Volume 17 is the second in a special topic series devoted to modern techniques in protein NMR, under the Biological Magnetic Resonance series. Volume 16, with the subtitle Modern Techniques in Protein NMR , is the first in this series. These two volumes present some of the recent, significant advances in the biomolecular NMR field with emphasis on developments during the last five years. We are honored to have brought together in these volume some of the world s foremost experts who have provided broad leadership in advancing this field. Volume 16 contains - vances in two broad categories: I. Large Proteins, Complexes, and Membrane Proteins and II. Pulse Methods. Volume 17 contains major advances in: I. Com- tational Methods and II. Structure and Dynamics. The opening chapter of volume 17 starts with a consideration of some important aspects of modeling from spectroscopic and diffraction data by Wilfred van Gunsteren and his colleagues. The next two chapters deal with combined automated assignments and protein structure determination, an area of intense research in many laboratories since the traditional manual methods are often inadequate or laborious in handling large volumes of NMR data on large proteins. First, Werner Braun and his associates describe their experience with the NOAH/DIAMOD protocol developed in their laboratory.

Optical microscopy and associated technologies have advanced rapidly along with laser technology. These techniques have stimulated further development of the optical imaging theory, including 3-dimensional microscopy imaging theory, the theory of imaging with ultrashort pulsed beam illumination and the aberration theory for high numerical-aperture objectives. This book introduces these new theories in modern optical microscopy, providing comparisons with classical imaging as appropriate.

Some of the more interesting elements in the chemistry of life are less commonly occuring ones such as nickel and molybdenum. This volume elucidates the chemistry of these elements in important enzymes and also explores the chemistry of elements that do not normally occur in biological molecules, but are useful in probing their structure and function. Topics include: Acquisition and transport of Ni. Mechanistic action of Ni in a wide variety of enzymes. Multielectron redox systems involving pterins in proteins. Chemistry of the pterin and flavin complexes of Mo, Fe, Cu and Ru ions. Replacement of iron in transferrin by a number of other metal ions. Use of polypyridyl complexes of ruthenium and other transition metals as probes of nucleic acid structure through photochemical reactions.

The basal forebrain has received considerable attention in recent years. This emphasis resulted from observations that the cortically projecting cholinergic neurons found in this region are critical for normal information processing. However, to achieve a complete understanding of such a complex function as "information processing" it is necessary to consider the basal forebrain not as an autonomous structure with a solitary task, but one that plays an integrative role; a structure that is connected intimately with many brain regions. This view evolved from the realization that the basal forebrain interfaces cognitive and reward functions with motor outputs. It is from this integrative and functional perspective that the present book was organized. The book is a unique collection of reports pertaining to the basal forebrain that encompasses a diversity of research approaches and techniques. It provides the reader with a progression of information that begins with anatomical descriptions of the afferent and efferent systems, stressing the integrative nature of various neurotransmitters located within the basal forebrain. The chapters focusing on anatomy are complemented by electrophysiologic studies that merge anatomical concepts with synaptic pharmacology and behavior. In vitro experiments demonstrate physiologic variations in anatomically identified neuronal subtypes and, together with in vivo techniques, provide pharmacologic descriptions of neuronal consequences to various neurotransmitter influences. Additional in vivo reports correlate changes in neuronal activity with specific motivational states and motor behaviors. These functional approaches culminate with behavioral studies that overview current understanding of basal forebrain involvement in mnemonic, reward, and motor processes.

The fundamental understanding of the production of biological effects by ionizing radiation may well be one of the most important scientific objectives of mankind; such understanding could lead to the effective and safe utilization of the nuclear energy option. In addition, this knowledge will be of immense value in such diverse fields as radiation therapy and diagnosis and in the space program. To achieve the above stated objective, the U. S. Department of Energy (DOE) and its predecessors embarked upon a fundamental interdisciplinary research program some 35 years ago. A critical component of this program is the Radiological and Chemical Physics Program (RCPP). When the RCPP was established, there was very little basic knowledge in the fields of physics, chemistry, and biology that could be directly applied to understanding the effects of radiation on biological systems. Progress of the RCPP program in its first 15 years was documented in the proceedings of a conference held at Airlie, Virginia, in 1972. At this conference, it was clear that considerable progr:ess had been made in research on the physical and chemical processes in well-characterized systems that could be used to understand biological effects. During this period of time, most physical knowledge was obtained for the gas phase because the technology and instru mentation had not progressed to the point that measurements could be made in liquids more characteristic of biological materials.

