For this Workshop, the organizers have attempted to invite experts from all known centers which are engaged in neutron beam development for neutron capture therapy. The Workshop was designed around a series of nineteen invited papers which dealt with neutron source design and development and beam characterization and performance. Emphasis was placed on epithermal beams because they offer clinical advantages and are more challenging to implement than thermal beams. Fission reactor sources were the basis for the majority of the papers; however three papers dealt with accelerator neutron sources. An additional three invited papers provided a summary of clinical results of Ncr therapy in Japan between 1968 and 1989 and overviews of clinical considerations for neutron capture therapy and of the status of tumor targeting chemical agents for Ncr. Five contributed poster papers dealing with NCT beam design and performance were also presented. A rapporteurs' paper was prepared after the Workshop to attempt to summarize the major aspects, issues, and conclusions which resulted from this Workshop. Many people contributed to both the smooth functioning of the Workshop and to the preparation of these proceedings. Special thanks are reserved for Ms. Dorothy K.

This is the proceedings of the fourth in a series of inter national gatherings on kindling held on the University of British Columbia campus, June 15-17, 1989. Since the last gath ering in 1985, kindling continues to attract an ever-increasing number of investigators as reflected by the phenomenal increase in the number of kindling-related research reports. No other acute or chronic model has been exploited so extensively using electrophysiological, pharmacological, biochemical and behav ioural approaches involving a variety of brain sites and ani mal species. The continuing search, during the past few years, for the mechanism underlying the enduring change induced by kindling is beginning to shed some light on aspects of its molecular basis and to suggest the future direction of research. The late Graham Goddard, the original kindler, would have been delighted with this development. We were all shocked and saddened by his tragic death, but his spirit is very much alive among all of us who gathered together to share new information and collectively reassess the present state of knowledge at this symposium. I must say that we miss him very, very much. We know he is happy in his heaven knowing that he accomplished more in a short lifetime than most and that his love for mankind, and life's challenges, remain as a legacy, and goal, for us all.

In contrast to common practice, we have always tried to include as many discussions held at the meeting in our proceedings as possible, so as to enable readers to properly evaluate each paper presented, as well as to learn of future prospects in this field of research. Although the policy of including discussions occasions a long publication delay, we believe that it is worth repeating in our future publication, as we have met a number of young investigators fascinated by the discussions in our proceedings.... In the concluding remarks in this volume, Dr. Hugh E. Huxley, a principal architect of the sliding filament mechanism of muscle contraction, states that the molecular mechanism of myofilament sliding remains mysterious to all of us. We hope that this volume will stimulate muscle investigators to design and perform novel experiments to clarify the mysteries in muscle contraction.' Haruo Sugi and Gerald H. Pollack, excerpted from the Preface.

These Proceedings are a product of the International Workshop on Seeds held in Williamsburg, Virginia, USA, at the College of William and Mary, during the week of August 6-11, 1989. Sixty-eight participants attended. The location provided a scenic and historical setting for the excellent work presented. Good facilities and amenities also contributed to the success of the meeting. The Proceedings present the substance of the main lectures given at this meeting. In addition, there were 29 brief paper presentations and 30 poster presentations which have been summarized in abstract form in a separate publication. This meeting represents the third such meeting of a diverse group of scientists interested in the behavior of seeds, both in an agricultural sense and as tools for the advancement of more particular s~bject matter. The first meeting was held in Jerusalem, Israel in 1980 and the second in Wageningen, The Netherlands in 1985. A fourth meeting is being planned. The Editor and Organizer wishes to thank not only the contributors to this volume for their efforts but also all the other participants whose combined efforts made this meeting a great success.

