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."

The Molecular Biology ofChloroplasts and a genetic dissection ofphotosynthesis was first Mitochondria in Chlamydomonas is the seventh recognized by Paul Levine. Together with his volume to be published in the series Advances in coworkers, he initiated along-rangegenetic approach Photosynthesis of Kluwer Academic Publishers which proved to be highly successful. It provided (Series Editor: Govindjee). Volume 1 dealtwith The genetic support for the linear Z scheme of Molecular Biology of Cyanobacteria; Volume 2 with photosynthesis and led to the identification ofnew Anoxygenic PhotosyntheticBacteria; Volume 3 with components ofthe photosynthetic electron transfer BiophysicalTechniques in Photosynthesis; Volume 4 chain such astheRieskeproteinofthe cytochrome with Photosynthesis and the Environment; and complex. Volume 6 with Lipids in Photosynthesis: Structure, During the past 20 years, the powerful techniques of molecular biology and genetics, and the Function and Genetics. The main goal ofthis book is to provide a development ofmethods for efficient nuclear and comprehensive overview ofcurrent research with chloroplast transformation of C. reinhardtii have the green alga Chlamydomonas on chloroplast and greatly enhanced the potential ofthis organism as an mitochondrial biogenesis and function, with special experimental system for studying chloroplast emphasis on the assembly and structure-function biogenesis. This has led to impressive advances in relationships ofthe constituents ofthe photosynthetic our understanding of the regulation of chloroplast apparatus.

In 1998, we published the data compilation PROTEIN STABILITY AND FOLDING which covered the data from the early beginnings of thermodynamic studies of protein folding until 1996. Since then, the amount of available thermodynamic data has increased nearly twice. The data constitute very important additions to the information on the protein folding problem, the construction of mutant protein, and the practical application of proteins in various fields. The Supplement covers the period 1997-1999 and is designed to make the vast amount of present data accessible to multidisciplinary research where chemistry, physics, biology, and medicine are involved and also biotechnology, pharmaceutical and food research. At the same time the data could be helpful to identify problems unsolved so far, and to avoid unnecessary duplication of scientific work. The structure of the Supplement is the same as in the previous data compilation. However, some additional data characterizing protein-denaturant interaction and protein unfolding by trifluoroethanol have been added. In that context, some previous data have been reconsidered. The author wishes to thank everyone who provided data, ideas, or even unpublished results. Furthermore, support by the Deutsche Forschungsgemeinschaft (INK 16 BI-I) is gratefully acknowledged. Finally, I would like to thank the staff of Springer Verlag for their efforts and for excellent assistance during the production of the data collections.

On the current status of research activity, providing new information on the applications of SQUIDs, including magnetocardiography, immunoassays, and laser-SQUID microscopes, all of which are close to being commercially available.

EPR of Free Radicals in Solids: Trends in Methods and Applications, 2nd ed. presents a critical two volume review of the methods and applications of EPR (ESR) for the study of free radical processes in solids. Emphasis is on the progress made in the developments in EPR technology, in the application of sophisticated matrix isolation techniques and in the advancement in quantitative EPR that have occurred since the 1st edition was published. Improvements have been made also at theoretical level, with the development of methods based on first principles and their application to the calculation of magnetic properties as well as in spectral simulations. EPR of Free Radicals in Solids II focuses on the trends in applications of experimental and theoretical methods to extract structural and dynamical properties of radicals and spin probes in solid matrices by continuous wave (CW) and pulsed techniques in nine chapters written by experts in the field. It examines the studies involving radiation- and photo-induced inorganic and organic radicals in inert matrices, the high-spin molecules and metal-based molecular clusters as well as the radical pro-cesses in photosynthesis. Recent advancements in environmental applications in-cluding measurements by myon resonance of radicals on surfaces and by quantitative EPR in dosimetry are outlined and the applications of optical detection in material research with much increased sensitivity reviewed. The potential use of EPR in quantum computing is considered in a newly written chapter. This new edition is aimed to experimentalists and theoreticians in research involving free radicals, as well as for students of advanced courses in physical chemis-try, chemical physics, materials science, biophysics, biochemistry and related fields.

