This thesis reports studies on the substrate specificity of crucial ketosynthase (KS) domains from trans-AT Polyketide Synthases (PKSs). Using a combination of electrospray ionisation-mass spectrometry (ESI-MS) and simple N-acetyl cysteamine (SNAC) substrate mimics, the specificity of a range of KS domains from the bacillaene and psymberin PKSs have been succsessfully studied with regard to the initial acylation step of KS-catalysis. In addition, the ability to alter the substrate tolerance of KS domains by simple point mutations in the active site has been demonstrated. A series of acyl-ACPs have been synthesised using a novel methodology and employed to probe the substrate specificity of both KS domains and the previously uncharcterised acyl hydrolase domain, PedC. KS-catalysed chain elongation reactions have also been conducted and monitored by ESI-MS/MS. All KS domains studied exhibited higher substrate specificity at the elongation step than in the preceeding acylation step. Furthermore, a mechanism of reversible acylation is proposed using the PsyA ACP1-KS1 di-domain. The findings in this thesis provide important insights into mechanisms of KS specificity and show that mutagenesis can be used to expand the repertoire of acceptable substrates for future PKS engineering.

This volume presents current advanced technologies and methods used in super-resolution microscopy. The chapters in this book cover a wide range of topics such as introducing super-resolution microscopy into a core facility; two-photon STED microscopy for nanoscale imaging of neural morphology in vivo; correlative SIM-STORM microscopy; two-color single-molecule tracking in live cells; and correlative single molecule localization microscopy and confocal microscopy. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, Super-Resolution Microscopy: Methods and Protocols is a valuable resource for both established and novel researchers and users in this field.

This book is written for researchers, undergraduate students and postgraduate students, physicians and traditional medicine practitioners who develop research in the field of neurosciences, phytochemistry and ethnopharmacology or can be useful for their practice. Topics discussed include the description of depression, its biochemical causes, the targets of antidepressant drugs, animal and cell models commonly used in the research of this pathology, medicinal plants and bioactive compounds with antidepressant activity used in traditional medicine, advances in nanotechnology for drug delivery to the brain and finally the future challenges for researchers studying this pathology.

Authored by world renowned scientists, this book expertly reviews all the imaging techniques and exciting new methods for the analysis of the pain, including novel tracers, biomarker, metabolomic and gene-array profiling, together with cellular, genetic, and molecular approaches. Recent advances in human brain imaging techniques have allowed a better understand of the functional connectivity in pain pathways, as well as the functional and anatomical alterations that occur in chronic pain patients. Modern imaging techniques have permitted rapid progress in the understanding of networks in the brain related to pain processing and those related to different types of pain modulation. Neuroimaging of Pain is designed to be a valuable resource for radiologists, neuroradiologists, neurologists and neuroscientists, working in hospitals and universities from junior trainees to consultants.

The first contribution presents coumarins, the largest group of 1-benzopyran derivatives found in plants. Coumarin chemistry remains one of the major interest areas of phytochemists, especially because of their structural diversity and medicinal properties, along with the wide-ranging bioactivities of these compounds, inclusive of analgesic, anticoagulant anti-HIV, anti-inflammatory, antimicrobial, antineoplastic, antioxidant, and immunomodulatory effects. The second contribution presents a comprehensive survey of the many aspects of PAD biochemistry and physiology. The third contribution gives a comprehensive overview of secondary metabolites from higher fungi, with more than 700 references highlighting the isolation, structure elucidation, biological activities, chemical synthesis, and biosynthesis of pigments, nitrogen-containing compounds, and terpenoids from mushrooms.

This thesis describes the inception, design, and implementation of stereoselective desymmetrization reactions in the total synthesis of the natural products pactamycin and paspaline. In the case of pactamycin, the author develops a novel asymmetric Mannich reaction and symmetry-breaking reduction strategy to enable facile construction of the complex core architecture in fifteen steps using commercially available materials - the shortest synthesis to date. He subsequently demonstrates the flexibility of this approach in SAR investigations by highlighting the preparation of twenty-five unique pactamycin structural congeners. For paspaline, the author develops a biocatalytic desymmetrization strategy that allows the highly controlled synthesis of core stereochemistry and provides a platform for the development of new conceptual disconnections in the synthesis of "steroid-like" natural products. This thesis offers a valuable resource for students embarking on a PhD in total synthesis.