Technological systems become organized by commands from outside, as when human intentions lead to the building of structures or machines. But many nat ural systems become structured by their own internal processes: these are the self organizing systems, and the emergence of order within them is a complex phe nomenon that intrigues scientists from all disciplines. Unfortunately, complexity is ill-defined. Global explanatory constructs, such as cybernetics or general sys tems theory, which were intended to cope with complexity, produced instead a grandiosity that has now, mercifully, run its course and died. Most of us have become wary of proposals for an "integrated, systems approach" to complex matters; yet we must come to grips with complexity some how. Now is a good time to reexamine complex systems to determine whether or not various scientific specialties can discover common principles or properties in them. If they do, then a fresh, multidisciplinary attack on the difficulties would be a valid scientific task. Believing that complexity is a proper scientific issue, and that self-organizing systems are the foremost example, R. Tomovic, Z. Damjanovic, and I arranged a conference (August 26-September 1, 1979) in Dubrovnik, Yugoslavia, to address self-organizing systems. We invited 30 participants from seven countries. Included were biologists, geologists, physicists, chemists, mathematicians, bio physicists, and control engineers. Participants were asked not to bring manu scripts, but, rather, to present positions on an assigned topic. Any writing would be done after the conference, when the writers could benefit from their experi ences there."

This book summarizes the experimental work conducted during a trans-disciplinary research program conducted for six years by the German Research Foundation. Each chapter includes introductory remarks written by internationally recognized scientists in their research areas.

Contributiing authors representing outstanding German scientists from such different disciplines as Physics, Biochemistry, Plant Nutrition, Botany, and Molecular Biology not only report original research but also review the state of knowledge in their fields of research.

It has been acknowledged that the physiological effects of dietary fiber are an exceedingly complex matter which requires a multidisciplinary research effort. The increased scientific involvement of the medical community, nutritionists, chemists and physicists is not only warranted but it has become mandatory. This is because we are entering a more advanced research phase in which the observed . in vivo effects should not be only recorded, but they should be systematically correlated with the physicochemical and analytical properties of the individual dietary fibers. The Division of Agricultural and Food Chemistry of the American Chemical Society has recognized this for some time, and has asked us to organize another International Symposium, similar to one in 1982, which would address the latest developments in this field. We decided to ask a cross section of leading experts from industrial and academic research institutions to assess the state of the art in dietary fiber, namely in the areas of the physiological effects, physicochemical attributes, and in existing and proposed analytical methods. We also felt that chemistry and physical chemistry should playa greater role in fiber research to complement and better explain the existing . in vivo data. There is a large volume of animal and human physiological and nutritional data available. Unfortunately, the generated information is frequently confusing. One reason is that this research is not conducted with well characterized compounds, but rather with loosely defined complex mixtures or entities.

In this volume of Methods in Pharmacology we have brought together experts in the field of ion channels to provide the reader with an in-depth view of current biochemical and electrophysiological methods. The focus is on cation-selective ion channels (voltage controlled Of ligand controlled) that are of special pharmacological interest. The con- tents are divided into three sections that exemplify {I) molecular and biochemical characterization of ion channels, (II) functional analysis of ion channels (after recon- stitution or expression, or in cells), and (III) specific methods and tools. The editors thank the contributors for their cooperation in assembling this volume. We are convinced that the reader will enjoy the chapters, written by leading scientists in their respective disciplines, as much as we did. Hartmut Glossmann Jarg Striessnig Innsbruck, Austria vii Contents I MOLECULAR AND BIOCHEMICAL CHARACTERIZA nON OF ION CHANNELS 1 Purification and Pharmacological Analysis of the Omega-Conotoxin 3 GVIA Receptor from Rat Brain Maureen W McEnery 2 Molecular Characterization of the Charybdotoxin-Sensitive, 41 High-Conductance, Calcium-Activated Potassium Channel Margarita Garda-Calvo, Gregory J. Kaczorowski, and Maria L. Garda 3 Characterization of the Sulfonylurea-Sensitive ATP-Modulated 61 Potassium Channel Henri Bernardi and Michel Lazdunski II FUNCTIONAL ANALYSIS OF ION CHANNELS 4 Xenopus Oocytes as an Expression System for Ion Channels 79 Alan L. Goldin ix x Contents 5 Reconstitution of Muscle Calcium Channel Function in Bilayer 99 Membranes: From the First Steps to Results Dieter J. Pelzer, Terence F.

X-ray crystallography is an established method for studying the structure of proteins and other macromolecules. As the importance of proteins grows, researchers in many fields have found that a working knowledge of X-ray diffraction is an indispensable tool. In this new edition of his essential work, the internationally recognized researcher Dr. Jan Drenth offers an up-to-date and technically rigorous introduction to the subject, providing the theoretical background necessary to understand how the structure of proteins is determined at atomic resolution. New material in the 3rd edition includes a section on twinning, an additional chapter on crystal growth and a discussion of single-wavelength anomalous dispersion.

