NATO Science Series A: – serie

A very good piece of work, I assure you, and a merry. -Now, good Peter Quince, call forth your actors by the scroll. -Masters, spread yourselves. A Midsummer Night's Dream. Act 1, Sc. 2 This volume is the outcome of a NATO Advanced Study Institute held in August 1979 at Bishop's University, Lennoxville, Quebec, Canada. About 130 participants from all the countries of the aJiiance as well as India and Japan attended this event which lasted two weeks. Seventeen of these participants had been invited to present reviews of chosen topics, usually in their specialty. This book is constituted mainly of these presentations, which were prepared as chapters. In addition, six of the participants, whose seminars were found to complement the main chapters, were coopted by the invited lectures/authors to provide additional chapters. Although a lecture was given on electric fields, a chapter on this matter is unfortunately absent due to the lack of preparation time. One may say that Environmental Physiology of Fishes as a discipline originated in Canada. Having been involved as a teacher and worker in this field since 19 54, it was but natural that I was tempted to organise an ASI and get a volume out on the matter. I was encouraged by discussions with colleagues and the acceptance on the part of a large number of eminent colleagues to attend the ASI, deliver lectures and write chapters.

In the l~nited States and in Europe~ there has been an increasing interest in the relationship between individual behavior and disease. The American National Academy of Sciences (Hamberg, Elliott, and Parron, 1982)' through its Institutes of Medicine, has estimated that as many as 50 percent of chronic disease cases can be traced to individual behaviors such as smoking, diet, exercise, etc. Similar conclusions have been reached by a variety of European investigators and institutes. The World Health Organization has also expressed considerable interest in individual behavior in relation to the development of chronic disease. Thus, throughout the NATO countries there has been increased awareness of the relationship between behavior and disease. However, communication among investigators in different countries has been rather limited. Further, many different scientific disciplines including psychology, sociology, medicine, microbiology, statistics, and epidemiology have all developed new and different literatures in this field. One purpose of this book is to bring together contributions from scientists in each of these fields. Much of the variance in individual health behavior occurs across countries rather than within countries. Thus, we can learn much from comparing behavior-disease relationships across countries. To date, there have been few studies which have had an adequate international basis for these comparisons. Interest in behavioral epidemiology is a relatively recent phenomena. Thus, many scientists are entering the field without uniform background, experience, or training. This book discusses approaches common in a variety of NATO countries.

The concept of using mathematical models to investigate crop growth and productivity has attracted much attention in recent years. A major reason is that modelling can allow an expert in one area to assess the impact of his ideas in the light of other advances in our understanding of crop performance. Whether or not many of the claims made for or the demands made of models can ever be satisfied, this role as a focus for quantitative definition of crop growth is an important one. One consequence is that the development and appraisal of such models requires the efforts of scientists from a wide range of disciplines. This NATO Advanced Research workshop was designed to bring together such a range of scientists to consider the wheat crop, and assess our understanding of the crop and our ability to model its growth and yield. The ideas and organization behind the workshop involved many people. The U. K. interest in a computer model of wheat growth was instigated by Dr. Joe Landsberg (then of Long Ashton Research Station, but now Director of CSIRO Division of Forest Research), who in 1979 started a modelling exercise as part of a collaborative study of the causes of yield variation in winter wheat, involving four research institutes supported by the Agricultural and Food Research Council. Dr.

The order Rodentia is the most abundant and successful group of mammals, and it has been a focal point of attention for compar­ ative and evolutionary biologists for many years. In addition, rodents are the most commonly used experimental mammals for bio­ medical research, and they have played a central role in investi­ gations of the genetic and molecular mechanisms of speciation in mammals. During recent decades, a tremendous amount of new data from various aspects of the biology of living and fossil rodents has been accumulated by specialists from different disciplines, ranging from molecular biology to paleontology. Paradoxically, our understanding of the possible evolutionary relationships among different rodent families, as well as the possible affinities of rodents with other eutherian mammals, has not kept pace with this information "explosion. " This abundance of new biological data has not been incorporated into a broad synthesis of rodent phylo­ geny, in part because of the difficulty for any single student of rodent evolution to evaluate the phylogenetic significance of new findings from such diverse disciplines as paleontology, embryology, comparative anatomy, molecular biology, and cytogenetics. The origin and subsequent radiation of the order Rodentia were based primarily on the acquisition of a key character complex: specializations of the incisors, cheek teeth, and associated mus­ culoskeletal features of the jaws and skull for gnawing and chewing.

