Since 1958, when the first cardiac pacing system was implanted, the exemplary collaboration between medicine and engineering has developed into an extremely successful therapy. The book highlights many of the recent and most important technological advances and shows the multidisciplinary nature of the technical task of pacemaker development which is based on the diverse components of physiology, electronics, physics, electrochemistry and the material sciences.

It is in the receptors of the vertebrate retina that the characteristic visual process - the transduction of radiational energy into physiological activtty of a different kind - takes place. The way these receptors modify or redistribute the incident radiation and thereby control the light ab sorption by the visual pigments they contain, is the central theme of this book. As far back as 1843 Brucke put forward a well-reasoned model for the optics of a receptor, assuming simple ray optics, and it is already some forty-seven years since the dependence of receptor sensitivity on retinal angle of incidence was established experimentally as an important factor in human vision and as one by which the direction of alignment of receptors in the living eye might be determined. But it is to Professor J. M. Enoch, editor and author of several major contributions to this volume, that we owe the first experimental demonstration (in 1961) of the wave-mode propa gation of light in vertebrate visual receptors, as well as the results of some thirty years devoted research concerned with all questions of receptor optics, particularly directional sensitivity and receptor alignment, both for normal vertebrate eyes and for pathologically modified eyes. His work on the latter has opened up a whole range of clinical possibilities."

The International Conference on Lasers and Applications was held in Rio de Janeiro, Brazil from 29 June to 3 July 1980. This conference was held to commemorate the memory of Professor Sergio Porto who died suddenly about one year earlier while attending a laser conference in the Soviet Union. The sub ject matter covered the active areas of laser devices, photochemistry, non linear optics, high-resolution spectroscopy, photokinetics, photobiology, photomedicine, optical communication, optical bistability, and Raman spec troscopy. The conference was attended by over 150 people including scientists from Japan, France, England, West Germany, Norway, Italy, Brazil, Chile, Argentina, India, Canada, and the United States. Amemorial session attended by members of the Porto family and ranking Brazilian government dignitaries preceded the start of the conference. The location of the conference in Rio de Janeiro, Brazil, was chosen be cause it was in the homeland of Sergio Porto and provided an opportunity for his friends, colleagues, and countryrnen to pay hornage to hirn. The setting on Copacabana Beach afforded access to the lovely beaches, restaurants, and nightlife of one of the most beautiful and exciting cities of the world. There were tours of the city together with a banquet that featured a performance by one of the best Samba Schools in Rio. Financial support from many sponsors in Brazil and the United States is gratefully acknowledged in making this working conference a fitting tribute to the memory of Professor S.P.S. Porto."

This monograph is the result of a course given to graduate students and to the faculty of the Dept. of Medical Physics and Biophysics of Nijmegen University, Nijmegen, The Netherlands, in the fall of 1984 and 1985. The course was intended to put together experi ment, theory, and analysis methods in order to study neural in teraction and coding in the brain. The following pages give a survey of neural interaction and its experimental substrate: cor related neural activity. The basic reason for restricting myself to vertebrate brains was to keep the material concise. As the text developed, however, it became more of a review, than a research monograph, in the attempt to balance theoretical and experimen tal aspects in brain research. Consequently, the book can be read from various points of view: that of requiring an overview of theories and theoretical principles, or an overview of experimental studies in neural interaction and the methods that can be used, or with the conviction that theory and experiment cannot be separat ed. In the latter case the book should be read from beginning to end. A way to read through the theoretical sections and the ex perimental sections of the book is presented in the following flow chart; Theory: /Chap. 2 -Chap. 4 -Chap. 5 ___ ~ Introduction -+ Chap. 1 \, Chap. 10 -+ Chap. 14 Experim~Chap. 3 -Chap. 6 -Chap. 7 -Chap. 8 ~ Chap.

Structural biology is undergoing a revolution in both the sophistication of new biophysical methods and the complexity of problems in biomolecular structure and organization opened up for study. These changes are directly attributable to major advances in computer technology, computational methods, development of high intensity synchrotron radiation sources, new magnetic resonance methods, laser optical techniques, etc. Structure-function problems previously considered intractable may now be solved. As this area of specialisation continues to expand, there is a need to review the various physical methods currently being used and developed in struc tural molecular biology. At the same time that individual techniques and their applications become more specialized, the need for effect ive communication between investigators gains in imperative. It is vital to forge links among sub-disciplines and to emphasise the complementary nature of results observed by different biophysical methods. This publication contains the review lectures given at a meeting on "Current Methods in Structural Molecular Biology" spon sored by NATO as an Advanced Study Institute and by FEBS s Advanced Course No. 78. The aim of the meeting was to bring together, in a teaching environment, students and specialists in diverse biophysical methodologies with the specific purpose of exploring, questioning and critically assessing the present and future state of biological structure research. The scientific content of the interdisciplinary Study Institute centred around three interrelated aspects; biophysical methods and instrumentation, their application to biological structure problems, and derivation of structural information and insights."

