some Do and Do Not Recommendations. Chapter VII. SAFIRE Computer Program for Emergency Relief Sizing. 1. Background. 1.1 History. 1.2 Overview. 2. Program Description. 2.1 Overall Architecture. 2.2 Pure-Component Physical Properties. 2.3 Mixture handling Rules. 2.4 Flash Calculations. 2.5 Chemical Reactions. 2.6 Vent Flow Calculations. 2.7 Vessel Hydrodynamics. 2.8 External Heat Fluxes. 2.9 Mass and Energy Balances. 3. Data Input. 4. Sample Problem. 5. Experience with Program. 6. References. Appendix VII-A Input Data Forms. Appendix VII-B Sample Input/Output. Index.

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Book SynopsisFirst-line managers have to maintain the integrity of facilities, control manufacturing processes, and handle emergency situations, as well as respond to the pressures of production demand. This book offers these managers how-to information on process safety management program execution in the operations and maintenance departments.Table of ContentsPreface. Acknowledgments. List of Tables. List of Figures. Glossary. 1. INTRODUCTION. 1.1 Process Safety Management Activities of the Center for Chemical Process Safety (CCPS). 1.2 Process Safety Activities of Governmental Agencies and Trade Organizations. 1.3 Target Audience and Objective of This Document. 1.4 Use of This Document. 1.5 References. 2. ROLE OF OPERATIONS AND MAINTENANCE IN PROCESS SAFETY MANAGEMENT. 2.1 Accountability. 2.2 Process Knowledge and Documentation. 2.3 Capital Project Review and Design Procedures. 2.4 Process Risk Management. 2.5 Process and Equipment Integrity. 2.6 Human Factors. 2.7 Training and Performance. 2.8 Incident Investigation. 2.9 Standards, Codes, and Regulations. 2.10 Audits and Corrective Action. 2.11 Enhancement of Process Safety Knowledge. 2.12 Management of Change. 2.12.1 Importance of Changes. 2.12.2 Examples of Lessons To Be Learned from the Failure to Manage Change. 2.12.3 What Constitute Change? 2.12.4 Process Change Authorization. 2.13 Summary. 2.14 References. 3. PLANT DESIGN. 3.1 Operations and Maintenance Departments’ Roles. 3.2 Documentation. 3.3 Process Hazard Reviews. 3.4 Designing for Inherent Process Safety. 3.4.1 Process Fluids. 3.4.2 Inventory Minimization. 3.4.3 Operating and Storage Conditions. 3.5 Controlling of Hazards to Reduce Risks. 3.6 Plant Layout. 3.6.1 Site Planning. 3.6.2 Process Area Layout. 3.7 Plant Standards and Practices. 3.8 Human Factors in Plant Design. 3.9 Maintenance Considerations. 3.10 Management of Change. 3.11 References. 4. PLANT CONSTRUCTION. 4.1 Roles of the Operations and Maintenance Department. 4.1.1 Communication and Coordination with Project Team. 4.1.2 Control of Specific Construction-Related Activities. 4.1.3 Inspection of Equipment Installation. 4.2 Materials of Construction. 4.3 Custom Equipment Fabrication and Inspection. 4.4 Field Installation. 4.4.1 Piping Installation. 4.4.2 Pressure-Relief/Vent Collection. 4.4.3 Other Safety Systems. 4.5 Equipment Recordkeeping. 4.6 Summary. 4.7 References. 5. PRE-STARTUP AND COMMISSIONING. 5.1 Organization and Roles. 5.1.1 Startup Team. 5.1.2 Role of Operations and Maintenance Departments. 5.2 Planning. 5.3 Preparation for Startup. 5.3.1 Staffing Operations and Maintenance Departments. 5.3.2 Training. 5.3.3 Maintenance Activities during Pre-startup. 5.3.4 Development of Operating Procedures. 5.4 Pre-startup Safety Review. 5.5 Commissioning. 5.5.1 Commissioning Utilities. 5.5.2 Commissioning Equipment. 5.5.3 Instruments, Computer, and Control. 5.6 Final Preparations for Startup. 5.7 References. 6. STARTUP. 6.1 Roles and Responsibilities. 6.2 Initial Startup. 6.2.1 Final Preparation. 6.2.2 Introduction of Process Chemicals and Materials. 6.2.3 Process and Process Equipment Monitoring. 6.2.4 Baseline Data. 6.2.5 Updating Startup Procedures. 6.3 Restart. 6.4 Startup after Turnaround. 6.5 Startup after Extended Outage. 6.6 Resources. 6.7 Summary. 6.8 References. 7. OPERATION. 7.1 Roles and Responsibilities. 7.2 Routine Operations. 7.2.1 Operating within Process and Equipment Limits. 7.2.2 Written Procedures. 7.2.3 Communication. 7.2.4 Communication During Shift Changes. 7.2.5 Special Safety Considerations of Batch Processes. 7.2.6 Process Control Software. 7.3 Nonroutine Operations. 7.3.1 Abnormal Operations. 7.3.2 Standby Operations. 7.4 Emergency Operations. 7.5 Management of Change. 7.6 Safety Protective Systems. 7.6.1 Safety Shutdown Systems. 7.6.2 Pressure Relief Equipment. 7.7 Operator Training. 7.7.1 Refresher Training. 7.7.2 Playing “What-If” Games. 7.8 Incident Investigation. 7.8.1 Recognizing and Reporting Incidents. 7.8.2 The Investigation. 7.8.3 Investigation Results and Followup. 7.9 Human Factors. 7.9.1 Human-Process Interfaces. 7.9.2 Behavioral Issues. 7.9.3 Spontaneous Response. 7.10 Audits, Inspections, Compliance Reviews. 7.11 Summary. 7.12 References. 8. MAINTENANCE. 8.1 Roles and Responsibilities. 8.2 Routine Maintenance. 8.2.1 Preventive Maintenance. 8.2.2 Predictive Maintenance. 8.2.3 Communication between the Maintenance and Operations Departments. 8.2.4 Communication at Shift Change. 8.3 Nonroutine Maintenance. 8.3.1 Breakdown Maintenance. 8.3.2 Troubleshooting Maintenance. 8.4 Management of Change. 8.5 Aging Equipment. 8.5.1 Corrosion, Erosion, and Fatigue. 8.5.2 Wear, Intermittent Operation, and Fouling. 8.6 Critical Instrumentation and Safety Interlocks. 8.6.1 Proof Testing. 8.6.2 Critical Instrumentation and Interlock Classification. 8.7 Maintenance Training. 8.7.1 Upgrade and Refresher Training. 8.7.2 Loss of Plant-Specific Maintenance Knowledge. 8.8 Work Permits. 8.9 Maintenance Management Information Systems. 8.9.1 Work Order Tracking. 8.9.2 Process Equipment Files. 8.9.3 Process and Equipment Drawings. 8.10 Quality Control. 8.10.1 Replacement Parts. 8.10.2 Inspection. 8.10.3 Certified Equipment. 8.10.4 Continuous Improvement. 8.11 Contractor Safety. 8.12 Incident Investigation. 8.13 Summary. 8.14 References. Addition References. 9. SHUTDOWN. 9.1 Normal Shutdown. 9.1.1 Pre-shutdown Planning. 9.1.2 Shutdown Sequence Steps. 9.1.3 Testing Safety Protective Systems. 9.1.4 Shutdown Period Maintenance Activities. 9.1.5 Unit Restart after Maintenance. 9.1.6 Formal Review of Shutdown. 9.2 Extended or Mothball Shutdown. 9.3 Sudden or Emergency Shutdown. 9.3.1 Preplanning for Student Shutdown. 9.3.2 Shutdown Sequences. 9.3.3 Safety Interlock Failures. 9.3.4 Investigation of Sudden Shutdown. 9.4 Emergency Response. 9.5 Summary. 9.6 References. 10. DECOMMISSIONING AND DEMOLITION. 10.1 Decommissioning/Demolition Plan. 10.2 Operation and Maintenance Roles. 10.3 Decommissioning Procedures. 10.4 Maintenance of Decommissioned Status. 10.5 Demolition Concerns. 10.6 Summary. 10.7 References. Appendix A. Summary of the Process Safety Management Rule Promulgated by the Occupational Safety and Health Administration, United States Department of Labor. Appendix B. Example Management Guidelines for the Safe Dismantling and Demoliton of Process Plants. Appendix C. Examples of Site-Specific Demolition Checklist/Questionnaire. Index.

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Book SynopsisDeals with prevention, preparedness, response and recovery, which are the key components of emergency planning. This book first describes PSM (Process Safety Management), then goes on to consider the main features of a preparedness program, including recognizing credible incidents, planning strategy to deal with these incidents, and more.Table of ContentsPreface. Acknowledgments. Acronyms. PART A. PREVENTION. 1. Prevention Through Process Safety Management. 1.1 Technical Management of Chemical Process Safety: Basic Elements. 1.2 The Role of Emergency Preparedness. References Cited. 2. Prevention And Mitigation. 2.1 Introduction. 2.2 Principles of Prevention. 2.2.1 Process Hazard Recognition. 2.2.2 Inherently Safer Plants. 2.2.3 Process Design Modification. 2.3 Principles of Mitigation. 2.3.1 Plant Siting/Buffers. 2.3.2 Unit Siting in Plant Design. 2.3.3 Principles of Mitigating Chemical Releases. 2.3.4 Postrelease Mitigation Systems. 2.3.5 Principles of Mitigrating Fires and Explosions. References Cited. PART B. PREPAREDNESS. 3. Identification of Credible Incidents. 3.1 Introduction. 3.2 Defining Credible Incidents. 3.3 Screening Techniques to Identify Focus Areas. 3.3.1 NFPA Fire Hazard Indices. 3.3.2 Toxicity/Mobility/Quantity Index. 3.3.3 Chemical Process Risk Indices. 3.4 Techniques For Identifying Credible Incidents For Emergency Planning. 3.4.1 Informal “Expert” Review. 3.4.2 Hazard Review to Support Emergency Planning. 3.4.3 Using Process Hazard Analysis to Support Emergency Planning. 3.5 Prioritizing Emergency Planning Incidents for Consequence Assessment. 3.6 Assessing Consequences and Impacts. 3.6.1 Tools. 3.6.2 Criteria for Defining Sensitive Areas. 3.6.3 Unexpected Hazards. 3.6.4 Other Effects. 3.7 Criteria for Selecting Incidents for Emergency Planning. 3.8 Reviewing Mitigation Systems. References Cited. Appendix A, Emergency Planning Guidelines: ERPGs/EEPGs. 4. Conceptual Approach to Emergency Response. 4.1 Introduction. 4.2 Capability and Resource Assessment. 4.2.1 Trained Personnel. 4.2.2 On-Site Response Equipment. 4.2.3 Response Equipment Available Off-Site. 4.2.4 Facilities. 4.2.5 Specialized Supplies and Contractors. 4.3 Determine Concept of Emergency Operations. 4.3.1 Effective Use of Inside and Outside Response. 4.3.2 Organizing for Credible Incident. 4.3.3 Classification of Emergencies. 4.4 Regulatory Considerations. 4.5 The Effect of Change on Emergency Preparedness. References Cited. 5. Developing Response Tactics. 5.1 Introduction. 5.2 Principles of Responding to Fires. 5.2.1 Plant Fire Response Organization. 5.2.2 Integration of On-Site Fire Brigades and Off-Site Departments. 5.2.3 Response Tactics. 5.3 Hazardous Materials. 5.3.1 Hazardous Materials Response Regulations. 5.3.2 Hazmat Initial Assessment and Size-Up. 5.3.3 Hazmat Reconnaissance. 5.3.4 Work Zones. 5.5.5 Hazmat Tactical Action Plan. 5.5.6 Continual Reassessments. 5.5.7 Termination. References Cited. 6. Physical Facilities and Systems. 6.1 Introduction. 6.2 Facilities. 6.2.1 Short-Term Shelters and Safe Havens. 6.2.2 Emergency Operations Center (EOC). 6.2.3 Incident Scene Areas. 6.2.4 Media Information Center (MIC). 6.2.5 Control Rooms. 6.2.6 Medical Support Facilities. 6.2.7 Adequate Water Supplies. 6.3 Systems. 6.3.1 Detection/Early Warning Systems. 6.3.2 Communications System Design. 6.3.3 Community and Site Alerting and Notification Systems. 6.3.4 Computer Systems for Emergency Management. 6.3.5 Site Maps and Diagrams for Emergency Management. 6.3.6 Emergency Power Systems. 6.3.7 Weather Stations. References Cited. 7. Response Equipment and Supplies. 7.1 Introduction. 7.2 Fire Apparatus. 7.3 Extinguishing Agents. 7.3.1 Water 7.3.2 Foams. 7.3.3 Dry Chemicals. 7.3.4 Dry Powders. 7.3.5 Halon. 7.3.6 Carbon Dioxide. 7.3.7 Miscellaneous Agents. 7.4 Inhibitors, Neutralizers, Sorbents. 7.4.1 Inhibitors. 7.4.2 Neutralizers. 7.4.3 Sorbents. 7.5 Personal Protective Equipment. 7.5.1 Materials for Protective Clothing. 7.5.2 Considerations. 7.5.3 Flash Protection. 7.5.4 Thermal Protection. 7.5.5 Choosing Appropriate Levels of Protection. 7.5.6 Respiratory Protection. 7.6 Heavy Equipment. 7.7 Adequate Inventory and Alternate/Outside Sources of Supply. References Cited. Appendix A. Channel Industry Standards for Apparatus. 8. Developing a Workable Plan. 8.1 Introduction. 8.2 Review Existing Plans or Procedures. 8.2.1 Review Existing Emergency-Related Facility Plans. 8.2.2 Review Neighboring Facility Plans. 8.2.3 Review Community Plans. 8.3 Determining Appropriate Plan Type. 8.3.1 Plan Types. 8.3.2 Plans, Procedures, and Instructions. 8.3.3 Coordination and Commonalty. 8.4 Determining Content. 8.5 Preparedness. 8.5.1 Training. 8.5.2 Drills and Exercises. 8.5.3 Supplies and Equipment. 8.5.4 Community Awareness. 8.5.5 Medical Surveillance Program. 8.6 General Response Procedures. 8.6.1 Alerting and Warning. 8.6.2 Communications. 8.6.3 Management Functions. 8.6.4 Evacuation and Personnel Accountability. 8.6.5 Emergency Shutdown Procedures. 8.6.6 Security. 8.6.7 Mutual Aid. 8.6.8 Public Information/Media. 8.6.9 Special Notifications and Fatality Procedure. 8.6.10 Reporting Requirements. 8.7 Hazard-Specific Procedures. 8.7.1 Fire. 8.7.2 Chemical Release. 8.7.3 Medical and Rescue. 8.7.4 Hurricane. 8.7.5 Tornado and High Wind. 8.7.6 Freeze/Winter Storm. 8.7.7 Flood. 8.8 Writing the Plan. 8.9 Ensure Integration with Other Plans. 8.10 Plan Review and Maintenance. 8.11 Exercise Regularly/Critique to verify Planning Assumptions. 8.11.1 Planning an Exercise. 8.11.2 Exercising without Interfering with Plant Operations. References Cited. Appendix A. Regulations Applicable to Emergency Equipment and Supplies. Appendix B. Sample Emergency Procedures Format and Instruction. 9. Using Modeling for Emergency Planning. 9.1 Introduction. 9.2 Consequence Analysis. 9.3 Using Models for Developing Emergency Response Plans. 9.3.1 Input Data Needs. 9.3.2 Interpretation of Results. 9.4 Utilizing Appropriate Models. 9.5 Real-Time Emergency Response Modeling Systems. References Cited. 10. Training Requirements. 10.1 Introduction. 10.2 General Requirements. 10.2.1 OSHA Emergency Training Requirements. 10.2.2 Basic Emergency Training. 10.2.3 Operating Personnel. 10.3 Emergency Response Personnel. 10.3.1 General. 10.3.2 Fire Brigade Training. 10.3.3 Hazardous Materials Response Training. 10.4 Support Personnel. 10.4.1 Media and Community Relations. 10.4.2 Medical. 10.4.3 Specialist Employees. 10.4.4 Security. 10.4.5 Skilled Support Personnel. References Cited. PART C. RESPONSE. 11. Key Response Functions. 11.1 Incident Command System. 11.1.1 Definition. 11.1.2 Characteristics of an ICS. 11.1.3 Considerations for ICS. 11.2 Strategy Development. 11.2.1 Assessment and Decision Making. 11.2.2 Evaluate Additional Resources Needs. 11.3 Determine Mitigation Tactics. 11.3.1 Evaluate Need for Off-Site Warnings. 11.4 Implement Tactical Plan and Evaluate. 11.5 Response Team Decontamination. 11.5.1 Types of Contamination. 11.5.2 Prevention of Contamination. 11.5.3 Decontamination Methods. 11.5.4 Determining Effectiveness. 11.5.5 Planning for Decontamination. 11.6 Medical Decontamination/Triage/Treatment. 11.7 Using Dispersion Modeling During Emergencies. 11.8 Termination. References Cited. Appendix A. Channel Industries Mutual Aid ICS Worksheet. 12. Support Functions, Systems, and Facilities. 12.1 Introduction. 12.2 Functions. 12.2.1 Internal Management and Technical Support. 12.2.2 Security. 12.2.3 Legal. 12.2.4 Outside Technical Support. 12.2.5 Reporting Requirements. 12.2.6 Public Relations. 12.3 Systems. 12.3.1 Mutual Aids. 12.3.2 Communications System Operation. References Cited. PART D. RECOVERY. 13. Managing Recovery. 13.1 Introduction. 13.2 Management During Recovery. 13.3 Scene Security and Safety. 13.4 Employee Assistance. 13.4.1 General. 13.4.2 Supervisors’ Role. 13.4.3 Human Resources Department. 13.4.4 Federal Assistance. 13.5 Damage Assessment. 13.6 Process Data collection. 13.7 Incident Investigation. 13.8 Restoring Safety and Emergency Systems. 13.9 Legal. 13.10 Insurance. 13.11 Public Information and Communication. 13.11.1 Business Relationships. References Cited. Appendix A. Sample Recovery Management Checklist. Appendix B. Sample Damage Assessment Checklist. 14. Cleanup of Facilities. 14.1 Introduction. 14.2 Types and Forms of Contamination. 14.2.1 Chemical Contamination. 14.2.2 Radioactive Contamination. 14.3 Preventing the Spread of Contamination. 14.4 Decontamination Methods. 14.4.1 Small-Scale Decontamination. 14.4.2 Large-Scale Decontamination of Facilities. 14.5Contractor Qualifications for Cleanup. 14.6 Determining the Effectiveness. General References. Bibliography. Glossary. Index.

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Book SynopsisGood written procedures can reduce the number of accidents caused by human error. This book shows how to remedy this problem through selecting and implementing actions that promote safe, efficient operations and maintenance, improve quality and cost control. It also includes practical samples of procedure formats, checklists and many references.Table of ContentsPreface. Acknowledgments. Glossary. Chapter 1. Introduction to Effective Procedure Writing. 1.1. Why Was This Book Written? 1.2. Book Objectives. 1.3. The Current Worldwide Trend Toward Procedures. 1.4. Who Should Use This Book? 1.5. Where Do You Go From Here? Chapter 2. Process Safety Environmental, and Quality Considerations. 2.1. Purpose. 2.2. Understanding the Guidelines and Regulations. 2.3. Voluntary Guidelines. 2.4. Governmental Regulations. 2.5. Quality Considerations. 2.6. Some Elements of Effective Procedures and Procedure. Management Systems. 2.7. Additional Considerations. 2.8. Conclusion. Endnotes. Chapter 3. How to Design An Operating and Maintenance Procedure Management System. 3.1. Purpose. 3.2. The Importance of Written Procedures. 3.3. Elements of a Comprehensive Procedure Management System. 3.4. Determining Procedure Management System Requirements. 3.5. Evaluating Your Current Practices. 3.6. Identifying Your Resources. 3.7. Designing and Implementing Your Procedures Management System. 3.8. How to Determine Which Procedures to Write. 3.9. Implementing a Procedure Project. 3.10. Procedure Training. 3.11. Maintaining and Improving Your Procedure Management System. 3.12. Conclusion. Chapter 4. Writing Operating and Maintenance Procedures. 4.1. Purpose. 4.2. What Resources Do You Need Before You Begin Writing? 4.3. What Do We Know About the Procedure. 4.4. Considerations for Effective Procedures. 4.5. Importance of Procedure Format. 4.6. Introductory Sections. 4.7. Procedure Steps Section. 4.8. Drafting the Procedure. 4.9. The Procedure Review and Approval Cycle. 4.10. Special Considerations for Maintenance Procedures. 4.11. Batch Process Considerations. Chapter 5. Elements of Effective Procedures. 5.1. Purpose. 5.2. Importance of Procedure Evaluation Criteria. 5.3. Who Will Use the Procedure Evaluation Criteria? 5.4. Procedure Checklists Elements. Endnotes. Chapter 6. Writing Emergency Operating Procedures. 6.1. Purpose. 6.2. Defining Events Requiring Emergency Operating Procedures. 6.3. Identifying Emergency Situations. 6.4. Developing and Writing Emergency Operating Procedures. 6.5. Directing the User to the Correct Emergency Operating Procedure. 6.6. Incorporating Human Factors in Emergency Operating Procedures. 6.7. using Decision Aids. 6.8. How Emergency Operating Procedures Link to the Emergency Response Plan. Endnotes. Chapter 7. Procedure Control. 7.1. Purpose. 7.2. What Is Procedure Control? 7.3. Controlling Procedure Revisions and Development. 7.4. Who Should Review the Procedures? 7.5. Procedure Approval. 7.6. Evaluating Procedures In Use. 7.7. Electronic Document Control. Chapter 8. Procedure Development Costs and Benefits. 8.1. Purpose. 8.2. reasons for Procedure Development. 8.3. Procedure Development Costs. 8.4. Return on Investment: Improvements You Can Expect from Effective Procedures. Endnotes. Appendix A. Selected Procedure Initiatives, Consensus Codes, and Regulations Affecting Procedures. Appendix B. Common Points of API, OSHA, and EPA. Appendix C. How to Determine the Tasks That Require Written Procedures. Appendix D. Procedure Performance Evaluation. Appendix E. Procedure Criteria Checklist. Appendix F. Sample Procedure Formats. Appendix G. Sample Formats of Operating Limits Tables. General References. Index.