The first symposium of the Society for the Study ofInborn valuable overview of advances in the application of Errors of Metabolism (SSIEM) on the organic acid urias chemical analysis of amniotic fluid to their early prenatal was held in Leeds in 1971 and published by the Society in diagnosis. The continuing complexity of diagnosis, 1972 (the 9th Annual SSIEM Symposium). Although biochemistry and aetiology ofthe dicarboxylic acid urias relatively few of these disorders were recognized at that has been admirably reduced by the papers from Dr time, the symposium was prompted by the then recent Gregersen and Dr Goodman, with Dr Goodman clearly identification between 1966 and 1970 of isovaleric identifying the primary defect in the polycystic variant of acidaemia, methylmalonic aciduria, propionic aci- multiple acyl CoA dehydrogenase deficiency ("glutaric daemia, pyroglutamic aciduria and 3-methylcrotonyl- aciduria type II") as a deficiency of electron transfer glycinuria. Identification and diagnosis of diseases of this flavoprotein (ETF) dehydrogenase. Dr Engel's paper kind had greatly improved primarily through the also provides a useful overview from currently available application of gas chromatography and mass spectro- data of the place of L-carnitine in the organic acid urias, metry to medicine, although the complexity of the an area in which rapid developments are occurring. The underlying biochemistry and the genetic heterogeneity of emerging understanding of the aetiologies of the the organic acidurias was not then realised.

This book explores the non-interventional aspects of interventional pulmonology, focusing on diseases of the central airways. As the field of bronchology and interventional pulmonology expands, newer conditions involving the central airways are being recognized with increasing frequency. Current literature has mainly focused on technical aspects of the subspecialty, but this book illuminates what else interventional pulmonology has to offer the pulmonologist, including diagnosis and alternate therapeutic options. Diseases of the Central Airways: A Clinical Guide presents techniques for the diagnoses, management and treatment of patients with intriguing central airway conditions such as: black bronchoscopy, tracheobronchomalacia, endobronchial tuberculosis, and tracheobronchopathia osteochondroplastica. In-depth chapters are written by international experts and are up-to-date and comprehensive reviews. This important new book will contribute significantly to the welfare of patients with lung ailments of the central airways.

This thesis focuses on the development of gold- and non-classical platinum-based anti-cancer agents that display distinctively different anti-cancer mechanisms compared to the commonly used cisplatin. These metal complexes contain N-heterocyclic carbene (NHC) ligands which are able to form strong M-C(NHC) bonds, conferring high stability and favorable lipophilicity, reactivity and binding specificity of metal complexes on biomolecules. The author demonstrates significant advances made in anti-cancer gold(III), gold(I) and platinum(II) complexes. Detailed chemical synthesis, in vitro and/or in vivo anti-cancer activities are clearly presented including: (i) a class of Au(III) complexes containing a highly fluorescent N^N^N ligand and NHC ligand that simultaneously act as fluorescent thiol "switch-on" probes and anti-cancer agents; (ii) a dinuclear gold(I) complex with a mixed diphosphine and bis(NHC) ligand displaying favorable stability and showing significant inhibition of tumor growth in two independent mice models with no observable side effects; and (iii) a panel of stable luminescent cyclometalated platinum(II) complexes exhibiting high specificity to localize to the endoplasmic reticulum (ER) domain, inducing ER stress and cell apoptosis. These works highlight the clinical potential that gold and platinum complexes offer for cancer treatment.

This book offers an overview of our current understanding of host defense peptides and their potential for clinical applications as well as some of the obstacles to this. The chapters, written by leading experts in the field, detail the number and diversity of host defense peptides, and discuss the therapeutic potential not only of antibacterial, but also of antifungal, antiviral, plant antimicrobial and anticancer host defense peptides. The authors provide new insights into their mechanisms of action and their immunomodulatory properties, and review recent advances in the design of novel therapeutic molecules. Lastly, their potential to prevent preterm births and Staphylococcus aureus infections is highlighted. The book is of interest to researchers, industry and clinicians alike.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

This thesis reports the latest developments in the direct amination of various C H bonds using an H Zn exchange/electrophilic amination strategy. McDonald and co-workers reveal this approach to be a rapid and powerful method for accessing a variety of functionalized amines. The material outlined in this book shows how McDonald achieved C H zincation using strong, non-nucleophilic zinc bases and subsequent electrophilic amination of the corresponding zinc carbanions with copper as a catalyst and O-benzoylhydroxylamines as the electrophilic nitrogen source. McDonald's findings are of relevance to medicinal chemistry, drug discovery and materials science. Her thesis is a source of inspiration for scientists entering the field and students beginning their PhD in a related area.