This book has its origin in my experience as a teacher of pharmacokinetics in many universities in four different continents. It was not my intention to write a popular book; what distinguishes this one from many others on the same subject is its large use of algebra and calculus. For this I make no apologies; in fact a serious study of pharmacokinetics without the help of mathematics is, in my opinion, impossible. The exact definition of many pharmacokinetic quantities, even the most common, and the correct use of many equations, even the most simple, requires the constant use of mathematical language. On the other hand I have made a considerable effort to use only elementary algebra and elementary calculus, as commonly taught in most introductory university courses. For the few exceptions, when less common mathematical concepts were needed, I have supplied the necessary explanations in four appendices. The first three chapters are a general introduction to the scientific method. Chapters 4 to 12 show different specific methods to deal with pharmacokinetic pr- lems. There is considerable overlap among those chapters; this is intentional and its p- pose is to convince the reader that every problem can be solved in more than one way, including ways that were not mentioned in this book and that intelligent readers can find for their own pleasure. Chapters 13 to 17 show how different parameters of importance in pharmacokinetics can be exactly defined and measured.

The twu-day sympusium held un the campus uf Augustana Cullege, Ruck Island, Illinuis, April 5 and 6, 1967, explured the interrelatiunship between the life sciences and engineering and attempted tu make the scientific cummunity mure aware uf an interdisciplinary appruach tu engineering. The sympusium suught tu stimulate new mechanical engineering cuncepts perhaps nut pussible utilizing data available unly thruugh ideas derived frum the traditiunal physical sciences. Devuted tu clused luup biomechanical systems in which biulugical furces and feedback influence mechanical, physical, and chemical systems, this first Ruck Island Arsenal Biumechanics Sympusium was cuspunsured by Ruck Island Arsenal, u. S. Army Weapuns Cummand, U. S. Army Research Office Durham, and Augustana Cullege. It strived fur academic excellance, and the spunsurs are indebted tu the Advisury Cummittee in pruviding the guidance and participatiun required tu achieve this ubjective as reflected in these pruceedings. Persunal thanks are extended tu Drs. Russ C. Bean, Geurge Bugliarellu, Rubert G. Gesteland, Warren S. MCCulluugh, Lawrence M. Patrick, Ali Seirig, and Heinz Vun Fuerster. The planning cummittee, which included Pruf. Juhn E. Ekblad, Edwin M. Vaughan, Alan G. Galbavy, and the editurs, are also. tu be cummended fur their ef- furts in arranging this successful sympusium.

The study of the interaction between light and matter has played a fundamental role in the development of natural sciences. Synchrotron radiation has characteristics of intensity, width and continuity of \Jave length range, time structure, tunability and polarization which are far superior to those of most other sources. It is possible with synchrotron radiation to perform experiments ~Jhich could previously be only thought about and to routinely carry out measureEents ~Jhich were once made only with great dif- ficulties. The study of the enormously complicated but imF-ensely interesting biological structures seems to be particularly suited to this new approach. The above considerations lead us to consider the opportunity of critically discussing the achievements and perspectives of the use of synchrotron radiation in biology and presenting them to a selected audience within the framework of an advanced school. From the very beginning we were encouraged in our initiative by many discussions with colleagues in the Rome area, who were later to become r.:.embers of the Scientific Committee of this Course. \oie were fully aware that ~y of the results obtained so far were of a pre- liminary nature; we feIt, however, that they were sufficiently promising to justify this venture, which seemed particularly im- portant in consideration of the increasing nur.:.ber of centers, where synchrotron radiation is becoming available.