It is difficult to overestimate the importance of the mould genera Penicillium and Aspergillus in the natural world and in the affairs of man. These are large and ub1quitous genera; several species are beneficial to mankind because of their role in food fermentation or the production of useful antibiotics and enzymes. Others are important as agents of food spoilage. In recent years, these moulds have ga1ned attention because a number of species produce toxic metabo- lites. The great impact of mycotoxicology on food problems, particularly in developing countries has generated a vast body of research. The ecological roles of Aspergillus and Penicil- lium species in nature is also of importance. For the past several decades, the taxonomic treatments of Raper and Thorn (1949) and Raper and Fennell (1965) ~lere the only standard descciptive monographs of Penicillium and Asper- gillus. However, in practice, the identification of these economically important moulds was problematic and caused con- siderable confusion in the literature and subsequently in applied research.In the past ten years, several laboratories have carried out taxonomic research resulting in a number of valuable publications. However, the differences in methodo- logy and species concepts made comparison between the diffe- rent classifications difficult. This confusion in the taxo- nomy and nomenclature of common species is a great handicap to applied and industrial research.

Somite development is a unique and important topic; unique because somitic mesoderm is the first tissue to become segmented, important because the somites - once established - exert a profound influence on other seg­ mental structures which form later. Somite development is of interest at a number of levels. In one aspect, demarcation of a specific number of somites and size regulation, it is a particularly intriguing example of embryonic pattern formation, 'especially in vew of its possible relation to homoeobox-controlled segmentation in insects. At another level, somite development has long been studied by compara­ tive anatomists, but only recently has new light been thrown on such sub­ jects as segmentation of the head, proposed in the 18th century by Goethe and now a live issue for developmental biologists. Somit es are simple when they first appear, but very complex structures arise from them. These include the vertebrae and the axial and other muscles and consequently there is a wealth of morphogenetic problems to be explored. Sometimes their morphogenesis is disturbed, by genetic or environ­ mental factors, and there are many clinical conditions which arise as a result.

Recent years have seen enormous advances in the field of protein and peptide engineering and a greater understanding in the way in which biological response modifiers function in the body. It is now possible through the use of recombinant DNA techniques, or by solid phase protein synthesis, to produce significant quantities of a wide variety of regulatory agents that are therapeutically applicable. The list of these response modifiers expands almost daily to include interferons, macrophage activation factors, neuropeptides and agents that may have potential in cardiovascular disease, inflammation, contraception etc. Prospects to use some of these materials in medicine have reached the stage where products have either been approved by regulatory authorities or are the subject of applications as investigatory drugs or as new therapeutic agents. In some uses the pertinent agent will be administered on an acute basis in the form of a simple injection, as, for example, the use of a tissue plasminogen activator for the treatment of coronary infarct. In other cases regulatory proteins and peptides are indicated for chronic therapy and here they will need to be administered by an appropriate delivery system. Unfortunately, the research on delivery systems for peptides and proteins has not kept pace with the rapid progress in biotechnology and, consequently, there are presently few systems that are entirely appropriate for the administration of macromolecular drugs according to complex dosage regimens, (eg intermittent and pulsed therapy). Furthermore essential pharmacokinetic and pharmacodynamic data may be missing.

In recent years experimental and numerical studies have shown that chaos is a widespread phenomenon throughout the biological hierarchy ranging from simple enzyme reactions to ecosystems. Although a coherent picture of the fundamental mechanisms responsible for chaotic dynamics has started to appear it is not yet clear what the implications of such dynamics are for biological systems in general. In some systems it appears that chaotic dynamics are associated with a pathological condi­ tion. In other systems the pathological condition has regular periodic dynamics whilst the normal non-pathological condition has chaotic dyna­ mics. Since chaotic behaviour is so ubiquitous in nature and since the phenomenon raises some fundamental questions about its implications for biology it seemed timely to organize an interdisciplinary meeting at which leading scientists could meet to exchange ideas, to evaluate the current state of the field and to stipulate the guidelines along which future research should be directed. The present volume contains the contributions to the NATO Advanced Research Workshop on "Chaos in Biological Systems" held at Dyffryn House, St. Nicholas, Cardiff, U. K. , December 8-12, 1986. At this meeting 38 researchers with highly different backgrounds met to present their latest results through lectures and posters and to discuss the applica­ tions of non-linear techniques to problems of common interest. . In spite of their involvement in the study of chaotic dynamics for several years many of the participants met here for the first time.