This book surveys recent advances in theranostics based on magnetic nanoparticles, ultrasound contrast agents, silica nanoparticles and polymeric micelles. It presents magnetic nanoparticles, which offer a robust tool for contrast enhanced MRI imaging, magnetic targeting, controlled drug delivery, molecular imaging guided gene therapy, magnetic hyperthermia, and controlling cell fate. Multifunctional ultrasound contrast agents have great potential in ultrasound molecular imaging, multimodal imaging, drug/gene delivery, and integrated diagnostics and therapeutics. Due to their diversity and multifunctionality, polymeric micelles and silica-based nanocomposites are highly capable of enhancing the efficacy of multimodal imaging and synergistic cancer therapy. This comprehensive book summarizes the main advances in multifunctional nanoprobes for targeted imaging and therapy of gastric cancer, and explores the clinical translational prospects and challenges. Although more research is needed to overcome the substantial obstacles that impede the development and availability of nanotheranostic products, such nontrivial nanoagents are expected to revolutionize medical treatments and help to realize the potential of personalized medicine to diagnose, treat, and follow-up patients with cancer. Zhifei Dai is a Professor at the Department of Biomedical Engineering, College of Engineering, Peking University, China.

This volume of Modern Aspects of Electrochemistry reviews the latest developments in electrochemical science and technology related to biomedical and pharmaceutical applications. In particular, this book discusses electrochemical applications to medical devices, implants, antimicrobially active materials, and drug delivery systems.

Measurement of solid tumor response to treatment relies mainly on imaging. WHO tumor response criteria and, more recently, RECIST (response evaluation criteria in solid tumors) have provided means to objectively measure tumor response in clinical trials with imaging. These guidelines have been rapidly adopted in clinical practice to monitor patient treatment and for therapy planning. However, relying only on anatomical information is not always sufficient when evaluating new drugs that will reduce a tumor's functionality while preserving its size. Finding more reliable and reproducible measures of tumor response is one of the most important and difficult challenges facing modern radiology as it requires an entirely new approach to imaging. The aim of this book is to address the assessment of response to treatment by adopting a multidisciplinary perspective, just as occurs in real life in a comprehensive cancer center. Oncologists and imaging experts consider two cancer models, locally advanced disease and metastatic disease, jointly exploring both conventional and advanced means of measuring response to standard treatment protocols and new targeted therapies.

The horizons of sophisticated imaging have expanded with the use of combined positron emission tomography (PET) and computed tomography (CT). PET-CT has revolutionized medical imaging by adding anatomic localization to functional imaging, thus providing physicians with information that is vital for the accurate diagnosis and treatment of pathologies. Since the integration of PET and CT several years ago, PET/CT procedures are now routine at leading medical centers throughout the world. This has increased the importance of nuclear medicine physicians acquiring a broad knowledge in sectional anatomy for image interpretation. The Atlas of Sectional Radiological Anatomy for PET/CT is a user-friendly guide presenting high-resolution, full-color images of anatomical detail and focuses solely on normal FDG distribution throughout the head & neck, thorax, abdomen, and pelvis, the primary sites for cancer detection and treatment through PET/CT.

An einem der Geschichte der Krebsforschung entnommenen Fall wird untersucht, wie sich Wissensentwicklung zum Wandel sozialer Formen des Forscherverkehrs verhalt und welche Rolle dabei wissenschaftliche Kontroversen spielen: Sie zersetzen nicht allein uberkommene Paradigmen, sondern uberdies die gegebenen sozialen Gliederungen und schaffen so Bedingungen fur den Wandel derselben (Disziplinen, Institutionen). Dieser Ansatz erlaubt die Abwehr eines Konzeptes, wonach die Schliessung einer Kontroverse auf die Favorisierung einer der strittigen Positionen hinauslauft. Ein solcher Prozess wird von Forschern eingeleitet, die das Verhaltnis gegeneinander vertretener Konzepte zu harmonisieren trachten, ohne dabei auf eine transdisziplinare bzw. theoretisch schlussige Vermittlungsbasis zu verweisen.

The Springer Handbook of Enzymes provides concise data on 4,457 enzymes - and here is the second, updated edition. The enzymes are sufficiently well characterized for application in analytical, synthetic and biotechnology processes as well as in food industry. Data sheets are arranged in their EC-Number sequence. The new edition reflects considerable progress in enzymology: the total material has more than doubled, and the complete 2nd edition consists of 39 volumes plus synonym index.