We take great pleasure in presenting Vol. IV of Biological Magnetic Resonance, a series that continues to give us pride. In this volume, we are pleased to have our first chapter on the applications of ESR to problems in medicine, written by Butterfield. Armitage and Otvos describe their extensive Cd-l13 NMR study in a chapter that should delight the spectroscopists as well as the biochemists, since the systems investigated have not yet been modeled. Kaptein presents an eloquent exposition of the principles and applications to biological systems of the photo-CIDNP technique, to which he has made pioneering contributions. Perkins tells everything one always wanted to know about the applications of ring current calculations in structural studies of biological macromolecules. Our philosophy has been, and continues to be, to present topics of current interest by authors who are active in their field, while maintaining the inter national flavor of the series. Ideally, the coverage of each topic should approach that found both in a textbook and in a reference book, rather than being a mere literature review. We are grateful to the authors for their cooperation in this respect. We continue to solicit the comments and suggestions of our readers and our colleagues, and thank those who have already responded, including the reviewers in the periodicals. Lawrence J. Berliner Jacques Reuben ix Contents Chapter 1 Spin Labeling in Disease D. Allan Butterfield 1. Introduction ...................................... . 2. Membrane Structure . . . . . . . . . . . . . . . . . . . . . . . . . . 2 . . . . . . . 2.1. General Principles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 2.2. The Erythrocyte Membrane. . . . . . . . . . . . . . . . . . . 4 . . . . .

Subtilisin is the most extensively studied model system for protein engineering. The primary motivating factor for the interest in subtilisin is the commercial utility of this class of proteases. The subtilisin symposium was the first international meeting to bring together a large number of groups that have focused on the subtilisins and the subtilases-the protein superfamily of subtilisin-like enzymes. The results presented at the symposium are in this way a unique compendium of a broad spectrum of work largely focused on harnessing the potential of site-directed mutagenesis to understand and deliberately alter the function of these enzymes toward a desired end. This sort of protein engineering has been extremely successful in subtilisin, with many such "engineered" enzymes now widely used in commer cial enterprises. In this regard the experience derived from subtilisin does represent practical protein engineering. It is becoming clear that subtilisin represents a larger class of enzymes, the subtilases, that include many of the human pro hormone-converting enzymes. As international collabo rative efforts to sequence entire genomes continue, we can reasonably expect that additional members of the subtilase class will be encountered. Whenever interest in a member of this class of enzyme arises, the work on subtilisin will serve as a guide to the analysis for what in bacillus, fungi, and industry is an everyday workhorse enzyme.

The scientific contribution of Mike Bradbury to the study of the blood-brain barrier is considerable and wide-ranging, starting with his M.D. thesis in 1962 and still continuing today. The varied spectrum of topics relating to the blood-brain barrier presented in this volume and the many geographical locations from which both speakers and participants gathered to attend the symposium are a fitting testament both to Mike's wide-spread influence in the field and to the esteem in which he is held. When we first had the idea of afestschrift to mark Mike's retirement as Professor of Physiology at King's College London and the beginning of a new vie libre as scientist and yachtsman the plan was initially for a gathering of all of the many colleagues, collaborators and students who had worked with him over the years. However what we had not taken into account was the closeness of the international community of workers in the field, the widespread influence that Mike had wielded and the speed with which word would spread. We should have anticipated all three. The final outcome was an excellent symposium with the majority of the world's key workers either contributing or attending. We hope that this volume presents an adequate record of the meeting.

The fractal concept has become an important tool for understanding irregular complex systems in various scientific disciplines. This book discusses in great detail fractals in biology, heterogeneous chemistry, polymers, and the earth sciences. Beginning with a general introduction to fractal geometry it continues with eight chapters on self-organized criticality, rough surfaces and interfaces, random walks, chemical reactions, and fractals in chemistry, biology, and medicine. A special chapter entitled "Computer Exploration of Fractals, Chaos, and Cooperativity" presents computer demonstrations of fractal models.

Intracellular Signalling Proteins, Volume 116, presents an overview of the current developments in mechanisms of intracellular signaling and involvement of these mechanisms in the development of a number of disorders and diseases. Opportunities for targeting the intracellular signaling cascades for benefiting patients are also discussed, along with chapters that focus on Voices from the Dead: The Complex Language of Dead Cells, Nucleobindins and Encoded Peptides: From Cell Signalling to Physiology, Estrogen Receptor Signaling Mechanisms, Intracellular Signaling of the AMP-Activating Protein Kinase, the Relationship between Mitofusin 2 and Cancer, Molecular Signaling in Bone Cells: Regulation Cell Differentiation and Survival, and more.