This volume contains the contributions from the speakers at the NATO Advanced Research Workshop on "Structure of the Photosynthetic Bacterial Reaction Center X-ray Crystallography and Optical Spectroscopy with Polarized Light" which was held at the "Maison d'Hotes" of the Centre d'Etudes Nucleaires de Cadarache in the South of France, 20-25 September, 1987. This meeting continued in the spirit of a previous workshop which took place in Feldafing (FRG), March 1985. Photosynthetic reaction centers are intrinsic membrane proteins which, by performing a photoinduced transmembrane charge separation, are responsible for the conversion and storage of solar energy. Since the pioneering work of Reed and Clayton (1968) on the isolation of the reaction center from photosynthetic bacteria, optical spectroscopy with polarized light has been one of the main tools used to investigate the geometrical arrangement of the various chromophores in these systems. The recent elucidation by X-ray crystallography of the structure of several bacterial reaction centers, a breakthrough initiated by Michel and Deisenhofer, has provided us with the atomic coordinates of the pigments and some details about their interactions with neighboring aminoacid residues. This essential step has given a large impetus both to experimentalists and to theoreticians who are now attempting to relate the X-ray structural model to the optical properties of the reaction center and ultimately to its primary biological function.

The NATO Advanced Research Workshop on "Behavioural Adaptation to Intertidal Life" held in Castiglioncello, Italy (May, 1987) was attended by 50 participants, most of whom presented requested lectures. It was perhaps the first time that specialists of various animal groups, from cnidarians to birds, were able to meet and discuss the importance of behavioural adaptation to this peculiar, sometimes very harsh environment. But the taxonomic barrier is not the only one which the meeting attemped to over­ come. Lately, the research on intertidal biology has spread from pure taxonomy and static analysis of community structure to such dynamic aspects as intra- and interspecific relationships, and physiological mechanisms aimed at avoiding stress and exploitation of limited-resources. This increasing interest stems not only from an inclination for this particular ecological system and some of its typical inhabitants, but also from the realization that rocky and sandy shore communities are suitable models for testing and improving some global theories of evolutionary biology, behavioural ecology and sociobiology. The number of eco-physiological and eco-ethological problems emerging from the study of intertidal animals is fascinatingly large and a complete understanding of this environment cannot be reached using a strictly "reductionistic" or a pure "holistic" approach.

This volume is based on the proceedings of an Advanced Study Institute (ASI) sponsored by the North Atlantic Treaty Organization (NATO) held October 1987 in Corfu, Greece. The Institute received financial support from the National Aeronautics and Space Administration, U.S.A. Armed Forces Radiobiology Research Institute, U.S.A. Department of Energy, U.S.A. Deutsche Forschungs-und Versuchanstalt fur Luft­ und Raumfahrt e.v., Kaln, Germany The advent of the shuttle era is providing fresh impetus for large space ventures such as communication centers, solar power stations, astronomical observatories, orbiting factories, and space based radar. Such ventures will rely heavily on an extensive and prolonged human presence in space doing in-orbit construction, maintenance, and opera­ tion. Among the advantages of location in space are the near zero gravity environment, commanding location, and the reception of solar energy and astronomical signals unattenuated by the atmosphere. Central to long-term manned space missions are the problems associated with the effects of exposure to ionizing radiations on humans. Manned space mis­ sions in the past have encountered relatively benign radiation environ­ ments because of their very short duration and orbit configuration. However, crew stay time of up to a year has been recently achieved by the Soviet space program; and Mars missions lasting several years are under serious consideration.