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Book SynopsisChemical process quantitative risk analysis (CPQRA) is used to identify incident scenarios and evaluate their risk by defining the probability of failure, the various consequences and the potential impact of those consequences. This edition offers a guide to applying these risk-analysis techniques, particularly to risk control studies.Table of ContentsPreface. Preface to the First Edition. Acknowledgments. Acknowledgments to the First Edition. Management Overview. Organization of the Guidelines. Acronyms. 1. CHEMICAL PROCESS QUANTITATIVE RISK ANALYSIS. 1.1 CPQRA Definitions. 1.2 Component Techniques of CPQRA. 1.2.1 Complete CPQRA Procedure. 1.2.2 Prioritized CPQRA Procedure. 1.3 Scope of CPQRA Studies. 1.3.1 The Study Case. 1.3.2 Typical Goals of CPQRAs. 1.4 Management of Incident Lists. 1.4.1 Enumeration. 1.4.2 Selection. 1.4.3 Tracking. 1.5 Applications of CPQRA. 1.5.1 Screening Techniques. 1.5.2 Applications within Existing Facilities. 1.5.3 Applications within New Projects. 1.6 Limitations of CPQRA. 1.7 Current Practices. 1.8 Utilization of CPQRA Results. 1.9 Project Management. 1.91. Study Goals. 1.9.2 Study Objectives. 1.9.3 Depth of Study. 1.9.4 Special User Requirements. 1.9.5 Construction of a Project Plan. 1.9.6 Project Execution. 1.10 Maintenance of Study Results. 1.11 References. 2. CONSEQUENCE ANALYSIS. 2.1 Source Models. 2.1.1 Discharge Rate Models. 2.1.2 Flash and Evaporation. 2.1.3 Dispersion Models. 2.2 Explosions and Fires. 2.2.1 Vapor Cloud Explosions (VCE). 2.2.2 Flash Fires. 2.2.3 Physical Explosion. 2.2.4 BLEVE and Fireball. 2.2.5 Confined Explosions. 2.2.6 Pool Fries. 2.2.7 Jet Fires. 2.3 Effect Models. 2.3.1 Toxic Gas Effects. 2.3.2 Thermal Effects. 2.3.3 Explosion Effects. 2.4 Evasive Actions. 2.4.1 Background. 2.4.2 Description. 2.4.3 Example Problem. 2.4.4 Discussion. 2.5 Modeling Systems. 2.6 References. 3. EVENT PROBABILITY AND FAILURE FREQUENCY ANALYSIS. 3.1 Incident Frequencies from the Historical Record. 3.1.1 Background. 3.1.2 Description. 3.1.3 Sample Problem. 3.1.4 Discussion. 3.2 Frequency Modeling Techniques. 3.2.2 Event Tree Analysis. 3.3 Complementary Plant-Modeling Techniques. 3.3.1 Common Cause Failure Analysis. 3.3.2 Human Reliability Analysis. 3.3.3 External Events Analysis. 3.4 References. 4. MEASUREMENT, CALCULATION, AND PRESENTATION OF RISK ESTIMATES. 4.1 Risk Measures. 4.1.1 Risk Indices. 4.1.2 Individual Risk. 4.1.3 Societal Risk. 4.1.4 Injury Risk Measures. 4.2 Risk Presentation. 4.2.1 Risk Indices. 4.2.2 Individual Risk. 4.2.3 Societal Risk. 4.3 Selection of Risk Measures and Presentation Format. 4.3.1 Selection of Risk Measures. 4.3.2 Selection of Presentation Format. 4.4 Risk Calculations. 4.4.1 Individual Risk. 4.4.2 Societal Risk. 4.4.3 Risk Indices. 4.4.4 General Comments. 4.4.5 Example Risk Calculation Problem. 4.4.6 Sample Problem Illustrating That F-N Curves Cannot be Calculated from individual Risk Contours. 4.5 Risk Uncertainty, Sensitivity, and Importance. 4.5.1 Uncertainty. 4.5.2 Sensitivity. 4.5.3 Importance. 4.6 References. 5. CREATION OF CPQRA DATA BASE. 5.1 Historical Incident Data. 5.1.1 Types of Data. 5.1.2 Sources. 5.2 Process and Plant Data. 5.2.1 Plant Layout and System Description. 5.2.2 Ignition Sources and Data. 5.3 Chemical Data. 5.3.1 Types of Data. 5.3.2 Sources. 5.4 Environmental Data. 5.4.1 Population Data. 5.4.2 Meteorological Data. 5.4.3 Geographical Data. 5.4.4 Topographic Data. 5.4.5 External Event Data. 5.5 Equipment Reliability Data. 5.5.1 Terminology. 5.5.2 Types and Sources of Failure Rate Data. 5.5.3 Key Factors Influencing Equipment Failure Rates. 5.5.4 Failure Rate Adjustment Factors. 5.5.5 Data Requirements and Estimated Accuracy. 5.5.6 Collection and Processing of Raw Plant Data. 5.5.7 Preparation of the CPQRA Equipment Failure Rate Data Set. 5.5.8 Sample Problem. 5.6 Human Reliability Data. 5.7 Use of Expert Opinions. 5.8 References. 6. SPECIAL TOPICS AND OTHER TECHNIQUES. 6.1 Domino Effects. 6.1.1 Background. 6.1.2 Description. 6.1.3 Sample Problem. 6.1.4 Discussion. 6.2 Unavailability Analysis of Protective Systems. 6.2.1 Background. 6.2.2 Description. 6.2.3 Sample Problem. 6.2.4 Discussion. 6.3 Reliability Analysis of Programmable Electronic Systems. 6.3.1 Background. 6.3.2 Description. 6.3.3 Sample Problem. 6.3.4 Discussion. 6.4 Other techniques. 6.4.1 MORT Analysis. 6.4.2 IFAL Analysis. 6.4.3 Hazard Warning Structure. 6.4.4 Markov Processes. 6.4.5 Monte Carlo Techniques. 6.4.6 GO Methods. 6.4.7 Reliability Book Diagrams. 6.4.8 Cause-Consequence Analysis. 6.4.9 Multiple Failure/Error Analysis (MFEA). 6.4.10 Sneak Analysis. 6.5 References. 7. CPQRA APPLICATION EXAMPLES. 7.1 Simple/Consequence CPQRA Examples. 7.1.1 Sample/Consequence CPQRA Characterization. 7.1.2 Application to a New Process Unit. 7.1.3 Application to an Existing Process Unit. 7.2 Intermediate/Frequency CPQRA Examples. 7.2.1 Intermediate/Frequency CPQRA Characterization. 7.2.2 Application to a New Process Unit. 7.2.3 Application to Existing Process Unit. 7.3 Complex/Risk CPQRA Examples. 7.3.1 Complex/Risk Cpqra Characterization. 7.3.2 Application to a New or Existing Process Unit. 7.4 References. 8. CASE STUDIES. 8.1 Chlorine Rail Tank Car Loading Facility. 8.1.1 Introduction. 8.1.2 Description. 8.1.3 Identification, Enumeration, and Selection of Incidents. 8.1.4 Incident Consequence Estimation. 8.1.5 Incident Frequency Estimation. 8.1.6 Risk Estimation. 8.1.7 Conclusions. 8.2 Distillation Column. 8.2.1 Introduction. 8.2.2 Description. 8.2.3 Identification, Enumeration, and Selection of Incidents. 8.2.4 Incident Consequence Estimation. 8.2.5 Incident Frequency Estimation. 8.2.6 Risk Estimation. 8.2.7 Conclusions. 8.3 References. 9. FUTURE DEVELOPMENTS. 9.1 Hazard Identification. 9.2 Source and Dispersion Models. 9.2.1 Source Emission Models. 9.2.2 Transport and Dispersion Models. 9.2.3 Transient Plume Behavior. 9.2.4 Concentration Fluctuations and the Time Averaging of Dispersion Plumes. 9.2.5 Input Data Uncertainties and Model Validation. 9.2.6 Field Experiments. 9.2.7 Model Evaluation. 9.3 Consequence Models. 9.3.1 Unconfined Vapor Cloud Explosion (UVCE). 9.3.2 Boiling Liquid Expanding Vapor Explosions (BLEVES) and Fireballs. 9.3.3 Pool and Jet Fires. 9.3.4 Toxic Hazards. 9.3.5 Human Exposure Models. 9.4 Frequency Models. 9.4.1 Human Factors. 9.4.2 Electronic Systems. 9.4.3 Failure Rate Data. 9.5 Hazard Mitigation. 9.6 Uncertainty Management. 9.7 Integration of Reliability Analysis, CPQRA, and Cost-Benefit Studies. 9.8 Summary. 9.9 References. Appendix A. Loss-of-Containment Causes in the Chemical Industry. Appendix B. Training Programs. Appendix C. Sample Outline for CPQRA Reports. Appendix D. Minimal Cut Set Analysis. Appendix E. Approximation Methods for Quantifying Fault Trees. Appendix F. Probability Distributions, Parameters, and Technology. Appendix G. Statistical Distributions Available for Use as Failure Rate Models. Appendix H. Errors from Assuming That Time-Related Equipment Failure Rates Are Constant. Appendix I. Data Reduction Techniques: Distribution Identification and Testing Methods. Appendix J. Procedure for Combining Available Generic and Plant-Specific Data. Conversion Factors. Glossary. Index.

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Book SynopsisAt last, smaller chemical processing operations have truly easy access to process safety and risk management programs tailored to meet their needs. Written as a "how to" book with checklists, it offers sufficient information for managers of facilities with small chemical operations to implement a process safety program and meet existing regulations.Table of ContentsPreface. Acknowledgments. Acronyms. Chapter 1. Introduction. Chapter 2. Developing Understanding: A Summary of the Risk Management Program Rule. Chapter 3. Developing an RMP Implementation Plan. Chapter 4. Hazard Assessment. Chapter 5. Prevention Program. Chapter 6. Emergency Response. Chapter 7. Developing the Risk Management Plan. Chapter 8. Status of Proposed Revisions to the Rule. Appendix A. Text of the EPA Risk Management Program Rule 40 CFR Part 68. Appendix B. RMP List of Regulated Substances. Appendix C. Text of the OSHA Process Safety Management (PSM) Standard. Appendix D. Comparison of OSHA and EPA Lists of Highly Hazardous Chemicals and Regulated Substances. Appendix E. Example RMPlan-Propane Industry. References. Glossary.

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Book SynopsisThis CCPS Concept book shows designers and operators of chemical facilities how to realistically estimate the flammable mass in a cloud of accidentally released material that is capable of igniting. It provides information on industry experience with flammable vapour clouds, basic concepts of fires and explosions, and an overview of related computer programs.Table of ContentsPreface. Acknowledgments. Glossary. Nomenclature. 1. Introduction. 1.1 Why Calculate Flammable Mass? 1.2 How Are Flammable Mass Estimates Used? 1.3 Other CCPS Publications. 2. Overview. 2.1 Context. 2.2 Objectives. 2.3 How to Use Thus Book. 3. Industry Experiences with Flammable Vapor Clouds. 3.1 Property Losses from Vapor Cloud Accidents. 3.2 Examples of Vapor Clouds Events. 3.2.1 Bangkok, Thailand, LPG Vapor Cloud. 3.2.2 Saint Herblain, France, Gasoline Cloud, October 7, 1991. 3.2.3 Pampa, Texas, Hoechst-Celanese Explosion, November 17, 1987. 3.2.4 Monsanto Ethanol Explosion, Autumn, 1970. 3.2.5 Mexico City Vapor Cloud and Explosion, November 19, 1984. 3.2.6 Pasadena, Texas Fire and Explosion, October 23, 1989. 3.3 Examples with Postaccident Determination of Flammable Mass. 3.3.1 Fixborough Vapor Cloud Explosion, June 1, 1974. 3.3.2 Piper Alpha North Sea Platform Fire, July 6, 1988. 3.3.3 DSM Naphtha Cracker, Beek, the Netherlands, 7 November 1975. 4. Basic Concept—Fluid Flow, Fires, and Explosions. 4.1 Discharge Characteristics. 4.1.1 Single-Phase Discharge Rates from Tanks. 4.1.2 Single-Phase Discharge Rates from Pipes. 4.1.3 Two-Phase Discharge Rates from Tanks. 4.1.4 Two-Phase Discharge Rates from Pipes. 4.1.5 Aerosol Formation and Drop Size Correlations. 4.1.6 Rainout. 4.1.7 Pool Spread and Evaporation on Land. 4.2 Dispersion Factors. 4.2.1 Jet Mixing. 4.2.2 Meteorology. 4.2.3 Surface Roughness and Terrain. 4.2.4 Averaging Time. 4.2.5 Impingement and Catering. 4.2.6 Obstacle Effects. 4.3 Sources of Ignition. 4.4 Flame Characteristics. 4.4.1 Flammable Limits. 4.4.2 Flammable Limits with Inerts. 4.4.3 Autoignition Temperature for Gases. 4.4.4 Minimum Ignition Energy for Gases. 4.4.5 Flash Point. 4.4.6 Laminar Burning Velocity and Turbulent Flame Speed. 4.5 Aerosol Flammability. 4.6 Turbulence Effects. 4.6.1 Turbulence Effects of Jet Plume Ignition. 4.6.2 Turbulence and Pockets of Flammable Material. 4.7 Flash Fires. 4.8 Explosions. 4.8.1 Confinement and Congestion. 4.8.2 Effects of Concentration on Explosion Overpressure. 4.8.3 TNT Equivalence Explosion Models. 4.8.4 Volume Source Explosion Models. 4.8.5 Determining Fuel Reactivity. 4.8.6 Determining Degree of Confinement. 4.8.7 Determining Level of Congestion. 4.8.8 Multiple Congested Volumes. 4.9 Minimum Flammable Mass for Vapor Cloud Explosions. 4.10 Probability of Vapor Cloud Ignition and Explosion. 5. Determination of Flammable Mass. 5.1 Estimation Methods by Degree of Confinement. 5.2 Methods for Finding the Flammable Mass in Unconfined Vapor Clouds. 5.2.1 Screening Rules of Thumb. 5.2.2 Calculating Flammable Mass with Dispersion Models. 5.3 Methods for Finding the Flammable Mass in Partially Confined Vapor Clouds. 5.3.1 Estimating Flammable Mass for Potential Explosion Sites. 5.4 Methods for Finding the Flammable Mass in Confined Vapor Clouds. 5.4.1 Flammable Mass in Well-Mixed Room from Spill Outdoors. 5.4.2 Flammable Mass from Indoor Release in Well-Mixed Room with Low Ventilation. 6. Overview of Related Computer Programs. 7. Worked Examples. 7.1 Example 10, Unconfined Vapor Cloud—Vapor and Liquid Propane Releases. 7.2 Example 11, Unconfined Vapor Cloud—Effect of Wind Speed. 7.3 Example 12, Partially Confined Vapor Cloud Explosion—Vinyl Chloride Monomer Release. 7.4 Example 13, Partially Confined Vapor Cloud Explosion—Total Petroleum LaMede Refinery Explosion, November 1992. 7.5 Example 14, Partially Confined Vapor Cloud—Multiple Congested Areas. 7.6 Example 15, Confined Vapor Clouds. 8. Recommendations for Future Work. 8.1 Calculating Flammable Mass Profiles Along a Vapor Cloud. 8.2 Resolving the Minimum Explosive Mass Issue. 8.3 Contribution of Aerosols to Explosive Mass. 8.4 Dispersion Modeling Around Plant Structure. 8.5 Improved Modeling of Jets Impacting Surfaces. 8.6 Models That Account for Turbulence Spectra. 8.7 Reconciling Indoor and Outdoor Explosion Models. 8.8 Calculate Net Efficiencies for TNT Equivalent Models from Historical Events. Appendix A. Atmosphere Stability Classification Schemes. Appendix B. Vertical Wind Profiles. Appendix C. Flammability Properties. Appendix D. Correlation for Flash Point. Appendix E. Polydisperse Drop Size Distributions. Appendix F. Multicomponent Pool Evaporation for Spills on Land. Appendix G. Generalized Indoor Concentration Build-Up or Decay. Appendix H. Calculating Concentration for Indoor Releases. Appendix I. Evaluating Flammable Mass for Gaussian Dispersion Models: Instantaneous, Point Source. Appendix J. Evaluating Flammable Mass for Gaussian Dispersion Models: Continous Release, Approximate Method. Appendix K. Evaluating Flammable Mass for Gaussian Dispersion Model—Continuous Release, Rigorous Solution. Appendix L. Numerical Integration to Find Flammable Mass. Appendix M. Expansion Velocity and Discharge Coefficients. Appendix N. Conversion Factors. References. Index.

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Book SynopsisThere are many different types of explosions, each with its own complex mechanism. This work provides information on explosions for everyone involved in the operation, design, maintenance, and management of chemical processes, helping enhance understanding of the nature of explosions and the methods required to prevent them from occurring.Table of ContentsPREFACE ix ACKNOWLEDGMENTS xi 1 INTRODUCTION 1 1.1. Accident Loss History 3 1.2. The Accident Process (AIChE, 2000) 4 1.3. A Case History—Flixborough, England 4 1.4. Hazard Identification and Evaluation 6 1.5. Inherently Safer Design 7 2 FUNDAMENTALS OF FIRES AND EXPLOSIONS 9 2.1. Gases and Vapors 13 2.1.1. Flammability Diagram 18 2.1.2. Estimating Flammability Limits 28 2.1.3. Temperature Effect on Flammability 30 2.1.4. Pressure Effect on Flammability 31 2.1.5. Flammability of Gaseous Mixtures 31 2.1.6. Minimum Ignition Energies 32 2.1.7. Autoignition Temperature 34 2.1.8. Example Applications 34 2.2. Liquids 37 2.2.1. Flashpoints of Mixtures of Liquids 40 2.2.2. Example Applications 42 2.3. Aerosols and Mists 43 2.4. Dusts 43 2.5. Hybrid Mixtures 48 2.6. Kinetics and Thermochemistry 48 2.6.1. Calculated Adiabatic Flame Temperatures (CAFT) 50 2.6.2. Example Application 52 2.7. Gas Dynamics 54 2.7.1. Detonations and Deflagrations 58 2.7.2. Estimating Peak Side-on Overpressures 61 2.7.3. Example Applications 62 2.7.4. Pressure Piling and Deflagration to Detonation Transition 63 2.8. Physical Explosions 64 2.8.1. BLEVEs 65 2.8.2. Rapid Phase Transition Explosions 67 2.9. Vapor Cloud Explosions 68 2.9.1. TNT Equivalency 70 2.9.2. TNO Multi-Energy Method 71 2.9.3. Baker-Strehlow-TangMethod(AIChE, 1999a) 77 2.9.4. Computational Fluid Mechanics (CFD) Method 82 2.9.5. Example Applications 83 2.10. Runaway Reactions 85 2.10.1. Steady-State and Dynamic Reactor Behavior 88 2.10.2. Experimental Characterization 92 2.11. Condensed Phase Explosions 94 2.12. Fireballs, Pool, Flash, and Jet Fires 96 2.13. Explosion Effects 98 2.13.1. Thermal Exposure 98 2.13.2. Overpressure Exposure 99 2.14. Ignition Sources 103 2.14.1. Static Electricity 105 3 PREVENTION AND MITIGATION OF EXPLOSIONS 113 3.1. Additional References 113 3.2. Inherently Safer Design 113 3.3. Using the Flammability Diagram to Avoid Flammable Atmospheres 117 3.4. Inerting and Purging 120 3.4.1. Vacuum Purging 121 3.4.2. Pressure Purging 123 3.4.3. Combined Pressure-Vacuum Purging 124 3.4.4. Sweep Purging 126 3.4.5. Siphon Purging 127 3.4.6. Advantages and Disadvantages of the Various Inerting Procedures 127 3.4.7. Inert Gas Blanketing of Storage Vessels 128 3.4.8. Inert Purging and Blanketing during Drumming Operations 128 3.5. Example Application 130 3.6. Explosion Venting 132 3.7. Grounding and Bonding 132 3.8. Ventilation 138 3.9. Sprinkler and Deluge Systems 139 3.10. Charging and Drumming Flammable Liquids 142 3.11. Example Application 142 3.12. Charging Powders 145 3.13. Electrical Equipment in Hazardous (Classified) Areas 148 3.13.1. Protection Techniques 156 Appendix A DETAILED EQUATIONS FOR FLAMMABILITY DIAGRAMS 161 Part A: Equations Useful for Gas Mixtures 161 Part B: Equations Useful for Placing Vessels Into and Out of Service 165 Appendix B EQUATIONS FOR DETERMINING THE ENERGY OF EXPLOSION 169 B.l. Example Application 171 Appendix C FLAMMABILITY DATA FOR SELECTED MATERIALS 173 Appendix D PROCEDURE FOR EXAMPLE 3.2 177 Appendix E COMBUSTION DATA FOR DUST CLOUDS 191 REFERENCES 193 GLOSSARY 203 INDEX 209

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Book SynopsisDesigned for personnel involved in the design, operation, and maintenance of facilities and equipment where deflagration and detonation flame arresters (DDFAs) may be required, this book fosters effective application and operation of DDFAs through treatment of their principles of operation, selection, installation, and maintenance methods.Table of ContentsPreface. Acknowledgments. Acronyms and Abbreviations. 1. Introduction. 1.1 Intended Audience. 1.2 Why This Book Was Written. 1.3 What Is Covered in This Book. 1.4 What the Reader Should Learn From This Book. 1.5 Units of Measure. 2. History and State-of-the Art. 2.1 Historical Development of Flame Arresters. 2.2 Case Histories of Successful and Unsuccessful Applications of Flame Arresters. 2.2.1 Successful Applications. 2.2.2 Unsuccessful Applications. 2.3 Evolution of Standards and Codes. 2.3.1 United States. 2.3.2 Canada. 2.3.3 United Kingdom. 2.3.4 Europe and International. 2.4 Safety Concerns and Environmental Regulations: Tradeoffs and Conflicts. 2.5 References. 3. Overview of Deflagration and Detonation Prevention and Protection Practices. 3.1 Introduction. 3.2 Deflagration and Detonation Flame Arresters. 3.3 Deflagration Venting. 3.4 Oxidant Concentration Reduction. 3.5 Combustible Concentration Reduction. 3.6 Deflagration Suppression. 3.7 Deflagration Pressure Containment. 3.8 Equipment and Piping Isolation. 3.9 References. 4. Overview of Combustion and Flame Propagation Phenomena Related to DDAs. 4.1 Introduction to the Chemistry and Physics of Flame Propagation. 4.1.1 Combustion Chemistry and Thermodynamics. 4.1.2 Flammability Characteristics. 4.1.3 Decomposition Flames. 4.2 Dynamic of Flame Propagation. 4.2.1 Burning Velocity and Flame Speed. 4.2.2 Flame Acceleration and Deflagration-to-Detonation Transition (DDT). 4.2.3 Detonations. 4.3 Ignition and Quenching. 4.4 Theoretical Basis for Flame Arrester Design and Operation. 4.5 References. 5. Deflagration and Detonation Flame Arrester Technology. 5.1 Where Flame Arresters May Be Needed. 5.2 Types of Flame Arresters. 5.2.1 Introduction. 5.2.2 Crimped Metal Ribbon. 5.2.3 Parallel Plate. 5.2.4 Expanded Metal Cartridge. 5.2.5 Perforated Plate. 5.2.6 Wire Gauze. 5.2.7 Sintered Metal. 5.2.8 Ceramic Balls. 5.2.9 Metal Shot. 5.2.10 Hydraulic (Liquid Seal) Flame Arrester. 5.2.11 Packed Bed Flame Arrester. 5.2.12 Velocity Flame Stopper. 5.2.13 High Velocity Vent Valve. 5.2.14 Conservation Vent Valves as Flame Arresters. 5.3 Selection and Design Criteria/Considerations. 5.3.1 Classification According to NEC Groups and MESGs. 5.3.2 Reactions and Combustion Dynamics of Fast-Burning Gases. 5.3.3 Flame Propagation Direction. 5.3.4 Quenching Diameter, Quenching Length, and Flame Velocity. 5.3.5 Burnback Resistance. 5.3.6 Pressure Drop Limitations. 5.3.7 Fouling and Plugging Potential and Protection. 5.3.8 Unwanted Phases. 5.3.9 Material Selection Requirements. 5.3.10 Special Design Options. 5.3.11 System Constraints. 5.3.12 Mixture Composition. 5.3.13 Operating Temperature and Pressure. 5.3.14 Ignition Location. 5.3.15 Changes in Pipe Diameter. 5.3.16 Location and Orientation. 5.3.17 Reliability. 5.3.18 Monitoring and Instrumentation. 5.3.19 Inspection and Maintenance Requirements. 5.4 Special Applications. 5.4.1 Hydrogen. 5.4.2 Acetylene. 5.4.3 Ethylene Oxide. 5.5 Information That Should Be Provided to Manufacturers. 5.6 References. 6. Installation in Process Systems. 6.1 Design Considerations with Respect to Other System Components. 6.2 Piping and Flame Arrester System Design Considerations. 6.3 Maintaining Reliability. 6.4 Optimum Location in System. 6.5 Supports for Static and Dynamic Forces. 6.6 References. 7. Inspection and Maintenance of Flame Arresters. 7.1 Need and Importance of Maintenance. 7.2 Mechanical Integrity Issues. 7.2.1 Inspection. 7.2.2 Current Maintenance Practices. 7.2.3 Documentation and Verification of Flame Arrester Maintenance. 7.3 Training and Competence Issues for Operating and Maintenance Personnel. 7.4 On-Stream Isolation and Switching of Parallel Spares. 7.5 Check List for Inspection. 7.6 References. 8. Regulations, Codes, and Standards. 8.1 Regulations, Codes, and Standards Summaries. 8.1.1 United States. 8.1.2 Canada. 8.1.3 United Kingdom. 8.1.4 Europe and International. 8.2 Comparison of Various Flame Arrester Standards and Codes. 8.3 Standards and Codes in Preparation. 8.4 References. 9. Illustrative Examples, Calculations, and Guidelines for DDA Selection. 9.1 Introduction. 9.2 Example 1-Protective Measures for a Vent Manifold System. 9.3 Example 2-Sizing of an End-of-Line Deflagration Flame Arrester. 9.4 Example 3-Calculation of Limiting Oxidant Concentration (LOC). 9.5 Example 4-Calculation of the LFL and UFL of Mixtures. 9.6 Example 5-Calculation of the MESG of Mixtures. 9.7 Determination If a DDT Can Occur. 9.8 Typical Locations in Process Systems. 9.9 List of Steps in the Selection of a DDA or Other Flame Propagation Control Method. 9.10 References. 10. Summary. 10.1 Status of DDA Technology. 10.2 Recommended Practices. 10.3 Why Flame Arresters Fail. 10.4 Future Technology Development. 10.5 References. Appendix A. Flame Arrester Specification Sheet for Manufacturer Quotation. Appendix B. List of Flame Arrester Manufacturers. Appendix C. UL and FM Listings and Approvals. Appendix D. Suggested Additional Reading. Glossary. Index.

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Book SynopsisMany companies that stray too far from their core business fail. So how is it that General Electric, a major electrical manufacturing company, ended up as one of the top U.S. chemical producers - with 1998 sales of $6. 6 billion? In Unlikely Victory, Jerome T.Table of ContentsPreface v Acknowledgments ix 1. What's General Electric Doing in the Chemical Business? 1 2. Early Years of GE Chemistry 1900 - 1948 9 Electrical Insulation; Silicones; GE Forms a Chemical Division 3. GE Silicones: 1940 - 1964 27 Forms Shaky Start to Successful Business 4. Loctite 45 An Invention that Got Away 5. Synthetic Diamond 49 GE Break-Through Caps Two Centuries of Research 6. Lexan Polycarbonate: 1953 - 1968 69 The "Unbreakable" Thermoplastic 7. Noryl Thermoplastic: 1956 - 1968 83 Victory Snatched from Jaws of Defeat 8. GE Engineering Plastics: 1968 - 1987 91 Headlong Growth to World Leadership 9. Growth by Means of a Major Acquisition: 1988 - 1991 113 ABS Plastics Up for Bid; A New Polycarbonate Process 10. Laminates and Insulating Materials 123 GE Core-businesses Decline in Importance 11. GE Silicones: 1965 - 1998 139 Sealants Leadership; Word Participation 12. GE Engineering Plastics: 1992 - 1998 139 After Recession, Growth Resumes 13. People Make the Difference 159 Four Scientist: Eugene G. Rochow, H. Tracy Hill and the GE Diamond Research Team, Daniel W. Fox, Allan S. Hay. Five Managers: Abraham L. Marshall, Charles E. Reed, John F. Wells, Jr., Glen H. Hiner, Gary L. Rogers 14. Summation 178 How Big an Achievement? How Attained? Nine Strategies Glossary 195 A. Thermoplastic Polymers, Compounds, and Blends 195 B. Trade-names, Companies, and Chemical Terms 196 C. GE Organization Notes 199 Chapter References 201 Names Index 211 Subject Index 215

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Book SynopsisHelps engineers and managers identify the technologies that best fit their plant and/or processes. This text is a reference to various "tail-end" SO2 control processes, providing a "snapshot" of where this technology stands in industry. The technologies are divided into waste producing processes and byproduct processes.

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Book SynopsisPresented in a CD-ROM format, this title shows how to systematically incorporate the principles of water conservation, recycling, and reuse into the design of new plants, retrofits of existing systems, and technology development.Table of ContentsSection. Foreword. Acknowledgments. Abbreviations and Acronyms. Chapter 1. Introduction. 1.1. Project Purpose. 1.2. Water Reuse- A Historical Context. 1.3. The Center for Waste Reduction Technologies. 1.4. Monograph Tasks and Scope. Chapter 2. The Systematic Approach. 2.1. Overview of Approach. 2.2. Step 1 - Establish Leadership and Commitment. 2.3. Step 2 - Frame the Problem. 2.4. Step 3 - Develop Alternatives. 2.5. Step 4 - Select a Course of Action. 2.6. Step 5 - Implement the Course of Action. 2.7. Step 6 - Review and Update. Chapter 3. water Reclamation Strategies and Technologies. 3.1. Guidance. 3.2. Industry Standard Water Management Strategies. 3.3. Technology Summaries. Exhibits. Chapter 4. Case Studies. 4.1. Basis for Selection. 4.2. Case Study # 1: Aluminum Smelting Plant. 4.3. Case Study # 2: Pulp Mill. 4.4. Case Study # 3: Transportation Equipment Facility. 4.5. Case Study # 4: Electric Power Plant. 4.6. Case Study # 5: Semiconductor Fabricator. 4.7. Case Study # 6: Aerospace Manufacturer. Chapter 5. Water Use in Industries of the Future. 5.1. Overview. 5.2. Agriculture Industry. 5.3. Aluminum Industry. 5.4. Chemical Industry. 5.5. Forest Products Industry. 5.6. Mining Industry. 5.7. Petroleum Industry. 5.8. Steel Industry. Chapter 6. Developments to Watch. 6.1. Basis. 6.2. Process Issues. 6.3. Regulatory Developments and Voluntary Programs. 6.4. Resource Limitations. References. Appendices. A. Water Reuse Questionnaire. B. Surveyed Organizations and Responses. C. Water Analysis Data. D. Decision Making Using Environmental, Health, and Safety Costs in a Coherent Model. E. Glossary.

