Biomechanics has a distinguished history extending at least to the 16th Century. However the later half oftbis century has seen an explosion ofthe field with it being viewed as affering exciting challenges for physical scientists and engineers interested in the life sciences, and wonderful opportunities for life scientists eager to collaborate with physical scientists and engineers and to render their scientific work more fundamental. That the field is now weil established and expanding is demonstrated by the formation of a World Committee for Biomechanics and the success and large participation in the 1st and 2nd World Congresses of Biomechanics, held respectively in San Diego in 1990 and in Amsterdam in 1994. With more than 1350 scientific papers delivered at the 2nd World Congress, either within symposia or oral or poster sessions, it would have been out of the question to try to produce comprehensive edited proceedings. Moreover, we are confident that most of the papers have been or will be published in one ofthe excellentjoumals covering the field. But of effort contributed by the plenary lecturers and the tutorial we thought that the large amount and keynote speakers of various symposia deserved tobe recognised in the form of a specific publication, thus also allowing those unable to attend the presentatiops . . tC\ sh?r~ in the findings. Furthermore, we feel that there is now a need to review aspects 'oftlie freld.

Originally published in 1948, this book covers the main papers published on animal colour changes between 1910 and 1943. It is a continuation of the work of van Rynberk and Fuchs, who produced important reviews of the topic in 1906 and 1914 respectively. During the period covered, the topic underwent a considerable growth in interest. This is reflected in a bibliographical list of over 1200 items at the end of the text, over twice the number given by Fuchs for the whole period up to 1914. Containing rigorous analysis and illustrations throughout, this book will be of value to anyone with an interest in chromatophores and the history of science.

Over the last twenty years there has been an explosive growth in our understanding of the molecular, cellular, and anatomical changes that occur in the days and weeks following brain injury. It is now clear that training and exposure to certain environments can modify and shape neuronal plasticity in lower animals and humans. In humans, in particular, there are new ways of charting neuronal plasticity at the ensemble or regional level using functional neuroimaging techniques such as positron emission tomography and functional magnetic resonance imaging. Thus, the time seems right for transporting the laboratory results to the clinic so that experimental findings can be tested in the "field." This volume provides some impetus to moving the field of cognitive neuroscience a little further in its efforts to improve the lives of patients who have suffered a debilitating brain injury.

Once Nietzsche said that human beings may be divided into two categories: Apollonians and Dionysians*. By this the philosopher meant that there are human beings a) who know what they are going to do in the long-term future (what we now call the grant application for the next 5 years), i. e. , Apollonians, and b) who barely know what they are going to do tomorrow morning before breakfast, i. e. , Dionysians. ** To organize a symposium, this symposium in particular, a committee had to be formed either of individuals sharing both Nietzschean characteristics or of individuals possessing either characteristic. Considering the rarity of the former type of subject, this organizing committee was spontaneously formed by a typical sample of both types of individuals. We first met in Perugia in 1988. Those of us who were Apollonians had thus a chance to organize a programme. The Dionysians knew what was going to happen to them, but, of course, did not know yet how to cope with it. They duly did so every day of the meeting, after breakfast. The organizers decided that it would be a useful exercise to assemble experts having different perspectives but all pursuing a very rapidly developing aspect of cell biology. They also hoped that these selected Apollonians and Dionysians would not merely recount their results but try to project the future through active interchanges of ideas and opinions with other attendees.

In the last two decades, our knowledge on regulatory peptides and their cognate receptors, most of which are members of the seven transmembrane receptor families, has increased enormously. Regulatory peptides are small proteins which, besides their hormonal functions in regulating cellular metabolism in various tissues, may also act as neurotransmitters, and thus they often carry the prefix "neuro." Many of the cognate receptors involved in transducing the peptidergic signal across the cell membrane via a family of G proteins exist in multiple forms, the number of which frequently exceeds that of the corresponding peptide ligands. In this book, various peptide-receptor systems are discussed, e.g. CRF, somatostatin, TRH, opioid peptides, vasopressin, and oxytocin. It also discusses new strategies such as "reverse physiology" to uncover new peptides and orphan receptors.