V Pentostam, an uncharacterized complex of Sb and carbohydrate derived from gluconic acid, is concentrated by Leishmania amastigotes via protein binding. Biochemical consequences of the interaction of amastigotes with Pentostam are inhibition of parasite bioenergetics and inhibition of ATP synthesis. REFERENCES 1. J.C. Mottram and G.H. Coombs. Enzyme activities of amastigotes and promastigotes and their inhibition by antimonials and arsenicqls. Exper. Parasitol. 59:151 (1985). 125 2. S.L. Croft, K.D. Neame and C.A. Homewood. Accumulation of [ Sb] sodium stibogluconate by Leishmania mexicana amazonensis and Leishmania donovani in vitro. Compo Biochem. Physiol. 68c:95 (1981). 3. J.D. Berman, J.V. Gallalee, and B.D. Hansen. Leishmania mexicana: uptake of sodium stibogluconate (Pentostam) and pentamidine by parasite and macrophages. Exper. Parasitol. 64:127 (1987). 4. J.D. Berman, D. Waddell and B.D. Hanson. Biochemical meChanisms of the antileishmanial activity of sodium stibogluconate. Antimicrobial Agents Chemotherapy. 27:916 (1985). 5. J.D. Berman, J.V. Gallalee, and J.M. Best.Sodium stibogluconate (Pentostam) inhibition of glucose catabolism via the glycolytic pathway, and fatty acid B-oxidation in Leishmania mexicana amastigotes. Biochem. Pharmacol. 36:197 (1987). 6. D.T. Hart and G.H. Coombs. Leishmania mexicana: Energy metabolism of amastigotes and promastigotes. Exper. Parasitol. 54:397 (1982). 478 EFFECTS OF SINEFUNGIN ON CELLULAR AND BIOCHEMICAL EVENTS IN PROMASTIGOTES OF LEISHMANIA d. donovani Fran~oise Lawrence, and MaIka Robert-Cero Institut de Chimie des Substances Naturelles C.N.R.S.

During the last ZO years great progress has been achieved in our understanding of both earth history and vertebrate evolution. The result is that climatic/tectonic events in earth history can now be placed in a more precise and global time frame, that permit their evaluation as abiotic causal factors which might trigger extinction and dispersal events in vertebrate history. Great strides have also been made in genetics and cell biology, providing new insight into phylogenetic relationships among many vertebrates. These new data, along with data on chronologie resolution of earth history, provide tests of previous interpretations regarding ancestral-descendant relationships based solely on the fossil record. It is fitting and proper that a volume on European Neogene mammal chronology is produced at this time, to ensure that new interpretations of vertebrate evolution and chronology are based on the most accurate and current data. Vertebrate paleon­ tologists believe that the fossil record is the only secure data for measuring the actual course and tempo of vertebrate evolution. Knowledge of the fossil record must keep pace with advances in other areas of science so that inferences on vertebrate evolu­ tion are accurate and meaningful.

In our view, the First International Penicillium and Aspergillus Workshop held in Baarn and Amsterdam in May, 1985, was a great success. The assembly in one place of so many specialists in these two genera produced both interesting viewpoints and lively discussions. But more particularly, a remarkable cohesion of ideas emerged, borne primarily of the realisation that taxonomy has passed from the hands of the solitary morphologist. The future of taxonomy lay in collaborative and multidisciplinary studies embracing morphology, physiology and newer methodologies. Penicillium and Aspergillus Workshop was borne logically The Second International from the first, and was held in Baarn on May 8-12, 1989. It was attended by 38 scientists from 16 countries. At this Workshop we have attempted to move further into new methods, especially by bringing together molecular biologists, medical and food mycologists and biochemists as well as more traditional taxonomists. We feel that the meeting contributed greatly to dialogue between taxonomists, and also fundamental and applied mycologists. At the meeting, we became aware that the approach to taxonomy of these genera is now becoming more pragmatic, with an increasing emphasis on consensus, and on stability of names. This is a noteworthy development, which we, as editors, welcome. So many species in Penicillium and Aspergillus are economically important in biotechnology, foods and medicine, and practical, stable taxonomy is of vital importance. These Proceedings comprise 40 papers divided into 9 chapters.