Researchers in academia and industry who are interested in techniques for measuring intermolecular forces will find this an essential text. It presents a review of modern force spectroscopy, including fundamentals of intermolecular forces, technical aspects of the force measurements, and practical applications. The handbook begins with a review of the fundamental physics of loading single and multiple chemical bonds on the nanometer scale. It contains a discussion of thermodynamic and kinetic models of binding forces and dissipation effects in nanoscale molecular contacts, covers practical aspects of modern single-molecule level techniques, and concludes with applications of force spectroscopy to chemical and biological processes. Computer modeling of force spectroscopy experiments is also addressed.

Sixth Annual Graduate Hospital Research Symposium REGULATION OF SMOOTH MUSCLE PROGRESS IN SOLVING THE PUZZLE Every so often a scientific conference comes at a time when everyone has new and exciting information, when old "dogmas" do not seem to be as well established, and when speakers and participants alike are ready to challenge interpretations of old and new experimental data. This was such a conference. What turns on a smooth muscle cell? The precise answer to this question has eluded scientists for much longer than I have been involved in the field. We know that an increase in cytosolic calcium is necessary and we know that phosphorylation of the 20 kDa myosin light chain is an important step in the process. We do not know if other processes are necessary for the initiation and lor maintenance of a smooth muscle contraction nor do we know if other processes modulate the regulation of contraction. The goal of the symposium on which this volume is based was to explore the most current hypotheses for the answers to these questions. I believe that after reading the chapters included in this volume, you will agree that this goal was achieved. The importance of calcium and calmodulin dependent myosin light chain phosphoryla tion in the regulation of smooth muscle contraction was reinforced by many presentations. However, the status of myosin light chain phosphorylation as a simple calcium dependent switch came under serious suspicion."

The present book relates to the scientific records of a workshop held in Patras, Greece, in June 1989, under the auspices and with financial support of the European Economic Communities (Concerted Action EUROBIOMAT - Hemocompatibility - of the Medical Research Programme, Project: 11.1.212). This concerted action promotes the collaboration on science and technology on the particular field of hemocompatible biomaterials: exchange of experts, scholarships and scientific workshops within the EC-member countries and COST countries such as Sweden, Finland, Turkey, Switzerland. The first part of this monography refers to the oral presentations of the par ticipants. The second part gives the book its unique character: the scientific discussion on updated aspects of protein adsorption of synthetic polymers in contact with blood. This second part is subdivided into nine chapters where specific topics were discussed freely, open-minded and even controversially. This book intends to elucidate recurrent questions concerning the initial event when blood contacts artificial surfaces. Young investigators will consider this book to be appropriate to get familiar with the scientific background and the most relevant techniques and methods."

The very first major reference text on this topic, this book provides a unique collection of articles reviewing the state of the art in the field. It gives particular emphasis to emerging technologies, from bioengineering and bio-tissues to nanotechnology. The integration of the different topics is presented via a combination of theoretical and applied methodology to provide a self-contained major reference that is appealing to both the scientist and the engineer.

The theory of stochastic processes originally grew out of efforts to describe Brownian motion quantitatively. Today it provides a huge arsenal of methods suitable for analyzing the influence of noise on a wide range of systems. The credit for acquiring all the deep insights and powerful methods is due ma- ly to a handful of physicists and mathematicians: Einstein, Smoluchowski, Langevin, Wiener, Stratonovich, etc. Hence it is no surprise that until - cently the bulk of basic and applied stochastic research was devoted to purely mathematical and physical questions. However, in the last decade we have witnessed an enormous growth of results achieved in other sciences - especially chemistry and biology - based on applying methods of stochastic processes. One reason for this stochastics boom may be that the realization that noise plays a constructive rather than the expected deteriorating role has spread to communities beyond physics. Besides their aesthetic appeal these noise-induced, noise-supported or noise-enhanced effects sometimes offer an explanation for so far open pr- lems (information transmission in the nervous system and information p- cessing in the brain, processes at the cell level, enzymatic reactions, etc.). They may also pave the way to novel technological applications (noise-- hanced reaction rates, noise-induced transport and separation on the na- scale, etc.). Key words to be mentioned in this context are stochastic r- onance, Brownian motors or ratchets, and noise-supported phenomena in excitable systems.