The Progress in Medical Radiation Physics series presents in-depth reviews of many of the significant developments resulting from the application of physics to medicine. This series is intended to span the gap between research papers published in scientific journals, which tend to lack details, and complete textbooks or theses, which are usually far more detailed than necessary to provide a working knowledge of the subject. Each chapter in this series is designed to provide just enough information to enable readers to both fully understand the development described and apply the technique or concept, if they so desire. Thorough references are provided for those who wish to consider the original literature. In this way, it is hoped that the Progress in Medical Radiation Physics series will be a catalyst encouraging medical physicists to apply new techniques and developments in their daily practice. Colin G. Orton ix Contents 1-1. The Tracking Cobalt Project: From Moving-Beam Therapy to Three-Dimensional Programmed Irradiation W. A. Jennings 1. Introduction 2. Establishing Moving-Beam Techniques at the Royal Northern Hospital, 1945-1955 4 2.1. Alternative Moving-Beam Techniques 4 2.2.

Unlike most natural colours that are based on pigment absorption, the striking iridescent and intense colouration of many butterflies, birds or beetles stems from the interaction of light with periodic sub-micrometer surface or volume patterns, so called "photonic structures". These "structural colours" are increasingly well understood, but they are difficult to create artificially and exploit technologically. In this thesis the field of natural structural colours and biomimetic photonic structures is covered in a wide scope, ranging from plant photonics to theoretical optics. It demonstrates diffractive elements on the petal surfaces of many flowering plant species; these form the basis for the study of the role of structural colours in pollinator attraction. Self-assembly techniques, combined with scale able nanofabrication methods, were used to create complex artificial photonic structures inspired by those found in nature. In particular, the colour effect of a Papilio butterfly was mimicked and, by variation of its design motive, enhanced. All photonic effects described here are underpinned by state-of-the-art model calculations.

There is a tradition of theoretical brain science which started in the forties (Wiener, McCulloch, Turing, Craik, Hebb). This was continued by a small number of people without interruption up to the present. It has definitely provided main guiding lines for brain science, the devel opment of which has been spectacular in the last decades. However, within the bulk of experimental neuroscience, the theoreticians some times had a difficult stand, since it was felt that the times were not ripe yet and the methods not yet available for a development of a true theoretical speciality in this field. Thus theory remained in the hands of a fairly small club which recruited its members from theoretical physicists, mathematicians and some experimentalists with amateurish theoretical leanings. The boom of approaches which go by the name of 'computational neuroscience', 'neuronal networks', 'associative mem ory', 'spinglass theory', 'parallel processing' etc. should not blind one for the fact that the group of people professionally interested in real istic models of brain function up to the present date remains rather small and suffers from a lack of professional organization. It was against this background that we decided to organize a meet ing on Theoretical Brain Science. The meeting was held April 18 - 20, 1990 and took place at Schloss Ringberg, West-Germany, a facility sponsored by the Max-Planck-Society.

Knowledge in the field of the biology of the extracellular matrix, and in particular of collagen, has made considerable progress over the last ten years, especially in mammals, birds and ln man with respect to very important applied medical aspects. Basic knowledge in the animal kingdom overall has increased more slowly and haphazardly. We, therefore, considered it useful to organize a meeting specifically devoted to the study of the invertebrate and lower vertebrate collagens. The NATO Scientific Division financed an Advanced Research Workshop aimed at bringing together experts qualified in collagen biology (with morphological, biochemical and genetic specialization) with researchers who are currently studying collagenous tissues of invertebrates and lower vertebrates. The Medical-Biology Committee of the CNR-Rome and the University of Milan also supplied interest and support for the organization of this Meeting. The format of the workshop consisted in: 1) main lectures on the most recent aspects of collagen biology; 2) minireviews on the current knowledge of collagenous tissues in the various invertebrate phyla and in fish; 3) contributed papers on particular aspects of research in specific fields; 4) workshops on the methodology of studying collagen. As we had intended, the Workshop gave a comprehensive overview of acquired knowledge and of the present state of research actlvlty. It permitted wide interdisciplinary discussion, enabling collabora tions to be established and new research themes to be chosen. This volume contains the text of all the contributions presented at the Meeting, including posters."

This volume is a result of an International Symposium on pain and neuroimmune interactions, held in Beirut, Lebanon, in May of 1999. The results of research on the neural mechanisms that relate tissue damage to pain show that the sensation of pain and suffering can be considered as part of mechanisms that involve not only sizeable areas in the brain but also simultaneous activations of the immune and the endocrine systems. Pain involves the sharing of molecular mechanisms between the nervous, immune and endocrine systems that can interact at peripheral and, ultimately, central levels. Chronic pain can then be viewed as a corollary of the imbalance in the cross-talk between these systems, which could lead to new treatment strategies. The aim of this volume is not to deal with acute pain that serves as an alarm signal, but to attempt to explain the molecular mechanisms of chronic pain considered as a multifactorial syndrome or disease.