This book provides an introduction to design of biomedical optical imaging technologies and their applications. The main topics include: fluorescence imaging, confocal imaging, micro-endoscope, polarization imaging, hyperspectral imaging, OCT imaging, multimodal imaging and spectroscopic systems. Each chapter is written by the world leaders of the respective fields, and will cover: principles and limitations of optical imaging technology, system design and practical implementation for one or two specific applications, including design guidelines, system configuration, optical design, component requirements and selection, system optimization and design examples, recent advances and applications in biomedical researches and clinical imaging. This book serves as a reference for students and researchers in optics and biomedical engineering.

Adult and immature nervous system are capable of considerable "plasticity" and unravelling the underlying mechanisms is one of the principal and most fascinating goals of Neurobiology. A major contribution to our understanding of neural plasticity has come from recent studies in excitato- ry amino acids - which are thought to mediate a large part of the excitatory synaptic transmission on the brain. Important steps in this explosive field are: 1) the synthesis of relatively specific antagonists of the N-methyl-D aspartate (NMDA) and non-NMDA receptors subtypes, 2) the characterization of the unique features of the NMDA receptor channel complex notably its voltage dependent Mg++ blockade, its permeability to calcium and its allosteric modulation by glycine, 3) the demonstration that by virtue of their Ca++ permeability NMDA receptors are involved in many -but not all -synapses in the initiation but not the maintennce of long term potentiation (L TP) an experimented model of learning and memory processes. More recent studies also indicate tha excitatory amino acids also play an important role in developmental plasticity in vivo; in cell cultures low levels of excitatory amino acids have trophic roles and can inhibit or promote neurite growth. Excitatory amino acids also play an important role also in other forms of neural plasticity such as the use dependent permanent changes in neural circuit produced by brief seizures (epileptogenesis) as well as the reactive sprouting and neosynapse formation which take place in epilepsy models and after deafferentiation or lesions.

In spite of the enticing promises of the post-genomic era, the pharmaceutical world is in a state of disarray. Drug discovery seems now riskier and more uncertain than ever. Thus, projects get routinely terminated in mid-stage clinical trials, new targets are getting harder to find, and successful therapeutic agents are often recalled as unanticipated side effects are discovered. Exploiting the huge output of genomic studies to make safer drugs has proven to be much more difficult than anticipated. More than ever, the lead in the pharmaceutical industry depends on the ability to harness innovative research, and this type of innovation can only come from one source: fundamental knowledge. This book squarely addresses this crucial problem since it introduces fundamental discoveries in basic biomolecular research that hold potential to broaden the technological base of the pharmaceutical industry. The book takes a fresh and fundamental look at the problem of how to design an effective drug with controlled specificity. Since the novel transformative concepts are unfamiliar to most practitioners, the first part of this book explains matters very carefully starting from a fairly elementary physico-chemical level. The second part of the book is devoted to practical applications, aiming at nothing less than a paradigm shift in drug design. This book is addressed to scientists working at the cutting edge of research in the pharmaceutical industry, but the material is at the same time accessible to senior undergraduates or graduate students interested in drug discovery and molecular design.

The Physics of Music and Color deals with two subjects, music and color - sound and light in the physically objective sense - in a single volume. The basic underlying physical principles of the two subjects overlap greatly: both music and color are manifestations of wave phenomena, and commonalities exist as to the production, transmission, and detection of sound and light. This book aids readers in studying both subjects, which involve nearly the entire gamut of the fundamental laws of classical as well as modern physics. Where traditional introductory physics and courses are styled so that the basic principles are introduced first and are then applied wherever possible, this book is based on a motivational approach: it introduces a subject by demonstrating a set of related phenomena, challenging readers by calling for a physical basis for what is observed. The Physics of Music and Color is written at level suitable for college students without any scientific background, requiring only simple algebra and a passing familiarity with trigonometry. It contains numerous problems at the end of each chapter that help the reader to fully grasp the subject.