This book brings together contributions from internationally renowned experts in the biochip field. The authors present not only their latest research work, but also discuss current trends in biochip technology. Specific topics range from microarray technology and its applications to lab-on-a-chip technology.

Proceedings of the NATO Advanced Study Institute on Basic Concepts and Applications of Scanning Tunneling Microscopy, Erice, Italy, April 17-29, 1989

Biomedical devices that contact with blood or tissue represent a wide range of products. Depending on their potential harm to a body, medical devices are categorized according to the degree, so their safety can be assured. All biomaterials are by definition designed to contact with a body for a certain period of time. The nature of the body contact, as well as the duration a material contacts with the body may initiate unwanted biological In comparison with invasive devices Oike catheters and medical responses. implants contact directly with tissue or with the circulating blood) non invasive devices (like wound-dressings and contact lenses contact with the skin, the sclera, and the mucosa or with open wounds) have a lesser risk of hurting a patient. When blood contacts with a foreign material, plasma proteins become absorpted to the surface within a few seconds. The reactions that follow, the so-called intrinsic pathway lead to the formation of fibrin and activation of platelets and white blood cells, result in blood clot formation."

Nonlinear dynamics has become an important field of research in recent years in many areas of the natural sciences. In particular, it has potential applications in biology and medicine; nonlinear data analysis has helped to detect the progress of cardiac disease, physiological disorders, for example episodes of epilepsy, and others. This book focuses on the current trends of research concerning the prediction of sudden cardiac death and the onset of epileptic seizures, using the nonlinear analysis based on ECG and EEG data. Topics covered include the analysis of cardiac models and neural models. The book is a collection of recent research papers by leading physicists, mathematicians, cardiologists and neurobiologists who are actively involved in using the concepts of nonlinear dynamics to explore the functional behaviours of heart and brain under normal and pathological conditions. This collection is intended for students in physics, mathematics and medical sciences, and researchers in interdisciplinary areas of physics and biology.

For anybody capable of an emotional response to it, any view of a developing organism should give birth to a feeling of amazement and even admiration, whether this development is seen directly, or in the form of a time lapse film, or even if mentally reconstructed from a series of static images. We ask ourselves how such seemingly primitive eggs or pieces of tissue, without any obvious intervention from outside, so regularly transform themselves into precisely constructed adult organisms. If we try to formulate what amazes us most of all about development, the answer will probably be that it is the internal capacity of developing organisms themselves to create new structures. How, then, can we satisfy our amazement in ways that are more or less reasonable, as well as scientifically valuable? This depends, first of all, on what position we choose to regard embryonic development as occupying among other structure creating processes, even including human activities. On the one hand, one might regard the development of organisms as a highly specialized class of processes, unique to themselves and alien to the general laws of nature, or at least not derivable from them and more akin to the deliberate acts of our own human behaviour. In that case our task would become reduced to a search for some specific 'instructions' for each next member of such a class. Whether in an overt or hidden form, some such ideology seems to dominate in present day developmental biology.

Rhythms of the heart and of the nervous and endocrine system, breathing, locomotory movements, sleep, circadian rhythms and tissue cell cycles are major elements of the temporal order of man. The dynamics of these systems are characterized by changes in the properties of an oscillator, transitions from oscillatory states into chaotic or stationary states, and vice versa, coupling or uncoupling between two or more oscillators. Any deviation from the normal range to either more or less ordered states may be defined as temporal disorder. Pathological changes of temporal organization, such as tremor, epileptic seizures, Cheyne-Stokes breathing, cardiac arrhythmicities and circadian desynchronization, may be caused by small changes in the order (control) parameters. One major aspect of the symposium was the analysis of characteristic features of these temporal control systems, including nonlinear dynamics of interactions, positive, negative and mixed feedback systems, temporal delays, and their mathematical description and modelling. The ultimate goal is a better understanding of the principles of temporal organization in order to treat periodic diseases or other perturbations of "normal" dynamics in human oscillatory systems.

