Structure-based Design of Drugs and Other Bioactive Molecules

Dr. Paris has written an honest, balanced presentation of the ways in which psychiatric drugs are evaluated and prescribed. He highlights the complexity of the task, the limits of what is known and the mixed picture that research often produces. His conclusions are refreshing because they are built from an even-handed, pragmatic assessment of the empirical evidence. The result is a stimulating look at the world of treatments for emotional disorders that acknowledges the usefulness of both biological and psychosocial explanations where appropriate. His recommendations provide helpful roadmaps for patients, practitioners and researchers alike. The book is sure to serve as a welcome catalyst for the continuing debates about which treatments are likely to produce the best outcomes. —Roger P. Greenberg, Ph.D. Distinguished Professor and Head, Psychology Division Dept. of Psychiatry & Behavioral Science SUNY Upstate Medical University, NY, USA The message of this book is that psychiatrists have some very good drugs, but can expect bad results when they are over-used, prescribed outside of evidence-based indications, or given to the wrong patients. While acknowledging that many current agents are highly effective and have revolutionized the treatment of certain disorders, Joel Paris criticizes their use outside of an evidence base. Too many patients are either over-medicated or are misdiagnosed to justify aggressive treatment. Dr. Paris calls for more government funding of clinical trials to establish, without bias, the effectiveness of these agents. He has written this book for practitioners and trainees to show that scientific evidence supports a more cautious and conservative approach to drug therapy. After describing the history of psychopharmacology, including its early successes, Dr. Paris reviews the relationship between psychiatry and the pharmaceutical industry. This problem has received considerable popular attention in recent years and Dr. Paris documents initiatives to increase transparency and decrease the influence of pharmaceutical marketing on diagnosis and prescribing habits. Dr Paris then examines some major controversies. One is the fact that newer drugs have not been shown to be superior to older agents. Another is that while the number of prescriptions for antidepressants has increased dramatically, meta-analyses show that their value is more limited than previously believed. Still another is the widespread prescription of mood stabilizers and antipsychotic drugs for patients, including children and adolescents, who do not have bipolar illness. Polypharmacy is an especially contentious area: very few drug combinations have been tested in clinical trials, yet many patients end up on a cocktail of powerful drugs, each with its own side effects. Dr Paris briefly considers alternatives to pharmacology and again calls for more clinical trials of these approaches. He also discusses the current trend to medicalizing what many would describe as normal distress and states succinctly: Some things in life are worth being upset about.

All the latest tools needed to plan and perform the synthesis of complex bioactive molecules Focusing on organic, organometallic, and bio-oriented processes, this book explores the impact and use of the latest synthetic tools for the synthesis of complex biologically active compounds. Readers will discover step by step how these synthetic tools have provided new, elegant solutions to many synthetic puzzles. Moreover, they will discover innovative methods that make it possible to control the exact connectivity of atoms within a molecule in order to set precise three-dimensional arrangements. Modern Tools for the Synthesis of Complex Bioactive Molecules features sixteen chapters, each one written by one or more leading experts in organic synthesis from around the world. It covers a broad range of topics that enable readers to take advantage of the latest methods for synthesizing complex molecules, including: Modern catalysis, emphasizing key transformations such as C-H functionalizations, cross-couplings, gold-catalyzed reactions, metathesis-based syntheses, and asymmetric organocatalysis Eco-compatible transformations, including rearrangements and domino reactions Tools for the synthesis of carbohydrates and alkaloids New techniques, including the use of fluorous tags and engineered biosynthesis The last two chapters explore target- and diversity-oriented organic synthesis as well as the use of DNA-based asymmetric catalysis, which are all promising tools for the successful synthesis of complex bioactive molecules. Modern Tools for the Synthesis of Complex Bioactive Molecules is ideal for students and researchers who need to plan and perform the synthesis of complex molecules as efficiently as possible. The book's expert advice will help these readers quickly resolve a broad range of problems that can arise in organic syntheses.

Plant anatomy and physiology and a broad understanding of basic plant processes are of primary importance to a basic understanding of plant science. These areas serve as the first important building blocks in a variety of fields of study, including botany, plant biology, and horticulture. Structure and Function of Plants will serve as a text aimed at undergraduates in the plant sciences that will provide an accurate overview of complex plant processes as well as details essential to a basic understanding of plant anatomy and physiology. Presented in an engaging style with full-color illustrations, Structure and Function of Plants will appeal to undergraduates, faculty, extension faculty, and members of Master Gardener programs.

Drug abuse has been, and continues to be, a global societal issue with diverse sets of impacts. Drugs of Abuse: Pharmacology and Molecular Mechanisms introduces the basic principles of pharmacology and neuroscience of drug abuse. Understanding the chemistry of commonly abused drugs and their impact on brain function will provide students and researchers with a more profound understanding of the molecular basis of drug abuse and addiction. Drugs of Abuse: Pharmacology and Molecular Mechanisms opens with a brief history of drug use and abuse. Subsequent sections look at specific families of drugs, including stimulants, depressants, and hallucinogens among others, and explore how their chemical make-up interacts with brain function. The final chapter provides a brief overview of clinical substance abuse treatment. Providing a concise, accessible introductory overview of the topic, Drugs of Abuse: Pharmacology and Molecular Mechanisms will be a valuable resource for students, researchers, and others interested in how drugs interact with the brain. Introduces readers to the basic principles of neuroscience and pharmacology as related to drug use and abuse. Explores how the chemical make-up of drugs interact with the brain and can lead to addiction Includes coverage of a wide array of commonly abused families of drugs, including stimulants, depressants, hallucinogens, and others. Provides an essential introduction to the chemical and molecular underpinnings of drug use and abuse