This book represents the proceedings of a NATO Advanced Research Workshop of the same name, held at St. Andrews University, Scotland in July of 1989. It was the first meeting of its kind and was convened as a forum to review and discuss the phylogeny of some of the cell biological functions that underlie nervous system function, such matters as intercellular communication in diverse, lower organisms, and the electrical excitability of protozoans and cnidarians, to mention but two. The rationale behind such work has not necessarily been to understand how the first nervous systems evolved; many of the animals in question provide excellent opportunities for examining general questions that are unapproachable in the more complex nervous systems of higher animals. Nevertheless, a curiosity about nervous system evolution has invariably pervaded much of the work. The return on this effort has been mixed, depending to a large extent on the usefulness of the preparation under examination. For example, work on cnidarians, to many the keystone phylum in nervous system evolution simply because they possess the "first" nervous systems, lagged behind that carried out on protozoans, because the latter are large, single cells and, thus, far more amenable to microelectrode-based recording techniques. Furthermore, protozoans can be cultured easily and are more amenable to genetic and molecular analyses.

This book addresses the possibilities and challenges in mimicking biological membranes and creating membrane-based sensor and separation devices. Recent advances in developing biomimetic membranes for technological applications will be presented with focus on the use of integral membrane protein mediated transport for sensing and separation. Itdescribes the fundamentals of biosensing as well as separation and shows how the two processes are working in a cooperative manner in biological systems. Biomimetics is a truly cross-disciplinary approach and this is exemplified using the process of forward osmosis will be presented as an illustration of how advances in membrane technology may be directly stimulated by an increased understanding of biological membrane transport. In the development of a biomimetic sensor/separation technology, both channels (ion and water channels) and carriers (transporters) are important. An ideal sensor/separation device requires the supporting biomimetic matrix to be virtually impermeable to anything but the solute in question. In practice, however, a biomimetic support matrix will generally have finite permeabilities to water, electrolytes, and non-electrolytes. These non-protein mediated membrane transport contributions will be presented and the implications for biomimetic device construction will be discussed. New developments in our understanding of the reciprocal coupling between the material properties of the biomimetic matrix and the embedded proteins will be presented and strategies for inducing biomimetic matrix stability will be discussed. Once reconstituted in its final host biomimetic matrix the protein stability also needs to be maintained and controlled. Beta-barrel proteins exemplified by the E. Coli outer membrane channels or small peptides are inherently more stable than alpha-helical bundle proteins which may require additional stabilizing modifications. The challenges associated with insertion and stabilization of alpha-helical bundle proteins including many carriers and ligand and voltage gated ion (and water) channels will be discussed and exemplified using the aquaporin protein. Many biomimetic membrane applications require that the final device can be used in the macroscopic realm. Thus a biomimetic separation device must have the ability to process hundred of liters of permeate in hours effectively demanding square-meter size membranes. Scalability is a general issue for all nano-inspired technology developments and will be addressed here in the context biomimetic membrane array fabrication. Finally a robust working biomimetic device based on membrane transport must be encapsulated and protected yet allowing massive transport though the encapsulation material. This challenge will be discussed using microfluidic design strategies as examples of how to use microfluidic systems to create and encapsulate biomimetic membranes. The book provides an overview of what is known in the field, where additional research is needed, and where the field is heading."

Following the two meetings on Lactoferrin Structure and Function that were held in Honolulu, Hawaii, in 1993 and 1995, the Third International Conference on Lactoferrin Structure and Function was held in Le Touquet, France, and has successfully reinforced and diversified the previously created bridges between biochemists, clinicians, and companies. In fact, scientists, physicians, and people of industry from different domains have brought a wealth of recent information concerning biochemistry and technical advances in the identification of lactoferrin-derived compounds as well as cell biology, molecular biol ogy, pathology, and medical applications of lactoferrin and lactoferrin-derived com pounds. We were so delighted with the rapid growth of knowledge concerning many biologi cal and immunological functions of lactoferrins and the relationships between their struc ture and function, we wanted to share our pleasure with the readers interested in this field. The present book. which represents a review of some of the most exciting contributions, is intended to reflect the status of our knowledge and transmit our hopes for the future devel opment of in vivo applications of natural and recombinant lactoferrins. We would like to express our gratitude to the sponsors who contributed to the or ganization of the meeting in such a pleasant place and allowed the participation of several young researchers. We would also like to thank all the participants who have answered with enthusiasm our invitation and to every one of the Laboratoire de Chimie Biologique for the constant and efficient help."