B. Raymond Fink Sheldon Roth and Keith Miller have asked me to record that the Third Conference on Molecular and Cellular Mechanisms of Anesthesia was held in Calgary last May "in my honor. " Such was my dear friends' gracious way of continuing a series that began at the University of Washington, where I hosted two, four, or five previous ones, 1,3-6 depending 2 on how far back one wishes to count. At that, Seattle took up where Paris left off in 1951. These occasions create their own unforgettable memories. This book captures the fine, invigorating ambience of the University of Calgary and the exciting explorations and com panionship of a gathering in a frontier territory of neuroscience. So, floreant symposia. They have progressively refined the quarry, from pathway to synapse to lipoprotein membrane to receptor and single channel, in heuristic convergences of neuronal physiology, biochemistry, and pharmacology. Nevertheless, the anesthesiologist in me senses a certain disquiet, a certain claustrophobia provoked by the narrow confines of micropipettes. How much more tubular must tunnel vision become before the desired broad view emerges? At present, the advances in molecular neurobiology seem continually to increase the apparent complexity of the total problem and the conceptual distance between the reductionists in the laboratories and the holists in the operating rooms. Happily, what is also growing is the excitement in trying to bridge the gap. Perhaps it would be timely to regard general anesthesia not as a state but as a syndrome."

This volume contains the Proceedings of the NATO Advanced Research Workshop (ARW) and Emil-Warburg-Symposium (EWS) "Nonlinear Coherent Structures in Phy sics and Biology" held at the University of Bayreuth from June 1 -4, 1993. Director of the ARW was K. H. Spatschek, while F.G. Mertens acted as the co-director, host, and organizer of the EWS. The other members of the scientific organizing committee were A.R. Bishop (Los Alamos), J.C. Eilbeck (Edinburgh), and M. Remoissenet (Dijon). This was the eighth meeting in a series of interdisciplinary workshops founded by our French colleagues who had organized all the previous workshops, e.g. 1989 in Montpel lier and 1991 in Dijon. We were asked to organize the meeting this time in Germany. Of course, we wanted to keep the character defined by the previous meetings, which were always characterized by an open and friendly atmosphere, being not too large in quantity, but high in quality. This time altogether 103 participants attended the workshop. During the past years most of the participants met several times and discussed problems connected with the generation of nonlinear coherent structures in physics and biology."

The two-word title of this book can only give an indication about its content and approach to the subject it deals with. In the course of time, the term has gradually become somewhat blurred. The reason is easy to see: similar problems are now more and more frequently studied by different branches of natural science. The term "mixed crystals" has acquired specific connotations in physics, chemistry, biology, and geology. One and the same term can now serve as a name for things which are either not quite the same or sometimes quite different. And this is precisely what happened to the two words in the title of the book. One of them, the term "crystal," for which crystallography had an un ambiguous definition, is now employed by biologists to describe the structure of cell membranes and by chemists who use it to denote degrees of polymer crystallinity. "Crystal" has thus become a broad term that can help describe any solid, or just a condensed state of a substance, if the solid has a suf ficient degree of order in the arrangement of its components. But the book is called " lixed Crystals." The other word in its title, the adjective "mixed," has also developed several meanings. It is now thought ap plicable to both homogeneous and heterogeneous systems, that is, to crystals composed of different molecules and also to solids that are a mixture of crys tals with different structures."

Lanthanides have fascinated scientists for more than two centuries now, and since efficient separation techniques were established roughly 50 years ago, they have increasingly found their way into industrial exploitation and our everyday lives. Numerous applications are based on their unique luminescent properties, which are highlighted in this volume. It presents established knowledge about the photophysical basics, relevant lanthanide probes or materials, and describes instrumentation-related aspects including chemical and physical sensors. The uses of lanthanides in bioanalysis and medicine are outlined, such as assays for in vitro diagnostics and research. All chapters were compiled by renowned scientists with a broad audience in mind, providing both beginners in the field and advanced researchers with comprehensive information on on the given subject.

"

There has been a convergence in recent years of people from the physical and biological sciences and from various engineering disciplines who are interested in analyzing the electrical activity of nerve and muscle quantita tively. Various courses have been established at the graduate level or final-year undergraduate level in many universities to teach this subject matter, yet no satisfactory short text has existed. The present book is an attempt to fill this gap, and arises from my experience in teaching this material over the past fifteen years to students on both sides of the Atlantic. Although covering a wide range of biophysi cal topics from the level of single molecules to that of complex systems, I have attempted to keep the text relatively short by considering only examples of the most general interest. Problems are included whenever possible at the end of each chapter so the reader may test his understand ing of the material presented and consider other examples which have not been included in the text."

