Nanobiotechnology of Biomimetic Membranes describes the current state of research and development in biomimetic membranes for nanobiotechnology applications. The application areas in nanobiotechnology range from novel nanosensors, to novel methods for sorting and delivering bio-active moleculres, to novel drug-delivery systems. The success of these applications relies on a good understanding of the interaction and incorporation of macromoleculres in membranes and the funamental properties of the membrane itself.

Introduces concepts from nonlinear dynamics using an almost exclusively biological setting for motivation, and includes examples of how these concepts are used in experimental investigations of biological and physiological systems. One novel feature of the book is the inclusion of classroom-tested computer exercises. This book will appeal to students and researchers working in the natural and physical sciences wanting to learn about physiological systems from a mathematical perspective.

The past half century has seen an extraordinary growth in the fields of cellular and molecular biology. From simple morphologi cal concepts of cells as the essential units of living matter there has been an ever-sharper focus on functional organization of living systems, with emphasis on molecular dynamics. Thus, life forms have come to be defined increasingly in terms of metabolism, growth, reproduction and responses to environmental perturbations. Since these properties occur in varying degrees in systems below the level of cellular organization, there has been a blurring of older models that restricted the concepts of life to cellular systems. At the same time, a search has begun for elemental as pects of molecular and atomic behavior that might better define properties common to all life forms. This search has led to an examination of nonlinear behavior in biological macromolecules, whether in response to electrical or chemical stimulation, for example, or as a means of signaling along a molecular chain, or as a means of energy transfer. Experimental knowledge in this area has grown rapidly in the past decade, and in some respects has outstripped theoretical models adequate to ex plain these new observations. Nevertheless, it can be claimed that there is now an impressive body of experiments implicating non linear, nonequilibrium processes as fundamental steps in sequential operations of biological systems."

Since the early times of the Greek philosophers Leucippus and Democritus, and later of the Roman philosopher Lucretius, a simple, fundamental idea emerged that brought the life sciences into the realm of the physical sciences. Atoms, after various interactions, were assumed to acquire stable configurations that corresponded either to the living or to the inanimate world. This simple and unitary theory, which has evolved in successive steps to our present time, remarkably maintained its validity despite several centuries of alternative vicissitudes, and is the foundation of modern biophysics. Some of the recent developments of this ancient idea are the discovery of the direct relationship between spatial structures and chemical activity of such molecules as methane and benzene, and the later discovery of the three-dimensional structure of double-helical DNA, and of its relationship with biological activity. The relationship between the structure of various macromolecules and the function of living cells was one of the most striking advancements of modern science, obtained by the cooperation of physicists, chemists, mathematicians, engineers, biologists, and physicians. This crossing of the life and physical sciences has given rise to new and exciting frontiers, and to a new synthesis where there is a frequent interconnection of expertise, and where there is an exchange of roles among traditionally separated soft and hard sciences. Even if knowledge is still transmitted to new generations within univer sities as separate disciplines, new knowledge is acquired today in the laboratory by truly interdisciplinary teams."

Experimentalists tend to revel in the complexity and multidimensionality of biological processes. Modelers, on the other hand, generally look towards parsimony as a guiding prin ciple in their approach to understanding physiological systems. It is therefore not surprising that a substantial degree of miscommunication and misunderstanding still exists between the two groups of truth-seekers. However, there have been numerous instances in physiology where the marriage of mathematical modeling and experimentation has led to powerful in sights into the mechanisms being studied. Respiratory control represents one area in which this kind of cross-pollination has proven particularly fruitful. While earlier modeling ef forts were directed primarily at the chemical control of ventilation, more recent studies have extended the scope of modeling to include the neural and mechanical aspects pertinent to respiratory control. As well, there has been a greater awareness of the need to incorpo rate interactions with other organ systems. Nevertheless, it is necessary from time to time to remind experimentalists of the existence of modelers, and vice versa. The 4th Annual Biomedical Simulations Resource (BMSR) Short Course was held in Marina Del Rey on May 21-22,1989, to acquaint respiratory physiologists and clinical researchers with state-of-the art methodologies in mathematical modeling, experiment design and data analysis, as well as to provide an opportunity for experimentalists to challenge modelers with their more recent findings."

Emergent Computation emphasizes the interrelationship of the different classes of languages studied in mathematical linguistics (regular, context-free, context-sensitive, and type 0) with aspects to the biochemistry of DNA, RNA, and proteins. In addition, aspects of sequential machines such as parity checking and semi-groups are extended to the study of the Biochemistry of DNA, RNA, and proteins. Mention is also made of the relationship of algebraic topology, knot theory, complex fields, quaternions, and universal turing machines and the biochemistry of DNA, RNA, and proteins.