Provides comprehensive coverage of the interpretation of LC–MS–MS mass spectra of 1300 drugs and pesticides Provides a general discussion on the fragmentation of even-electron ions (protonated and deprotonated molecules) in both positive-ion and negative-ion modes This is the reference book for the interpretation of MS–MS mass spectra of small organic molecules Covers related therapeutic classes of compounds such as drugs for cardiovascular diseases, psychotropic compounds, drugs of abuse and designer drugs, antimicrobials, among many others Covers general fragmentation rule as well as specific fragmentation pathways for many chemical functional groups Gives an introduction to MS technology, mass spectral terminology, information contained in mass spectra, and to the identification strategies used for different types of unknowns

A timely and topical survey of modern simulation tools and their applications in real-life drug discovery, allowing for better and quicker results in structure-based drug design. The first part of this practical guide for industry professionals describes common tools used in the biomolecular simulation of drugs and their targets. A critical analysis of the accuracy of the predictions, the integration of modeling with other experimental data combined with numerous case studies from different therapeutic fields enable users to quickly adopt these new methods for their current projects. The second part then shows how these tools can be applied to drug discovery and development projects. Modeling experts from the pharmaceutical industry and from leading academic institutions present real-life examples for important target classes such as GPCRs, kinases and amyloids as well as for common challenges in structure-based drug discovery. With its inclusion of novel methods and strategies for the modeling of drug-target interactions in the framework of real-life drug discovery and development, this application-oriented reference is tailor-made for medicinal chemists and those working in the pharmaceutical industry.

Combining the approaches of preventative and restorative dentistry, this is a revised and updated guide to the clinical techniques and procedures necessary for managing tooth disorders and disease. Introduces minimally invasive dentistry as a model to control dental disease and then restore the mouth to optimal form, function, and aesthetics Contains several student-friendly features, including a new layout, line drawings and clinical photographs to illustrate key concepts Covers fundamental topics, including the evolutionary biology of the human oral environment; caries management and risk assessment; remineralization; principles of cavity design; lifestyle factors; choices between restorative materials and restoration management Includes a companion website with self-assessment exercises for students and a downloadable image bank for instructors

Magnets are widely used in industry, medical, scientific instruments, and electrical equipment. They are the basic tools for scientific research and electromagnetic devices. Numerical methods for the magnetic field analysis combined with mathematical optimization from practical applications of the magnets have been widely studied in recent years. It is necessary for professional researchers, engineers, and students to study these numerical methods for the complex magnet structure design instead of using traditional «trial-and-error» methods. Those working in this field will find this book useful as a reference to help reduce costs and obtain good magnetic field quality. Presents a clear introduction to magnet technology, followed by basic theories, numerical analysis, and practical applications Emphasizes the latest developments in magnet design, including MRI systems Provides comprehensive numerical techniques that provide solutions to practical problems Introduces the latest computation techniques for optimizing and characterizing the magnetostatic structure design Well organized and adaptable by researchers, engineers, lecturers, and students Appendix available on the Wiley Companion Website As a comprehensive treatment of the topic, Practical Design of Magnetostatic Structure Using Numerical Simulation is ideal for researchers in the field of magnets and their applications, materials scientists, structural engineers, and graduate students in electrical engineering. The book will also better equip mechanical engineers and aerospace engineers.

Presents an integrated view of the expression of bacterial genetic information, genome architecture and function, and bacterial physiology and pathogenesis This book blends information from the very latest research on bacterial chromosome and nucleoid architecture, whole-genome analysis, cell signaling, and gene expression control with well-known gene regulation paradigms from model organisms (including pathogens) to give readers a picture of how information flows from the environment to the gene, modulating its expression and influencing the competitive fitness of the microbe. Structure and Function of the Bacterial Genome explores the governance of the expression of the genes that make a bacterium what it is, and updates the basics of gene expression control with information about transcription promoter structure and function, the role of DNA as a regulatory factor (in addition to its role as a carrier of genetic information), small RNAs, RNAs that sense chemical signals, ribosomes and translation, posttranslational modification of proteins, and protein secretion. It looks at the forces driving the conservation and the evolution of the dynamic genome and offers chapters that cover DNA replication, DNA repair, plasmid biology, recombination, transposition, the roles of repetitive DNA sequences, horizontal gene transfer, the defense of the genome by CRISPR-Cas, restriction enzymes, Argonaute proteins and BREX systems. The book finishes with a chapter that gives an integrated overview of genome structure and function.  Blends knowledge of gene regulatory mechanisms with a consideration of nucleoid structure and dynamics Offers a 'DNA-centric' approach to considering transcription control Views horizontal gene transfer from a gene regulation perspective Assesses the opportunities and limitations of designing synthetic microbes or rewiring existing ones Structure and Function of the Bacterial Genome is an ideal book for graduate and undergraduate students studying microbial cell biology, bacterial pathogenesis, gene regulation, and molecular microbiology. It will also appeal to principal investigators conducting research on these and related topics and researchers in synthetic biology and other arms of biotechnology.

System reliability, availability and robustness are often not well understood by system architects, engineers and developers. They often don't understand what drives customer's availability expectations, how to frame verifiable availability/robustness requirements, how to manage and budget availability/robustness, how to methodically architect and design systems that meet robustness requirements, and so on. The book takes a very pragmatic approach of framing reliability and robustness as a functional aspect of a system so that architects, designers, developers and testers can address it as a concrete, functional attribute of a system, rather than an abstract, non-functional notion.