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 collects together papers given at a NATO Advanced Research Workshop held at Il Ciocco (Lucca), Italy, from the 9th to the 15th April, 1989. It sets out to present the current state of understanding of the principles governing the way fluxes and concentrations are maintained and controlled in metabolic systems. Although this is a topic that has held the interest of biochemists for many years, it is only quite recently that the methods of analysing the kinetics of multi-enzyme pathways developed over the past two decades have come to be widely discussed or applied experimentally. Many biochemists remain sceptical that the new methods offer a real advance (except in complexity) over the landmark discoveries of the 1950s and 1960s relating to inhibition of enzymes at branch-points by the end products of metabolic pathways, and the interpretation of allosteric effects and cooperativity. Even those who have become convinced that the classical ideas provide only the starting point for understanding metabolic control have been by no means unanimous in their assess­ ment of the direction in which one should advance. In this book we have tried to include all of the current points of view, including the view that the classical theories tell us all that we need to know. We have not seen it as our role as editors to paper over the cracks that exist and to pretend that we can speak to the world with one voice.

This book evolved through the efforts of several organizations and the dedication of many individuals. In 1987, we received arequest to propose a workshop topic for the Fifth International Theriological Congress (ITC) to be held in August 1989 in Rome, Italy. After looking up the meaning of the word "theriological" in the dictionary and discovering that it pertains to mammalian behavior, we decided a symposium on sensory abilities of whales and dOlphins would be an interesting topic. The ITC convenes only every five years and has the distinction of being very weIl attended by scientists from around the world. We thought that hosting a workshop in conjunction with the ITC would attract a variety of international scientists that rarely have the opportunity to interact. Fortunately for all involved, our prediction was correct. The first two days of the workshop, 23-24 August 1989, were held in conjunction with ITC and the nearly 1,000 attending scientists were able to view our posters and listen to lectures. The third day was limited to only ab out 65 invited scientists who were divided into topical working groups chaired by a rapporteur.

The fIrst edition of the Science 0/ Photobiology edited by Kendric C. Smith (plenum Press, 1977) was a comprehensive textbook of photobiology, devoting a chapter to each of the subdisciplines of the fIeld. At the end of many of these chapters there were brief descriptions of simple experiments that students could perform to demonstrate the principles discussed. In the succeeding years some photobiologists felt that a more complete publica­ tion of experiments in photobiology would be a useful teaching tool. Thus, in the 1980s the American Society for Photobiology (ASP) attempted to produce a laboratory manual in photobiology. Cognizant of these efforts, Kendric Smith elected to publish the second edition of The Science o/Photobiology (1989) without experiments; anticipating the comple­ tion of the ASP laboratory manual. Unfortunately, the initial ASP efforts met with limited success, and several years were to pass before a photobiology laboratory manual became a reality. One of the major stumbling blocks to production of an accurate and reliable laboratory manual was the requirement that the experiments be tested, not just by the author who is familiar with the techniques, but by students who may be quite new to photobiology. How could this be accomplished with limited resources? Many ideas were considered and discarded, before a workable solution was found. The catalyst that enabled the careful screening of all experiments in this book was a NATO Advanced Study Institute (ASI) devoted entirely to this purpose.

Of the three organizers of this NATO Advanced Research Workshop on "Neocortex: Onto- geny and Phylogeny", one derived most of his knowledge about neocortex from studies on birds, another had never studied any animal but the cat and could probably recognize not more than ten animal species, and the third had very limited experience with mountaineering. They had in common the belief that evolutionary thinking permeates what biologists do, but that evolution of species and structures cannot be directly experimentally addressed. Although the fossil record can provide some major insights, the inroad to the evolution of the brain is indirect, via comparative anatomy and developmental biology. By identifying similarities and differences between brain structures in the species at hand, comparative anatomy generates hypotheses of evolutionary transformations. By understanding the rules of morphological transformation, developmental biology can, in principle, estimate the likelihood that a given transformation may have actually occurred. The meeting was a way to check if this notion is viable, by gathering together scientists from these two fields. Standing, left to right: F. Ebner, V.Caviness, M. Weisskopf, B. Fritszch, N. Swindale, J. Walter, H. Karten, J. Pettigrew, E. Welker, M. Cynader, D. Frost, L. Lopez-Mascaraque, P. Katz, H. Jerison, E. Soriano, Mayor of Alagna, Dr. G. Guglielmina, and associate, H. Van der Loos, B. Finlay, H. Scheich, C. Ruela. Seated: S. Pallas, T. Lohmann, J. De Carlos, F. Valverde, G. Innocenti, M. Diamond v "Gathering" does not accurately describe what really happened.