The present volume originated from the workshop "Transduction in Biological Sys tems," held at the Marine Biological Station of the Universidad de Valparaiso, Mon temar, Chile, May 23-30, 1988, and contains contributions from most of the partici pants in the workshop. The title of both the workshop and the book reflects accurately the central theme discussed during several days of intense debate and profound intellectual exchange in the peaceful environment offered by the central coast of Chile. It was apparent that the workshop was a great success-a sentiment expressed by many seasoned attendees, some of whom dared opinions as strong as "It was the best ever." There is no single reason to explain why this workshop was so successful. Certainly instrumental was the incredible effort displayed by the Chilean Organizing Committee in selecting adequate facilities and in organizing social events that supplemented the scien tific sessions and provided an authentic fraternal environment for the participants. Equally important were the foreign participants, who enthusiastically gave of their time to take part in the event, and the students, who came from Chile as well as from several other Latin American countries, and who applied the necessary pressure in their repeated demands for scientific clarity, accuracy, and sincerity."

This book has a dual purpose, to review in depth the control of fuel homeostasis in the brain and the role of the nervous system in the control of fuel deposition in the body. From the methodological point of view the emphasis is on the application of advanced technologies to assess fuel transport and brain metabolism, the role of peptides in the neuroendocrine system and the response of the brain to hypoglycemia. These technologies include positron emmission tomography, nuclear magnetic resonance, immunocytochemistry, molecular biology, autoradiography. To study fuel homeostasis in the body advanced tracer methods that include modelling are set out. From the pathophysiological point of view the emphasis is on abnormalities in stress, brain metabolism in diabetes, eating and degenerative disorders. This book contains contributions from endocrinologists, physiologists, neurologists, psychoneuroendocrinOlogists, biophysicists, biochemists and experts in nutrition. This authorship represents a unique diversity of researchers who, for the first time, cover comprehensively the interaction between the nervous system and fuel homeostasis, both in health and disease. We hope this book will be an important source of information for both researchers and practicing clinicians. Mladen Vranic Suad Efendic Charles Hollenberg v ACKNOWLEDGEMENTS The Symposium from which this volume arose (University of Toronto, June 27-28, 1990) was the first Toronto-Stockholm symposium on Perspectives in Diabetes Research. These Symposia are organized triennially by the Banting and Best Diabetes Centre, University of Toronto and the Department of Endocrinology, Karolinska Institute, Stockholm.

This volume contains the Proceedings of a two-week NATO Advanced Study Institute on "Laser Systems for Photobiology and Photomedicine", conducted from May 11 to 20, 1990 in Erice, Italy. This is the 15th annual course of the International School of Quantum Electronics (ISQE), organized under the auspices of the "Ettore Majorana" Center for Scientific Culture. The application of lasers to medicine and surgery has made amazing progress since the last ISQE Course on this subject in 1983. The present Proceedings give a tutorial introduction to today's most important areas, as well as a review of current results by leading researchers. Among the possible approaches to a NATO Advanced Study Institute on Laser Systems for Photobiology and Photomedicine, we chose to emphasize the scientific and technological aspects of advanced laser systems when applied to laboratory and clinical tests. Since it is the policy of the School to stress the advanced scientific and techn*ological achievements in the field of Quantum Electronics, the Course broadly covers performance already achieved and potential applications.

In the mid-sixties, John Robson and Christina Enroth-Cugell, without realizing what they were doing, set off a virtual revolution in the study of the visual system. They were trying to apply the methods of linear systems analysis (which were already being used to describe the optics of the eye and the psychophysical performance of the human visual system) to the properties of retinal ganglion cells in the cat. Their idea was to stimulate the retina with patterns of stripes and to look at the way that the signals from the center and the antagonistic surround of the respective field of each ganglion cell (first described by Stephen Kuffier) interact to generate the cell's responses. Many of the ganglion cells behaved themselves very nicely and John and Christina got into the habit (they now say) of calling them I (interesting) cells. However. to their annoyance, the majority of neurons they recorded had nasty, nonlinear properties that couldn't be predicted on the basis of simple summ4tion of light within the center and the surround. These uncoop erative ganglion cells, which Enroth-Cugell and Robson at first called D (dull) cells, produced transient bursts of impulses every time the distribution of light falling on the receptive field was changed, even if the total light flux was unaltered."