Systems-level neuronal mechanisms that coordinate the temporally, anatomically, and functionally distributed neuronal activity into coherent cognitive operations in the human brain have remained poorly understood. In humans, neuronal oscillations and synchronization can be recorded non-invasively with electro- and magnetoencephalography (EEG and MEG) that have excellent temporal resolution and an adequate spatial resolution when combined with source-reconstruction methods. In this book, leading authors in the field describe how recent methodological advances have paved the way to several major breakthroughs in the observations of large-scale synchrony from human non-invasive MEG data. This volume also presents the caveats influencing analyses of synchronization. These include the non-homogeneous sensitivity of MEG to superficial cortical sources, and, most importantly, the multitude of consequences of linear mixing. Linear mixing is an immense confounder in the sensor-level analyses of synchronization, but is also present at the source level. Approaches that can be used to avoid or compensate for these issues are then discussed. Thereafter, several authors take up a number of the functional roles that large-scale synchronization has in cognition. The authors assess how the spatio-temporal and -spectral organization and strength of both local and large-scale synchronized networks are associated with conscious sensory perception, visual working memory functions, and attention. These chapters summarize several lines of research showing how the strength of local and inter-areal oscillations in both cortical and subcortical brain structures is correlated with cognitive functions. Together these data suggest that synchronized neuronal oscillations may be a systems-level neuronal mechanism underlying the coordination of distributed processing in human cognition. In line with this argument, other authors go on to describe how oscillations and synchronization are altered in clinical populations, complementing the data presented on healthy subjects. Importantly, this book includes chapters from authors using many different approaches to the analyses of neuronal oscillations, ranging from local oscillatory activities to the usage of graph theoretical tools in the analyses of synchronization. In this way the present volume provides a comprehensive view on the analyses and functional significance of neuronal oscillations in humans. This book is aimed at doctoral and post-doctoral students as well as research scientists in the fields of cognitive neuroscience, psychology, medicine, and neurosciences.

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.

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 volume comprises of 21 selected chapters, including two overview chapters devoted to abdominal imaging in clinical applications supported computer aided diagnosis approaches as well as different techniques for solving the pectoral muscle extraction problem in the preprocessing part of the CAD systems for detecting breast cancer in its early stage using digital mammograms. The aim of this book is to stimulate further research in medical imaging applications based algorithmic and computer based approaches and utilize them in real-world clinical applications. The book is divided into four parts, Part-I: Clinical Applications of Medical Imaging, Part-II: Classification and clustering, Part-III: Computer Aided Diagnosis (CAD) Tools and Case Studies and Part-IV: Bio-inspiring based Computer Aided diagnosis techniques.

Artificial organs may be considered as small-scale process plants, in which heat, mass and momentum transfer operations and, possibly, chemical transformations are carried out. This book proposes a novel analysis of artificial organs based on the typical bottom-up approach used in process engineering. Starting from a description of the fundamental physico-chemical phenomena involved in the process, the whole system is rebuilt as an interconnected ensemble of elemental unit operations. Each artificial organ is presented with a short introduction provided by expert clinicians. Devices commonly used in clinical practice are reviewed and their performance is assessed and compared by using a mathematical model based approach. Whilst mathematical modelling is a fundamental tool for quantitative descriptions of clinical devices, models are kept simple to remain focused on the essential features of each process. Postgraduate students and researchers in the field of chemical and biomedical engineering will find that this book provides a novel and useful tool for the analysis of existing devices and, possibly, the design of new ones. This approach will also be useful for medical researchers who want to get a deeper insight into the basic working principles of artificial organs.

This volume covers state-of-the-art applications of solid-state and solution nuclear magnetic resonance( NMR) spectroscopy to study protein structure, dynamics and interactions. Chapters detail various aspects of data acquisition and processing, determination of the structure, multi-timescale dynamics of entities ranging from individual proteins to large macromolecular complexes to intact viral assemblies. The final two chapters will highlight the promise of NMR beyond field strengths of 1 GHz to study the structure, dynamics and interactions of a larger class of proteins and protein complexes of extraordinary biological interest. Written in the highly successful Methods in Molecular Biology series format, chapters provide detailed laboratory protocols and troubleshooting tips that would be of great practical help to NMR spectroscopists with different levels of expertise. Authoritative and cutting-edge, Protein NMR: Methods and Protocol aims to ensure successful results in the further study of this vital field.

This book begins with the basic terms and definitions and takes a student, step by step, through all areas of medical physics. The book covers radiation therapy, diagnostic radiology, dosimetry, radiation shielding, and nuclear medicine, all at a level suitable for undergraduates. This title not only describes the basics concepts of the field, but also emphasizes numerical and mathematical problems and examples. Students will find An Introduction to Medical Physics to be an indispensible resource in preparations for further graduate studies in the field.

This thesis offers readers a comprehensive introduction to amyloid proteins and the computational methods used with them. Katrine Skeby critically assesses and compares both the literature and the experiments performed by other researchers, which further elevates the quality and relevance of her own work. Amyloid proteins are highly complex, and this research provides unparalleled insights, especially with regard to the origin of cytotoxicity and to developing technologies for early detection, revealing in detail the molecular mechanisms behind hIAPP behavior. Several studies within the thesis answer difficult questions which promote future research into the properties of amyloid proteins.

This book reviews the fundamental aspects of quinoxaline chemistry: synthesis, reactions, mechanisms, structure, properties, and uses. The first four chapters present a survey of the developments in quinoxaline chemistry since the publication of the monograph on "Condensed Pyrazines" by Cheeseman and Cookson in 1979. These chapters give comprehensive coverage of all the methods of the synthesis of quinoxalines and the important quinoxaline-containing ring systems such as thiazolo[3,4-a]-, pyrrolo[1,2-a]-, and imidazo[1,5-a]quinoxalines. Chapter five describes many new methods for the construction of quinoxaline macrocycles, which are important in applications such as optical devices and materials. The final chapter reviews all previously known rearrangements of heterocyclic systems that lead to benzimidazole derivatives. Mamedov critically analyses these transformations to reveal a novel acid-catalyzed rearrangement of quinoxalinones giving 2-heteroarylbenzimidazoles and 1-heteroarylbenzimidazolones in the presence of nucleophilic reactants (MAMEDOV Heterocycle Rearrangement). This book is of interest to researchers in the fields of heterocyclic and synthetic organic chemistry.

The series Topics in Heterocyclic Chemistry presents critical reviews on present and future trends in the research of heterocyclic compounds. Overall the scope is to cover topics dealing with all areas within heterocyclic chemistry, both experimental and theoretical, of interest to the general heterocyclic chemistry community. The series consists of topic related volumes edited by renowned editors with contributions of experts in the field. All chapters from Topics in Heterocyclic Chemistry are published Online First with an individual DOI. In references, Topics in Heterocyclic Chemistry is abbreviated as Top Heterocycl Chem and cited as a journal.

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.

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.

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.