During May 21-June 1 1990, the eleventh course of the International School of Pure and Applied Biostructure, a NATO Advanced Study Institute, was held at the Ettore Majorana Center for Scientific Culture in Erice, Italy, co-sponsored by the Italian Ministry of Universities and of Scientific and Technological Research, the North Atlantic Treaty Organization, the Italian National Research Council, the Sicilian Regional Government and Technobiochip. The subject of the course was "Molecular Basis of Human Cancer" with participants selected worldwide from 15 different countries. The purpose of the course was to address, in a tutorial and structural fashion, the molecular basis of human cancer, including the mechanism of signal transduction in mammalian cells, the genetic mechanism of malignant transformation in man, growth factors, hormone receptors, cell membrane and cytoskeleton, and DNA high order structure. The course had this as its major objective and the resulting book reflects it. The participants were exposed to a critical evaluation of current knowledge about cancer and to some of the key problems that remain as stumbling blocks to our eventual understanding of this important biological and medical problem. Through the media of formal and informal lectures, workshops, symposia and informal discussions, a select group of interested young and senior scientists were acquainted with many of the aspects of human cancer.

This book constitutes the proceedings of a NATO Advanced Research Workshop held at Chateau de Bonas (France) from 10-15 July 1990 on the Midbrain Periaqueductal Gray Matter (PAG). The aim of this meeting was to review and integrate our knowledge about the functional, anatomical and neuro­ chemical organization of the PAG. The PAG has been the subject of many investi­ gations during the last decade usually on different topics (e.g., pain modulation, defensive and sexual behavior) and generally there has been little interchange between the different research areas. The main purpose of this meeting was to bring together, for the first time, scientists who have worked on the PAG from different perspectives. This book does not pretend to present an exhaustive review of the data collected during the last 20 years of research on the PAG. The contributors to this book have been selected because their data provide key elements in the search to understand both the organization of the PAG and the role of this structure in the integration of behavior. We believe that this book will provide clues that will assist in unraveling the organization of the PAG in the coming years.

This volume is a summary of material presented in the course given in the International School of Phannacology on "Drug Epidemiology and Post-Marketing Surveillance" between September 27 and October 8, 1990, at the "Ettore Majorana Center for Scientific Culture" in Erice, Sicily. The course, which was a NATO Advanced Study Institute, included lectures and workshops presented by experts in the new field of phannacoepidemiology. The material covered includes various approaches to spontaneous reporting of adverse drug reactions, including aggregate approaches, such as those used in France, and detailed analyses of individual reports, such as that done in The Netherlands and in Sweden. Also, included are studies using traditional epidemiology methods. In addition, modern pharmacoepidemiology makes considerable use of automated databases. As such, information is presented on their use as well. Phannacoepidemiology started in hospitals and some of the newest work in the field is returning to the hospital as a site for studies. Material on these topics was presented as well. Finally, selected new methodologic developments were outlined in specific examples presented that were of regulatory and commercial importance. This new field of phannacoepidemiology is exploding in interest internationally. Evidence of this is the increasing development of pharmacoepidemiology programs in industry, medical schools, pharmacy schools, and schools of public health. Also, there is a new International Society ofPhannacoepidemiology. Practitioners in this field tend to specialize in either analyses of spontaneous reporting or the use of formal epidemiologic techniques.

This volume is the scientific chronicle of the NATO Advanced Research Workshop on Computational Aspects of the Study of Biological Macro­ molecules by Nuclear Magnetic Resonance Spectroscopy, which was held June 3-8, 1990 at Il Ciocco, near Barga, Italy. The use of computers in the study of biological macromolecules by NMR spectroscopy is ubiquitous. The applications are diverse, including data col­ lection, reduction, and analysis. Furthermore, their use is rapidly evolv­ ing, driven by the development of new experimental methods in NMR and molecular biology and by phenomenal increases in computational perfor­ mance available at reasonable cost. Computers no longer merely facilitate, but are now absolutely essential in the study of biological macromolecules by NMR, due to the size and complexity of the data sets that are obtained from modern experiments. The Workshop, and this proceedings volume, provide a snapshot of the uses of computers in the NMR of biomolecules. While by no means exhaustive, the picture that emerges illustrates both the· importance and the diversity of their application.