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Book SynopsisIn its recent investigation of chemical reactivity accidents, the US Chemical Safety Board noted a gap in technical guidance and regulatory coverage. This volume closes the gap in technical guidance, helping small and large companies alike identify, address, and manage chemical reactivity hazards. It guides the reader through an analysis of the potential for chemical reactivity accidents to help prevent fires, explosions, toxic chemical releases or chemical spills. This volume is applicable to processes at any scale and is particularly useful for chemists, safety managers, and engineers involved in scale-up. An enclosed CD-ROM provides portable checklists, analysis tools, and a list of additional references. Note: CD-ROM/DVD and other supplementary materials are not included as part of eBook file.

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Book SynopsisOver 40 papers and posters that share the latest practices in emergency planning related to fixed chemical, pharmaceutical, LNG, and petroleum facilities, storage facilities, transportation, and security.Table of ContentsEmergency Response Plenary Session. Three Incidents: Tank Truck Explosion, Television Interview Railcar Fire, and International Destruction of Acrylic Acid Railcar Using "Vent and Burn". - Bob Rosen. World Wide Electronic Specialty Gas Emergency Response Program. - Eugene Y. Ngai. Unplanned Shutdown Plus Lack of Knowledge equals Incidents. - Albert Ness. Community Involvement Plenary Session. Community Involvement Requirements for the Albertan Upstream Petroleum Industry. - Gary L. Neilson, P. Phys. Existing Side-By-Side: A Look at Community Alert & Emergency Response Issues in the Petro-Chemical Industry. - Johnnie A. Banks. Joint Leveraging of Industrial and Community Assets: A Partnership Between Industry and the Community to Improve Emergency Response Capabilities. - Max E. Middleton. Trash to Treasures. - Ted Low, Kris Smith. Liquefied Natural Gas Issues Planery Session. Safety and Fire Protection Consideration for LNG Terminals. - John A. Alderman. Blast Wave Damage to Process Equipment as a Trigger of Domino Effects. - E. Salzano, V. Cozzani. LNG Terminal Operations Hazard Zones. - Robin Pitblado. International Issues Plenary Session. Emergency Response of Toxic Substances in Taiwan: The System and case Studies. - Jeng-Renn Chen, Chung-Hsun Hung, K.S. Fan, Ta-Cheng Ho, Fan-Lun Chen, J.J. Horng, Wen-Der Chen, Shun-Chin Ho. Improved Safety at Reduced Operating Costs in a German Chemical Plant. - W.Steinert, M. Begg, R. von Dincklage. Active Shooter Table Top Exercise Process for Schools. - Larry G. Holloway. Consequence Assessment Plenary Session. Applying Inherent Safety to Mitigate Offsite Impact of a Toxic Liquid Release. - Douglas J. Ferguson. Extended Indoor Explosion Model with Vertical Concentration Profiles and Variable Ventilation Rates. - John Woodward, J. Kelly Thomas. Accounting for Dynamic Processes in Process Emergency Response using Even tree Modeling. - Raghu Raman. Fuzzy Logic Methodology for Accident Frequency Assessment in Hazardous Materials Transportation. - Yuanhua Qiao, Michela Gentile, M. Sam Mannan. Case Histories I Plenary Session. Development of Detailed Action Plans in the Even of a Sodium Hydride Spill/Fire. - Claire Fluegeman, Timothy Hilton, Kenneth P. Moder, Robert Stankovich. System Improvements Utilizing FMEA and Fault Tree Analysis. - Tracy Whipple, Michelle Roberson. Lessons from Grangemouth: A Case History. - Michael Broadribb, William Ralph, Neil Macnaughton. Transportation and Value Chain Plenary Sessions. A Graphical Method for Planning Security Vulnerability Analyses of Transportation and Value-Chain Activities. - Michael Hazzan, Irene Jones. Emergency Preplanning in Pipeline Construction. - Chuck Goode, Tim Brabazon. Reducing Value Chain Vulnerability to Terrorist Attacks - A.M. (Tony) Downes. Case Histories II Planery Session. Lessons Learned from a Major Accident Involving Uncontrolled Molten Sodium Release. - A. Wilson, R. De Cort, W. Crumpton. Emergency Response to a Non-Collision HAZMAT Release from a Railcar. - R.A. Ogle, D.R. Morrison, M. J. Viz. CSB Incident Investigation. - John B. Vorderbrueggen. Layer of Protection Analysis Plenary Session. Managing the Financial Risks of Major Accidents. - Luke Chippindall, Dennis Butts. Initiating Event Frequency Case Study: Electrolytic Cell Process. - Stanley Urbanik. Use of Layer of Protection Analysis (LOPA) within The Dow Chemical Company. - Tim Overton, Tim Wagner. Legal and Regulatory Issues Plenary Session. Implementing Personnel and Organizational Management of Change (P&O MOC) Processes. - Frank Broussard, Heather Harriss. Major Hazard Control in Canada: A Change in the Regulatory Landscape. - Graham D. Creedy, John S. Shrives, Gerry Phillips. Defending OSHA Facility Siting Citations. - Mark S. Dreux. The ATEX Directives: Explosion Safety and Regulation - The European Approach. - N.H.A. Versloot, A.J.J. Kelin, M. De Maaijer. Poster Session. Thermal Stability of Materials During Storage and Transport. - Bob Venugopal. Theory of Incident and its Prediction in the Process Industry. - Jenq-Renn Chen.

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Book SynopsisTom Pratt, a long-time process safety practitioner and lecturer in electrostatic safety, wrote this book to educate industry in the basics of electrostatics. It offers a selected collection of information designed to give readers the tools they need to examine the hazard potential of common industrial processes.Table of ContentsChapter 1. Basic Concepts. 1.1. The Electrostatic Charge. 1.1.1. Electrons, Protons, and Ions. 1.1.2. Charge Distribution: Point, Space, and Surface Charges. 1.2. The Electric Field. 1.2.1. Mapping Electric Fields. 1.2.2. Dielectrics. 1.2.3. Dielectric Breakdown. 1.3. Ground Potential. 1.3.1. Grounding. 1.3.2. Bonding. 1.4. Requirements for a Fire or an Explosion. 1.4.1. Ignitable Mixture. 1.4.2. Separation. 1.4.3. Accumulation. 1.4.4. Discharge. Chapter 2. Separation and Accumulation of Charge. 2.1. Mechanisms of Charge Generation. 2.2. Charge Alignment. 2.3. Contact and Frictional Charging. 2.3.1. Surface Charging. 2.3.2. Powder Charging. 2.4. Double Layer Charging. 2.5. Charging of Drops, Mists, and Aerosols. 2.6. Two Phase Flow. 2.7. Charge Separation at Phase Boundaries. 2.8. Charge Relaxation. 2.9. Host Material. 2.9.1. Bulk Conductivity. 2.9.2. Surface Conductivity. 2.9.3. Apparent Conductivity. 2.10. Separation vs. Relaxation. 2.10.1. constant Voltage Case. 2.10.2. Constant Amperage Case. 2.11. Induction. 3. Discharge. 3.1. Classification of Discharges. 3.2. Characteristics of Discharges. 3.2.1. Corona Discharge. 3.2.2. Brush Discharge. 3.2.3. Bulking Brush Discharge. 3.2.4. Propagating Brush Discharge. 3.2.5. Spark or Capacitor Discharge. 3.2.6. Lightning. Chapter 4. Minimum Ignition Energies. 4.1. Testing of Materials. 4.2. Minimum Ignition Energy, MIE. 4.2.1. MIEs of Gasses and Vapors. 4.2.2. MIEs of Dusts. 4.2.3. MIEs of Hybrid Mixtures. 4.2.4. MIEs in Enriched Oxygen Atmospheres. 4.2.5. MIEs of Explosives. Chapter 5. Discharge Energies. 5.1. Ignitions by Electrostatic Discharges. 5.2. Capacitive Discharges. 5.2.1. Human Sparks. 5.2.2. Clothing. 5.3. Brush Discharges. 5.3.1. Brush Discharges in Spaces. 5.3.2. Brush Discharges at Surfaces. 5.4. Bulking Brush Discharges. 5.5. Propagating Brush Discharges. 5.6. Corona Discharges. Chapter 6. Electrification in Industrial Processes. 6.1. Charges in Liquids. 6.1.1. Streaming Currents. 6.1.2. Charge Relaxation in Liquids. 6.1.3. Liquid Conductivity. 6.1.4. Antistatic Additives. 6.1.5. Sedimentation. 6.2. Charges in Mists. 6.2.1. Washing. 6.2.2. Splash Loading. 6.2.3. Steaming. 6.2.4. Carbon Dioxide. 6.2.5. Charge Decay From Mists. 6.3. Charges in Powders. 6.3.1. Streaming Currents in Powders. 6.3.2. Charge Compaction in Powder Bulking. 6.3.3. Charge Relaxation in Powders. 6.4. Surface Charges. 6.4.1. Triboelectric Charging. 6.4.2. Humidity. 6.4.3. Conductive Cloth and Plastics. 6.4.4. Neutralizers. 6.5. Intense Electrification. 6.6. Phase Separation Charges. 7. Design and Operating Criteria. 7.1. Grounding and Bonding. 7.1.1. Insulation from Ground. 7.1.2. Spark Promoters. 7.2. In-Process Relaxation Times. 7.2.1. Quiescent Relaxations. 7.2.2. Relaxation Downstream of Filters. 7.3. Simultaneous Operations. 7.4. Sounding Pipes. 8. Measurements. 8.1. Multimeters. 8.2. Electrometers. 8.3. Electrostatic Voltmeters. 8.4. Fieldmeters. 8.5. Faraday Cage. 8.6. Radios. 9. Quantification of Electrostatic Scenarios. 9.1. Approximations. 9.1.1. Approximating Capacitance. 9.1.2. Approximating Resistance. 9.1.3. Approximating Charge. 9.2. Examples of Approximations. 9.2.1. Refueling an Automobile. 9.2.2. Filling a Gasoline Can. 9.2.3. Flexible Intermediate Bulk Container (FIBC). 9.2.4. The Minimum Capacitor for Incendive Discharge. Chapter 10. Case Histories. 10.1. Vacuum truck Emptying a Sump. 10.2. Drawing Toluene into an Ungrounded Bucket. 10.3. Sampling while Loading a Railcar. 10.4. Vapor Ignition in a Roadtanker, I. 10.5. Vapor Ignition in a Roadtanker, II. 10.6. Instrumenting a Tank Containing Steam and a Flammable Atmosphere. 10.7. Conductive Liquid in a Plastic Carboy. 10.8. Chemical Hose with an Ungrounded Spiral. 10.9. Three incidents in a Pneumatic Transport System. 10.10. Offloading a Bulk Powder Truck. 10.11. Dumping Powder from a Drum with Metal chime. 10.12. Emptying a Powder from a Plastic Bag (Composite Case History). 10.13. Vapor Explosion in a Closed Tank. 10.14. Gas Well and Pipeline Blowouts. Appendix A. Units. Appendix B. Symbols Used in Equations. Appendix C. Equations. Appendix D. Atmospheric Electrostatics. Appendix E. Electric Field Calculations. Bibliography. Concordance A, General. Concordance B, Compounds and Materials.

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Book SynopsisIn 1975 workers at Life Science Products, a small makeshift pesticide factory in Hopewell, Virginia, became ill after exposure to Kepone, the brand name for the pesticide chlordecone. Gregory Wilson explores the conditions that put the Kepone factory and the workers there in the first place and the effects of the poison long after 1975.

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Book SynopsisIntroduction. Food Science as a Discipline. Characteristics of the Food Industry. Constituents of Foods. Properties and Significance. Nutritive Aspects of Food Constituents. Unit Operations in Food Processing. Quality Factors in Foods. Food Deterioration and Its Control. Heat Preservation and Processing. Cold Preservation and Processing. Food Dehydration and Concentration. Irradiation Microwave, and Ohmic Processing of Foods. Fermentation and Other Uses of Microorganisms. Milk and Milk Products. Meat, Poultry, and Eggs. Seafoods. Fats, Oils and Related Products. Cereal, Grains Legumes, and Oil Seeds. Vegetables and Fruits. Beverages. Confectionery and Chocolate Products. Principles of Food Packaging. Food Safety, Risks and Hazards. Governmental Regulation of Food and Nutrition Labeling. Hunger, Technology, and World Food Needs.Table of ContentsIntroduction. Food Science as a Discipline. Characteristics of the Food Industry. Constituents of Foods. Properties and Significance. Nutritive Aspects of Food Constituents. Unit Operations in Food Processing. Quality Factors in Foods. Food Deterioration and Its Control. Heat Preservation and Processing. Cold Preservation and Processing. Food Dehydration and Concentration. Irradiation Microwave, and Ohmic Processing of Foods. Fermentation and Other Uses of Microorganisms. Milk and Milk Products. Meat, Poultry, and Eggs. Seafoods. Fats, Oils and Related Products. Cereal, Grains Legumes, and Oil Seeds. Vegetables and Fruits. Beverages. Confectionery and Chocolate Products. Principles of Food Packaging. Food Safety, Risks and Hazards. Governmental Regulation of Food and Nutrition Labeling. Hunger, Technology, and World Food Needs.

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Book SynopsisWith the diverse teaching backgrounds of first year university students, the highly detailed traditional organic chemistry textbook does not provide an easily digestible presentation of the very basic information required by many students to begin their study of this exciting subject.Trade Review".a useful text to add to the recommended reading lists...provides a concise summary of the basics of first-year organic chemistry." Chemistry World "[The book is] ideal for the target audiences and priced and designed appropriately... well suited to the student who wishes to dip into organic chemistry over the course of a degree." The Times Higher Education Supplement, Feb 2004 "Organic Chemistry at a glance is a rare example of a short format textbook that covers a great deal of ground without sacrificing clarity in the persuit of brevity." Education in Chemistry "Good things come in small packages...the result is six chapters and less than one hundred pages of the most concentrated "essence" of organic chemistry that i have ever seen." Journal of Chemical EducationTable of ContentsSection 1: Atomic Structure. Section 2: Bonding and Molecular Structure. Section 3: Configurational Analysis. Section 3: Structure - Activity. Section 4: Reaction Types. Section 5: Compound Classes

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a huge range and FREE tracked UK delivery on ALL orders.

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Book SynopsisThis series includes monographs, research results, and state-of-the-art reviews of conservation literature by Institute staff and others.

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Book SynopsisThe authors skillfully present different approaches to the same problem and even different ways to look at the same type of data. If you have ever been stumped by a controversy in product assessment, the design of studies, or the analysis of data, you will find the answer in this book.Table of Contents1. The Role of Sensory Science in the Coming Decade. 2. International Sensory Science. 3. Sensory Mythology. 4. Contrasting R&D, Sensory Science, and Marketing Research Approaches. 5. Validity and Reliability in Sensory Science. 6. The Interface Between Psychophysics and Sensory Science: Methods vs. Real Knowledge. 7. Descriptive Panel/Experts vs. Consumers. 8. Sample Issues in Consumer Testing. 9. Hedonics, Just-About-Right, Purchase and Other Scales in Consumer Tests. 10. Asking Consumers to Rate Product Attributes. 11. Questionnaire Design. 12. Choice of Population in Consumer Studies. 13. Biases Due to Changing in Market Conditions. 14. Sample Size N or Number of Respondents. 15. The Use and Caveats of Qualitative Research in the Decision Making Process. 16. The Four D's of Sensory Science: Difference, Discrimination, Dissimilarity, Distance. 17. Replication in Sensory and Consumer testing. 18. Language Development in Descriptive Analysis and the Formation of Sensory Concepts. 19. Use of References in Descriptive Analysis. 20. Training Time in Descriptive Analysis. 21. Consumer-Descriptive Data Relationships in Sensory Science. 22. Product and Panelist Variability in Sensory Testing. 23. Foundations of Sensory Science by Daniel Ennis. 24. Applications of SAS Programming Language in Sensory Analysis by Maximo Gacula, Jr. 25. Advances and the Future of Data Collection Systems in Sensory Science by André Arborgast, Chris Findlay and Paul Lichtman. Index

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Book SynopsisThis thorough book collects methods and strategies to analyze proteomics data. It is intended to describe how data obtained by gel-based or gel-free proteomics approaches can be inspected, organized, and interpreted to extrapolate biological information. Organized into four sections, the volume explores strategies to analyze proteomics data obtained by gel-based approaches, different data analysis approaches for gel-free proteomics experiments, bioinformatic tools for the interpretation of proteomics data to obtain biological significant information, as well as methods to integrate proteomics data with other omics datasets including genomics, transcriptomics, metabolomics, and other types of data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detailed implementation advice that will ensure high quality results in the lab. Authoritative and practical, Proteomics Data Analysis serves as an ideal Table of ContentsPart I: Data Analysis for Gel-Based Proteomics 1. Two-Dimensional Gel Electrophoresis Image Analysis Elisa Robotti, Elisa Calà, and Emilio Marengo 2. Chemometric Tools for 2D-PAGE Data Analysis Elisa Robotti, Elisa Calà, and Emilio Marengo Part II: Data Analysis for Gel-Free Proteomics 3. Software Options for the Analysis of MS Proteomic Data Avinash Yadav, Federica Marini, Alessandro Cuomo, and Tiziana Bonaldi 4. Analysis of Label-Based Quantitative Proteomics Data Using IsoProt Johannes Griss and Veit Schwämmle 5. Quantification of Changes in Protein Expression Using SWATH Proteomics Clarissa Braccia, Nara Liessi, and Andrea Armirotti 6. Data Processing and Analysis for DIA-Based Phosphoproteomics Using Spectronaut Ana Martinez-Val, Dorte Breinholdt Bekker-Jensen, Alexander Hogrebe, and Jesper Velgaard Olsen 7. Enhanced Glycopeptide Identification Using a GlyConnect Compozitor-Derived Glycan Composition File Julien Mariethoz, Catherine Hayes, and Frédérique Lisacek 8. Elaboration Pipeline for the Management of MALDI-MS Imaging Datasets Andrew Smith, Isabella Piga, Vanna Denti, Clizia Chinello, and Fulvio Magni 9. Features Selection and Extraction in Statistical Analysis of Proteomics Datasets Marta Lualdi and Mauro Fasano Part III: Proteomics Data Interpretation 10. ORA, FCS, and PT Strategies in Functional Enrichment Analysis Marco Fernandes and Holger Husi 11. A Strategy for the Annotation and GO Enrichment Analysis of a List of Differentially Expressed Proteins Using ProteoRE Florence Combes, Valentin Loux, and Yves Vandenbrouck 12. Protein Subcellular Localization Prediction Elettra Barberis, Emilio Marengo, and Marcello Manfredi 13. Protein Secretion Prediction Tools and Extracellular Vesicles Databases Daniela Cecconi, Claudia Di Carlo, and Jessica Brandi 14. Databases for Protein-Protein Interactions Natsu Nakajima, Tatsuya Akutsu, and Ryuichiro Nakato 15. Machine and Deep Learning for Prediction of Subcellular Localization Gaofeng Pan, Chao Sun, Zijun Liao, and Jijun Tang 16. Deep Learning for Protein-Protein Interaction Site Prediction Arian R. Jamasb, Ben Day, Cătălina Cangea, Pietro Liò, and Tom L. Blundell Part IV: Proteomics Data Integration with Other -Omics 17. Integrative Analysis of Incongruous Cancer Genomics and Proteomics Datasets Karla Cervantes-Gracia, Richard Chahwan, and Holger Husi 18. Integration of Proteomics and Other Omics Data Mengyun Wu, Yu Jiang, and Shuangge Ma

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Book SynopsisThis detailed volume examines the complex study of the assessment of in situ bioavailability and toxicity of organic chemicals in aquatic systems with a toolbox of reliable techniques. Beginning with a section on approaches for chemical analytical and bioanalytical techniques in bioavailability research, the book continues with methods to monitor effects in situ and conduct bioassays to assess the effects of complex environmental samples. It concludes with descriptions of various computational models. Written for the Methods in Pharmacology and Toxicology series, chapters feature the kind of expert implementation advice that leads to greater success in the field. Authoritative and versatile, In Situ Bioavailability and Toxicity of Organic Chemicals in Aquatic Systems serves as an ideal guide to aid in tackling the challenge of analyzing and understanding chemical pollution in aquatic systems. Table of ContentsPart I: Chemical Analytical and Bioanalytical Techniques in Bioavailability Research: Passive Sampling/Dosing and Bioaccumulation Assessments 1. Equilibrium Sampling of Hydrophobic Organic Contaminants in Sediments Gesine Witt, Julia Bachtin, and Sabine Schäfer 2. Passive Sampling of Waterborne Contaminants Branislav Vrana, Foppe Smedes, and Klára Hilscherová 3. Using Tenax Extractable Concentrations to Determine the Bioavailable Contaminant Fraction in Sediments Amanda D. Harwood and Samuel A. Nutile 4. Quantifying Bioaccumulation in the Aquatic Environment Katrine Borgå and Anders Ruus Part II: Monitoring of Effects In Situ and Bioassays to Assess the Effects of Complex Environmental Samples 5. In Situ Determination of Genotoxic Effects in Fish Erythrocytes Using Comet and Micronucleus Assays Paula Suares Rocha, Björn Deutschmann, and Henner Hollert 6. Assessing Adverse Effects of Legacy and Emerging Contaminants in Fish Using Biomarker Analysis and Histopathology in Active Monitoring Scenarios Amaia Orbea, Eider Bilbao, and Miren P. Cajaraville 7. In Situ Exposure of Aquatic Invertebrates to Detect the Effects of Point and Non-Point Source-Related Chemical Pollution in Aquatic Ecosystems Mirco Bundschuh and Ralf Schulz 8. Whole Sediment Toxicity Bioassay to Determine Bioavailability and Effects of Aquatic Contaminants Using Zebrafish Embryos Sabrina Schiwy, Mirna Velki, and Henner Hollert 9. Nematode-Based Effect Assessment in Freshwater Sediments Arne Haegerbaeumer, Sebastian Höss, and Walter Traunspurger Part III: Computational Models for Interspecies Comparison and Extrapolation from the Lab to the Field 10. In Vitro-In Vivo Extrapolation to Predict Bioaccumulation and Toxicity of Chemicals in Fish Using Physiologically-Based Toxicokinetic Models Julita Stadnicka-Michalak and Kristin Schirmer 11. Cross-Species Extrapolation Using a Simplifed In Vitro Tissue Explant Assay in Fish Bryanna Eisner, Jon Doering, Shawn Beitel, and Markus Hecker 12. Extrapolation of Laboratory-Measured Effects to Fish Populations in the Field Charles R.E. Hazlerigg

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Book SynopsisThis book provides an introduction to the important methods of chiroptical spectroscopy in general, and circular dichroism (CD) in particular, which are increasingly important in all areas of chemistry, biochemistry, and structural biology. The book can be used as a text for undergraduate and graduate students and as a reference for researchers in academia and industry, with or without the companion volume in this set. Experimental methods and instrumentation are described with topics ranging from the most widely used methods (electronic and vibrational CD) to frontier areas such as nonlinear spectroscopy and photoelectron CD, as well as the theory of chiroptical methods and techniques for simulating chiroptical properties. Each chapter is written by one or more leading authorities with extensive experience in the field.Table of ContentsComprehensive Chiroptical Spectroscopy, Volume 1 PREFACE ix CONTRIBUTORS xi PART I INTRODUCTION 1 1 ON THE INTERACTION OF LIGHT WITH MOLECULES: PATHWAYS TO THE THEORETICAL INTERPRETATION OF CHIROPTICAL PHENOMENA 3 Georges H. Wagnière PART II EXPERIMENTAL METHODSANDINSTRUMENTATION 35 2 MEASUREMENT OF THE CIRCULAR DICHROISM OF ELECTRONIC TRANSITIONS 37 John C. Sutherland 3 CIRCULARLY POLARIZED LUMINESCENCE SPECTROSCOPY AND EMISSION-DETECTED CIRCULAR DICHROISM 65 James P. Riehl and Gilles Muller 4 SOLID-STATE CHIROPTICAL SPECTROSCOPY: PRINCIPLES AND APPLICATIONS 91 Reiko Kuroda and Takunori Harada 5 INFRARED VIBRATIONAL OPTICAL ACTIVITY: MEASUREMENT AND INSTRUMENTATION 115 Laurence A. Nafie 6 MEASUREMENT OF RAMAN OPTICAL ACTIVITY 147 Werner Hug 7 NANOSECOND TIME-RESOLVED NATURAL AND MAGNETIC CHIROPTICAL SPECTROSCOPIES 179 David S. Kliger, Eefei Chen, and Robert A. Goldbeck 8 FEMTOSECOND INFRARED CIRCULAR DICHROISM AND OPTICAL ROTATORY DISPERSION 203 Hanju Rhee and Minhaeng Cho 9 CHIROPTICAL PROPERTIES OF LANTHANIDE COMPOUNDS IN AN EXTENDED WAVELENGTH RANGE 221 Lorenzo Di Bari and Piero Salvadori 10 NEAR-INFRARED VIBRATIONAL CIRCULAR DICHROISM: NIR-VCD 247 Sergio Abbate, Giovanna Longhi, and Ettore Castiglioni 11 OPTICAL ROTATION AND INTRINSIC OPTICAL ACTIVITY 275 Patrick H. Vaccaro 12 CHIROPTICAL IMAGING OF CRYSTALS 325 John Freudenthal, Werner Kaminsky, and Bart Kahr 13 NONLINEAR OPTICAL SPECTROSCOPY OF CHIRAL MOLECULES 347 Peer Fischer 14 IN SITU MEASUREMENT OF CHIRALITY OF MOLECULES AND MOLECULAR ASSEMBLIES WITH SURFACE NONLINEAR SPECTROSCOPY 373 Hong-fei Wang 15 PHOTOELECTRON CIRCULAR DICHROISM 407 Ivan Powis 16 MAGNETOCHIRAL DICHROISM AND BIREFRINGENCE 433 G. L. J. A. Rikken 17 X-RAY DETECTED OPTICAL ACTIVITY 457 Jose Goulon, Andrei Rogalev, and Christian Brouder 18 LINEAR DICHROISM 493 Alison Rodger 19 ELECTRO-OPTICAL ABSORPTION SPECTROSCOPY 525 Hans-Georg Kuball and Matthias Stolte PART III THEORETICAL SIMULATIONS 541 20 INDEPENDENT SYSTEMS THEORY FOR PREDICTING ELECTRONIC CIRCULAR DICHROISM 543 Gerhard Raabe, Joerg Fleischhauer, and Robert W. Woody 21 AB INITIO ELECTRONIC CIRCULAR DICHROISM AND OPTICAL ROTATORY DISPERSION: FROM ORGANIC MOLECULES TO TRANSITION METAL COMPLEXES 593 Jochen Autschbach 22 THEORETICAL ELECTRONIC CIRCULAR DICHROISM SPECTROSCOPY OF LARGE ORGANIC AND SUPRAMOLECULAR SYSTEMS 643 Lars Goerigk, Holger Kruse, and Stefan Grimme 23 HIGH-ACCURACY QUANTUM CHEMISTRY AND CHIROPTICAL PROPERTIES 675 T. Daniel Crawford 24 AB INITIO METHODS FOR VIBRATIONAL CIRCULAR DICHROISM AND RAMAN OPTICAL ACTIVITY 699 Kenneth Ruud 25 MODELING OF SOLVATION EFFECTS ON CHIROPTICAL SPECTRA 729 Magdalena Pecul 26 COMPLEXATION, SOLVATION, AND CHIRALITY TRANSFER IN VIBRATIONAL CIRCULAR DICHROISM 747 Valentin Paul Nicu and Evert Jan Baerends INDEX 783