This book will serve as an ideal guide to the relatively new and complex field of bioelectromagnetics for students and researchers interested in the interaction of biological systems and electromagnetic fields. Coverage details: (1) biological responses of human and animals, both in vivo and in vitro methodologies, to magnetic and/or electromagnetic field exposure, (2) characteristics of effective fields, (3) hypotheses to explain possible mechanisms of interaction between the fields and cells, and (4) induced current in ELF and induced heat in RF fields as key interaction mechanisms.

Thermoluminescence (TL) is a well-established technique widely used in do- metric and dating applications. Although several excellent reference books exist which document both the t- oretical and experimental aspects of TL, there is a general lack of books that deal withspeci?cnumericalandpracticalaspectsofanalyzingTLdata. Manytimesthe practicaldetailsofanalyzingnumericalTLglowcurvesandofapplyingtheoretical models are dif?cult to ?nd in the published literature. The purpose of this book is to provide a practical guide for both established researchers and for new graduate students entering the ?eld of TL and is intended to be used in conjunction with and as a practical supplement of standard textbooks in the ?eld. Chapter1laysthemathematicalgroundworkforsubsequentchaptersbyprese- ingthefundamentalmathematicalexpressionsmostcommonlyusedforanalyzing experimental TL data. Chapter2presentscomprehensiveexamplesofTLdataanalysisforglowcurves following ?rst-, second-, and general-order kinetics. Detailed analysis of num- ical data is presented by using a variety of methods found in the TL literature, with particular emphasis in the practical aspects and pitfalls that researchers may encounter. Special emphasis is placed on the need to use several different me- ods to analyze the same TL data, as well as on the necessity to analyze glow curves obtained under different experimental conditions. Unfortunately, the lit- ature contains many published papers that claim a speci?c kinetic order for a TL peak in a dosimetric material, based only on a peak shape analysis. It is hoped that the detailed examples provided in Chapter 2 will encourage more comprehensive studies of TL properties of materials, based on the simultaneous use of several different methods of analysis.

This book is formulated from a number of presentations made at a one-day workshop on the subject of Photon Migration in Tissues. The meeting was held in Philadelphia at the University of Pennsylvania, April, 1988. The workshop was an impromptu effort to bring together scientists to discuss photon migration in animal tissues and appropriate models. The rapid emergence of the ideas of Townes and Schalow in their invention of the then called maser, now laser opened up completely unexpected possibilities for biomedical research. Timing of rapid biochemical reaction, identification of unstable intermediates, spectroscopy of short lived fluorescent states were all goals to be expected and achieved. At the same time continuous light spectroscopy of tissue slices and of the myocardium, and eventually of the brain have the to the the neonate emerged over years. Shifting red end of spectrum, Butler and Norris clearly showed how transparent plant materials and the human hand could be illuminated in this region and Jobsis applied their idea to the neonate brain using a multiwavelength technique.

This book evolved from a graduate course on applications of statistical thermody- namics to biochemical systems. Most of the published papers and books on this subject used in the course were written by experimentalists who adopted the phenomenological approach to describe and interpret their results. Two outstanding papers that impressed me deeply were the c1assical papers by Monod, Changeux, and Jacob (1963) and Monod, Wyman, and Changeux (1965), where the allosteric model for regulatory enzymes was introduced. Reading through them I feIt as if they were revealing one of the c1everest and most intricate tricks of nature to regulate biochemical processes. In 1985 I was glad to see T. L. HilI's volume entitled Cooperativity Theory in Biochemistry, Steady State and Equilibrium Systems. This was the fIrst book to systematically develop the molecular or statistical mechanical approach to binding systems. HilI demonstrated how and why the molecular approach is so advanta- geous relative to the prevalent phenomenological approach of that time. On page 58 he wrote the following (my italics): The naturalness of Gibbs' grand partition function for binding problems in biology is evidenced by the rediscovery of what is essentially the grand partition function for this particular type of problem by various physical biochentists, including E. Q. Adams, G.

This book surveys a wide variety of mathematical models of diffusion in the ecological context. It is written with the primary intent of providing scientists, particularly physicists but also biologists, with some background in the mathematics and physics of diffusion, and shows how they can be applied to ecological problems. The secondary intent is to provide a specialized textbook for graduate students who are interested in mathematical ecology. The reader is assumed to have a basic knowledge of probability and differential equations. Each chapter in this new edition has been substantially updated by appropriate leading researchers in the field, and contains much new material covering developments in the field in the last 20 years.