The book is designed for end users in the field of digital imaging, who wish to update their skills and understanding with the latest techniques in image analysis. The book emphasizes the conceptual framework of image analysis and the effective use of image processing tools. It uses applications in a variety of fields to demonstrate and consolidate both specific and general concepts, and to build intuition, insight and understanding. Although the chapters are essentially self-contained they reference other chapters to form an integrated whole. Each chapter employs a pedagogical approach to ensure conceptual learning before introducing specific techniques and "tricks of the trade". The book concentrates on a number of current research applications, and will present a detailed approach to each while emphasizing the applicability of techniques to other problems. The field of topics is wide, ranging from compressive (non-uniform) sampling in MRI, through automated retinal vessel analysis to 3-D ultrasound imaging and more. The book is amply illustrated with figures and applicable medical images. The reader will learn the techniques which experts in the field are currently employing and testing to solve particular research problems, and how they may be applied to other problems.

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.

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.

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.

Distance measurements in biological systems by EPR The foundation for understanding function and dynamics of biological systems is knowledge of their structure. Many experimental methodologies are used for determination of structure, each with special utility. Volumes in this series on Biological Magnetic Resonance emphasize the methods that involve magnetic resonance. This volume seeks to provide a critical evaluation of EPR methods for determining the distances between two unpaired electrons. The editors invited the authors to make this a very practical book, with specific numerical examples of how experimental data is worked up to produce a distance estimate, and realistic assessments of uncertainties and of the range of applicability, along with examples of the power of the technique to answer biological problems. The first chapter is an overview, by two of the editors, of EPR methods to determine distances, with a focus on the range of applicability. The next chapter, also by the Batons, reviews what is known about electron spin relaxation times that are needed in estimating distances between spins or in selecting appropriate temperatures for particular experiments. Albert Beth and Eric Hustedt describe the information about spin-spin interaction that one can obtain by simulating CW EPR line shapes of nitroxyl radicals. The information in fluid solution CW EPR spectra of dual-spin labeled proteins is illustrated by Hassane Mchaourab and Eduardo Perozo.

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."

The first part is devoted to colloidal particles and stochastic dynamics, mainly concerned with recent authoritative results in the study of interactions between colloidal particles and transport properties in colloids and ferrocolloids. Recent advances in non-equilibrium statistical physics, such as stochastic resonance, Brownian motors, ratchets and noise-induced transport are also reported. The second part deals with biological systems and polymers. Here, standard simulation methodology to treat diffusional dynamics of multi-protein systems and proton transport in macromolecules is presented. Results of nervous system, spectroscopy of biological membrane models, and Monte Carlo simulations of polymers chains are also discussed. The third part is concerned with granular materials and quantum systems, in particular an effective-medium theory for a random system is reported. Additionally, a comprehensive treatment of spin and charge order in the vortex lattice of the cuprates, both theoretical and experimental, is included. Thermodynamics analogies between Bose-Einstein condensation and black-body radiation are also presented.The last part of the book contains recent developments of certain topics of liquid crystals and molecular fluids, including nonequilibrium thermal light scattering from nematic liquid crystals, relaxation in the kinetic Ising model on the periodic in homogeneous chain, models for thermotropic liquid-crystals, thermodynamic properties of fluids with discrete potentials as well as of fluids determined from the speed of sound effective potentials, and second viral coefficient for polar fluids.

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 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.

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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."

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."