Playback is the technique of rebroadcasting natural or synthetic signals to animals and observing their response. The ability to present a putative signal in isolation, without the potential confounding effects of other activities of the signaller, is the main reason for the depth and range of our knowledge of communication systems. To date, playback of sound signals has predominated, but playback of electric signals and even video playback of visual signals suggests that playback will become just as prevalent in studies of communication in other sensory modalities. This book is one of the outcomes of a workshop on playback held at Thombridge Hall in the Peak District National Park, England during August 1991. There were two reasons for organising the workshop. First, the considerable and lively debate in the literature about the design and analysis of playback experiments -the pseudoreplication debate -was in danger of generating more heat than light. A workshop forum seemed the obvious place to clarify and, if possible, resolve the debate. Second, with the number of new playback and analysis techniques increasing rapidly, it seemed an opportune moment to discuss these techniques and to review some rapidly developing areas of interest in sound communication.

The papers contained in this book were presented at a NATO Advanced Research Workshop (ARW) held at Cape Sounion, Athens, Greece, 19-24 May, 1991. The twenty-eight more comprehensive papers represent the key subjects of the ARW covered by invited speakers. The thirty-four short papers pre­ sented in a research format are contributions of those invited to participate in the ARW. There was a total of 70 participants from 21 countries. The objectives of the ARW were as follows: to review current knowledge of biological control of plant diseases and plant parasitic nematodes, with emphasis on mechanisms at the molecular, cellular, organismal, and ecosystem level; to examine and expand on current concepts and synthesize new concepts; to identify and prioritize limitations in the use of biological control for plant diseases and nematodes and the scientific research needed to overcome these limitations; and to develop strategies for biological control through management of resident agents or introduction of natural or modified agents.

The NATO Advanced Research Workshop entitled "The Photosynthetic Bacterial Reaction Center: Structure, Spectroscopy, and Dynamics" was held May 10-15, 1992, in the Maison d'H6tes of the Centre d'Etudes Nuc1eaires de Cadarache near Aix-en-Provence in the south of France. This workshop is the most recent of a string of meetings which started in Feldafing (Germany) in March 1985, soon after the three-dimensional structure of the bacterial reaction center had been elucidated by X-ray crystallography. This was followed, in September 1987, by a workshop in Cadarache and, in March 1990, by a second meeting in Feldafing. Although one of the most important processes on Earth, photosynthesis is still poorly understood. Stimulated by the breakthrough of solving the bacterial reaction center structure at atomic resolution, the field of relating this structure to the function of the reaction center, i. e. the remarkably efficient conversion and storage of solar energy, has been developing vigorously. Once the general organization of the cofactors and some details of the protein-cofactor interactions were known, it became possible to combine a variety of spectroscopic techniques with the powerful tool of site-directed mutagenesis in order to address increasingly incisive questions about the specific role of some amino acid residues in the electron transfer process. Still another promising tool is being developed, namely the exchange of a number of the native bacteriochlorophyll and bacteriopheophytin cofactors by chemically modified pigments.

The disorders induced by iodine deficiency affect at least one billion people. Because ofits effects on brain development, iodinedeficiency is the single most preventable cause of mental retardation in the world. Therefore, the United Nations and the Heads of State of almost all the world's countries represented at the Summit for Children in 1990 adopted resolutions to eradicate the disorders induced by iodine deficiency (IDD) by the year 2000. For geological and socio-economic reasons, most of the populations affected by iodine deficiency disorders live in isolated and usually mountainous areas, in pre­ industrialized parts ofthe world. The problem of iodine deficiency in Europe has been greatly underestimated in the last decades. After the remarkable studies on the effects of iodine deficiency and their prevention and correction in Switzerland, IDD was generally considered no longer a significant public health problem in Europe. However, surveys carried out in the early 1980's under the auspices of the European Thyroid Association, clearly demonstrated the persistence of moderately or even severely affected areas. These surveys also highlighted the lack ofinformation about large parts ofEurope, especially its eastern part. It is only quite recently, following major changes in international relations and thanks to the support of UNICEF, WHO, the International Council for the Control of Iodine Deficiency Disorders and the European Thyroid Association, that more extensive surveys have been conducted in several parts of Europe hitherto almost unexplored. These surveys showed that most European countries were iodine deficient.