Experientia Supplementum – serie

This volume contains a collection of papers presented at the Symposium on Control Problems in Industry, held on July 22-23, 1994 in San Diego. The Symposium, conducted by the Society for Industrial and Applied Math­ ematics (SIAM), with the cooperation of the Institut National Recherche Informatique et Automatique (INRIA) , focused on industrial control ap­ plications that have benefited from recent mathematical and technological developments. A partial list of themes featured by the Symposium is listed below. 1) Applications of Control Techniques in a) the aerospace industry, b) the automotive industry, c) the environmental science, d) manufacturing processes, e) the petroleum industry. 2) Optimal Shape Design in Aerospace Applications 3) Optimal Design of Micro-optics 4) Robust Control and H-infinity Methods The purpose of this meeting was to bring together experts from in­ dustry and academia to share their experience and present new results and new trends in modern control theory, with a focus on real industrial applications. The presentations were selected primarily for the practical significance of the problem solved, though all had significant mathemati­ cal components. Control theory is an interdisciplinary field which, in its broadest sense, encompasses contributions ranging from classical engineer­ ing disciplines (circuit theory, automata theory, electronics, manufacturing, mechanical engineering, material science), to theoretical engineering (sys­ tem theory, computer science) and various areas of mathematics such as ODE, PDE, complex analysis, function theory, algebraic and differential geometry, numerical analysis, etc.

The inflammasome is a protein complex composed of an intracellular sensor—typically a Nod-like receptor (NLR), the precursor procaspase-1, and the adaptor ASC. Inflammasome activation leads to the maturation of caspase-1 and the processing of its substrates, IL-1β and IL-18. The inflammasome has been implicated numerous diseases, and blockade of inflammasome-derived IL-1β has beneficial effects on several of these diseases. Different books have been edited about the biology of inflammasomes and about methods to study, however, the implication of this complex in the different diseases and pathological conditions show the need of a book about the clinical implications and therapeutic options. This project will show the context where inflammasomes are being studied and the molecular implications in the medical and clinical contexts.Other important topic of the inflammasomes will be the development of pharmacological inhibitors in order to improve new clinical applications. In this sense, we can find new drugs with inhibitory effects or old drugs with an inhibitory potential effect. There is a need for re-establishing the real benefits of the inflammasome inhibitions in pathological situations and the management of the differents diseases where inflammasomes are implicated.

This work was compiled to serve as a convenient source that covers a number of techniques (and details of their use) in the rather large field of nanomedicine, with special attention paid to gene delivery. As principal investigators working in the field of nanomedicine, we sought to put together the most current and relevant topics in gene delivery, imaging and evaluation systems. We expect the work to serve very well for scientists and graduate students in the nanomedicine field.

This book focuses on host–pathogen interactions at the metabolic level. It explores the metabolic requirements of the infectious agents, the microbial metabolic pathways that are dedicated to circumvent host immune mechanisms as well as the molecular mechanisms by which pathogens hijack host cell metabolism for their own benefit. Finally, it provides insights on the possible clinical and immunotherapeutic applications, as well as on the available experimental and analytical methods. The contributions break new ground in understanding the metabolic crosstalk between host and pathogen.

This book provides a comprehensive overview of the genetic basis underlying endocrine diseases. It covers both the molecular and clinical consequences of these genetic defects, as well as the relevance for clinical care, highlighting issues of genetic counseling. Several endocrine diseases have a genetic background, and contemporary research in the field plays a crucial role in the clinical care of endocrine diseases. In recent years, there have been major developments in our understanding of the genetic basis of endocrine diseases. Several novel genes and mutations predisposing individuals to monogenic endocrine diseases have been discovered, and with the advent of next generation sequencing, a huge amount of new data has become available. Further, novel molecular mechanisms, such as genomic imprinting, have been implicated in the pathogenesis of endocrine diseases.A better understanding of the genetic background of these diseases is relevant not only from the research perspective, but also in terms of clinical care. As such, this book is an essential read for both researchers and clinicians working in the field.

This book provides a comprehensive overview of the genetic basis underlying endocrine diseases. It covers both the molecular and clinical consequences of these genetic defects, as well as the relevance for clinical care, highlighting issues of genetic counseling. Several endocrine diseases have a genetic background, and contemporary research in the field plays a crucial role in the clinical care of endocrine diseases. In recent years, there have been major developments in our understanding of the genetic basis of endocrine diseases. Several novel genes and mutations predisposing individuals to monogenic endocrine diseases have been discovered, and with the advent of next generation sequencing, a huge amount of new data has become available. Further, novel molecular mechanisms, such as genomic imprinting, have been implicated in the pathogenesis of endocrine diseases.A better understanding of the genetic background of these diseases is relevant not only from the research perspective, but also in terms of clinical care. As such, this book is an essential read for both researchers and clinicians working in the field.