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Book SynopsisThis book covers important advances in enzymology, explaining the behavior of enzymes and how they can be utilized to develop novel drugs, synthesize known and novel compounds, and understand evolutionary processes. Advances in Enzymology focuses on enzymes, the primary catalysts of life processes. The explanation of the behavior of enzymes can be found via studies of their chemical mechanisms and can be utilized to develop novel drugs, synthesize known and novel compounds, and understand evolutionary processes. The transglutaminases, first described in 1957, are a large, widely-distributed family of enzymes canonically responsible for the amidation/transamidation of protein side chains. The extraordinary diversity of names associated with various enzymatic activities now recognized and aggregated as transglutaminase bears witness to the remarkable diversity of biological roles associated with the activity, including myriad human diseases.Table of ContentsContributors vii Preface ix Structure and Regulation of Type 2 Transglutaminase in Relation to Its Physiological Functions and Pathological Roles 1 Carlo M. Bergamini, Russell J. Collighan, Zhuo Wang, and Martin Griffin Physiopathological Roles of Human Transglutaminase 2 47 Vittorio Gentile Transglutaminase in Epidermis and Neurological Disease or What Makes a Good Cross-Linking Substrate 97 Guylaine Hoffner, Amandine VanHoutteghem, William Andre, and Philippe Djian Transglutaminase 2: A New Paradigm for NF-B Involvement in Disease 161 Soo-Youl Kim Transglutaminase 2 At the Crossroads between Cell Death and Survival 197 Mauro Piacentini, Manuela D’Eletto, Laura Falasca, Maria Grazia Farrace, and Carlo Rodolfo Tissue Transglutaminase and Its Role in Human Cancer Progression 247 Bo Li, Richard A. Cerione, and Marc Antonyak Transglutaminase 2 Dysfunctions in the Development of Autoimmune Disorders: Celiac Disease and TG2−/−Mouse 295 Zsuzsa Szondy, Ilma Korponay-Szabo, Robert Kiraly, and Laszlo Fesus Effects and Analysis of Transglutamination on Protein Aggregation and Clearance in Neurodegenerative Diseases 347 Zoltan Nemes Transglutaminase-Mediated Remodeling of the Human Erythrocyte Membrane Skeleton: Relevance for Erythrocyte Diseases with Shortened Cell Lifespan 385 Laszlo Lorand, S. N. Prasanna Murthy, Anwar A. Khan, Weihua XUE, Oksana Lockridge, and Athar H. Chishti Irreversible Inhibitors of Tissue Transglutaminase 415 Jeffrey W. Keillor, Nicolas Chabot, Isabelle Roy, Amina Mulani, Olivier Leogane, and Christophe Pardin Methionine Adenosyltransferase (S-Adenosylmethionine Synthetase) 449 Marıa A. Pajares and George D. Markham Index 523

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Book SynopsisDiscover a new generation of organic nanomaterials and their applications Recent developments in nanoscience and nanotechnology have given rise to a new generation of functional organic nanomaterials with controlled morphology and well-defined properties, which enable a broad range of useful applications. This book explores some of the most important of these organic nanomaterials, describing how they are synthesized and characterized. Moreover, the book explains how researchers have incorporated organic nanomaterials into devices for real-world applications. Featuring contributions from an international team of leading nanoscientists, Organic Nanomaterials is divided into five parts: Part One introduces the fundamentals of nanomaterials and self-assembled nanostructures Part Two examines carbon nanostructures?from fullerenes to carbon nanotubes to graphene?reporting on properties, theoretical studies, and applications<Table of ContentsPreface vii Contributors ix 1 A Proposed Taxonomy and Classification Strategy for Well-Defined, Soft-Matter Nanoscale Building Blocks 1Jørn B. Christensen and Donald A. Tomalia 2 On the Role of Hydrogen-Bonding in the Nanoscale Organization of π-Conjugated Materials 33Albertus P. H. J. Schenning and David González-Rodríguez 3 Chiral Organic Nanomaterials 59David B. Amabilino 4 Biochemical Nanomaterials based on Poly(ε-caprolactone) 79Irakli Javakhishvili and Søren Hvilsted 5 Self-Assembled Porphyrin Nanostructures and their Potential Applications 103John A. Shelnutt and Craig J. Medforth 6 Nanostructures and Electron-Transfer Functions of Nonplanar Porphyrins 131Shunichi Fukuzumi and Takahiko Kojima 7 Tweezers and Macrocycles for the Molecular Recognition of Fullerenes 147David Canevet, Emilio M. Pérez, and Nazario Martín 8 Covalent, Donor–Acceptor Ensembles based on Phthalocyanines and Carbon Nanostructures 163Giovanni Bottari, Maxence Urbani, and Tomás Torres 9 Photoinduced Electron Transfer of Supramolecular Carbon Nanotube Materials Decorated with Photoactive Sensitizers 187Francis D’Souza, Atula S. D. Sandanayaka, and Osamu Ito 10 Interfacing Porphyrins/Phthalocyanines with Carbon Nanotubes 205Juergen Bartelmeß and Dirk M. Guldi 11 Organic Synthesis of Endohedral Fullerenes Encapsulating Helium, Dihydrogen, and Water 225Michihisa Murata, Yasujiro Murata, and Koichi Komatsu 12 Fundamental and Applied Aspects of Endohedral Metallofullerenes as Promising Carbon Nanomaterials 241Michio Yamada, Xing Lu, Lai Feng, Satoru Sato, Yuta Takano, Shigeru Nagase, and Takeshi Akasaka 13 An Update on Electrochemical Characterization and Potential Applications of Carbon Materials 259Fang-Fang Li, Adrián Villalta-Cerdas, Lourdes E. Echegoyen, and Luis Echegoyen 14 Solvating Insoluble Carbon Nanostructures by Molecular Dynamics 311Matteo Calvaresi and Francesco Zerbetto 15 Inorganic Capsules: Redox-Active Guests in Metal Cages 331Andrew Macdonell and Leroy Cronin 16 Stimuli-Responsive Monolayers 347Francesca A. Scaramuzzo, Mario Barteri, Pascal Jonkheijm, and Jurriaan Huskens 17 Self-Assembled Monolayers as Model Biosurfaces 369Anna Laromaine and Charles R. Mace 18 Low-Dimensionality Effects in Organic Field Effect Transistors 397Stefano Casalini, Tobias Cramer, Francesca Leonardi, Massimiliano Cavallini, and Fabio Biscarini 19 The Growth of Organic Nanomaterials by Molecular Self-Assembly at Solid Surfaces 421José M. Gallego, Roberto Otero, and Rodolfo Miranda 20 Biofunctionalized Surfaces 447Marisela Vélez 21 Carbon Nanotube Derivatives as Anticancer Drug Delivery Systems 469Chiara Fabbro, Tatiana Da Ros, and Maurizio Prato 22 Porous Nanomaterials for Biomedical Applications 487Henning Lülf, André Devaux, Eko Adi Prasetyanto, and Luisa De Cola 23 Dicationic Gemini Nanoparticle Design for Gene Therapy 509Mahmoud Elsabahy, Ildiko Badea, Ronald Verrall, McDonald Donkuru, and Marianna Foldvari 24 Sensing Hg(II) Ions in Water: From Molecules to Nanostructured Molecular Materials 529Imma Ratera, Alberto Tárraga, Pedro Molina, and Jaume Veciana 25 Organic Nanomaterials for Efficient Bulk Heterojunction Solar Cells 549Pavel A. Troshin and Niyazi Serdar Sariciftci 26 Mesoscopic Dye-Sensitized Solar Cells 579Mohammad Khaja Nazeeruddin, Jaejung Ko, and Michael Grӓtzel Index 599

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Book SynopsisThe development of catalytic versions of cascade reactions has become one of the most active and burgeoning reaction areas in organic synthesis.Table of ContentsContributors xi Preface xiii 1 Amine-Catalyzed Cascade Reactions 1 Aiguo Song and Wei Wang 1.1 Introduction, 2 1.2 Enamine-Activated Cascade Reactions, 3 1.2.1 Enamine–Enamine Cascades, 3 1.2.2 Enamine–Iminium Cascades, 8 1.2.3 Enamine Catalysis Cyclization, 19 1.3 Iminium-Initiated Cascade Reactions, 21 1.3.1 Design of Iminium–Enamine Cascade Reactions, 21 1.3.2 Iminium-Activated Diels–Alder Reactions, 22 1.3.3 Iminium-Activated Sequential [4 + 2] Reactions, 24 1.3.4 Iminium-Activated [3 + 2] Reactions, 25 1.3.5 Iminium-Activated Sequential [3 + 2] Reactions, 27 1.3.6 Iminium-Activated [2 + 1] Reactions, 30 1.3.7 Iminium-Activated Multicomponent Reactions, 35 1.3.8 Iminium-Activated [3 + 3] Reactions, 37 1.4 Cycle-Specific Catalysis Cascades, 42 1.5 Other Strategies, 45 1.6 Summary and Outlook, 46 References, 46 2 Brønsted Acid–Catalyzed Cascade Reactions 53 Jun Jiang and Liu-Zhu Gong 2.1 Introduction, 54 2.2 Protonic Acid–Catalyzed Cascade Reactions, 55 2.2.1 Mannich Reaction, 55 2.2.2 Pictect–Spengler Reaction, 56 2.2.3 Biginelli Reaction, 58 2.2.4 Povarov Reaction, 59 2.2.5 Reduction Reaction, 60 2.2.6 1,3-Dipolar Cycloaddition, 61 2.2.7 Darzen Reaction, 65 2.2.8 Acyclic Aminal and Hemiaminal Synthesis, 66 2.2.9 Rearrangement Reaction, 67 2.2.10 a,b-Unsaturated Imine-Involved Cyclization Reaction, 69 2.2.11 Alkylation Reaction, 69 2.2.12 Desymmetrization Reaction, 70 2.2.13 Halocyclization, 71 2.2.14 Redox Reaction, 72 2.2.15 Isocyanide-Involved Multicomponent Reaction, 73 2.2.16 Other Protonic Acid–Catalyzed Cascade Reactions, 75 2.3 Chiral Thiourea (Urea)–Catalyzed Cascade Reactions, 75 2.3.1 Neutral Activation, 76 2.3.2 Anion-Binding Catalysis, 99 2.4 Brønsted Acid and Transition Metal Cooperatively Catalyzed Cascade Reactions, 104 2.4.1 Dual Catalysis, 105 2.4.2 Cascade Catalysis, 108 2.5 Conclusions, 116 References, 117 3 Application of Organocatalytic Cascade Reactions in Natural Product Synthesis and Drug Discovery 123 Yao Wang and Peng-Fei Xu 3.1 Introduction, 123 3.2 Amine-Catalyzed Cascade Reactions in Natural Product Synthesis, 125 3.2.1 Iminium-Ion-Catalyzed Cascade Reactions in Natural Product Synthesis, 125 3.2.2 Cycle-Specific Cascade Catalysis in Natural Product Synthesis, 129 3.3 Brønsted Acid–Catalyzed Cascade Reactions in Natural Product Synthesis, 137 3.4 Bifunctional Base/Brønsted Acid–Catalyzed Cascade Reactions in Natural Product Synthesis, 139 3.5 Summary and Outlook, 140 References, 142 4 Gold-Catalyzed Cascade Reactions 145 Yanzhao Wang and Liming Zhang 4.1 Introduction, 145 4.2 Cascade Reactions of Alkynes, 147 4.2.1 Cascade Reactions of Enynes, 147 4.2.2 Cascade Reactions of Propargyl Carboxylates, 156 4.2.3 Cascade Reactions of ortho-Substituted Arylalkynes, 161 4.2.4 Cascade Reactions of Other Alkynes, 165 4.3 Cascade Reactions of Allenes, 170 4.4 Cascade Reactions of Alkenes and Cyclopropenes, 173 4.5 Closing Remarks, 174 References, 174 5 Cascade Reactions Catalyzed by Ruthenium, Iron, Iridium, Rhodium, and Copper 179 Yanguang Wang and Ping Lu 5.1 Introduction, 179 5.2 Ruthenium-Catalyzed Transformations, 180 5.3 Iron-Catalyzed Transformations, 185 5.4 Iridium-Catalyzed Transformations, 191 5.5 Rhodium-Catalyzed Transformations, 194 5.6 Copper-Catalyzed Transformations, 202 5.7 Miscellaneous Catalytic Reactions, 215 5.8 Summary, 219 References, 219 6 Palladium-Catalyzed Cascade Reactions of Alkenes, Alkynes, and Allenes 225 Hongyin Gao and Junliang Zhang 6.1 Introduction, 226 6.2 Cascade Reactions Involving Alkenes, 226 6.2.1 Double Mizoroki–Heck Reaction Cascade, 226 6.2.2 Cascade Heck Reaction/C-H Activation, 227 6.2.3 Cascade Heck Reaction/Reduction/Cyclization, 230 6.2.4 Cascade Heck Reaction/Carbonylation, 231 6.2.5 Cascade Heck Reaction/Suzuki Coupling, 232 6.2.6 Cascade Amino-/Oxopalladation/Carbopalladation Reaction, 234 6.3 Cascade Reactions Involving Alkynes, 237 6.3.1 Cascade Heck Reactions, 238 6.3.2 Cascade Heck/Suzuki Coupling, 238 6.3.3 Cationic Palladium(II)-Catalyzed Cascade Reactions, 239 6.3.4 Cascade Heck Reaction/Stille Coupling, 241 6.3.5 Cascade Heck/Sonogashira Coupling, 243 6.3.6 Cascade Sonogashira Coupling–Cyclization, 244 6.3.7 Cascade Heck and C-H Bond Functionalization, 247 6.3.8 Cascade Reactions Initiated by Oxopalladation, 253 6.3.9 Cascade Reactions Initiated by Aminopalladation, 256 6.3.10 Cascade Reactions Initiated by Halopalladation or Acetoxypalladation, 259 6.3.11 Cascade Reactions of 2-(1-Alkynyl)-alk-2-en-1-ones, 263 6.3.12 Cascade Reactions of Propargylic Derivatives, 263 6.4 Cascade Reactions Involving Allenes, 264 6.4.1 Cascade Reactions of Monoallenes, 264 6.4.2 Cross-Coupling Cyclization of Two Different Allenes, 274 6.5 Summary and Outlook, 276 Acknowledgments, 277 References, 277 7 Use of Transition Metal–Catalyzed Cascade Reactions in Natural Product Synthesis and Drug Discovery 283 Peng-Fei Xu and Hao Wei 7.1 Introduction, 283 7.2 Palladium-Catalyzed Cascade Reactions in Total Synthesis, 284 7.2.1 Cross-Coupling Reactions, 284 7.2.1.1 Heck Reaction, 284 7.2.1.2 Stille Reaction, 291 7.2.1.3 Suzuki Coupling Reaction, 297 7.2.2 Tsuji–Trost Reaction, 301 7.2.3 Other Palladium-Catalyzed Cascade Reactions in Total Synthesis, 303 7.3 Ruthenium-Catalyzed Cascade Reactions in Total Synthesis, 305 7.4 Gold-and Platinum-Catalyzed Cascade Reactions in Organic Reactions, 318 7.5 Copper-and Rhodium-Catalyzed Cascade Reactions in Organic Synthesis, 322 7.6 Summary, 326 References, 326 8 Engineering Mono-and Multifunctional Nanocatalysts for Cascade Reactions 333 Hexing Li and Fang Zhang 8.1 Introduction, 334 8.2 Heterogeneous Monofunctional Nanocatalysts, 335 8.2.1 Metal-Based Monofunctional Nanocatalysts, 335 8.2.2 Metal Oxide–Based Monofunctional Nanocatalysts, 340 8.2.3 Orgamometallic-Based Monofunctional Nanocatalysts, 340 8.2.4 Graphene Oxide–Based Monofunctional Nanocatalysts, 343 8.3 Heterogeneous Multifunctional Nanocatalysts, 344 8.3.1 Acid–Base Combined Multifunctional Nanocatalysts, 344 8.3.2 Metal–Base Combined Multifunctional Nanocatalysts, 349 8.3.3 Organometallic–Base Combined Multifunctional Nanocatalysts, 349 8.3.4 Binary Organometallic–Based Multifunctional Nanocatalysts, 350 8.3.5 Binary Metal–Based Multifunctional Nanocatalysts, 352 8.3.6 Metal–Metal Oxide Combined Multifunctional Nanocatalysts, 353 8.3.7 Organocatalyst–Acid Combined Multifunctional Nanocatalysts, 353 8.3.8 Acid–Base–Metal Combined Multifunctional Nanocatalyst, 356 8.3.9 Triple Enzyme–Based Multifunctional Nanocatalysts, 356 8.4 Conclusions and Perspectives, 359 References, 360 9 Multiple-Catalyst-Promoted Cascade Reactions 363 Peng-Fei Xu and Jun-Bing Ling 9.1 Introduction, 363 9.2 Multiple Metal Catalyst–Promoted Cascade Reactions, 364 9.2.1 Catalytic Systems Involving Palladium, 365 9.2.2 Catalytic Systems Involving Other Metals, 368 9.3 Multiple Organocatalyst–Promoted Cascade Reactions, 370 9.3.1 Catalytic Systems Combining Multiple Amine Catalysts, 371 9.3.2 Catalytic Systems Combining Amine Catalysts and Nucleophilic Carbenes, 380 9.3.3 Catalytic Systems Combining Amine and Hydrogen-Bonding Donor Catalysts, 385 9.3.4 Catalytic Systems Involving Other Organocatalysts, 390 9.4 Metal/Organic Binary Catalytic System–Promoted Cascade Reactions, 394 9.4.1 Catalytic Systems Combining Secondary Amine and Metal Catalysts, 394 9.4.2 Catalytic Systems Combining Brønsted Acid and Metal Catalysts, 404 9.4.3 Catalytic Systems Combining Hydrogen-Bonding Donor and Metal Catalysts, 411 9.4.4 Catalytic Systems Combining Other Organo-and Metal Catalysts, 413 9.5 Summary and Outlook, 415 References, 415 Index 419

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Book SynopsisOffering a holistic view of the development of drug delivery systems, Advanced Drug Delivery presents the essential aspects necessary to understand and apply for effective drug delivery fundamentals, including practical issues, integration of pharmaceutics, and molecular biology.Trade Review“This book is a welcome addition to the range of study materials available at this level and can be unreservedly recommended to both aspiring and existing pharmaceutical professionals.” (ChemMedChem, 1 January 2015) “A suitable text for graduate and advanced undergraduate students, the book is logically divided into four sections: fundamentals, delivery approaches, disease applications, and future directions. Discussing design, in vitro studies, clinical evaluation, and regulatory approval, each chapter includes objectives and assessment questions.” (Newbooks.lib, 11 September 2014Table of ContentsPREFACE xi ABOUT THE AUTHORS xiii CONTRIBUTORS xv PART I INTRODUCTION AND BASICS OF ADVANCED DRUG DELIVERY 1 1 Physiological Barriers in Advanced Drug Delivery: Gastrointestinal Barrier 3 D. Alexander Oh and Chi H. Lee 2 Solubility and Stability Aspects in Advanced Drug Delivery 21 Hoo-Kyun Choi, Robhash K. Subedi, and Chi H. Lee 3 The Role of Transporters and the Efflux System in Drug Delivery 47 Varun Khurana, Dhananjay Pal, Mukul Minocha, and Ashim K. Mitra 4 Biomaterial in Advanced Drug Delivery 75 Megha Barot, Mitesh Patel, Xiaoyan Yang, Wuchen Wang, and Chi H. Lee PART II STRATEGIES FOR ADVANCED DRUG DELIVERY 103 5 Strategies of Drug Targeting 105 Ravi S. Shukla, Zhijin Chen, and Kun Cheng 6 Prodrug and Bioconjugation 123 Ramya Krishna Vadlapatla, Sujay Shah, Aswani Dutt Vadlapudi, and Ashim K. Mitra 7 Nanoscale Drug Delivery Systems 141 Mitan R. Gokulgandhi, Ashaben Patel, Kishore Cholkar, Megha Barot, and Ashim K. Mitra 8 Stimuli-Responsive Target Strategies 157 Chi H. Lee 9 Implants 183 Aswani Dutt Vadlapudi, Ashaben Patel, Ramya Krishna Vadlapatla, Durga Paturi, and Ashim K. Mitra 10 Aptamers in Advanced Drug Delivery 201 Weiwei Gao, Omid C. Farokhzad, and Nazila Kamaly 11 Nanofiber 219 Megha Barot, Mitan R. Gokulgandhi, Animikh Ray, and Ashim K. Mitra 12 Biomimetic Self-Assembling Nanoparticles 231 Maxim G. Ryadnov 13 Protein and Peptide Drug Delivery 241 Mitesh Patel, Megha Barot, Jwala Renukuntla, and Ashim K. Mitra 14 Delivery of Nucleic Acids 257 Shaoying Wang, Bin Qin, and Kun Cheng 15 Delivery of Vaccines 275 Hari R. Desu, Rubi Mahato, and Laura A. Thoma PART III TRANSLATIONAL RESEARCH OF ADVANCED DRUG DELIVERY 297 16 Regulatory Considerations and Clinical Issues in Advanced Drug Delivery 299 Mei-Ling Chen 17 Advanced Drug Delivery in Cancer Therapy 323 Wanyi Tai and Kun Cheng 18 Advanced Delivery in Cardiovascular Diseases 341 Gayathri Acharya, Wuchen Wang, Divya Teja Vavilala, Mridul Mukherji, and Chi H. Lee 19 Recent Advances in Ocular Drug Delivery 365 Varun Khurana, Deep Kwatra, Vibhuti Agrahari, and Ashim K. Mitra 20 Advanced Drug Delivery Against STD 381 Chi H. Lee 21 Advanced Drug Delivery to the Brain 405 Nanda K. Mandava, Mitesh Patel, and Ashim K. Mitra PART IV FUTURE APPLICATIONS OF ADVANCED DRUG DELIVERY IN EMERGING RESEARCH AREAS 423 22 Cell-Based Therapeutics 425 Zhaoyang Ye, Yan Zhou, Haibo Cai, and Wen-Song Tan 23 Biomedical Applications and Tissue Engineering of Collagen 445 Chi H. Lee and Yugyung Lee 24 Molecular Imaging of Drug Delivery 469 Zheng-Rong Lu ANSWERS 489 INDEX 511