Present knowledge of the mechanisms underlying any single sensory modality is so massive as to discourage effort directed towards completeness. The idea underlying the structure of this volume on "Sensory transduction" was to select just a few topics of general interest, which are currently being investigated and for which a reasonably clear picture is now available. During the last five years there has been a revolution in the way sensory physi ologists think about transduction, and a series of exciting advances have been made in understanding the basic processes of photo transduction, chemotransduction and mechan otransduction. It is clear that in many cases the fundamental processes by which nature attains optimization of performance are similar, and that they have much in common with more general processes of signal recognition by living structures. The molecular events underlying the detection of photons by visual cells, the recognition of a given molecule by a chemoreceptor, or the level of a hormone in the extracellular fluid by a target cell, are all very similar, and involve the activation of a sequence of events leading to a secon d messenger. The 20 papers that form the present volume cover various topics in the field of sensory transduction. They originate from the lectures, seminars and discussions which made up the XVIII Course of the International School of Biophysics held in Erice, 9th - 19th June 1988.

Among the different types of receptors for neurotransmitters, nicotinic acetyl choline receptors were the first to be studied systematically; at present they are very well characterized. This is due to the discovery of two very convenient objects that are endowed with nicotinic acetylcholine receptors - the skeletal muscle and the electric organ. The large size of skeletal muscle fibers, which simplifies the intra cellular recording of transmembrane potentials and currents, played a crucial role in obtaining the fIrst quantitative estimates of the activity of acetylcholine receptors and the kinetics of their interaction with ligands. On the other hand, the extremely high content of receptor protein in the electric organ tissue - two orders higher than in muscle tissue - rendered it highly suitable for studying the biochemistry of recep tors. The combination of pharmacological, electrophysiological, and biochemical approaches resulted in rapid progress in the investigation of acetylcholine receptors. Nicotinic acetylcholine receptors are also present in the neurons of autonomic ganglia, in the central nervous system of vertebrates, and in the ganglion neurons of invertebrates. Although each of these three types of receptors has its own pharma cological specificity, some of their properties are common and differ from those in the acetylcholine receptors of skeletal muscle and electric organ. One of these differences is that neuronal nicotinic receptors usually coexist in the same nerve cell with other receptors, e. g., muscarinic, serotoninergic, or peptidergic."

Biochemistry of Scandium and Yttrium gathers together existing knowledge about scandium and yttrium from a wide variety of disciplines. Part 2 addresses the biochemical aspects of these two elements, and the various medical and environmental applications. (Part 1 presents a comparative study of the physical and chemical properties of scandium and yttrium, looking at both their similarities and their differences.) While these elements are relatively rare in nature, these books will show that they have unusual physical and chemical properties, and a disproportionate number of important applications. Improved analytical techniques have revealed that scandium and yttrium are present throughout living matter, even though only a relatively limited number of species have been analyzed so far. This fact of course has far-ranging implications for biological and environmental concerns. The major impacts of scandium and yttrium in science, technology, and medicine will be of interest to a wide variety of researchers, including geochemists, inorganic and organic chemists, clinical biochemists, and those specializing in environmental protection.

The study of cell membranes began to attract increasing interest before the turn of the present century with the observations of 0 verton. Since that time many investigators have become interested in the broad problem of structure and function of the membrane and today we find ourselVes at a stage in which several branches of research, particularly physical chemistry, biochemistry, biophysics, physiology and pharmacology have come together, leading to the possibility of obtaining a better perspective of the overall problems. The purpose of this Symposium was to assemble in an orderly sequence representations of the knowledge of membranes achieved to date in the areas of the various disciplines. It was thought that to bring together many points of view on a problem should allow the conferees to see better what had been accomplished, what has been overlooked and what needs further development. It is to be hoped that efforts of this type have and will fulfill the desired purpose. This volume contains the majority of the papers contributed by the participants in the Symposium. In addition, it seemed logical to place at the beginning of each chapter at least one general survey of the subject which would help those who were less acquainted with the problem to derive the most benefit from their reading.