This book summarizes recent advances in antibody glycosylation research. Covering major topics relevant for immunoglobulin glycosylation - analytical methods, biosynthesis and regulation, modulation of effector functions - it provides new perspectives for research and development in the field of therapeutic antibodies, biomarkers, vaccinations, and immunotherapy.Glycans attached to both variable and constant regions of antibodies are known to affect the antibody conformation, stability, and effector functions. Although it focuses on immunoglobulin G (IgG), the most explored antibody in this context, and unravels the natural phenomena resulting from the mixture of IgG glycovariants present in the human body, the book also discusses other classes of human immunoglobulins, as well as immunoglobulins produced in other species and production systems. Further, it reviews the glycoanalytical methods applied to antibodies and addresses a range of less commonly explored topics, such as automatization and bioinformatics aspects of high-throughput antibody glycosylation analysis. Lastly, the book highlights application areas ranging from the ones already benefitting from antibody glycoengineering (such as monoclonal antibody production), to those still in the research stages (such as exploration of antibody glycosylation as a clinical or biological age biomarker), and the potential use of antibody glycosylation in the optimization of vaccine production and immunization protocols. Summarizing the current knowledge on the broad topic of antibody glycosylation and its therapeutic and biomarker potential, this book will appeal to a wide biomedical readership in academia and industry alike.Chapter 4 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book summarizes recent advances in antibody glycosylation research. Covering major topics relevant for immunoglobulin glycosylation - analytical methods, biosynthesis and regulation, modulation of effector functions - it provides new perspectives for research and development in the field of therapeutic antibodies, biomarkers, vaccinations, and immunotherapy.Glycans attached to both variable and constant regions of antibodies are known to affect the antibody conformation, stability, and effector functions. Although it focuses on immunoglobulin G (IgG), the most explored antibody in this context, and unravels the natural phenomena resulting from the mixture of IgG glycovariants present in the human body, the book also discusses other classes of human immunoglobulins, as well as immunoglobulins produced in other species and production systems. Further, it reviews the glycoanalytical methods applied to antibodies and addresses a range of less commonly explored topics, such as automatization and bioinformatics aspects of high-throughput antibody glycosylation analysis. Lastly, the book highlights application areas ranging from the ones already benefitting from antibody glycoengineering (such as monoclonal antibody production), to those still in the research stages (such as exploration of antibody glycosylation as a clinical or biological age biomarker), and the potential use of antibody glycosylation in the optimization of vaccine production and immunization protocols. Summarizing the current knowledge on the broad topic of antibody glycosylation and its therapeutic and biomarker potential, this book will appeal to a wide biomedical readership in academia and industry alike.Chapter 4 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Now, it its second edition, this book summarizes the role of immune cells in tumor suppression and progression. It describes in detail why tumor cells can survive and spread in spite of the antitumor response of immune cells. Since immunotherapy is an attractive approach to cancer therapy, this book also provides information on the two main strategies: monoclonal antibodies and adaptive T cell immunotherapy, with a focus on recent human clinical trials. A newly added chapter also focuses on the role of Natural Killer cells in tumor progression. The book provides a state-of-the-art, comprehensive overview of immune cells in cancer and is an indispensable resource for researchers and practitioners working or lecturing in the field of cancer research and immunology.

Now, it its second edition, this book summarizes the role of immune cells in tumor suppression and progression. It describes in detail why tumor cells can survive and spread in spite of the antitumor response of immune cells. Since immunotherapy is an attractive approach to cancer therapy, this book also provides information on the two main strategies: monoclonal antibodies and adaptive T cell immunotherapy, with a focus on recent human clinical trials. A newly added chapter also focuses on the role of Natural Killer cells in tumor progression. The book provides a state-of-the-art, comprehensive overview of immune cells in cancer and is an indispensable resource for researchers and practitioners working or lecturing in the field of cancer research and immunology.