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Book SynopsisExplains why pipeline stress corrosion cracking happens and how it can be prevented Pipelines sit at the heart of the global economy. When they are in good working order, they deliver fuel to meet the ever-growing demand for energy around the world.Table of ContentsForeword xiii Preface xv List of Abbreviations and Symbols xix 1 Introduction 1 1.1 Pipelines as “Energy Highways” 2 1.2 Pipeline Safety and Integrity Management 3 1.3 Pipeline Stress Corrosion Cracking 3 References 5 2 Fundamentals of Stress Corrosion Cracking 7 2.1 Definition of Stress Corrosion Cracking 7 2.2 Specific Metal–Environment Combinations 9 2.3 Metallurgical Aspects of SCC 11 2.3.1 Effect of Strength of Materials on SCC 11 2.3.2 Effect of Alloying Composition on SCC 11 2.3.3 Effect of Heat Treatment on SCC 11 2.3.4 Grain Boundary Precipitation 12 2.3.5 Grain Boundary Segregation 12 2.4 Electrochemistry of SCC 13 2.4.1 SCC Thermodynamics 13 2.4.2 SCC Kinetics 14 2.5 SCC Mechanisms 15 2.5.1 SCC Initiation Mechanisms 15 2.5.2 Dissolution-Based SCC Propagation 16 2.5.3 Mechanical Fracture–Based SCC Propagation 18 2.6 Effects of Hydrogen on SCC and Hydrogen Damage 20 2.6.1 Sources of Hydrogen 20 2.6.2 Characteristics of Hydrogen in Metals 21 2.6.3 The Hydrogen Effect 21 2.6.4 Mechanisms of Hydrogen Damage 25 2.7 Role of Microorganisms in SCC 27 2.7.1 Microbially Influenced Corrosion 27 2.7.2 Microorganisms Involved in MIC 29 2.7.3 Role of MIC in SCC Processes 31 2.8 Corrosion Fatigue 32 2.8.1 Features of Fatigue Failure 33 2.8.2 Features of Corrosion Fatigue 34 2.8.3 Factors Affecting CF and CF Management 35 2.9 Comparison of SCC, HIC, and CF 35 References 37 3 Understanding Pipeline Stress Corrosion Cracking 43 3.1 Introduction 43 3.2 Practical Case History of SCC in Pipelines 44 3.2.1 Case 1: SCC of Enbridge Glenavon Pipelines (SCC in an Oil Pipeline) 45 3.2.2 Case 2: SCC of Williams Lake Pipelines (SCC in a Gas Pipeline) 46 3.3 General Features of Pipeline SCC 46 3.3.1 High-pH SCC of Pipelines 47 3.3.2 Nearly Neutral–pH SCC of Pipelines 48 3.3.3 Cracking Characteristics 48 3.4 Conditions for Pipeline SCC 50 3.4.1 Corrosive Environments 50 3.4.2 Susceptible Line Pipe Steels 53 3.4.3 Stress 58 3.5 Role of Pressure Fluctuation in Pipelines: SCC or Corrosion Fatigue? 62 References 68 4 Nearly Neutral–pH Stress Corrosion Cracking of Pipelines 73 4.1 Introduction 73 4.2 Primary Characteristics 73 4.3 Contributing Factors 75 4.3.1 Coatings 75 4.3.2 Cathodic Protection 79 4.3.3 Soil Characteristics 81 4.3.4 Microorganisms 83 4.3.5 Temperature 85 4.3.6 Stress 85 4.3.7 Steel Metallurgy 88 4.4 Initiation of Stress Corrosion Cracks from Corrosion Pits 89 4.5 Stress Corrosion Crack Propagation Mechanism 96 4.5.1 Role of Hydrogen in Enhanced Corrosion of Steels 96 4.5.2 Potential-Dependent Nearly Neutral–pH SCC of Pipelines 99 4.5.3 Pipeline Steels in Nearly Neutral–pH Solutions: Always Active Dissolution? 101 4.6 Models for Prediction of Nearly Neutral–pH SCC Propagation 104 References 111 5 High-pH Stress Corrosion Cracking of Pipelines 117 5.1 Introduction 117 5.2 Primary Characteristics 117 5.3 Contributing Factors 118 5.3.1 Coatings 118 5.3.2 Cathodic Protection 119 5.3.3 Soil Characteristics 123 5.3.4 Microorganisms 125 5.3.5 Temperature 125 5.3.6 Stress 125 5.3.7 Metallurgies 128 5.4 Mechanisms for Stress Corrosion Crack Initiation 128 5.4.1 Electrochemical Corrosion Mechanism of Pipeline Steels in a Thin Layer of Carbonate–Bicarbonate Electrolyte Trapped Under a Disbonded Coating 128 5.4.2 Conceptual Model for Initiation of Stress Corrosion Cracks in a High-pH Carbonate–Bicarbonate Electrolyte Under a Disbonded Coating 133 5.5 Mechanisms for Stress Corrosion Crack Propagation 137 5.5.1 Enhanced Anodic Dissolution at a Crack Tip 137 5.5.2 Enhanced Pitting Corrosion at a Crack Tip 143 5.5.3 Relevance to Grain Boundary Structure 144 5.6 Models for the Prediction of a High-pH Stress Corrosion Crack Growth Rate 144 References 145 6 Stress Corrosion Cracking of Pipelines in Acidic Soil Environments 149 6.1 Introduction 149 6.2 Primary Characteristics 150 6.3 Electrochemical Corrosion Mechanism of Pipeline Steels in Acidic Soil Solutions 151 6.4 Mechanisms for Initiation and Propagation of Stress Corrosion Cracks 151 6.5 Effect of Strain Rate on the SCC of Pipelines in Acidic Soils 154 References 157 7 Stress Corrosion Cracking at Pipeline Welds 159 7.1 Introduction 159 7.2 Fundamentals of Welding Metallurgy 160 7.2.1 Welding Processes 160 7.2.2 Welding Solidification and Microstructure 160 7.2.3 Parameters Affecting the Welding Process 162 7.2.4 Defects at the Weld 162 7.3 Pipeline Welding: Metallurgical Aspects 163 7.3.1 X70 Steel Weld 163 7.3.2 X80 Steel Weld 163 7.3.3 X100 Steel Weld 164 7.4 Pipeline Welding: Mechanical Aspects 164 7.4.1 Residual Stress 164 7.4.2 Hardness of the Weld 166 7.5 Pipeline Welding: Environmental Aspects 170 7.5.1 Introduction of Hydrogen into Welds 170 7.5.2 Corrosion at Welds 172 7.5.3 Electrochemistry of Localized Corrosion at Pipeline Welds 173 7.6 SCC at Pipeline Welds 178 7.6.1 Effects of Material Properties and Microstructure 178 7.6.2 Effects of the Welding Process 179 7.6.3 Hydrogen Sulfide SCC of Pipeline Welds 179 References 180 8 Stress Corrosion Cracking of High-Strength Pipeline Steels 185 8.1 Introduction 185 8.2 Development of High-Strength Steel Pipeline Technology 186 8.2.1 Evolution of Pipeline Steels 186 8.2.2 High-Strength Steels in a Global Pipeline Application 187 8.3 Metallurgy of High-Strength Pipeline Steels 189 8.3.1 Thermomechanical Controlled Processing 189 8.3.2 Alloying Treatment 189 8.3.3 Microstructure of High-Strength Steels 190 8.3.4 Metallurgical Defects 192 8.4 Susceptibility of High-Strength Steels to Hydrogen Damage 193 8.4.1 Hydrogen Blistering and HIC of High-Strength Pipeline Steels 193 8.4.2 Hydrogen Permeation Behavior of High-Strength Pipeline Steels 196 8.5 Metallurgical Microelectrochemistry of High-Strength Pipeline Steels 199 8.5.1 Microelectrochemical Activity at Metallurgical Defects 199 8.5.2 Preferential Dissolution and Pitting Corrosion Around Inclusions 203 8.6 Strain Aging of High-Strength Steels and Its Implication on Pipeline SCC 207 8.6.1 Basics of Strain Aging 208 8.6.2 Strain Aging of High-Strength Pipeline Steels 212 8.6.3 Effect of Strain Aging on SCC of High-Strength Pipeline Steels 214 8.7 Strain-Based Design of High-Strength Steel Pipelines 216 8.7.1 Strain Due to Pipe–Ground Movement 217 8.7.2 Parametric Effects on Cracking of Pipelines Under SBD 218 8.8 Mechanoelectrochemical Effect of Corrosion of Pipelines Under Strain 219 References 225 9 Management of Pipeline Stress Corrosion Cracking 231 9.1 SCC in Pipeline Integrity Management 231 9.1.1 Elements of Pipeline Integrity Management 231 9.1.2 Initial Assessment and Investigation of SCC Susceptibility 234 9.1.3 Classification of SCC Severity and Postassessment 235 9.1.4 SCC Site Selection 236 9.1.5 SCC Risk Assessment 238 9.2 Prevention of Pipeline SCC 240 9.2.1 Selection and Control of Materials 241 9.2.2 Control of Stress 242 9.2.3 Control of Environments 243 9.3 Monitoring and Detection of Pipeline SCC 244 9.3.1 In-Line Inspections 244 9.3.2 Intelligent Pigs 247 9.3.3 Hydrostatic Inspection 248 9.3.4 Pipeline Patrolling 249 9.4 Mitigation of Pipeline SCC 249 References 251 Index 255

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Book SynopsisThis book consists of the latest in sustainable membrane technology for use in energy, water, and the environment.Trade ReviewReview copies sent out 6.4.12 THE ENVIRONMENTALIST BLOG SOCIETY AND NATURAL RESOURCES JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH JOURNAL OF ENVIRONMENTAL QUALITY JOURNAL OF AMERICAN WATER WORKS ASSOCIATION ENVIRONMENTAL SCIENCE AND TECHNOLOGYTable of ContentsFOREWORD ix PREFACE xi CONTRIBUTORS xv PART I MEMBRANE MATERIAL AND MEMBRANE DEVELOPMENT 1 1 Spinning Effect of Polyethersulfone Hollow Fiber Membrane Prepared by Water or Polyvinylpyrrolidone in Ternary Formulation 3Nurmin Bolong, Ahmad Fauzi Ismail, and Mohd Razman Salim 2 Effect of Inorganic Particle on the Performance of Polyethersulfone-Cellulose Acetate Ultrafi ltration Membranes 11Gangasalam Arthanareeswaran and Radhe Shyam Thakur 3 Characterizations of Newly Developed Bacterial Cellulose–Chitosan Membrane with Pyrroline 29Siti Nur Hidayah Mohamad, Norhayati Pa’e, Abdul Halim Mohammad Yusof, and Ida Idayu Muhamad 4 Effect of Posttreatment to Enhance the Performance of Nanofi ltration Asymmetric Membrane in Atrazine-Herbicide Removing Process 41Nora’aini Ali, Nurbaiti Abdul Hanid, Asmadi Ali, Ahmad Jusoh, and Marinah Ariffin 5 Polyacrylonitrile Nanofi ber Assembled by Electrospinning: Effect of Dope Concentrations on the Structural and Pore Characterizations 51Agung Mataram, Ahmad Fauzi Ismail, and Takeshi Matsuura PART II APPLICATIONS IN GAS AND VAPOR TREATMENT 59 6 Polymer Structures and Carbon Dioxide Permeation Properties in Polymer Membranes 61Shinji Kanehashi, Shuichi Sato, and Kazukiyo Nagai 7 Gas Permeability and Electrical Properties of 6FDA-Based Polyimide Membranes 75Shuichi Sato, Sou Miyata, Shinji Kanehashi, and Kazukiyo Nagai 8 Polymeric Nanocomposite Membranes for Gas Separation 87Ghader Khanbabaei, Jamal Aalaei, and Ali Rahmatpour 9 Preparation of Perovskite Titania Ceramic Membrane by Sol-Gel Method 95Abdul Latif Ahmad, Sani N. A. Abdullah, and Sharif Hussein Sharif Zein PART III APPLICATIONS IN WATER TREATMENT 105 10 Fouling Characteristics and Cleaning Strategies of a PVDF Tubular Ultrafi ltration Membrane in Natural Rubber Skim Latex Concentration Process 107Devaraj Veerasamy and Zairossani Mohd Nor 11 Removal of Diethanolamine (DEA) from Wastewater Using Membrane Separation Processes 123Binyam Seyoum, Hilmi Mukhtar, and Kok Keong Lau 12 The Effect of Chitosan Membrane Preparation Parameters on Removal of Copper Ions 143Azadeh Ghaee, Mojtaba Shariaty-Niassar, and Jalal Barzin 13 Analysis of Fouling and Flux Behavior in Cross-Flow Microfi ltration of Nonalcoholic Beer by Ceramic Membrane 157Mehdi Yazdanshenas, Seyyed Ali Reza Tabatabaei Nejad, Mohammad Soltanieh, and Luc Fillaudeau 14 Comparison and Upgrading of Wastewater Treatment Plants for Wastewater Reclamation and Reuse by Means of Membrane Bioreactor (MBR) Technology 169Mahdi Khosravi, Gagik Badalians Gholikandi, and Hamid Reza Tashaouei PART IV APPLICATIONS IN ENVIRONMENT 179 15 Surface Treatment and Characterization of Polypropylene Hollow Fibers by Sol-Gel Method for Liquid Phase Microextraction 181Mohd Marsin Sanagi, Yanuardi Raharjo, Wan Aini Wan Ibrahim, Ahmedy Abu Naim, Syairah Salleh, and Mazidatulakmam Miskam 16 Effect of Different Additives on the Properties and Performance of Porous Polysulfone Hollow Fiber Membranes for CO2 Absorption 191Amir Mansourizadeh, Ahmad Fauzi Ismail, and Mohammad Ali Aroon 17 Absorption of Carbon Dioxide through Flat-Sheet Membranes Using Various Aqueous Liquid Absorbents 203Abdul Latif Ahmad, Sunarti Abd Rahman, and W. James Noel Fernando 18 Preparation and Characterization of W/O Emulsion Liquid Membrane Containing Diethanolamine (DEA) for Carbon Dioxide Separation from Gas Mixtures 211Khairul Sozana Nor Kamarudin and Inamullah Bhatti 19 Removal of Dyes from Liquid Waste Solution: Study on Liquid Membrane Component Selection and Stability 221Norasikin Othman, Norlisa Mili, Ani Idris, and Siti Nazrah Zailani PART V APPLICATIONS IN ENERGY 231 20 Modeling and Analysis of Solar-Powered Membrane Distillation Unit for Seawater Desalination 233Fawzi Banat and Mohammed Al-Jarrah 21 Polystyrene Ionomers Functionalized with Partially Fluorinated Short Side-Chain Sulfonic Acid for Fuel Cell Membrane Applications 243Ying Chang and Chulsung Bae 22 Contribution of Nanoclays to the Barrier Properties of SPEEK/Cloisite15A® Nanocomposite Membrane for DMFC Application 251Juhana Jaafar and Ahmad Fauzi Ismail 23 Purification of Biogas Using Carbon Nanotubes Mixed Matrix Membrane: Effect of Functionalization of Carbon Nanotubes Using Silane Agent 267Tutuk Joko Kusworo, Abdullah Busairi, Ahmad Fauzi Ismail, Azeman Mustafa, and Buiyono 24 Selectivity of Polymeric Solvent Resistant Nanofiltration Membranes for Biodiesel Separation 277Rahimah Othman, Abdul Wahab Mohammad, Manal Ismail, and Jumat Salimon PART VI OTHER INDUSTRIAL APPLICATIONS 289 25 Pervaporation Performance of Methyl Tert Buthyl Ether/Methanol Mixtures through Natural Rubber/Polystyrene Interpenetrating Polymer Network Membranes 291Mohd Ghazali Mohd Nawawi, Nur Azrini Ramlee, and Fathie Ahmad Zakil 26 P-Xylene Separation from Ternary Xylene Mixture Over Silicalite-1 Membrane: Process Optimization 299Yin Fong Yeong, Ahmad Zuhairi Abdullah, Abdul Latif Ahmad, and Subhash Bhatia 27 Ammonia Removal from Saline Water by Direct Contact Membrane Distillation 309Rosalam Sarbatly and Chel-Ken Chiam INDEX 319

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Book SynopsisThe first book-length treatment of an exciting new technology, this volume explains the principles behind induced plasmonic current.Table of ContentsList of Contributors xi Preface xv 1 Plasmonic–Fluorescent and Magnetic–Fluorescent Composite Nanoparticle as Multifunctional Cellular Probe 1Arindam Saha, SK Basiruddin, and Nikhil Ranjan Jana 1.1 Introduction 1 1.2 Synthesis Design of Composite Nanoparticle 2 1.2.1 Method 1: Polyacrylate Coating–Based Composite of Nanoparticle and Organic Dye 3 1.2.2 Method 2: Polyacrylate Coating–Based Composite of Two Different Nanoparticles 3 1.2.3 Method 3: Ligand Exchange Approach–Based Composite of Two Different Nanoparticles 4 1.3 Property of Composite Nanoparticles 5 1.3.1 Optical Property 5 1.3.2 Fluorophore Lifetime Study 7 1.4 Functionalization and Labeling Application of Composite Nanoparticle 8 1.5 Conclusion 8 2 Compatibility of Metal–Induced Fluorescence Enhancement with Applications in Analytical Chemistry and Biosensing 13Fang Xie, Wei Deng, and Ewa M. Goldys 2.1 Introduction 13 2.2 Homogeneous Protein Sensing MIFE Substrates 14 2.2.1 Core–Shell Approach 14 2.2.2 Homogeneous Large Au Nanoparticle Substrates 16 2.2.3 Commercial Klarite™ Substrate 18 2.3 Ag Fractal Structures 19 2.3.1 Reasons for High Enhancement Factors in Nanowire Structures 19 2.3.2 Ag Dendritic Structure—Homogeneous Silver Fractal 22 2.4 MIFE with Membranes for Protein Dot Blots 25 2.5 MIFE with Flow Cytometry Beads and Single Particle Imaging 30 3 Plasmonic Enhancement of Molecule–Doped Core–Shell and Nanoshell on Molecular Fluorescence 37Jiunn–Woei Liaw, Chuan–Li Liu, Chong–Yu Jiang, and Mao–Kuen Kuo 3.1 Introduction 37 3.2 Theory 38 3.2.1 Plane Wave Interacting with an Multilayered Sphere 39 3.2.2 Excited Dipole Interacting with a Multilayered Sphere 40 3.2.3 EF on Fluorescence 40 3.3 Numerical Results and Discussion 41 3.3.1 Core–Shell 41 3.3.2 Nanoshelled Nanocavity 50 3.3.3 NS@SiO2 53 3.4 Conclusion 66 4 Controlling Metal–Enhanced Fluorescence Using Bimetallic Nanoparticles 73Debosruti Dutta, Sanchari Chowdhury, Chi Ta Yang, Venkat R. Bhethanabotla, and Babu Joseph 4.1 Introduction 73 4.2 Experimental Methods 74 4.2.1 Synthesis 74 4.2.2 Particle Characterization 75 4.2.3 Fluorescence Spectroscopy 76 4.3 Theoretical Modeling 79 4.3.1 Modeling SPR Using Mie Theory 79 4.3.2 Modeling of Metal–Enhanced Fluorescence Modified Gersten–Nitzan Model 81 4.3.3 Modeling MEF Using Finite–Difference Time–Domain (FDTD) Calculations 85 4.4 Conclusion and Future Directions 87 5 Roles of Surface Plasmon Polaritons in Fluorescence Enhancement 91K. F. Chan, K. C. Hui, J. Li, C. H. Fok, and H. C. Ong 5.1 Introduction 91 5.1.1 Surface Plasmon–Mediated Emission 91 5.1.2 Excitation of Propagating and Localized Surface Plasmon Polaritons in Periodic Metallic Arrays 93 5.1.3 Surface Plasmon–Mediated Emission from Periodic Arrays 95 5.2 Experimental 95 5.2.1 Sample Preparation 95 5.2.2 Optical Characterizations 96 5.3 Result and Discussion 97 5.3.1 The Decay Lifetimes of Metallic Hole Arrays 97 5.3.2 Dependence of Decay Lifetime on Hole Size 98 5.3.3 Comparison between Dispersion Relation and PL Mapping 100 5.3.4 Comparison of the Coupling Rate ΓB of Different SPP Modes 102 5.3.5 Photoluminescence Dependence on Hole Size 104 5.3.6 Dependence of Fluorescence Decay Lifetime on Hole Size 105 5.4 Conclusions 107 6 Fluorescence Excitation, Decay, and Energy Transfer in the Vicinity of Thin Dielectric/Metal/Dielectric Layers near Their Surface Plasmon Polariton Cutoff Frequency 111Kareem Elsayad and Katrin G. Heinze 6.1 Introduction 111 6.2 Background 111 6.3 Theory 112 6.4 Summary 120 7 Metal–Enhanced Fluorescence in Biosensing Applications 121Ruoyun Lin, Chenxi Li, Yang Chen, Feng Liu, and Na Li 7.1 Introduction 121 7.2 Substrates 121 7.3 Distance Control 128 7.4 Summary and Outlook 132 8 Long–Range Metal–Enhanced Fluorescence 137Ofer Kedem 8.1 Introduction 137 8.2 Collective Effects in NP Films 138 8.3 Investigations of Metal–Fluorophore Interactions at Long Separations 138 8.3.1 Distance–Dependent Fluorescence of Tris(bipyridine)ruthenium(II) on Supported Plasmonic Gold NP Ensembles 138 8.3.2 Lifetime 139 8.3.3 Intensity 141 8.3.4 Emission Wavelength and Linewidth 143 8.4 Conclusions 146 9 Evolution, Stabilization, and Tuning of Metal–Enhanced Fluorescence in Aqueous Solution 151Jayasmita Jana, Mainak Ganguly, and Tarasankar Pal 9.1 Introduction 151 9.1.1 Coinage Metal Nanoparticles in Metal–Enhanced Fluorescence 153 9.2 Metal–Enhanced Fluorescence in Solution Phase 154 9.2.1 Metal–Enhanced Fluorescence from Metal(0) in Solution 154 9.3 Applications of Metal–Enhanced Fluorescence 169 9.3.1 Sensing of Biomolecules 169 9.3.2 Sensing of Toxic Metals 171 9.4 Conclusion 174 10 Distance and Location–Dependent Surface Plasmon Resonance–Enhanced Photoluminescence in Tailored Nanostructures 179Saji Thomas Kochuveedu and Dong Ha Kim 10.1 Introduction 179 10.2 Effect of SPR in PL 181 10.2.1 Photoluminescence 181 10.2.2 Enhancement of Emission by SPR 182 10.2.3 Quenching of Emission by SPR 184 10.3 Effect of SPR in FRET 185 10.3.1 FRET 185 10.3.2 SPR–Induced Enhanced FRET 188 10.3.3 Effect of the Position, Concentration, and Size of Plasmonic Nanostructures in FRET System 189 10.4 Conclusions and Outlook 191 11 Fluorescence Quenching by Plasmonic Silver Nanoparticles 197M. Umadevi 11.1 Metal Nanoparticles 197 11.2 Fluorescence Quenching 197 11.3 Mechanism behind Quenching 198 12 AgOx Thin Film for Surface–Enhanced Raman Spectroscopy 203Ming Lun Tseng, Cheng Hung Chu, Jie Chen, Kuang Sheng Chung, and Din Ping Tsai 12.1 Introduction 203 12.1.1 SERS on the Laser–Treated AgOx Thin Film 203 12.1.2 Annealed AgOx Thin Film for SERS 206 12.2 Conclusion 206 13 Plasmon–Enhanced Two–Photon Excitation Fluorescence and Biomedical Applications 211Taishi Zhang, Tingting Zhao, Peiyan Yuan, and Qing–Hua Xu 13.1 Introduction 211 13.2 Metal–Chromophore Interactions 212 13.3 Plasmon–Enhanced One–Photon Excitation Fluorescence 214 13.4 Plasmon–Enhanced Two–Photon Excitation Fluorescence 215 13.5 Conclusions and Outlook 220 14 Fluorescence Biosensors Utilizing Grating–Assisted Plasmonic Amplification 227Koji Toma, Mana Toma, Martin Bauch, Simone Hageneder, and Jakub Dostalek 14.1 Introduction 227 14.2 SPCE in Vicinity to Metallic Surface 227 14.3 SPCE Utilizing SP Waves with Small Losses 230 14.4 Nondiffractive Grating Structures for Angular Control of SPCE 232 14.5 Diffractive Grating Structures for Angular Control of SPCE 234 14.6 Implementation of Grating–Assisted SPCE to Biosensors 236 14.7 Summary 237 15 Surface Plasmon–Coupled Emission: Emerging Paradigms and Challenges for Bioapplication 241Shuo–Hui Cao, Yan–Yun Zhai, Kai–Xin Xie, and Yao–Qun Li 15.1 Introduction 241 15.2 Properties of SPCE 242 15.3 Current Developments of SPCE in Bioanalysis 243 15.3.1 New Substrates Designing for Biochip 243 15.3.2 Optical Switch for Biosensing 244 15.3.3 Full–Coupling Effect for Bioapplication 245 15.3.4 Hot–Spot Nanostructure–Based Biosensor 248 15.3.5 Imaging Apparatus for High–Throughput Detection 249 15.3.6 Waveguide Mode SPCE to Widen Detection Region 251 15.4 Perspectives 252 16 Plasmon–Enhanced Luminescence with Shell–Isolated Nanoparticles 257Sabrina A. Camacho, Pedro H. B. Aoki, Osvaldo N. Oliveira, Jr, Carlos J. L. Constantino, and Ricardo F. Aroca 16.1 Introduction 257 16.2 Synthesis of Shell–Isolated Nanoparticles 259 16.2.1 Nanosphere Au–SHINs 259 16.2.2 Nanorod Au–SHINs 260 16.3 Plasmon–Enhanced Luminescence in Liquid Media 262 16.4 Enhanced Luminescence on Solid Surfaces and Spectral Profile Modification 265 16.4.1 SHINEF on Langmuir–Blodgett Films 266 17 Controlled and Enhanced Fluorescence Using Plasmonic Nanocavities 271Gleb M. Akselrod, David R. Smith, and Maiken H. Mikkelsen 17.1 Introduction to Plasmonic Nanocavities 271 17.2 Summary of Fabrication 272 17.3 Properties of the Nanocavity 273 17.3.1 Nanocavity Resonances 273 17.3.2 Tuning the Resonance 274 17.3.3 Directional Scattering and Emission 276 17.4 Theory of Emitters Coupled to Nanocavity 277 17.4.1 Simulation of Nanocavity 278 17.4.2 Enhancement in the Spontaneous Emission Rate 278 17.5 Absorption Enhancement 280 17.6 Purcell Enhancement 282 17.7 Ultrafast Spontaneous Emission 286 17.8 Harnessing Multiple Resonances for Fluorescence Enhancement 288 17.9 Conclusions and Outlook 291 18 Plasmonic Enhancement of UV Fluorescence 295Xiaojin Jiao, Yunshan Wang, and Steve Blair 18.1 Introduction 295 18.2 Plasmonic Enhancement 295 18.3 Analytical Description of PE of Fluorescence 296 18.4 Overview of Research on Plasmon–Enhanced UV Fluorescence 297 18.4.1 Material Selection 297 18.4.2 Structure Choice 301 18.4.3 Experimental Measurement 303 18.5 Summary 306 Index 309