Blood science has become a cornerstone of multiple disciplines, including clinical chemistry, disease diagnosis, and therapeutic monitoring. Over the past decade, we have witnessed the advent of increasingly powerful proteomics technologies that allow greater fundamental insights into the blood proteome. These technological improvements have, in part, fuelled the quest for the discovery of novel blood-based biomarkers of disease. Serum/Plasma Proteomics: Methods and Protocols is a comprehensive resource of protocols for areas, pre-analytical through to analytical, of plasma and serum proteomics. Divided into five convenient sections, this detailed volume covers fractionation strategies for in-depth blood proteome analysis, defined procedures for blood collection, handling and storage, detailed protocols for performing both antibody-based and non-antibody based quantitative assays, proteome analysis of blood cell compartments, circulating nanomebraneous vesicles and blood-related fluids, and finally data management, statistical design, and bioinformatic challenges. This book, contributed to by leading experts in the field, provides a valuable foundation for the development and application of blood-based proteomics. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Serum/Plasma Proteomics: Methods and Protocols, with its well-honed methodologies, seeks to serve both professionals and investigators new to the field in an effort to further our knowledge of this fundamental science.

The future of oncology seems to lie in Molecular Medicine (MM). MM is a new science based on three pillars. Two of them are evident in its very name and are well known: medical science and molecular biology. However, there is a general unawareness that MM is firmly based on a third, and equally important, pillar: Systems Biomedicine. Currently, this term denotes multilevel, hierarchical models integrating key factors at the molecular, cellular, tissue, through phenotype levels, analyzed to reveal the global behavior of the biological process under consideration. It becomes increasingly evident that the tools to construct such complex models include, not only bioinformatics and modern applied statistics, as is unanimously agreed, but also other interdisciplinary fields of science, notably, Mathematical Oncology, Systems Biology and Theoretical Biophysics.

Con il secondo volume di Ingegneria Clinica, l'Autore intende fornire un panorama scientifico-didattico aggiornato dei principi fisici degli ultrasuoni, della tecnologia e degli aspetti realizzativi dell'ecotomografo.

La pubblicazione si articola in 12 capitoli che descrivono gli argomenti di fisica di base, la tecnologia, e le modalita operative per una buona conoscenza del funzionamento degli ecotomografi e contiene piu di 400 illustrazioni a colori originali, immagini tecniche e diagnostiche, fotografie e disegni illustrativi, molte delle quali costruite a partire da sperimentazioni condotte in laboratorio o da modelli utilizzati nel corso delle esperienze sulla formazione del fascio ultrasonoro.

Frutto dell'esperienza didattica dell'Autore e della sua volonta di presentare un testo completo e rigoroso usando sempre un linguaggio chiaro e semplice, l'opera costituisce uno strumento indispensabile per gli studenti di corsi di laurea in ingegneria clinica e biomedica.

This book combines orthopedists' and radiologists' perspectives to provide a comprehensive overview of the rapidly expanding use of ultrasound in orthopedic surgery. It also highlights the growing awareness of the potential of this non-invasive and portable, real-time imaging tool, which has led to its inclusion in the minimally invasive toolkit of upper limb surgeons.The book is divided into five parts - shoulder, elbow, forearm, hand and wrist and fingers. Each part focuses on a particular anatomic region or joint, carefully analyzing the sonoanatomy of its nerves, tendons and bones. For each region, experienced experts illustrate how to perform specific techniques under ultrasound control, ranging from classic procedures, like carpal tunnel release, to the treatment of less common conditions. Covering all the basic and practical aspects of this innovative, multi-disciplinary approach, as well as future perspectives, this unique book is a must-read for all orthopedists, radiologists, sports physicians and physiotherapist wanting to gain insights into this promising field.

SAVE when you buy these essential companions for your first two years of medical school From Tao Le, author of First Aid for the USMLE Step 1-the world's most popular medical review book! THE PACKAGE INCLUDES THESE TWO BOOKS THAT EVERY MEDICAL STUDENT SHOULD OWN: First Aid for the Basic Sciences, General Principles, Third Edition * Delivers comprehensive single-source coverage of the entire first year of medical school * Includes important background material most other reviews leave out * Covers the high-yield topics and facts tested on the USMLE * Offers full-color images, learning aids, tables, and concise text to streamline your study and help you excel in coursework and on the USMLE * Provides a framework for understanding anatomy and histology, embryology, behavioral science, biochemistry, microbiology, immunology, pathology, and pharmacology * Mirrors the table of content of First Aid for the USMLE Step 1 to facilitate study * Written BY students who aced the USMLE and reviewed by top faculty PLUS... First Aid for the Basic Sciences Organ Systems, Third Edition * Delivers comprehensive single-source coverage of the entire second year of medical school * Includes important background material most other reviews leave out * Covers the high-yield topics and facts tested on the USMLE * Offers full-color images, learning aids, tables, and concise text to streamline your study and help you excel in coursework and on the USMLE * Provides a practical framework for understanding the anatomy, physiology, pathophysiology, and pharmacology of each human organ system * Mirrors the table of content of First Aid for the USMLE Step 1 to facilitate study * Written by students who aced the USMLE and reviewed by top faculty