This book provides an up-to-date overview on the biology of microsporidia, focusing on areas where significant progress has been made in recent years. In particular, our understanding of the evolutionary position and the role of genome reduction in the biology of these enigmatic intracellular pathogens is discussed. This book also offers important updates on the mechanisms used by these organisms to modify the host cell biology of mammals, insects, nematodes, and aquatic animals, as well as the mechanisms controlling infection and host specificity. Readers gain a detailed overview of the structure and function of the polar tube, the unique invasion apparatus of microsporidia, as well as the physics and dynamics of spore firing. Particular attention is given to chronic infections in mammals caused by microsporidia, as well as common immune responses.Written by an international team of authors representing the main research groups working on microsporidianbiology, this book is a valuable resource for health management professionals, experienced microbiologists, and early career scientist alike who want to learn more about these fascinating parasites. The ideas and latest finding covered in this book contribute to UN Sustainable Development Goal 3: Good Health and Well-Being.  Chapter “Impact of Genome Reduction in Microsporidia“ is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book provides an up-to-date overview on the biology of microsporidia, focusing on areas where significant progress has been made in recent years. In particular, our understanding of the evolutionary position and the role of genome reduction in the biology of these enigmatic intracellular pathogens is discussed. This book also offers important updates on the mechanisms used by these organisms to modify the host cell biology of mammals, insects, nematodes, and aquatic animals, as well as the mechanisms controlling infection and host specificity. Readers gain a detailed overview of the structure and function of the polar tube, the unique invasion apparatus of microsporidia, as well as the physics and dynamics of spore firing. Particular attention is given to chronic infections in mammals caused by microsporidia, as well as common immune responses.Written by an international team of authors representing the main research groups working on microsporidianbiology, this book is a valuable resource for health management professionals, experienced microbiologists, and early career scientist alike who want to learn more about these fascinating parasites. The ideas and latest finding covered in this book contribute to UN Sustainable Development Goal 3: Good Health and Well-Being.  Chapter “Impact of Genome Reduction in Microsporidia“ is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book provides a comprehensive overview of non-coding RNAs (ncRNAs), a critical but often overlooked component of our genetic material. It sheds new light on the functional significance of ncRNAs in gene regulation, epigenetic regulation, development and differentiation, cellular processes and disease pathology.The book follows a logical structure, beginning with chapters introducing ncRNA classifications, biogenesis pathways, regulatory roles and recent advances in functional analysis techniques. The main part discusses their role as therapeutic targets and provides the reader with case studies highlighting the importance of ncRNAs in specific biological processes or diseases. Finally, the book concludes with an outlook on future directions and challenges in ncRNA research.Because of its scope and thorough introduction, this book is intended not only for researchers in molecular biology, genomics, transcriptomics and epigenetics, but also for students and related disciplines. It provides a holistic understanding of ncRNA biology, their contributions to gene regulation and role in health and disease.

Galanin is a neuropeptide found both in the central and peripheral nervous system. The 29-amino acid peptide (named after its N-terminal glycine and C-terminal alanine) was identified in 1983 by its C-terminal amidation. This 'reverse' approach, that is to discover a substance through a distinct chemical feature, and only subsequently to characterize its biological activity, was novel and has been successful in the identification of several other peptides. After the structure of galanin was determined in 1983, functional studies were performed with material purified from natural sources until the synthetic form of the peptide became available. Galanin can act as transmitter, modulator and trophic factor, and is involved in a number of physiological processes such as hormone secretion, cardiovascular mechanisms, feeding and cognition. This peptide may also be of significance for a number of pathological processes/disorders including pain, depression, Alzheimer's disease, epilepsy, addiction and cancer. This wide diversity of actions is mediated by three galanin receptor subtypes. The studies reviewed in this volume give a fairly complete overview of the spectrum of the biological actions and functions of galanin and its receptors and on possible therapeutic applications in a number of pathological conditions.

Galanin is a neuropeptide found both in the central and peripheral nervous system. The 29-amino acid peptide (named after its N-terminal glycine and C-terminal alanine) was identified in 1983 by its C-terminal amidation. This 'reverse' approach, that is to discover a substance through a distinct chemical feature, and only subsequently to characterize its biological activity, was novel and has been successful in the identification of several other peptides. After the structure of galanin was determined in 1983, functional studies were performed with material purified from natural sources until the synthetic form of the peptide became available. Galanin can act as transmitter, modulator and trophic factor, and is involved in a number of physiological processes such as hormone secretion, cardiovascular mechanisms, feeding and cognition. This peptide may also be of significance for a number of pathological processes/disorders including pain, depression, Alzheimer's disease, epilepsy, addiction and cancer. This wide diversity of actions is mediated by three galanin receptor subtypes. The studies reviewed in this volume give a fairly complete overview of the spectrum of the biological actions and functions of galanin and its receptors and on possible therapeutic applications in a number of pathological conditions.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in many physiological and pathological processes. The field of MMP research is very important due to the implications of the distinct paralogs in both human physiology and pathology. Over-activation of these enzymes results in tissue degradation, producing a wide array of disease processes such as rheumatoid arthritis, osteoarthritis, tumor growth and metastasis, multiple sclerosis, congestive heart failure, and others. Thus MMP inhibitors are candidates for therapeutic agents to combat a number of diseases.  The present book discusses the design and development of different classes of inhibitors of important classes of MMPs, such as gelatinases and collagenases. The articles focus specifically on structure-activity relationships of all classes of compounds and on their modes of action and specificity of binding with the receptors based on experimental and theoretical studies. These studies constitute a valuable asset for all those involved in drug development.