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Book SynopsisThis book describes biosynthetic methods to synthesize heterocyclic compounds, offering a guide for the development of new drugs based on natural products. The authors explain the role of natural products in chemistry and their formation along with important analytical methods and techniques for working with heterocycles. Covers methods and techniques: isotopic labelling, enzymes and mutants, and pathway identification Provides a thorough resource of information specifically on heterocyclic natural products and their practical biosynthetic relevance Explains the role of natural products in chemistry and their formation Discusses gene cluster identification and the use of biogenetic engineering in pharmaceutical applicationTable of ContentsPREFACE xiii ACKNOWLEDGMENTS xv 1 Introduction 1 1.1 Natural Products: Primary and Secondary Metabolites 4 1.2 Common Reactions in Secondary Metabolites 6 1.2.1 Alkylations 6 1.2.2 Wagner–Meerwein Rearrangements 16 1.2.3 Aldol and Claisen Reactions 17 1.2.4 Schiff Base Formation and Mannich Reactions 23 1.2.5 Transaminations 25 1.2.6 Decarboxylations 26 1.2.7 Oxidation and Reduction Reactions 31 1.2.8 Dehalogenation/Halogenation Reactions 39 1.2.9 Glycosylation Reactions 46 References 48 2 Techniques for Biosynthesis 51 2.1 Isotopic Labeling 52 2.1.1 Stable Isotopes 52 2.1.2 Radioactive Isotopes 61 2.2 Gene Coding for Enzymes 62 2.3 Combinatorial Biosynthesis 63 References 70 3 Three-Membered Heterocyclic Rings and Their Fused Derivatives 73 3.1 Aziridines and Azirines 73 3.1.1 Azicemicins 73 3.1.2 Miraziridine 74 3.1.3 Maduropeptin 75 3.1.4 Azinomycins 79 3.1.5 Ficellomycin 87 3.1.6 Mitomycins 89 3.1.7 Azirinomycin and Related Azirines 101 3.2 Oxiranes and Oxirenes 104 3.2.1 Fosfomycin 104 3.2.2 AK HC and AF toxins 111 3.2.3 Cerulenin 117 3.2.4 Polyhydroxyalkanoates 118 3.2.5 Epoxyrollins 118 3.2.6 Asperlactone Aspyrone Asperline 121 3.2.7 Tajixanthone 129 3.2.8 Cyclomarin 133 3.2.9 Cyclopenin 139 3.2.10 Ovalicin and Fumagillin 141 3.2.11 Methylenomycin A 143 3.2.12 Antibiotic LL-C10037 147 3.2.13 Manumycins 151 3.2.14 Scopolamine 164 3.2.15 Iridoid Glucosides 169 3.2.16 Cordiaquinone 172 3.2.17 Cyclizidine and Indolizomycin 172 3.2.18 Enediyne Antibiotics 175 3.2.19 Macrolides 195 3.2.20 Epothilones 225 3.2.21 Pimaricin 233 3.2.22 Hypothemycin 240 3.2.23 Radicicol and Monocillin I 243 3.2.24 Trichothecenes 248 3.2.25 Sporolides A and B 255 References 258 4 Four-Membered Heterocyclic Rings and Their Fused Derivatives 277 4.1 Azetidine and Azetines 277 4.1.1 Azetidine-2-carboxylic acid 277 4.1.2 Polyoxins 280 4.1.3 Mugineic Acids 288 4.1.4 Tabtoxin and Tabtoxinine-β-lactam 293 4.1.5 Nocardicins 296 4.1.6 Thienamycin 303 4.1.7 Clavulanic Acid and Clavams 311 4.1.8 Penicillins and Cephalosporins 319 4.2 Oxetanes 341 4.2.1 Oxetanocins 341 4.2.2 Salinosporamides 342 4.2.3 Taxol 352 4.3 Dithiethanes 363 4.3.1 Tropodithietic acid and Thiotropocin 363 References 367 5 Five-Membered Heterocyclic Rings and Their Fused Derivatives 379 5.1 Pyrroles (Including Tetrapyrroles) 379 5.1.1 2-Acetyl-1-pyrroline 379 5.1.2 Pyrrolnitrin 380 5.1.3 Broussonetines 385 5.1.4 Prodigiosin and Undecylprodigiosin 386 5.1.5 Anatoxin-a and Homoanatoxin-a 402 5.1.6 Nostopeptolides A 407 5.1.7 Pyrrolizidine Alkaloids 410 5.1.8 Toyocamycin and Sangivamycin 416 5.1.9 Tetrapyrroles 420 5.2 Indoles 428 5.2.1 Indole-3-acetic acid and Glucobrassicin 428 5.2.2 Camalexin 439 5.2.3 Cyclomarazines 444 5.2.4 Rebeccamycin and Staurosporine 445 5.2.5 Paxilline 455 5.3 Furans 460 5.3.1 Furanomycin 460 5.3.2 Xenofuranones A and B 462 5.3.3 Acyl α-L-Rhamnopyranosides and Rhamnosyllactones 463 5.3.4 Tuscolid and Tuscoron A and B 466 5.3.5 Tetronomycin and Tetronasin 469 5.3.6 Nonactin and Macrotetrolides 474 5.3.7 Furanonaphthoquinone I 481 5.4 Thiophenes 488 5.5 Pyrazoles 489 5.6 Imidazoles 490 5.6.1 Histidine 490 5.6.2 Amaranzole A 493 5.6.3 Oroidin 493 5.6.4 Nikkomycins 493 5.6.5 Anosmine 496 5.7 Thiazoles 497 5.7.1 Thiamin (Vitamin B1) 497 5.7.2 Polypeptide Antibiotics 502 5.7.3 Barbamide 508 5.7.4 BE-10988 508 5.7.5 Pheomelanins 510 5.8 Dithioles 511 References 516 6 Six-Membered Rings and Their Fused Derivatives 533 6.1 Pyridines and Piperidines 533 6.1.1 Pyridoxal 5′-phosphate 533 6.1.2 Nicotinamide Adenine Dinucleotide 536 6.1.3 Nicotine and Related Compounds 540 6.1.4 Tropane Alkaloids 542 6.1.5 Stenusine 543 6.1.6 Antidesmone 546 6.1.7 Quinolobactin 546 6.1.8 Pyridomycin 546 6.1.9 Lycopodine 550 6.1.10 Acridone Alkaloids 551 6.1.11 Benzylisoquinolines 551 6.1.12 Saframycins 559 6.2 Pyrans 561 6.2.1 Lovastatin and Compactin 561 6.2.2 Bafilomycins and Concanamycin 567 6.2.3 Citrinin 571 6.2.4 Aminocoumarin Antibiotics 571 6.2.5 Flavonoids 577 6.2.6 Actinorhodin and Granaticin 581 6.2.7 Trichothecenes 582 6.2.8 Gilvocarcins 582 6.3 Pyridazines 586 6.3.1 Kutznerides 586 6.3.2 Pyridazomycin 591 6.3.3 Azamerone 591 6.4 Pyrimidines 592 6.4.1 Purine and Pyrimidine Nucleotides 592 6.4.2 Methylxanthines and Methyluric Acids 602 6.4.3 Cytokinins 606 6.4.4 Uridyl Peptide Antibiotics 607 6.4.5 Riboflavin FMN and FAD 611 6.5 Pyrazines 613 6.5.1 Alkyl and Methoxy Pyrazines 613 6.5.2 Pteridines 616 6.5.3 Epipolythiodioxopiperazines 617 6.5.4 Roquefortine C and Related Compounds 621 6.6 Oxazines 622 6.6.1 Minimycin 622 6.6.2 Benzoxazinoids 625 6.7 Dioxanes 626 6.7.1 Plakortolides 626 6.7.2 Alnumycin 627 References 632 7 Seven- Eight-Membered and Larger Heterocyclic Rings and Their Fused Derivatives 649 7.1 Azepines 649 7.2 Oxepanes and Oxepines 657 7.3 Diazepines Oxazepines and Thiazepines 661 7.4 Diazocines 674 7.5 Oxocines 674 7.6 Erythromycin A 675 7.7 Tylosin 683 7.8 Zearalenone 690 7.9 Polyene Macrolide Antibiotics 693 7.9.1 Nystatin and Amphotericin 694 7.9.2 Candicidin D 705 7.10 Geldanamycin and Herbimycins 716 7.11 Rifamycins 724 7.12 Rapamycin 738 References 745 INDEX 757

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

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Book SynopsisPhosphorylation is the addition of a phosphate (PO 4) group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes, causing or preventing the mechanisms of diseases such as cancer and diabetes.Table of ContentsPreface xvii Acknowledgments xxi About the Author xxiii 1 Posttranslational Modification (PTM) of Proteins 1 1.1 Over 200 Forms of PTM of Proteins 1 1.2 Three Main Types of PTM Studied by MS 2 1.3 Overview of Nano-Electrospray/Nanofl ow LC-MS 2 1.3.1 Defi nition and Description of MS 2 1.3.2 Basic Design of Mass Analyzer Instrumentation 3 1.3.3 ESI 7 1.3.4 Nano-ESI 11 1.4 Overview of Nucleic Acids 15 1.5 Proteins and Proteomics 20 1.5.1 Introduction to Proteomics 20 1.5.2 Protein Structure and Chemistry 22 1.5.3 Bottom-Up Proteomics: MS of Peptides 27 1.5.3.1 History and Strategy 27 1.5.3.2 Protein Identifi cation through Product Ion Spectra 30 1.5.3.3 High-Energy Product Ions 36 1.5.3.4 De Novo Sequencing 37 1.5.3.5 Electron Capture Dissociation (ECD) 40 1.5.4 Top-Down Proteomics: MS of Intact Proteins 42 1.5.4.1 Background 42 1.5.4.2 GP Basicity and Protein Charging 42 1.5.4.3 Calculation of Charge State and Molecular Weight 44 1.5.4.4 Top-Down Protein Sequencing 46 1.5.5 Systems Biology and Bioinformatics 48 1.5.6 Biomarkers in Cancer 52 Reference 56 2 Glycosylation of Proteins 59 2.1 Production of a Glycoprotein 59 2.2 Biological Processes of Protein Glycosylation 59 2.3 N-Linked and O-Linked Glycosylation 60 2.4 Carbohydrates 60 2.4.1 Ionization of Oligosaccharides 64 2.4.2 Carbohydrate Fragmentation 65 2.4.3 Complex Oligosaccharide Structural Elucidation 70 2.5 Three Objectives in Studying Glycoproteins 72 2.6 Glycosylation Study Approaches 72 2.6.1 MS of Glycopeptides 73 2.6.2 Mass Pattern Recognition 75 2.6.2.1 High Galactose Glycosylation Pattern 75 2.6.3 Charge State Determination 76 2.6.4 Diagnostic Fragment Ions 76 2.6.5 High-Resolution/High-Mass Accuracy Measurement and Identification 76 2.6.6 Digested Bovine Fetuin 78 Reference 79 3 Sulfation of Proteins as Posttranslational Modification 81 3.1 Glycosaminoglycan Sulfation 81 3.2 Cellular Processes Involved in Sulfation 81 3.3 Brief Example of Phosphorylation 82 3.4 Sulfotransferase Class of Enzymes 82 3.5 Fragmentation Nomenclature for Carbohydrates 82 3.6 Sulfated Mucin Oligosaccharides 83 3.7 Tyrosine Sulfation 84 3.8 Tyrosylprotein Sulfotransferases TPST1 and TPST2 87 3.9 O-Sulfated Human Proteins 89 3.10 Sulfated Peptide Product Ion Spectra 89 3.11 Use of Higher Energy Collisions 93 3.12 Electron Capture Dissociation (ECD) 94 3.13 Sulfation versus Phosphorylation 95 Reference 97 4 Eukaryote PTM as Phosphorylation: Normal State Studies 99 4.1 Mass Spectral Measurement with Examples of HeLa Cell Phosphoproteome 99 4.1.1 Introduction 99 4.1.2 Protein Phosphatase and Kinase 99 4.1.3 Hydroxy-Amino Acid Phosphorylation 100 4.1.4 Traditional Phosphoproteomic Approaches 102 4.1.5 Current Approaches 103 4.1.5.1 Phosphoproteomic Enrichment Techniques 103 4.1.5.2 IMAC 104 4.1.5.3 MOAC 105 4.1.5.4 Methylation of Peptides prior to IMAC or MOAC Enrichment 107 4.1.6 The Ideal Approach 107 4.1.7 One-Dimensional (1-D) Sodium Dodecyl Sulfate (SDS) PAGE 108 4.1.8 Tandem MS Approach 108 4.1.8.1 pS Loss of Phosphate Group 109 4.1.8.2 pT Loss of Phosphate Group 112 4.1.8.3 pY Loss of Phosphate Group 113 4.1.9 Alternative Methods: Infrared Multiphoton Dissociation (IRMPD) and Electron Capture Dissociation (ECD) 115 4.1.10 Electron Transfer Dissociation (ETD) 115 4.2 The HeLa Cell Phosphoproteome 118 4.2.1 Introduction 118 4.2.2 Background of Study 118 4.2.3 What is Covered 119 4.2.4 Optimized Methods to Use for Phosphoproteomic Studies 119 4.2.4.1 Cell Culture 119 4.2.4.2 Extraction of HeLa Cell Proteins 120 4.2.4.3 Trizol Extraction and Tryptic Digestion 120 4.2.4.4 Solid-Phase Extraction (SPE) Desalting 120 4.2.4.5 Converting Peptide Carboxyl Moieties to Methyl Esters 121 4.2.4.6 Roche Complete Lysis-M, EDTA-Free Extraction 122 4.2.4.7 1-D SDS-PAGE Cleanup 122 4.2.4.8 In-Gel Reduction, Alkylation, Digestion, and Extraction of Peptides 122 4.2.4.9 Phosphopeptide Enrichment Using IMAC 123 4.2.5 Description of Instrumental Analyses 123 4.2.5.1 RP/Nano-HPLC Separation 123 4.2.5.2 MS Analysis 125 4.2.6 Current Approaches for Peptide Identification and False Discovery Rate (FDR) Determination 125 4.2.7 Results of the Protein Extraction and Preparation 126 4.2.7.1 Detergent Lysis, Trizol, and Ultracentrifugation 126 4.2.7.2 Nucleic Acid Removal with SDS-PAGE 127 4.2.8 HeLa Cell Phosphoproteome Methodology Comparison 128 4.2.8.1 Roche In-Solution versus Trizol Extraction 129 4.2.8.2 In-Solution and In-Gel Digests Phosphoproteome Coverage 129 4.2.9 Overall Conclusion 134 4.3 Nonphosphoproteome HeLa Cell Analysis 135 4.3.1 IMAC Flow Through Peptide Analysis 135 4.3.2 IMAC NaCl Wash Peptide Analysis 136 4.3.3 IMAC Flow Through versus NaCl Wash Comparison 138 4.3.4 Gene Ontology Comparison 138 4.3.5 IMAC Bed Nonspecifi c Binding Study 140 4.4 Reviewing Spectra Using the SpectrumLook Software Package 143 Reference 144 5 Eukaryote PTM as Phosphorylation: Perturbed State Studies 147 5.1 Study of the Phosphoproteome of HeLa Cells under Perturbed Conditions by Nano-High-Performance Liquid Chromatography HPLC Electrospray Ionization (ESI) Linear Ion Trap (LTQ)-FT/Mass Spectrometry (MS) 147 5.1.1 Introduction 147 5.1.2 Ataxia Telangiectasia Mutated (ATM) and ATM and Rad3-Related (ATR) 149 5.1.3 Background of Study 149 5.1.3.1 PP5 149 5.1.3.2 Functions of PP5 151 5.1.3.3 DDR of PP5 151 5.1.4 Review of Optimized Approach to Study 151 5.1.4.1 Producing Cell Cultures 151 5.1.4.2 Protein Extraction 152 5.1.4.3 Phosphopeptide Enrichment by IMAC 154 5.1.4.4 Reversed-Phase (RP)/Nano-HPLC Separation 155 5.1.4.5 LTQ-FT/MS/MS 156 5.1.4.6 Protein Identifi cation and False Discovery Rate (FDR) Determination 156 5.1.4.7 Phosphopeptide Quantitative Differential Comparison 157 5.1.4.8 Data Set Peak Matching and Alignment 157 5.1.4.9 Phosphopeptide Response Normalization 160 5.1.5 Phosphoproteome Gene Ontology (GO) Comparison 160 5.1.5.1 GO Cellular Component 162 5.1.6 Potential Regulated Target Proteins of PP5 162 5.1.6.1 Analysis of Variance (ANOVA) 162 5.1.6.2 Four Potential Target Proteins 166 5.1.7 GO Differential Comparison 167 5.1.7.1 GO Cellular Component 168 5.1.7.2 Infl uence of Classes or Categories of Proteins 168 5.1.7.3 Molecular Function Interacting Modules 168 5.1.8 Conclusion 175 5.1.9 Reviewing Spectra Using the SpectrumLook Software Package 175 Reference 176 6 Prokaryotic Phosphorylation of Serine, Threonine, and Tyrosine 181 6.1 Introduction 181 6.1.1 Serine (Ser)/Threonine (Thr)/Tyrosine (Tyr) Phosphorylation 181 6.1.2 Histidine (His) Phosphorylation 181 6.1.3 Caulobacter crescentus 181 6.1.4 Ser/Thr/Tyr Phosphorylation of C. crescentus 183 6.1.5 Ser/Thr/Tyr Phosphorylation of Bacillus subtilis and Escherichia coli 184 6.1.6 C. crescentus as Cell Cycle Model 185 6.1.7 Bacteria Starvation Response 187 6.1.8 First Coverage of C. crescentus Phosphoproteome 188 6.2 Optimized Methodology for Phospho Ser/Thr/Tyr Studies 188 6.2.1 Bacterial Strain and Growth Conditions 188 6.2.2 C. crescentus Cell Protein Extraction: Phosphoproteomics 189 6.2.3 Solid-Phase Extraction (SPE) Desalting 190 6.2.4 In Vitro Methylation of Peptides 190 6.2.5 Phosphopeptide Enrichment by IMAC 191 6.2.6 Normal Proteomics 192 6.2.7 pY Enrichment by IP 192 6.2.8 RP/Nano-High-Performance Liquid Chromatography (HPLC) Separation 192 6.2.9 LC-Linear Ion Trap (LTQ)-Orbitrap MS/MS 193 6.2.10 LTQ-Fourier Transform (FT)/MS/MS 193 6.2.11 Peptide Identification and False Discovery Rate (FDR) Determination 193 6.2.12 Peptide Quantitative Comparison 194 6.3 Identifi cation of the Components of the Ser/Thr/Tyr Phosphoproteome in C. crescentus Grown in the Presence and Absence of Glucose 194 6.3.1 Total Phosphoprotein Identifications 194 6.3.2 MSA Spectra 196 6.3.3 Phosphorylation Sites Identifi ed 196 6.3.4 Ser/Thr/Tyr Phosphoproteome of C. crescentus 205 6.3.5 Phosphorylated His and Aspartate 213 6.3.6 Cell Cycle His Kinase CckA 215 6.3.7 Phosphoglutamate 216 6.3.8 Enriched Tyr Phosphoproteome of C. crescentus 216 6.3.8.1 Sensor His Kinase KdpD 216 6.3.8.2 TonB-Dependent Receptor Proteins 216 6.3.9 Carbon Environment-Shared Phosphoproteome 217 6.3.9.1 Two-Component His Kinases 217 6.3.9.2 Multiply Phosphorylated Kinases 217 6.3.9.3 pTPLAALpSAQSRRAR Peptide as Sensor His Kinase 217 6.3.9.4 Aspartate Phosphorylated Tyr Kinase DivL 217 6.3.10 Carbon-Rich versus Carbon-Starved Class/Category 225 6.3.10.1 Localization of Phosphoproteome of C. crescentus 225 6.3.10.2 Integral Membrane Proteins 225 6.3.10.3 Function of Phosphoproteome of C. crescentus 225 6.3.11 Carbon-Rich versus Carbon-Starved Unique Phosphorylated Proteins 227 6.3.11.1 Carbon-Rich Environment Phosphorylated Proteins 227 6.3.11.2 Carbon-Starved Environment Phosphorylated Proteins 227 6.3.11.3 Decreased Normal Activity 232 6.3.12 Confi rmation of Decreased Energy Pathways 232 6.3.12.1 Carbon-Rich Mitochondrial Localization 232 6.3.12.2 Normal Proteome Glycolytic Pathway 233 6.3.12.3 Starvation Survival Response 233 6.3.13 Phosphopeptide Quantitative Differential Comparison 233 6.3.13.1 Upregulation in Phosphorylation 234 6.3.13.2 Adaptive Response with Phosphorylation 234 6.3.13.3 Upregulation NAD-Dependent GDH 234 6.3.13.4 Downregulation of Flagellin Protein 235 6.3.14 Carbon-Rich versus Carbon-Starved Normal Proteome Time Course Study 235 6.3.14.1 Entire Proteome Localization and Function 235 6.3.14.2 Regulated Proteins 237 6.3.14.3 Localization of Regulated Proteins 237 6.3.14.4 Function of Regulated Proteins 238 6.3.14.5 Normal Proteome Energy Pathways 239 6.3.14.6 Overlap of Phosphorylated Proteins and Regulated Normal Proteome 239 6.3.14.7 Differences of Phosphorylated Proteins 240 6.3.14.8 Localization of Phosphorylated Proteins 240 6.3.14.9 Direct Relationships Observed 240 6.3.15 Conclusions 243 6.3.16 Supplementary Material 243 6.3.16.1 Reviewing Spectra Using the SpectrumLook Software Package 243 Reference 244 7 Prokaryotic Phosphorylation of Histidine 249 7.1 Phosphohistidine as Posttranslational Modification (PTM) 249 7.2 Bacterial Kinases and the Two-Component System 250 7.3 Measurement of Phosphorylated His (pH) 251 7.3.1 Stabilities of Phosphorylated Amino Acids 251 7.3.2 Immobilized Metal Affinity Chromatography (IMAC) and Mass Spectrometry (MS) 252 7.4 In Vitro and In Vivo Study of pH-Containing Peptides by Nano-ESI Tandem MS 255 7.4.1 Introduction 255 7.4.2 Background of Study 257 7.4.2.1 Bacteria Models of Ser/Thr/Tyr Phosphorylation 257 7.4.2.2 Prokaryotic Phosphorylation of His 258 7.4.2.3 C. crescentus 258 7.4.2.4 Mass Spectral Measurement of Phosphohistidine 258 7.4.3 Optimized Methodology for Phosphohistidine Studies 259 7.4.3.1 In Vitro Selective pHis Phosphorylation 259 7.4.3.2 In Vitro Phosphorylation of Angio II (Sar1Thr8) 261 7.4.3.3 In Vitro Methylation of Peptides 262 7.4.3.4 C. crescentus Cell Protein Extraction with V-8 Protease Digestion 262 7.4.3.5 1-D SDS-Polyacrylamide Gel Electrophoresis (PAGE) 263 7.4.3.6 Phosphohistidine Enrichment by Cu(II)-Based IMAC 264 7.4.3.7 Reversed-Phase (RP)/Nano-HPLC Separation 265 7.4.3.8 Nano-ESI Nano-HPLC MS 266 7.4.3.9 Peptide Identification and False Discovery Rate (FDR) Determination 268 7.4.4 C18 RP LC Behavior 268 7.4.5 Phosphohistidine Loses HPO3 and H3PO4 270 7.4.5.1 Rational for H3PO4 Loss 272 7.4.6 Q-TOF/MS/MS Product Ion Spectra 277 7.4.6.1 pH-Containing Peptide INpHDLR 277 7.4.6.2 Doubly Charged (2+) Peptide INpHDLR 279 7.4.6.3 pH-Containing Peptide pHLGLAR 279 7.4.6.4 Singly Charged (1+) Peptide pHLGLAR 280 7.4.7 Behavior of Monophosphohistidine and Diphosphohistidine Peptide 281 7.4.7.1 Peptide Angio I as DRVYIHPFHL 281 7.4.8 Behavior of Phosphotyrosine and Phosphohistidine Peptide 285 7.4.8.1 Peptide Angio II as DRVpYIHPF 285 7.4.8.2 Phosphorylated Angio II as DRVpYIpHPF 285 7.4.9 Behavior of Phosphotyrosine-, Phosphothreonine-, and Phosphohistidine-Containing Peptide 287 7.4.9.1 Peptide Angio II (Sar1Thr8) 287 7.4.10 Validation of Cu(II)-Based IMAC Phosphohistidine Enrichment 291 7.4.10.1 Fe(III)-Based IMAC versus Cu(II) Based 292 7.4.10.2 Cu(II)-Based IMAC of Angio I 292 7.4.10.3 Cu(II)-Based IMAC of Angio II 293 7.4.11 In Vivo Measurement of Phosphohistidine 293 7.4.11.1 Time-Based Digestion Study 293 7.4.11.2 Phosphohistidine-Containing Peptides 294 7.4.11.3 Phosphohistidine Product Ion Spectra 294 7.4.12 Gene Ontology of Phosphorylated Proteins 296 7.4.12.1 Localization of Phosphorylated Proteins 296 7.4.12.2 Function of Phosphorylated Proteins 304 7.4.13 Predicted Regulatory Protein Motif Study 307 7.4.14 Validation of Phosphohistidine-Containing Proteins 308 7.4.14.1 Phosphorylation Motif Study 308 7.4.14.2 Phosphohistidine Kinase Motif 309 7.4.15 The pDpH Motif 310 7.4.16 Conclusions 311 7.5 Supplementary Material 311 7.5.1 Reviewing Spectra Using the SpectrumLook Software Package 311 Reference 313 Appendix I Atomic Weights and Isotopic Compositions 317 Appendix II Periodic Table of the Elements 325 Appendix III Fundamental Physical Constants 327 Glossary 329 Index 345

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Book SynopsisAn increasingly popular analytical method, hydrophilic interaction chromatography (HILIC) has the ability to retain and separate polar compounds that are often difficult to analyze by reversed-phase high-performance liquid chromatography (HPLC) or other analytical methods.Trade Review“The well-balanced mixture with updated HILIC theory and detailed practical descriptions makes it a useful resource for scientists working in analytical chemistry, biochemistry, biotechnology, and bioinformatics, and a valuable resource for people in the analytical column industry.” (Analytical and Bioanalytical Chemistry, 22 September 2013) Table of ContentsPREFACE xiii CONTRIBUTORS xv CHAPTER 1 SEPARATION MECHANISMS IN HYDROPHILIC INTERACTION CHROMATOGRAPHY 1 David V. McCalley 1.1 Introduction 1 1.2 Historical Background: Recognition of the Contribution of Partition, Ion Exchange, and RP Interactions to the Retention Process 3 1.3 Recent Studies on the Contributory Mechanisms to HILIC Retention 7 1.4 Conclusions 38 References 38 CHAPTER 2 STATIONARY PHASES FOR HILIC 43 Mohammed E.A. Ibrahim and Charles A. Lucy 2.1 Introduction 43 2.2 HILIC Stationary Phases 44 2.3 Commercial HILIC Phases 61 2.4 Conclusions 77 Acknowledgments 77 References 77 CHAPTER 3 HILIC METHOD DEVELOPMENT 87 Yong Guo and Xiande Wang 3.1 Introduction 87 3.2 General Method Development Considerations 88 3.3 HILIC Method Development 93 3.4 Detection for HILIC Methods 104 3.5 Conclusions 107 References 108 CHAPTER 4 PHARMACEUTICAL APPLICATIONS OF HYDROPHILIC INTERACTION CHROMATOGRAPHY 111 Bernard A. Olsen, Donald S. Risley, V. Scott Sharp, Brian W. Pack, and Michelle L. Lytle 4.1 Introduction 112 4.2 Determination of Counterions 117 4.3 Main Component Methods 129 4.4 Determination of Impurities 135 4.5 Excipients 146 4.6 Chiral Applications 152 4.7 Conclusions 161 References 161 CHAPTER 5 HYDROPHILIC INTERACTION CHROMATOGRAPHY (HILIC) FOR DRUG DISCOVERY 169 Alfonso Espada and Mark Strege 5.1 Drug Discovery Model 169 5.2 HILIC Applications for In Vitro Biology 170 5.4 Practical Considerations 186 5.5 Conclusions 187 References 188 CHAPTER 6 ADVANCES IN HYDROPHILIC INTERACTION CHROMATOGRAPHY (HILIC) FOR BIOCHEMICAL APPLICATIONS 195 Fred Rabel and Bernard A. Olsen 6.1 Introduction 195 6.2 Carbohydrates 196 6.2.1 Mono- and Disaccharides 196 6.3 Nucleobases and Nucleosides 203 6.4 Oligonucleotides 205 6.5 Amino Acids and Peptides 206 6.6 Proteins 209 6.7 Phospholipids 209 6.8 Conclusions 211 References 212 CHAPTER 7 HILIC-MS FOR TARGETED METABOLOMICS AND SMALL MOLECULE BIOANALYSIS 219 Hien P. Nguyen, Heather D. Tippens, and Kevin A. Schug 7.1 Introduction 219 7.2 The Role of HILIC-MS in Targeted Metabolomics versus Other LC Modes 221 7.3 Strategies for Method Development Based on Retention Behavior of Targeted Metabolites on HILIC Stationary Phases 223 7.4 Summary 231 Acknowledgments 232 References 232 CHAPTER 8 HILIC FOR FOOD, ENVIRONMENTAL, AND OTHER APPLICATIONS 239 Michael A. Koupparis, Nikolaos C. Megoulas, and Aikaterini M. Gremilogianni 8.1 Introduction 239 8.2 Food Applications for HILIC 240 8.3 Environmental and Other Applications of HILIC 254 8.4 Conclusions 257 References 259 CHAPTER 9 THEORY AND PRACTICE OF TWO-DIMENSIONAL LIQUID CHROMATOGRAPHY SEPARATIONS INVOLVING THE HILIC MODE OF SEPARATION 265 Stephen R. Groskreutz and Dwight R. Stoll 9.1 Fundamentals of Multidimensional Liquid Chromatography 265 9.2 Complementarity of HILIC Selectivity to Other Separation Modes 278 9.3 Instrumentation and Experimental Considerations 278 9.4 Applications 291 9.5 The Future of HILIC Separations in 2DLC 298 References 298 INDEX 307