Our purposes in this preface are, first, to reiterate our view of Current Ornithology's role; second, to describe briefly the contents of this vol ume; and third, to acknowledge the generous help of our Editorial Board and of the reviewers we have consulted about the contents of Volumes 13 and 14. As far as we know, Current Ornithology is the only English-lan guage publication currently devoted exclusively to extensive reviews and syntheses of topics pertaining to all aspects of the biology of birds. Its chapters deal with subjects falling under such diverse rubrics as ecology, evolution, behavior, phylogeny, behavioral ecology, anatomy and physiology, and conservation biology, but all focus primarily on birds. Its authors, whether members of the National Academy or young investigators just beginning their careers, are leading authorities on their subjects, and its referees are selected for their knowledge and expertise in the topics covered by the chapters they are asked to review.

blends materials, fabrication, and structure issues of developing nanobio devices in a single volume. treats major nanobio application areas such as drug delivery, molecular diagnostics, and imaging. chapters written by the leading researchers in the field.

This is the only single authored text on biological polymers available for bioengineering and biomedical engineering students. The book describes the structure of polymers and how these molecules are put together to make the tissues of the body and also their role in surgical implants and in structural diseases. It provides essential reading for biomedical engineers, biologists, physicians, health care professionals and other biomedical researchers who are interested in understanding how physical forces affect the biology, physiology and pathophysiology of humans. The author is an expert on the effect of mechanical forces on extracellular matrix.

For out of olde hokes, in good feyth, Cometh all this newe science that men lere. Geoffrey Chaucer The Parliament of Fowls During the past two decades knowledge of the human menstrual cycle and of normal and abnormal reproduc- tive function has increased at a dramatic rate. As rec- ognized in this volume, this explosion of knowledge is due in large measure to the development of radio- immunoassays for the measurement of the minute quantities of reproductive hormones found in the cir- culation. Yet the foundations for the many recent developments were laid well in advance. The concepts and hypotheses tested were often suggested even be- fore the hormones involved were identified and iso- lated. A consideration of the historic aspects of re- search in this field places recent research in the appropriate perspective. Moreover, as presented by Drs. vii viii FOREWORD Gruhn and Kazer, the history of progress in this field makes fascinating reading. A review of the history of reproductive endocri- nology should be required reading for all students of the subject and reproductive endocrinologists in train- ing. Dr. Griff T. Ross, a noted reproductive endocri- nologist, often instructed his students that every hy- pothesis he tested could be found in some form in the publications of previous scientists. The answers to present and future questions are often hidden in the lessons of the past.

'Further establishes the reputation of the series...an invaluable resource.' -Trends in Pharmacological Sciences, from a review of Volume 3 Volume 4 explores such emergent topics as: three-dimensional conceptions of ion channel proteins based on the available structural and functional data; the structure, pharmacology, and regulation of the GABAA receptors; and the Ca2+-dependent K+ channels in adrenal chromatic cell membranes.

The following are the proceedings of the Third International Workshop on Perception held in Pavia, Italy, on September 27-30, 1993, under the auspices of four institutions: the Group of Cybernetic and Biophysics (GNCB)s of the National Research Council (CNR), the Italian Association for Artificial Intelligence (AI * IA), the Italian Association of Psychology (AlP), and the Italian Chapter of the International Association for Pattern Recognition (IAPR). The theme of this third workshop was: "Human and Machine Vision: Analogies and Divergencies." A wide spectrum of topics was covered, ranging from neurophysiology, to computer architecture, to psychology, to image understanding, etc. For this reason the structure of this workshop was quite different from those of the first two held in Parma (1991), and Trieste (1992). This time the workshop was composed of just eight modules, each one consisting of two invited lectures (dealing with vision in nature and machines, respectively) and a common panel discussion (including the two lecturers and three invited panellists).

When I first proposed this book, one of the hopes was that it would be the stage upon which would be conducted a quiet, well reasoned discussion of the various techniques of stereotactic radio surgery. At that time, there was quite a bit of rancorous debate that tended to obscure the scientific and medical merits of each of the separate methods. At the present time, I am happy to report that the field of stereotactic radiosurgery is much less riven by such inappropriate posturing. The field has taken many steps towards maturity, both technically and medically. In the course of this mat uration process, there have been many grandiose plans and speeches made on behalf of stereotactic radiosurgery. Inevitably, the reality will not live up to the hype, but such is the natural course of devel opment in these sorts of matters. However, even though events may not match our hopes, we should keep in mind the words of Herbert Parker. Recognizing that new modalities for the treatment of cancer do not stand much chance of revolutionary success, nevertheless, he quite correctly pointed out that " . . . with any type of radiatiQn, the margin between success and failure is small. If the chance of success is a little greater . . . thi~ might well be classed as a great advance. " Mark H.