This book summarizes the state-of-the art in the development of T cell-based in vitro assays, which offer useful tools for hazard identification, risk assessment and improvement of diagnostics. It will be of interest to scientists, the chemical and pharmaceutical industry, and regulators involved in the replacement of animal testing methods.The identification of hazardous chemicals and drugs is essential to ensuring human health. The ban on animal testing for the cosmetics industry since 2009 and international efforts to reduce and replace animal testing in research and immunotoxicology call for alternative in vitro methods. The most specific immune response to chemicals and drugs that cause allergic contact dermatitis, respiratory disease and adverse drug reactions is the highly antigen-specific T lymphocyte response. Therefore the use of T cells as tools for identifying contact allergens and drugs that may cause health problems is of great interest.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in many physiological and pathological processes. The field of MMP research is very important due to the implications of the distinct paralogs in both human physiology and pathology. Over-activation of these enzymes results in tissue degradation, producing a wide array of disease processes such as rheumatoid arthritis, osteoarthritis, tumor growth and metastasis, multiple sclerosis, congestive heart failure, and others. Thus MMP inhibitors are candidates for therapeutic agents to combat a number of diseases.  The present book discusses the design and development of different classes of inhibitors of important classes of MMPs, such as gelatinases and collagenases. The articles focus specifically on structure-activity relationships of all classes of compounds and on their modes of action and specificity of binding with the receptors based on experimental and theoretical studies. These studies constitute a valuable asset for all those involved in drug development.

This book focuses on the application of fluorescence to study motor proteins (myosins, kinesins, DNA helicases and RNA polymerases). It is intended for a large community of biochemists, biophysicists and cell biologists who study a diverse collection of motor proteins. It can be used by researchers to gain an insight into their first experiments, or by experienced researchers who are looking to expand their research to new areas. Each chapter provides valuable advice for executing the experiments, along with detailed background knowledge in order to develop own experiments.

MicroRNAs as the endogenous mediators of RNA interference have experienced an unprecedented career in recent years, highlighting their pathogenic, diagnostic and potential therapeutic relevance. Beside tissue microRNAs, they are also found in body fluids, most notably in blood. Significant differences of circulating microRNA levels have been found in various diseases, making them candidates for minimally invasive markers of disease, for example tumor malignancy. The book focuses on the potential diagnostic applicability of circulating microRNAs in various diseases and their potential biological significance.

This book brings together lmportant work on the structure and function of the dehydrogenases requiring nicotinamide coenzymes. The structure and function of lactate dehydrogen- ase, alcohol dehydrogenase, and glyceraldehyde 3-phosphate dehydrogenase are compared. These are the relatively simple oligomeric dehydrogenases for which very extensive structural and mechanistic information is available. Kinetic studies are dealt with in general terms, with selected examples. Genetic and structural relationships revealed by primary structure are discussed. General features of the specificity of dehydrogen- ase reactions are described. The pyridine nucleotide - disulphide oxidoreductases exemplify a type of multicomponent enzyme complex. Lipoamide dehydrogenase, glutathione reductase, and thioredoxin reduct- ase are described and compared. The fatty acid synthesizing systems of some organ- isms are nonaggregated, whereas in other organisms they are multienzyme complexes containing, in animal tissues for example, two closely related multifunctional polypeptide chains.The dehydrogenase activities of the fatty acid syn- thesizing systems afford many points of interest, which are described and discussed. Hydroxymethylglutaryl-CoA reductase occupies a key position in the synthesis of isoprenoid compounds, including cholesterol. It probably occurs in all forms of life; in animal cells it is a microsomal enzyme. Its properties are reviewed.