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Book SynopsisAn informative and comprehensive book on the applications and techniques of dried blood spot sampling Dried blood spot (DBS) sampling involves the collection of a small volume of blood, via a simple prick or other means, from a study subject onto a cellulose or polymer paper card, which is followed by drying and transfer to the laboratory for analysis. For many years, this method of blood sample collection has been extensively utilized in some important areas of human healthcare (for example, newborn screening for inherited metabolic disorders and HIV-related epidemiological studies). Because of its advantages over conventional blood, plasma, or serum sample collection, DBS sampling has been valued by the pharmaceutical industry in drug research and development. Dried Blood Spots: Applications and Techniques features contributions from an international team of leading scientists in the field. Their contributions present a unique resource on the history, pTable of ContentsPREFACE viii CONTRIBUTORS x PART I HISTORY, APPLICATIONS, AND HEALTHCARE 1 Overview of the History and Applications of Dried Blood Samples 3 W. Harry Hannon and Bradford L. Therrell, Jr. 2 Dried Blood Spot Cards 16 Brad Davin and W. Harry Hannon 3 Dried Blood Spot Sample Collection, Storage, and Transportation 21 Joanne Mei 4 Dried Blood Spot Specimens for Polymerase Chain Reaction in Molecular Diagnostics and Public Health Surveillance 32 Chunfu Yang 5 Application of Enzyme Immunoassay Methods Using Dried Blood Spot Specimens 40 Mireille B. Kalou 6 Applications of Dried Blood Spots in Newborn and Metabolic Screening 53 Donald H. Chace, Alan R. Spitzer, and Víctor R. De Jesús 7 Dried Blood Spots for Use in HIV-Related Epidemiological Studies in Resource-Limited Settings 76 Sridhar V. Basavaraju and John P. Pitman 8 Use of Dried Blood Spot Samples in HCV-, HBV-, and Influenza-Related Epidemiological Studies 95 Harleen Gakhar and Mark Holodniy 9 Applications of Dried Blood Spots in General Human Health Studies 114 Eleanor Brindle, Kathleen A. O’Connor, and Dean A. Garrett 10 Applications of Dried Blood Spots in Environmental Population Studies 130 Antonia M. Calafat and Kayoko Kato 11 The Use of Dried Blood Spots and Stains in Forensic Science 140 Donald H. Chace and Nicholas T. Lappas PART II PHARMACEUTICAL APPLICATIONS 12 Pharmaceutical Perspectives of Use of Dried Blood Spots 153 Christopher Evans and Neil Spooner 13 Punching and Extraction Techniques for Dried Blood Spot Sample Analysis 160 Philip Wong and Christopher A. James 14 Considerations in Development and Validation of LC-MS/MS Method for Quantitative Analysis of Small Molecules in Dried Blood Spot Samples 168 Wenkui Li 15 Challenges and Experiences with Dried Blood Spot Technology for Method Development and Validation 179 Chester L. Bowen and Christopher A. Evans 16 Clinical Implications of Dried Blood Spot Assays for Biotherapeutics 188 Matthew E. Szapacs and Jonathan R. Kehler 17 Potential Role for Dried Blood Spot Sampling and Bioanalysis in Preclinical Studies 195 Qin C. Ji and Laura Patrone 18 Clinical and Bioanalytical Evaluation of Dried Blood Spot Sampling for Genotyping and Phenotyping of Cytochrome p450 Enzymes in Healthy Volunteers 202 Theo de Boer, Izaak den Daas, Jaap Wieling, Johan Wemer, and LingSing Chen 19 Application of Dried Blood Spot Sampling in Clinical Pharmacology Trials and Therapeutic Drug Monitoring 216 Kenneth Kulmatycki, Wenkui Li, Xiaoying (Lucy) Xu, and Venkateswar Jarugula 20 Automation in Dried Blood Spot Sample Collection, Processing, and Analysis for Quantitative Bioanalysis in Pharmaceutical Industry 229 Leimin Fan, Katty Wan, Olga Kavetskaia, and Huaiqin Wu 21 Beyond Dried Blood Spots—Application of Dried Matrix Spots 235 Shane R. Needham PART III NEW TECHNOLOGIES AND EMERGING APPLICATIONS 22 Direct Analysis of Dried Blood Spot Samples 245 Paul Abu-Rabie 23 Paper Spray Ionization for Direct Analysis of Dried Blood Spots 298 Jiangjiang Liu, Nicholas E. Manicke, R. Graham Cooks, and Zheng Ouyang 24 Direct Solvent Extraction and Analysis of Biomarkers in Dried Blood Spots Using a Flow-Through Autosampler 314 David S. Millington, Haoyue Zhang, M. Arthur Moseley, J. Will Thompson, and Peter Smith 25 Development of Biomarker Assays for Clinical Diagnostics Using a Digital Microfluidics Platform 325 David S. Millington, Ramakrishna Sista, Deeksha Bali, Allen E. Eckhardt, and Vamsee Pamula 26 Applications and Chemistry of Cellulose Papers for Dried Blood Spots 332 Jacquelynn Luckwell, Åke Danielsson, Barry Johnson, Sarah Clegg, Mark Green, and Alan Pierce 27 Derivatization Techniques in Dried Blood Spot Analysis 344 Ann-Sofie M.E. Ingels, Nele Sadones, Pieter M.M. De Kesel, Willy E. Lambert, and Christophe P. Stove INDEX 355

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Book SynopsisThis is a practical guidebook about cyclopropanes that thoroughly surveys derivatives and transformations, synthetic methods, and experimental efficiency as a gateway for further research and development in the field.Table of ContentsPreface ix Part I Reactivity and availability 1 Introduction, 1 Reference, 2 1 Structure and Reactivity of the Cyclopropane Species 3 1.1 Geometry and Bonding, 3 1.2 Energy, 4 1.3 Spectra, 5 1.4 Cyclopropyl Cations, 5 1.5 Cyclopropyl Anions, 6 1.6 Cyclopropyl Radicals, 7 1.7 Cyclopropylidenes, 7 1.8 Cyclopropylcarbinyl Cations, 8 1.9 Cyclopropylcarbinyl Anions, 8 1.10 Cyclopropylcarbinyl Radicals, 10 1.11 Cyclopropylcarbenes, 10 1.12 Conclusion, 11 References, 13 2 Ring Cleavage Reactions 15 2.1 Cyclopropyl Activation, 16 2.1.1 Halogen, Oxy, and Sulfur Substituted Cyclopropanes, 16 2.1.2 Alkylidenecyclopropanes, 19 2.2 Cyclopropylcarbinyl Activation, 23 2.2.1 Halogeno, Oxy, Acyl and Metallomethyl Cyclopropanes, 23 2.2.2 Alkylidenecyclopropanes, 27 2.2.3 Vinyl and Ethynyl Cyclopropanes, 29 2.2.4 1,2]Divinylcyclopropanes, 33 2.2.5 Acceptor Cyclopropanes, 35 2.2.6 Donor Cyclopropanes, 38 2.2.7 Donor–Acceptor Cyclopropanes, 43 2.3 Conclusion, 48 References, 49 3 Synthesis of Cyclopropanes 57 3.1 1,3]Cyclization Reactions, 57 3.1.1 Cyclizations with Cleavage of Two Single Bonds, 58 3.1.2 Cyclizations with Cleavage of One Double Bond and One Single Bond, 59 3.1.3 Cyclizations with Cleavage of Two Double Bonds, 62 3.2 [2 + 1] Cyclization Reactions, 65 3.2.1 Cycloaddition of Carbene Equivalents to Olefins, 66 3.2.2 Coupling of 1,1]Carbodianion and 1,2]Carbodication Equivalents, 79 3.2.3 Coupling of 1,1]Carbodication and 1,2]Carbodianion Equivalents, 83 3.3 Addition Reactions to the Double Bond of Cyclopropenes, 88 3.4 Interconversion of Cyclopropanes, 90 3.5 Conclusion, 90 References, 90 Part Ii Synthetic Application 99 Introduction, 99 References, 100 4 Triangulation Retrosynthetic Analysis 103 4.1 Retrosynthetic Triangulation, 103 4.2 Conclusion, 108 References, 108 5 Acyclic Compounds 109 5.1 Formation of Carbon Substituents, 109 5.1.1 Nonactivated Cyclopropane Precursors, 109 5.1.2 Cyclopropylcarbinyl Activated Precursors, 112 5.1.3 Cooperatively Activated Precursors, 138 5.2 Formation of Olefin Groups, 139 5.2.1 Cyclopropylcarbinyl Activated Precursors, 139 5.2.2 Cyclopropyl Activated Precursors, 142 5.2.3 Fragmentation of the Cyclopropane Precursors, 146 5.2.4 Cooperatively Activated Cyclopropane Precursors, 147 5.3 Formation of Carbonyl Groups, 151 5.3.1 Cyclopropylcarbinyl Precursors, 151 5.3.2 Cooperatively Activated Precursors, 156 5.4 Retrosynthetic Account, 162 References, 163 6 Cyclobutane Derivatives 167 6.1 Grandisol Syntheses, 167 6.2 Cyclobutane Synthetic Intermediates, 169 6.3 Retrosynthetic Account, 183 References, 184 7 Cyclopentanes 187 7.1 Vinylcyclopropane–Cyclopentene Rearrangement, 187 7.1.1 Cyclopropylcarbinyl Activated Precursors, 187 7.1.2 Cooperatively Activated Precursors, 188 7.2 Cycloaddition Reactions, 221 7.2.1 Cyclopropylcarbinyl Activated Precursors, 221 7.2.2 Cooperatively Activated Precursors, 221 7.3 Modification of Substituents, 223 7.3.1 N onactivated Cyclopropane Precursors, 223 7.3.2 Cyclopropylcarbinyl Activated Precursors, 224 7.3.3 Cooperatively Activated Precursors, 231 7.3.4 Fragmentation Reactions, 245 7.4 Retrosynthetic Account, 246 References, 246 8 Cyclohexanes 251 8.1 Intramolecular Cyclization Reactions, 251 8.2 Cycloaddition Reactions, 255 8.3 Modification of Substituents, 269 8.3.1 Cyclopropylcarbinyl Activated Precursors, 269 8.3.2 Cyclopropyl Activated Precursors, 275 8.3.3 Cooperatively Activated Precursors, 277 8.4 Retrosynthetic Account, 282 References, 283 9 Cycloheptanes 285 9.1 Divinylcyclopropane–Cycloheptadiene Rearrangement, 285 9.2 Cycloaddition Reactions, 315 9.3 Modification of Substituents, 318 9.3.1 Nonactivated Cyclopropane Precursors, 318 9.3.2 Cyclopropylcarbinyl Activated Precursors, 318 9.3.3 Cyclopropyl Activated Precursors, 323 9.3.4 Cooperatively Activated Precursors, 325 9.4 Retrosynthetic Account, 329 References, 330 10 Cyclooctanes and Larger Carbocycles 333 10.1 Cycloaddition Reactions, 333 10.2 Modification of Substituents, 334 10.2.1 Cyclopropylcarbinyl Activated Precursors, 334 10.2.2 Cyclopropyl Activated Precursors, 338 10.3 Retrosynthetic Account, 340 References, 340 11 Heterocyclic Compounds 341 11.1 Intramolecular Cyclization Reactions, 341 11.1.1 Nonactivated Cyclopropane Precursors, 341 11.1.2 Cyclopropylcarbinyl Activated Precursors, 342 11.1.3 Cyclopropyl Activated Precursors, 378 11.1.4 Cooperatively Activated Precursors, 380 11.2 Cycloaddition Reactions, 387 11.2.1 Cyclopropylcarbinyl Activated Precursors, 387 11.2.2 Cooperatively Activated Precursors, 390 11.3 Modification of Substituents, 400 11.3.1 Cyclopropylcarbinyl Activated Substrates, 400 11.3.2 Cyclopropyl Activated Substrates, 402 11.3.3 Cooperatively Activated Substrates, 402 11.4 Retrosynthetic Account, 409 References, 410 CONCLUSION 415 AUTHOR Index 417

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Book SynopsisExplains how to perform and analyze the results of the latest physicochemical methods With this book as their guide, readers have access to all the current information needed to thoroughly investigate and accurately determine a compound''s pharmaceutical properties and their effects on drug absorption. The book emphasizes oral absorption, explaining all the physicochemical methods used today to analyze drug candidates. Moreover, the author provides expert guidance to help readers analyze the results of their studies in order to select the most promising drug candidates. This Second Edition has been thoroughly updated and revised, incorporating all the latest research findings, methods, and resources, including: Descriptions and applications of new PAMPA models, drawing on more than thirty papers published by the author''s research group Two new chapters examining permeability and Caco-2/MDCK and permeability and the blood-brain barriTable of ContentsPreface xxiii Preface to the First Edition xxvii List of Abbreviations xxxi Nomenclature xxxv Commercial Trademarks xli 1 Introduction 1 1.1 Bulldozer Searching for a Needle in the Haystack? 1 1.2 As the Paradigm Turns 4 1.3 Screen for the Target or ADME First? 5 1.4 ADME and Multimechanism Screens 6 1.5 ADME and the Medicinal Chemist 7 1.6 The “Absorption” in ADME 8 1.7 It Is Not Just a Number It Is a Multimechanism 9 References 9 2 Transport Model 12 2.1 Permeability–Solubility–Charge State and pH-Partition Hypothesis 12 2.2 Properties of the Gastrointestinal Tract (GIT) 17 2.3 pH Microclimate 22 2.4 Intracellular pH Environment 23 2.5 Tight Junction Complex 23 2.6 Structure of Octanol 23 2.7 Biopharmaceutics Classification System 25 References 26 3 pKa Determination 31 3.1 Charge State and the pKa 32 3.2 Methods of Choice for the Determination of the pKa 34 3.3 Titration with a Glass-Membrane pH Electrode 34 3.4 Equilibrium Equations and the Ionization Constant 38 3.5 “Pure Solvent” Activity Scale 41 3.6 Ionic Strength and Debye–Hückel/Davies Equation 41 3.7 “Constant Ionic Medium” Activity Scale 43 3.8 Temperature Dependence of pKa Values 47 3.9 Electrode Calibration and Standardization 55 3.10 Bjerrum Plot: Most Useful Graphical Tool in pKa Analysis 66 3.11 Cosolvent Methods for pKa Determination of Practically Insoluble Substances 78 3.12 Other Methods for pKa Measurement 96 3.13 pKa Microconstants 102 3.14 pKa Compilations 107 3.15 pKa Prediction Programs 107 3.16 Database of pKa (25°C and 37°C) 107 Appendix 3.1 Quick Start: Determination of the pKa of Codeine 127 Appendix 3.2 Tutorial for Measurements with Glass-Membrane pH Electrode 130 Appendix 3.3 pH Convention Adopted by IUPAC and Supported by NIST 137 Appendix 3.4 Liquid-Junction Potentials (LJP) 140 Appendix 3.5 pKa Refi nement by Weighted Nonlinear Regression 146 Appendix 3.6 Molality to Molarity Conversion 157 References 158 4 Octanol–Water Partitioning 174 4.1 Overton–Hansch Model 175 4.2 Tetrad of Equilibria 175 4.3 Conditional Constants 177 4.4 log P Data Sources 178 4.5 log D Lipophilicity Profile 178 4.6 Ion-Pair Partitioning 183 4.7 Micro-log P 187 4.8 Methods for log P Determination 188 4.9 Dyrssen Dual-Phase Titration log P Method 189 4.10 Ionic Strength Dependence of log P 194 4.11 Temperature Dependence of log P 194 4.12 Calculated versus Measured log P of Research Compounds 194 4.13 log D versus pH Case Study: Procaine Structural Analogs 196 4.14 Database of Octanol–Water log PN log PI and log D7.4 201 References 209 5 Liposome–Water Partitioning 220 5.1 Biomimetic Lipophilicity 221 5.2 Tetrad of Equilibria and Surface Ion-Pairing (SIP) 221 5.3 Data Sources 222 5.4 Location of Drugs Partitioned into Bilayers 222 5.5 Thermodynamics of Partitioning: Entropy- or Enthalpy-Driven? 223 5.6 Electrostatic and Hydrogen Bonding in a Low Dielectric Medium 224 5.7 Water Wires H+/OH− Currents and Permeability of Amino Acids and Peptides 227 5.8 Preparation Methods: MLV SUV FAT LUV ET 228 5.9 Experimental Methods 229 5.10 Prediction of log PMEM from log POCT 229 5.11 log DMEM diff log PMEM and Prediction of log PSI M P EM from log PI OCT 233 5.12 Three Indices of Lipophilicity: Liposomes IAM and Octanol 238 5.13 Getting It Wrong from One-Point log DMEM Measurement 239 5.14 Partitioning into Charged Liposomes 240 5.15 pKa MEM Shifts in Charged Liposomes and Micelles 240 5.16 Prediction of Absorption from Liposome Partition Studies? 241 5.17 Database of log PMEM and log PSI M P EM 242 References 245 6 Solubility 251 6.1 It’s Not Just a Number 252 6.2 Why Is Solubility Measurement Difficult? 252 6.3 Mathematical Models for Solubility–pH Profiles 255 6.4 Experimental Methods 270 6.5 Correction for the DMSO Effect by the “Δ-Shift” Method 287 6.6 Case Studies (Solubility–pH Profi les) 289 6.7 Limits of Detection—Precision versus Accuracy 306 6.8 Data Sources and the “Ionizable-Drug Problem” 308 6.9 Database of log S0 308 References 310 7 Permeability—PAMPA 319 7.1 Permeability in the Gastrointestinal Tract 320 7.2 Historical Developments in Permeability Models 323 7.3 Rise of PAMPA—A Useful Tool in Early Drug Discovery 336 7.4 PAMPA-HDM -DOPC -DS Models Compared 343 7.5 Modeling Biological Membranes 354 7.6 Permeability–pH Relationship and the Mitigating Effect of the Aqueous Boundary Layer 362 7.7 pKa FLUX-Optimized Design (pOD) 386 7.8 Cosolvent PAMPA 389 7.9 UV versus LC/MS Detection 397 7.10 Assay Time Points 400 7.11 Buffer Effects 402 7.12 Apparent Filter Porosity 404 7.13 PAMPA Errors: Intra-Plate and Inter-Plate Reproducibility 407 7.14 Human Intestinal Absorption (HIA) and PAMPA 409 7.15 Permeation of Permanently Charged Molecules 416 7.16 Permeation of Zwitterions/Ampholytes—In Combo PAMPA 424 7.17 PAMPA in Formulation: Solubilizing Excipient Effects 433 7.18 Database of Double-Sink PAMPA log P0 log Pm 6.5 and log Pm 7.4 448 Appendix 7.1 Quick Start: Double-Sink PAMPA of Metoprolol 460 Appendix 7.2 Permeability Equations 465 Appendix 7.3 PAMPA Paramembrane Water Channels 481 References 484 8 Permeability: Caco-2/MDCK 499 8.1 Permeability in the Gastrointestinal Tract 500 8.2 Cell-Based In Vitro Permeability Model 505 8.3 In Situ Human Jejunum Permeability (HJP) Model 514 8.4 Passive Intrinsic Permeability Coefficients of Caco-2 and MDCK Compared 515 8.5 Theory (Stage 1): Paracellular Leakiness and Size Exclusion in Caco-2 MDCK and 2/4/A1 Cell Lines 516 8.6 Theory (Stage 2): Regression Method for In Vitro Cellular Permeability 524 8.7 Case Studies of Cell-Based Permeability as a Function of pH 525 8.8 Human Jejunal Permeability Predicted Directly from Caco-2/MDCK 533 8.9 Caco-2/MDCK Database and Its In Combo PAMPA Prediction 550 References 563 9 Permeability: Blood–Brain Barrier 575 9.1 The Blood–Brain Barrier: A Key Element for Drug Access to the Central Nervous System 576 9.2 The Blood–Brain Barrier 576 9.3 Noncellular BBB Models 580 9.4 In Vitro BBB Cell-Based Models 586 9.5 In Vivo BBB Models 589 9.6 Paradigm Shift 592 9.7 In Silico BBB Models 608 9.8 Biophysical Analysis of In Vitro Endothelial Cell Models 608 9.9 In Situ Brain Perfusion Analysis of Flow 618 9.10 In Combo PAMPA–BBB Model for Passive BBB Permeability 631 References 663 10 Summary and Some Simple Approximations 681 Index 685