Emergent Computation tries to avoid an emphasis upon mathematical abstraction ("elegance") at the expense of ignoring scientific facts known to Biochemists. Emergent Computation is based entirely upon papers published by scientists in well-known and respected professional journals. These papers are based upon current research. A few examples of what is not ignored to gain "elegance":

- DNA exists as triple and quadruple strands

- Watson-Crick complementary bases have mismatches

- There can be more than four bases in DNA

- There are more than sixty-four codons

- There may be more that twenty amino acids in proteins

While Emergent Computation emphasizes bioinformatics applications, the last chapter studies mathematical linguistics applied to areas such as languages found in birds, insects, medical applications, anthropology, etc.

Emergent Computation tries to avoid unnecessary mathematical abstraction while still being rigorous. The demands made upon the knowledge of chemistry or mathematics is minimized as well. The collected technical references are valuable in itself for additional reading.

The papers collected in this hugely useful volume cover the principle physical and biological aspects of radiation therapy and in addition, address practical clinical considerations in the planning and delivering of that therapy. The importance of the assessment of uncertainties is emphasized. Topics include an overview of the physics of the interactions of radiation with matter and the definition of the goals and the design of radiation therapy approaches.

Computational and Instrumental Methods in EPR is devoted to both instrumentation and computation aspects of EPR, while addressing applications such as spin relaxation time measurements. However, this is the first comprehensive volume to offer practical, non-invasive spectroscopic methods of analyzing the rheology of biopolymers: comparative studies of polymer fluidity using traditional methods (e.g. viscosity) and nuclear magnetic resonance.

During the past few decades we have witnessed an era of remarkable growth in the field of molecular biology. In 1950 very little was known of the chemical constitution of biological systems, the manner in which information was trans mitted from one organism to another, or the extent to which the chemical basis of life is unified. The picture today is dramatically different. We have an almost bewildering variety of information detailing many different aspects of life at the molecular level. These great advances have brought with them some breath-taking insights into the molecular mechanisms used by nature for rep licating, distributing and modifying biological information. We have learned a great deal about the chemical and physical nature of the macromolecular nucleic acids and proteins, and the manner in which carbohydrates, lipids and smaller molecules work together to provide the molecular setting of living sys tems. It might be said that these few decades have replaced a near vacuum of information with a very large surplus. It is in the context of this flood of information that this series of monographs on molecular biology has been organized. The idea is to bring together in one place, between the covers of one book, a concise assessment of the state of the subject in a well-defined field. This will enable the reader to get a sense of historical perspective-what is known about the field today-and a description of the frontiers of research where our knowledge is increasing steadily."

Biomechanics is concerned with the response of living matter to forces, and its study has taken long strides in recent years. In the past two decades, biomechanics has brought improved understanding of normal and patho physiology of organisms at molecular, cellular, and organ levels; it has helped developing medical diagnostic and treatment procedures; it has guided the design and manufacturing of prosthesis and instruments; it has suggested the means for improving human performance in the workplace, sports, and space; it has made us understand trauma in war and in peace. Looking toward the future, we see many more areas of possible development such as: reduction in heart diseases and atherosclerosis improved vascular assist and replacement devices, including a permanent artifical heart enhanced oxygen transport in the lung understanding and control of growth and changes mechanics of neuromuscular control and robotics prevention of joint degeneration permanent total joint replacements prevention of low back pain workplace designs to enhance productivity ambulation systems for the handicapped fully implantable hearing aids improved understanding of the mechanisms for permanent disability injuries identification of factors such as alcohol use and disease influence on impact tolerance improved cellular bioreactor designs mechanics of DNA and its application in biotechnology. * Obviously, the attainment of these prospects will greatly improve the quality of human life and reduce the costs of living. * This list is from a report by the U. S. National Committee on Biomechanics, April, 1985."

This book demonstrates the applications of synchrotron radiation in certain aspects of cell microbiology, specifically non-destructive elemental analyses, chemical-state analyses and imaging (distribution) of the elements within a cell. The basics for understanding and applications of synchrotron radiation are also described to make the contents more easily understood for a wide group of researchers in medical and biological sciences who might not be familiar with the physics of synchrotron radiation.

During the past decade there has been a dramatic expansion of our knowledge on phospholipases in general, and phospholipase A2 (PLA2) in particular. Progress in this field has been evident on many fronts, with novel information rapidly accumulating in the literature regarding the chemistry and molecular biology of this enzyme and its role in many important physiological processes. These include cellular signal transduction via the G-protein cycle, and in the generation of many cellular mediators, such as the platelet activating factor (PAF) and the eicosanoids that participate in the initiation and propagation of inflammation, to mention a few. This symposium was organized to obtain an overview of current investigations on this enzyme from the standpoint of its chemistry, molecular biology and physiology. Another important focus of this symposium concerns the regulation of PLA2, including endogenous and synthetic inhibitors and activators of this enzyme. To review these important areas in PLA2 research we invited scientists who made significant contributions in this field. The papers in this volume are organized to emphasize the recent advances in several areas of investigation, including: (I) the structure and mechanism of action of PLA2, (2) mechanism of activation of PLA2, (3) molecular biology, physiology and endogenous inhibitors of this enzyme and finally, (4) clinical investigations emphasizing the pathophysiological role of this enzyme in human diseases. The first article in this volume is by Dr.

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 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.