In spite of all emphasis on objectivity, a scientific discipline needs for its development outstanding research workers with exceptional personal qualities. A scientist with these qualities is honoured here, on the occasion of his 70th birthday, by his pupils, friends and colleagues: Arthur Linder is respected as a researcher, advisor and teacher in the field of Applied Statistics. Professor Dr. Dr. h. c. A. Linder has demonstrated the utility of statistical methods in science and technology; these are recognised today as being essen- tial for an objective evaluation of data. His contacts with Sir R. A. Fisher, C. 1. Bliss, G. M. Cox, W. G. Cochran, P. C. Mahalanobis and many other ex- perts, have helped him to achieve his almost legendary authority on sampling and on the evaluation of statistical data.Linder has won many friends and adherents to the cause of Biometry, Econometry and Technometry, firstly through his teaching activity at the universities of Berne, Geneva and Lausanne and the Swiss Federal Institute of Technology in Zurich, and as visiting lecturer at the Indian Statistical Institute, the International Statistical Education Centre in Calcutta, the Uni- versity of North Carolina and the University of Natal in Durban, secondly through his contributions to the literature as author of the monographs 'Sta- tistische Methoden' and 'Planen und Auswerten von Versuchen', as editor of METRIKA and co-editor of other journals, and thirdly through his active collaboration in the founding of The Biometric Society, to the presidency of

The 7th International Cyclotron Conference, In addition to 25 invited papers, a total of held in ZUrich from 19-22 August, 1975, was atten­ 103 papers were submitted for presentation at the ded by 231 registered . participants from 21 different conference. In order to avoid parallel sessions, countries. Visitors came from all 5 continents, only 30 papers were selected for oral presentation. showing the truly international character of the The rest of the papers were displayed, with great so-called cyclotron family. After a slight slump success, in two poster sessions, with the authors around 1970 in science funding in general, it is explaining in detail to interested participants encouraging to see that cyclotrons emerge again their reports. The high-light of the banquet was the with a promising future, rich in applications. For after dinner speech by M. S. Livingston on the history an informal summary of the topics and highlights of of the cyclotron. The hit of the ladies program was this conference, the reader is referred to the back the visit to a local chocolate factory. The rumour inside cover of these proceedings. There Henry goes that some conference participants too preferred Blosser, from Michigan State University, a very this visit to the session talks! active pioneer in the cyclotron field, put down his impressions in a matter of ten minutes after some The list of old-timers who participated in all small pressure from the editor.

The Conference timetable had to be so arranged as to spread the main topics over several separate sessions. It was therefore decided to publish the material in these Proceedings under nine subject headings, irrespective of session. Within each chapter, which is preceded by a list of the sessions featuring the subject, all papers, invited and contributed, whether presented at the Conference or accepted for publication only, have been arranged in some lo­ gical order. The reports of the four Panel Discussions were edited or summarized by the respective Moderator in consultation with Panel Members. In one instance, shortened versions of the Introductory Papers precede the discussion. Where possible, verbatim accounts of the often lively exchanges have been retained. The customary catalogue of high-energy acceler­ ators has been published separately. The continuing world-wide activities in accelerator research, witl1 its ever larger pro­ jects, are reflected by the numerous contributions accepted for inclusion in these Proceedings, which have reached the limit of what a single volume can manageably contain, while making rapid publication even harder to achieve. All the more reason to extend the gratitude of all con­ cerned to those involved in the chain of production: - To the authors, for their prompt handing-in or timely posting of their papers. Thanks also to their secretaries who followed the guidelines for the presentation of camera-ready copy.

One of the most interesting aspects of thermogenesis research is that it quite naturally attracts workers from an extremely wide spectrum of interests, ranging from the mechanism of cellular respiratory control at the molecular level and neuro-hormonal control of energy dissipation both at the cellular level and that of the whole organisms to the mechanism of temperature control during the hibernating cycle and that of cold acclimatation. Thus, the Satellite Symposium on "The Effectors of Thermogenesis" brought together not only physiologists, but also biochemists, pharmacologists, zoologists and clinicians, and provided a forum for the airing of new ideas as well as for the confrontation of different points of view. These are now reproduced in this book in exactly the same form and order in which they were presented at the Symposium, in the hope of providing a bird's-eye view of the various facets of thermogenesis research. A "mini-review", summarizing the current knowledge in each domain, therefore precedes the corresponding papers. The editors are deeply indebted to the contributors of these introductory lectures for so competently selecting from the mass of available information in each field, only the most essential elements. This book is dedicated to Dr. Robert Emrie Smith, a pioneer and path-finder in this field, who organized the first meeting on thermogenesis as a satellite of the XXI International Congress of Physiological Sciences and took an active part in the four subsequent meetings. L. Girardier DEDICATION Dr.