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Book SynopsisAll about copolymers, this book comprehensively covers aspects of polymerization, methodology, and applications. With up-to-date discussion, the chapters cover synthetic techniques, copolymerization, and special topics, like renewable processes and sustainable development as well as newly formed polymeric materials and advances in the field.Table of ContentsPreface xii Contributors xv SECTION I SYNTHESIS OF COPOLYMERS 1 1 Trends in Synthetic Strategies for Making (CO)Polymers 3Anbanandam Parthiban 1.1 Background and Introduction, 3 1.2 Significance of Control Over Arrangement of Monomers in Copolymers, 5 1.3 Chain-Growth Condensation Polymerization, 5 1.3.1 Sequential Self-Repetitive Reaction (SSRR), 6 1.3.2 Poly(phenylene Oxide)s by Chain-Growth Condensation Polymerization, 8 1.3.3 Hydroxybenzoic Acids as AA′ Type Monomer in Nucleophilic Aliphatic Substitution Polymerization, 8 1.4 Sequence-Controlled Polymerization, 9 1.4.1 Sequence-Controlled Copolymers of N-Substituted Maleimides, 10 1.4.2 Alternating Copolymers by Ring-Opening Polymerization, 10 1.4.3 Selective Radical Addition Assisted by a Template, 11 1.4.4 Alternating AB-Type Sequence-Controlled Polymers, 11 1.4.5 Metal-Templated ABA Sequence Polymerization, 11 1.4.6 Sequence-Controlled Vinyl Copolymers, 12 1.4.7 Sequence-Regulated Polymerization Induced by Dual-Functional Template, 13 1.5 Processing of Thermoset Polymers: Dynamic Bond Forming Processes and Self-Healing Materials, 13 1.5.1 Plasticity of Networked Polymers Induced by Light, 14 1.5.2 Radically Exchangeable Covalent Bonds, 14 1.5.3 Self-Repairing Polyurethane Networks, 15 1.5.4 Temperature-Induced Self-Healing in Polymers, 15 1.5.5 Diels–Alder Chemistry at Room Temperature, 15 1.5.6 Trithiocarbonate-Centered Responsive Gels, 16 1.5.7 Shuffling of Trithiocarbonate Units Induced by Light, 16 1.5.8 Processable Organic Networks, 17 1.6 Miscellaneous Developments, 17 1.6.1 Atom Transfer Radical Polymerization (ATRP) Promoted by Unimolecular Ligand-Initiator Dual-Functional Systems (ULIS), 17 1.6.2 Unsymmetrical Ion-Pair Comonomers and Polymers, 20 1.6.3 Imidazole-Derived Zwitterionic Polymers, 21 1.6.4 Post-Modification of Polymers Bearing Reactive Pendant Groups, 22 1.7 Conclusion, 23 References, 24 2 Functional Polyolefins from the Coordination Copolymerization of Vinyl Monomers 29Fabio Di Lena and Jõao A. S. Bomfim 2.1 Molecular Aspects of Olefin Coordination to Metals, 29 2.2 Fundamentals of Homopolymerization of Alkenes, 30 2.3 Copolymerization of Ethene and other Alkenes, 34 2.4 Copolymerization of Alkenes and Carbon Monoxide, 35 2.5 Copolymerization of Alkenes and Polar Vinyl Monomers, 37 2.5.1 Migratory Insertion Polymerization, 37 2.5.2 Polymerization via a Dual Radical/Migratory Insertion Pathway, 40 2.5.3 Coordinative Group Transfer Polymerization, 41 2.6 Copolymerization of Polar Vinyl Monomers and Carbon Monoxide, 41 2.7 Why are Phosphine–Sulfonate Ligands so Special? 43 2.8 Telechelic and End-Capped Macromolecules, 44 2.9 On the Use of Chemoinformatics for a More Rapid Development of the Field, 44 2.10 Conclusion and Outlook, 45 References, 46 3 General Aspects of Copolymerization 54Alex Van Herk 3.1 Copolymerization in Chain Reactions, 54 3.1.1 Derivation of the Copolymerization Equation, 55 3.1.2 Types of Copolymers, 57 3.1.3 Polymerization Rates in Copolymerizations, 59 3.2 Measuring Copolymerization Parameters, 60 3.3 Influence of Reaction Conditions, 63 3.4 Short-Chain Effects in Copolymerization, 63 3.5 Synthesis of Block Copolymers With Controlled Chain Architecture, 64 References, 66 4 Polymers Bearing Reactive, Pendant Cyclic Carbonate (CC) Group: Syntheses, Post-Polymerization Modifications, and Applications 67Satyasankar Jana 4.1 Introduction, 67 4.2 Cyclic Carbonate (CC) Monomers and Polymers, 68 4.2.1 Cyclic Carbonate (CC) Monomers and Their Synthesis, 68 4.2.2 Polymerization of Cyclic Carbonate (CC) Monomers, 75 4.2.3 Alternative Route to Synthesize Pendant CC (Co)polymers by CO2 Addition/Fixation Reaction, 83 4.3 Chemical Modification of Pendant CC Polymers, 85 4.4 Applications of Pendant CC Polymers, 88 4.4.1 Fixing CO2 into Polymer, 88 4.4.2 Surface Coating, 90 4.4.3 Solid or Gel Polymer Electrolyte for Lithium-Ion Batteries, 90 4.4.4 Enzyme Immobilization, 91 4.4.5 Photopolymerization, 91 4.4.6 Polymer Blends, 92 4.5 Conclusion, 92 References, 93 5 Monomers and Polymers Derived from Renewable or Partially Renewable Resources 101Anbanandam Parthiban 5.1 Building Blocks from Renewable Resources, 101 5.2 Polyesters Incorporated with Isosorbide, 105 5.2.1 Poly(hydroxy ester)s Derived from Macrolides, 106 5.2.2 Semicrystalline Polymers from Fatty Acids, 107 5.2.3 Cyclic Ester Derived from a Natural Precursor, 107 5.2.4 Polymerization of Dilactone Derived from 12-Hydroxy Stearic Acid, 107 5.2.5 Thermoplastic Elastomers Derived from Polylactide and Polymenthide, 108 5.3 Rosin and Developments Associated with Rosin, 110 5.3.1 Polyamides and Polyesters Derived from Modified Levopimeric Acid, 110 5.3.2 Radical Polymerization of Modified Dehydroabietic Acid, 112 5.3.3 ATRP of Vinyl Monomers Derived from Dehydroabietic Acid, 112 5.3.4 Block Copolymers Derived from Dehydroabietic Acid Derivative, 112 5.4 Polyurethanes from Vegetable Oils, 113 5.4.1 Polyurethanes Derived from Plant Oil Triglycerides, 114 5.4.2 Long-Chain Unsaturated Diisocyanates Derived from Fatty Acids of Vegetable Origin, 114 5.5 CO2 as Renewable Resource Comonomer, 115 5.6 Renewable Triblock Copolymer-Based Pressure-Sensitive Adhesives (PSA), 115 5.7 Photocurable Renewable Resource Polyester, 116 5.8 Renewable Resource-Derived Waterborne Polyesters, 116 5.8.1 Polyesters Made Up of Isosorbide and Succinic Acid, 117 5.8.2 Polyesters Modified with Citric Acid, 117 5.9 Polymers Formed by Combining Renewable Resource Monomers with that Derived from Petroleum Feedstock, 117 5.10 Conclusion and Outlook, 120 References, 121 6 Microporous Organic Polymers: Synthesis, Types, and Applications 125Shujun Xu and Bien Tan 6.1 Introduction, 125 6.2 Preparations of MOPS, 126 6.2.1 Polymers of Intrinsic Microporosity, 126 6.2.2 Hypercrosslinked Polymer, 132 6.2.3 Covalent Organic Frameworks, 134 6.2.4 Conjugated Microporous Polymers, 138 6.3 Hydrogen Adsorption, 141 6.3.1 HCPs for Hydrogen Adsorption, 142 6.3.2 PIMs for Hydrogen Adsorption, 144 6.3.3 COFs for Hydrogen Adsorption, 145 6.3.4 CMPs for Hydrogen Adsorption, 145 6.4 Carbon Dioxide Capture, 145 6.5 Separations, 149 6.5.1 HCPs for Separations, 150 6.5.2 PIMs for Separations, 153 6.5.3 CMPs for Separations, 153 6.6 Catalysis, 153 6.7 Prospect, 155 References, 156 7 Dendritic Copolymers 165Srinivasa Rao Vinukonda 7.1 Introduction, 165 7.2 Synthesis Approaches or Strategies, 166 7.2.1 AB2 + A2 Approach, 166 7.2.2 AB2 + AB Approach, 167 7.2.3 B3 + A2 + B2 Approach (Biocatalyst), 167 7.2.4 Macromonomers Approach, 167 7.2.5 Dendrigraft Approach, 171 7.2.6 Linear–Dendritic Copolymers, 173 7.2.7 Living Anionic Polymerization, 178 7.2.8 Controlled Living Radical Polymerization, 185 7.2.9 Click Chemistry, 194 7.3 Properties of Dendritic Copolymers, 198 7.3.1 Molecular Weight and Molecular Weight Distribution, 198 7.3.2 Degree of Branching (DB), 200 7.3.3 Intrinsic Viscosity, 202 7.4 Applications of Dendritic Copolymers, 203 References, 204 SECTION II APPLICATIONS OF COPOLYMERS 215 8 A New Class of Ion-Conductive Polymer Electrolytes: CO2/Epoxide Alternating Copolymers With Lithium Salts 217Yoichi Tominaga 8.1 Introduction, 217 8.2 Experimental, 220 8.2.1 Preparation of Monomers and Catalyst, 220 8.2.2 Copolymerization of Epoxides with CO2, 220 8.2.3 Preparation of Electrolyte Membranes, 222 8.2.4 Measurements, 222 8.3 Results and Discussion, 222 8.3.1 NMR Characterization, 222 8.3.2 Characteristics of Polycarbonates, 224 8.3.3 Thermal Analysis of Polycarbonates, 225 8.3.4 Impedance Measurement of Copolymers, 228 8.3.5 FT-IR Measurement, 231 8.3.6 PEC System: Effect of Salt Concentration, 232 8.4 Conclusion, 235 References, 236 9 Block Copolymer Nanopatterns as Enabling Platforms for Device Applications—Status, Issues, and Challenges 239Sivashankar Krishnamoorthy 9.1 Introduction, 239 9.2 Block Copolymer Templates for Pattern Transfer Applications, 240 9.2.1 Dimensional Scalability and Fine-Tunability Down to Sub-10 nm Length Scales, 240 9.2.2 Directing Self-Assembly of Block Copolymers, 241 9.2.3 Block Copolymers for Directed Nanoscale Synthesis and Self-Assembly, 244 9.2.4 High Resolution Nanolithography, 244 9.2.5 Nanomanufacturing Material Patterns for Applications, 245 9.2.6 Top-Down Patterning of Block Copolymer Nanostructures, 249 9.3 Specific Instances in Exploitation of Block Copolymers in Device Applications, 251 9.3.1 Memory Devices, 251 9.3.2 Integrated Circuit Elements, 254 9.3.3 Photovoltaic and Optoelectronics Applications, 255 9.3.4 Sensors, 256 9.3.5 Nanoporous Membranes for Size-Exclusive Filtration or Sensing, 261 9.4 Conclusions, 263 References, 263 10 Stimuli-Responsive Copolymers and Their Applications 274He Tao 10.1 Introduction, 274 10.2 Temperature-Responsive Copolymers and Applications, 275 10.2.1 Temperature-Responsive Copolymers Based on LCST, 276 10.3 pH-Responsive Copolymers and Applications, 284 10.3.1 pH-Responsive Segments, 285 10.3.2 Polymer Nanoparticles/Micelles Prepared from pH-Responsive Copolymers, 287 10.3.3 pH-Responsive Surfaces and Hydrogels, 287 10.3.4 Typical Applications of pH-Responsive Copolymers, 289 10.4 Biologically Responsive Copolymers and Applications, 290 10.4.1 Glucose-Responsive Copolymers and Applications, 290 10.5 Field-Responsive Copolymers and Applications, 293 10.5.1 Electric-Responsive Copolymers, 294 10.5.2 Magneto-Responsive Copolymers, 294 10.5.3 Light-Responsive Copolymers, 295 10.6 Conclusion, 297 References, 297 11 Pharmaceutical Polymers 307Natarajan Venkatesan and Hideki Ichikawa 11.1 Introduction to Pharmaceutical Polymers, 307 11.2 Applications of Pharmaceutical Polymers, 308 11.2.1 Polymers as Excipients, 308 11.2.2 Functional Excipients, 317 11.2.3 Drug Delivery Agents, 320 11.2.4 Solubility and Bioavailability Enhancement, 322 11.2.5 Transdermal Drug Delivery, 324 11.2.6 Novel Polymeric Hydrogels for Drug Delivery Applications, 324 11.3 Summary, 329 References, 329 12 Polymer Conjugates of Proteins and Drugs to Improve Therapeutics 334Parijat Kanaujia and Ajazuddin 12.1 Introduction, 334 12.2 Polymers for Therapeutic Conjugation, 335 12.2.1 Poly(ethylene Glycol) Protein Conjugate, 336 12.2.2 Significance of PEG, 337 12.2.3 Chemistry of Protein–PEG Conjugation, 338 12.2.4 Biofate of PEGylated Proteins, 348 12.3 PEGylated Proteins in Clinical Practice, 351 12.3.1 PEG Conjugate with Low Molecular Weight Drugs, 351 12.3.2 PEG Structures for Small-Molecule PEGylation, 351 12.3.3 Advantages of PEGylated Drugs, 355 12.4 N-(2-Hydroxypropyl) Methacrylamide (HPMA) Copolymer Conjugate, 358 12.5 Poly(l-Glutamic Acid) Conjugates, 362 12.6 Polysialic Acid (PSA) Conjugates, 363 12.7 Conclusion, 364 References, 365 Index 373

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Book SynopsisOffers a physical organic chemistry and mechanistic perspective of the chemistry of thermal processes in the gas phase The book looks at all aspects of the chemical processing technique called gas-phase pyrolysis, including its methodology and reactors, synthesis, reaction mechanisms, structure, kinetics, and applications. It discusses combinations of pyrolytic reactors with physiochemical techniques, routes for and reactions for the synthesis of organic compounds, and the control of reaction rates. Gas-Phase Pyrolytic Reactions: Synthesis, Mechanisms, and Kinetics starts with in-depth chapter coverage of static pyrolysis, dynamic flow pyrolysis, and analytical pyrolysis. It then examines synthesis and applications, including flash vacuum pyrolysis in organic synthesis, elimination of HX, elimination of CO and CO2, pyrolysis of Meldrum's acid derivatives, and elimination of N2. A chapter on reaction mechanism comes next and includes Table of ContentsPreface xi List of Abbreviations xiii About the Author xv 1 Methodologies and Reactors 1 1.1 Static Pyrolysis 1 1.1.1 Sealed-Tube Reactor 2 1.1.1.1 Pyrolyzer 2 1.1.1.2 Reaction Tube 3 1.1.1.3 Kinetic Studies 3 1.1.1.4 Treatment of Kinetic Results 4 1.1.2 Static Apparatus 5 1.1.2.1 Reaction Chamber 6 1.1.2.2 The Pyrolysis Method 7 1.1.2.3 Treatment of the Results 7 1.2 Dynamic Flow Pyrolysis 8 1.2.1 Flash Vacuum Pyrolysis 8 1.2.2 Synthetic Applications of FVP 10 1.2.3 Gas-Flow Pyrolysis vs. STP 13 1.2.4 Limitations of FVP 13 1.2.5 Spray Pyrolysis 14 1.2.6 Falling-Solid Pyrolysis 17 1.3 Analytical Pyrolysis 19 1.3.1 Pyrolysis Gas Chromatography (Py-GC) 19 1.3.1.1 Online Py-GC 20 1.3.2 Pyrolysis Mass Spectrometry 22 1.3.2.1 Online Pyrolysis Gas Chromatography/Mass Spectrometry (Py-GC/MS) 22 1.3.3 FVP with Spectroscopy 22 1.3.4 Catalytic Gas-Phase Pyrolysis 24 References 27 2 Synthesis and Applications 31 2.1 Flash Vacuum Pyrolysis in Organic Synthesis 31 2.2 Elimination of HX 34 2.3 Elimination of CO and CO2 38 2.4 Pyrolysis of Meldrum’s Acid Derivatives 54 2.5 Elimination of N2 60 2.5.1 Deazetization Reactions of Allylic Diazenes 63 2.5.2 Pyrolysis of Benzotriazole Derivatives 65 2.5.3 Pyrolysis of Triazine Derivatives 68 References 72 3 Reaction Mechanism 79 3.1 Retro-ene Reactions 79 3.1.1 Acetylenic Compounds 80 3.1.2 Acyl Group Participation 82 3.1.3 Cyanates and Isocyanates 82 3.1.4 Esters 83 3.1.5 Amides 88 3.1.5.1 Acetamides and Thioacetamides 88 3.1.5.2 Benzamides 92 3.1.5.3 N-Substituted Amides 93 3.2 Reactive Intermediates 94 3.2.1 Radicals 94 3.2.2 Diradicals 97 3.2.3 Benzynes 98 3.2.3.1 o-Benzynes 99 3.2.3.2 m- and p-Benzynes 101 3.2.4 Carbenes 101 3.2.5 Nitrenes 108 References 120 4 Structure/Reactivity Correlation 127 4.1 Diketones 127 4.2 Cyanoketones 133 4.3 Ketoamides 135 4.4 Benzotriazoles 136 4.5 Hammett Correlation in Gas-Phase Pyrolysis 148 4.6 Alkoxy versus Amino Group 153 4.6.1 Neighboring Group Participation 155 4.6.2 Amino Esters 158 References 162 5 Functional Group and Structural Frame Interconversions 167 5.1 Functional Group Interconversion 167 5.1.1 Thermal Retro-Ene Reactions 167 5.1.1.1 α-Substituted Carboxylic Acids 173 5.1.1.2 2-Hydroxycarboxylic Acids 175 5.1.1.3 2-Alkoxycarboxylic Acids 176 5.1.1.4 2-Phenoxycarboxylic Acids 177 5.1.1.5 2-Aminocarboxylic Acids 180 5.1.1.6 2-Acetooxycarboxylic Acids 182 5.1.1.7 2-Ketocarboxylic Acids 184 5.1.1.8 α-Substituted Esters 186 5.1.1.9 β-Substituted Carboxylic Acids 188 5.2 Structural Frame Interconversion 191 5.2.1 Alkyl Heterocycles 195 References 197 6 Gas-Phase Pyrolysis of Hydrazones 201 6.1 Substituted Phenylhydrazones 203 6.2 N-Arylidineamino Heterocycles 213 6.3 Arylidene Hydrazine Heterocycles 221 References 231 7 Gas-Phase Pyrolysis of Phosphorus Ylides 235 7.1 Synthetic Applications 235 7.2 Haloalkynes 241 7.3 Terminal Alkynes 244 7.4 Diynes 247 7.5 Enynes and Dienes 250 7.6 Selective Elimination of Ph3PO from Di- and Tri-oxo-stabilized Phosphorus Ylides 252 7.7 Sulfonyl-Stabilized Phosphorus Ylides 257 7.8 Sulfinyl-Stabilized Phosphorus Ylides 262 7.9 Kinetic andThermal Reactivity of Carbonyl-Stabilized Phosphonium Ylides 266 References 277 Index 281

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Book SynopsisDiscover the experimental and theoretical developments in optical single-molecule spectroscopy that are changing the ways we think about molecules and atoms The Advances in Chemical Physics series provides the chemical physics field with a forum for critical, authoritative evaluations of advances in every area of the discipline. This latest volume explores the advent of optical single-molecule spectroscopy, and how atomic force microscopy has empowered novel experiments on individual biomolecules, opening up new frontiers in molecular and cell biology and leading to new theoretical approaches and insights. Organized into two partsone experimental, the other theoreticalthis volume explores advances across the field of single-molecule biophysics, presenting new perspectives on the theoretical properties of atoms and molecules. Single-molecule experiments have provided fresh perspectives on questions such as how proteins fold to specific conformations from highly heterogTable of ContentsPreface xiii Part One Developments on Single-Molecule Experiments Staring at a Protein: Ensemble and Single-Molecule Investigations on Protein-Folding Dynamics 3 By Satoshi Takahashi and Kiyoto Kamagata Single-Molecule FRET of Protein-Folding Dynamics 23 By Daniel Nettels and Benjamin Schuler Quantitative Analysis of Single-Molecule FRET Signals and its Application to Telomere DNA 49 By Kenji Okamoto and Masahide Terazima Force to Unbind Ligand–Receptor Complexes and the Internal Rigidity of Globular Proteins Probed by Single-Molecule Force Spectroscopy 71 By Atsushi Ikai, Rehana Afrin, and Hiroshi Sekiguchi Recent Advances in Single-Molecule Biophysics with the Use of Atomic Force Microscopy 89 By Masaru Kawakami and Yukinori Taniguchi Dynamical Single-Molecule Observations of Membrane Protein Using High-Energy Probes 133 By Yuji C. Sasaki Single-Molecular Gating Dynamics for the KcsA Potassium Channel 147 By Shigetoshi Oiki, Hirofumi Shimizu, Masayuki Iwamoto, and Takashi Konno Static and Dynamic Disorder in IN VITRO Reconstituted Receptor–Adaptor Interaction 195 By Hiroaki Takagi, Miki Morimatsu, and Yasushi Sako Part Two Developments on Single-Molecule Theories and Analyses Change-Point Localization and Wavelet Spectral Analysis of Single-Molecule Time Series 219 By Haw Yang Theory of Single-Molecule FRET Efficiency Histograms 245 By Irina V. Gopich and Attila Szabo Multidimensional Energy Landscapes in Single-Molecule Biophysics 299 By Akinori Baba and Tamiki Komatsuzaki Generalized Michaelis–Menten Equation for Conformation Modulated Monomeric Enzymes 329 By Jianlan Wu and Jianshu Cao Making it Possible: Constructing a Reliable Mechanism from a Finite Trajectory 367 By Ophir Flomenbom Free Energy Landscapes of Proteins: Insights from Mechanical Probes 395 By Zu Thur Yew, Peter D. Olmsted, and Emanuele Paci Mechanochemical Coupling Revealed by the Fluctuation Analysis of Different Biomolecular Motors 419 By Hiroaki Takagi and Masatoshi Nishikawa Author Index 437 Subject Index 467

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Book SynopsisExplains how GIS enhances the development of chemical fate and transport models Over the past decade, researchers have discovered that geographic information systems (GIS) are not only excellent tools for managing and displaying maps, but also useful in the analysis of chemical fate and transport in the environment. Among its many benefits, GIS facilitates the identification of critical factors that drive chemical fate and transport. Moreover, GIS makes it easier to communicate and explain key model assumptions. Based on the author''s firsthand experience in environmental assessment, GIS Based Chemical Fate Modeling explores both GIS and chemical fate and transport modeling fundamentals, creating an interface between the two domains. It then explains how GIS analytical functions enable scientists to develop simple, yet comprehensive spatially explicit chemical fate and transport models that support real-world applications. In addition, the book features:<Table of ContentsPreface xiii Contributors xvii Chapter 1 | Chemicals, Models, and GIS: Introduction 1 1-1 Chemistry, Modeling, and Geography 1 1-2 Mr. Palomar and Models 2 1-3 What Makes a Model Different? 4 1-4 Simple, Complex, or Tiered? 7 Compatibility of Emissions and Concentrations 9 Spatiotemporal Variability 10 Spatial Patterns 12 More Complex Models and the Tale of Horatii and Curiatii 15 1-5 For Whom is this Book Written? 17 References 19 Chapter 2 | Basics of Chemical Compartment Models and Their Implementation with GIS Functions 23 2-1 Introduction 23 2-2 Phase Partitioning 24 Air Compartment 24 Surface Water Compartment 25 Soil Compartment 25 2-3 Diffusion, Dispersion, and Advection 26 2-4 Fluxes at the Interfaces 28 Air–Ground Surface Interface 28 Water–Air and Water–Bottom Sediment Interface 28 Soil–Air and Soil–Water Interface 29 Parameterization of Advection Velocities and Diffusion/Dispersion Rates 29 2-5 Reactions 32 2-6 Transport Within an Environmental Medium: The Advection–Diffusion Equation (ADE) 33 Soils 37 Surface Water 38 Atmosphere 39 2-7 Analytical Solutions 40 Example: The Domenico Model 40 Example: Implementation of a River Plug Flow Model in a Spreadsheet 45 2-8 Box Models, Multimedia and Multispecies Fate and Transport 47 Example: Implementing a Box Model of Soil Contamination and Water Pollution Loading in a Spreadsheet 51 2-9 Spatial Models: Implicit, Explicit, Detailed Explicit, and GIS-Based Schemes 57 References 65 Chapter 3 | Basics of GIS Operations 71 3-1 What is GIS? 71 3-2 GIS Data 72 Coordinate Systems 72 Example: Coordinate Transformation 75 Example: Georeference a Map from a Paper Using ArcGIS 77 GIS Formats 81 3-3 GIS Software 92 3-4 GIS Standards 93 Exercise: Browse and Export Geographic Objects in KML and Combine Them with Layers from a WMS 94 3-5 A Classification of GIS Operations for Chemical Fate Modeling 99 3-6 Spatial Thinking 100 3-7 Beyond GIS 103 3-8 Further Progress on GIS 104 References 104 Chapter 4 | Map Algebra 107 4-1 Map Algebra Operators and Syntaxes 109 4-2 Using Map Algebra to Compute a Gaussian Plume 112 Example: Using Map Algebra to Compute Volatilization Rates from Water Bodies 119 4-3 Using Map Algebra to Implement Isolated Box Models 121 References 124 Chapter 5 | Distance Calculations 127 5-1 Concepts of Distance Calculations 127 Example: Feature Buffering 127 Example: Join Based on Distance 129 5-2 Distance Along a Surface and Vertical Distance 134 5-3 Applications of Euclidean Distance in Pollution Problems 135 5-4 Cost Distance 139 Exercise: Euclidean and Cost distance Calculations 140 References 148 Chapter 6 | Spatial Statistics and Neighborhood Modeling in GIS 149 6-1 Variograms: Analyzing Spatial Patterns 149 Exercise: Computing Variograms of Observed Atmospheric Contaminants 154 6-2 Interpolation 160 6-3 Zonal Statistics 163 6-4 Neighborhood Statistics and Filters 164 Exercise: Creating a Population Map from Point and Polygon Data 169 References 170 Chapter 7 | Digital Elevation Models, Topographic Controls, and Hydrologic Modeling in GIS 171 7-1 Basic Surface Analysis 171 7-2 Drainage 178 Example: Pit Filling, Flow Direction, Flow Accumulation, and Flow Length in ArcGIS 178 Example: Catchment Population in India 183 Example: Travel Time 185 7-3 Using GIS Hydrological Functions in Chemical Fate and Transport Modeling 187 7-4 Non-D8 Methods and the TauDEM Algorithms 190 7-5 ESRI’s ‘‘Darcy Flow’’ and ‘‘Porous Puff’’ Functions 191 References 193 Chapter 8 | Elements of Dynamic Modeling in GIS 195 8-1 Dynamic GIS Models 195 8-2 Studying Time-Dependent Effects With Simple Map Algebra 200 Intermittent Emissions 200 Lagged Release from Historical Stockpiles 201 Stepwise Constant Emission and Removal Processes 202 8-3 Decoupling Spatial and Temporal Aspects of Models: The Mappe Global Approach 203 References 206 Chapter 9 | Metamodeling and Source–Receptor Relationship Modeling in GIS 209 9-1 Introduction 209 9-2 Metamodeling 210 9-3 Source–Receptor Relationships 213 References 215 Chapter 10 | Spatial Data Management in GIS and the Coupling of GIS and Environmental Models 217 10-1 Introduction 217 10-2 Historical Perspective of Emergence of Spatial Databases in Environmental Domain 218 10-3 Spatial Data Management in GIS: Theory and History 221 Spatial Database Definition 221 Relational Data Model Foundations 221 Object Relational Concepts: A Foundation Model for Spatial Databases—Theoretical Background 224 PostgreSQL/PostGIS Object Relational Support 225 Oracle Object Relational Support 225 10-4 Spatial Database Solutions 226 ESRI Geodatabase 226 PostgreSQL and PostGIS 229 Oracle Locator and Spatial 230 10-5 Simple Environmental Spatiotemporal Database Skeleton and GIS: Hands-On Examples 230 Simple PostgreSQL/PostGIS Environmental Spatiotemporal Database Skeleton and QuantumGIS 231 Simple Oracle XE Environmental Spatiotemporal Database Skeleton 237 10-6 Generalized Environmental Spatiotemporal Database Skeleton and Geographic Mashups 244 Spatiotemporal Database Skeleton 244 Geographic Mashup 246 References 249 Chapter 11 | Soft Computing Methods for the Overlaying of Chemical Data with Other Spatially Varying Parameters 253 11-1 Introduction 253 11-2 Fuzzy Logic and Expert Judgment 258 11-3 Spatial Multicriteria Analysis 262 11-4 An Example of Vulnerability Mapping of Water Resources to Pollution 266 References 276 Chapter 12 | Types of Data Required for Chemical Fate Modeling 279 12-1 Climate and Atmospheric Data 280 12-2 Soil Data 286 12-3 Impervious Surface Area 289 12-4 Vegetation 289 12-5 Hydrological Data 291 12-6 Elevation Data 293 12-7 Hydrography 296 12-8 Lakes 298 12-9 Stream Network Hydraulic Data 298 12-10 Ocean Parameters 299 12-11 Human Activity 301 Land Use/Land Cover 303 Population 305 Stable Lights at Night 306 12-12 Using Satellite Images for the Extraction of Environmental Parameters 306 12-13 Compilations of Data for Chemical Fate and Transport Modeling 307 References 307 Chapter 13 | Retrieval and Analysis of Emission Data 311 13-1 Characterization of Emissions 311 13-2 Emissions based on Production Volumes 312 13-3 Estimation from Usage or Release Inventories 313 13-4 Emission Factors 313 13-5 Spatial and Temporal Distribution of Emissions 314 Diffuse Emissions at Local to Regional Scale 317 Example: Estimating Urban Runoff Contaminants from Land Use and Population Data in the Province of Naples, Italy 318 Exercise: Apportionment of Emissions Using a Geographic Pattern 318 13-6 Modeling Traffic Flows 322 References 326 Chapter 14 | Characterization of Environmental Properties and Processes 329 14-1 Physicochemical Properties and Partition Coefficients 329 14-2 Aerosol and Suspended Sediments 330 Exercise: Computing SPM in Rivers Using the Formula of Hakanson and Co-workers 332 14-3 Diffusive Processes 335 14-4 Dispersion 335 14-5 Advective Processes 336 Atmospheric Deposition 336 Soil Water Budget Calculations 338 Soil Erosion 344 14-6 River and Lake Hydraulic Geometry 344 References 350 Chapter 15 | Complex Models, GIS, and Data Assimilation 353 15-1 Atmospheric Transport Models 353 Example: Dispersion Modeling of an Atmospheric Emission in Australia 354 15-2 Transport in Groundwater and the Analytic Element Method 361 15-3 GIS Functions of Modeling Systems and Data Assimilation 361 References 363 Chapter 16 | The Issue of Monitoring Data and the Evaluation of Spatial Models of Chemical Fate 365 16-1 Existing Monitoring Programs 366 16-2 Distributed Sampling 366 16-3 Methods for the Comparison of Measured and Modeled Concentrations 367 Exercise: Comparison of Two PCB Soil Concentration Models 368 References 375 Chapter 17 | From Fate to Exposure and Risk Modeling with GIS 377 17-1 Exposure and Risk for Human Health 377 17-2 Models for the Quantification of Chemical Intake by Humans 382 Exercise: Human Exposure, Intake, and Cancer Risk Related to Ingestion of Aboveground Produce Contaminated by Gas and Dust Deposition of 2,3,7,8-TCDD Emitted from an Industrial Emission Source 386 17-3 Ecological and Environmental Risk Assessment 393 Exercise: Mapping Patch Area and Ecotones in South America 398 17-4 Data for GIS Based Risk Assessment 400 References 401 Chapter 18 | GIS Based Models in Practice: The Multimedia Assessment of Pollutant Pathways in the Environment (MAPPE) Model 405 18-1 Introduction 405 18-2 Environmental Compartments Considered in the Model 407 Atmosphere Compartment 409 Soil Compartment 412 Inland Water Compartment 413 Seawater 415 18-3 Implementation in GIS: Example with Lindane 416 Scalar Input Quantities 416 Maps Describing Landscape and Climate Parameters 418 Air Compartment Calculations 419 Soil Compartment Calculations 422 Inland Water Compartment Calculations 427 Seawater Compartment Calculations 434 18-4 Using the Model For Scenario Assessment 436 References 441 Chapter 19 | Inverse Modeling and Its Application to Water Contaminants 443 19-1 Introduction 443 Exercise: Inverse Modeling of Caffeine in Europe 447 References 451 Chapter 20 | Chemical Fate and Transport Indicators and the Modeling of Contamination Patterns 453 20-1 The Relative Risk Model 453 Example: Relative Risk Assessment for Coastal Ecosystems Due to Wastewater Emission in South Africa 456 20-2 Use of Chemical Fate and Transport Indicators in the Context of Relative Risk Assessment: An Example with Contaminants Applied to Soil 459 Example: Generic Modeling of Sewage Sludge Soil Application in Mexico 464 References 472 Chapter 21 | Perspectives: The Challenge of Cumulative Impacts and Planetary Boundaries 475 References 478 Index 481

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