This book deals with information processing in the primate temporal visual cortex, one of the higher visual association areas, which is believed to be important for the representation of complex stimuli and may also play a role in visual memory. Here, the need for rapid information processing shapes the functional architecture of all sensory systems, acting to reduce, where possible, wiring length and the number of synapses, to allow faster processing.

This book presents the latest in mammary gland transgenesis, the exploitation of transgenic technology for the production of therapeutic proteins by routine or conventional methods. Following a section with an overview of all relevant methodologies, readers will find relevant information on the regulation of milk gene expression and bioreactor species such as cattle, rabbits and pigs.

The annual Congress of the Italian Biochemical and Molecular Biology Society (SIB) was held in September 1999 in Alghero, Sardegna, Italy. The programme envisaged a symposium on molecular adaptations of haemoglobin function in ver- tebrates. Haemoglobin specialists from several countries were invited to speak at the symposium and paved the way for wide-ranging and stimulating discussions. The symposium contributions have been collected together in this volume. The structure/function relationship in haemoglobins from vertebrates (fishes populat- ing temperate and polar environments, diving birds, marine and terrestrial mam- mals) has been tackled from many angles, focusing on the adaptation of the oxy- gen-transport system to the constraints dictated by the environment. Eleven arti- cles review some of the most recent developments of the studies on this ancient oxygen-transport protein, characterized by high conservation during evolution. The volume offers the reader an updated, state-of-the-art summary of a field that is enjoying a true renaissance. Covering the topic from several viewpoints, the volume includes protein chemistry (amino acid sequence, secondary, tertiary and quaternary structures, thermodynamics of oxygen-binding features), molecular biology (globin gene structure, sequence, organization, expression and regulation) and evolution. In this representation of effective multidisciplinary and multina- tional collaborative efforts, reference is available to a wide range of disciplines and biological systems. The tools of the investigators comprise advanced and powerful methodologies developed in recent years, e. g.

Environmental conditions change considerably in the course of 24 h with respect to abiotic factors and intra- and interspecific interactions. These changes result in limited time windows of opportunity for animal activities and, hence, the question of when to do what is subject to fitness maximisation. This volume gives a current overview of theoretical considerations and empirical findings of activity patterns in small mammals, a group in which the energetic and ecological constraints are particularly severe and the diversity of activity patterns is particularly high. Following a comparative ecological approach, for the first time activity timing is consequently treated in terms of behavioural and evolutionary ecology, providing the conceptual framework for chronoecology as a new subdiscipline within behavioural ecology. An extensive Appendix gives an introduction to methods of activity modelling and to tools for statistical pattern analysis.

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.

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 is a compilation of the lectures and oral and poster communications presented at the Advanced Study. Institute on "Vascular Endothelium: Physiological Basis of Clinical Problems II," which took place between June 20 and 30, 1992 in Rhodes, Greece. This third in a series of ASIs on vascular endothelium continued on the theme of the first (1988) ASI on "Receptors and Transduction Mechanisms" and particularly expanded that of the 1990 conference on ''Physiological Basis of Clinical Problems. " We continued the successful practice of bringing together clinicians and scientists: this was reflected equally well in the composition of the organizing committee as in the background of the particiJ?ants. Endothelial cell functions and dysfunctions present as many challenges to the mvestigator as they do to the curious clinical practitioner. As these problems are necessarily different, this unique ten-day co-habitation of these individuals continued to offer fresh outlooks to each, stimulated potential collaborative efforts and, most importantly, advanced --ever so slightly--our knowledge of vascular biology. This year's conference was further enriched by the presence of several of our colleagues from Eastern Europe whom we are delighted to welcome as officially sponsored participants to this and future NATO-supported meetings. It is never superfluous to remind readers and participants that those signing at the bottom of this page, while responsible for many of the ASI's and the book's deficiencies, are but three of the many contributors to the successes.

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.

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.

The body of any animal can be viewed as a society or ecosystem whose individual members are cells, reproducing by cell division and organized into collaborative assemblies or tissues. In this ecosystem, the cells are born, live and die under various forms of selection pressure such as territorial limitation, population size, source of nutrients provided, infectious agents, etc. The body is a highly organized society of cells whose main task is the maintenance of homeostasis of the whole organism. The failure of control mechanisms which make the cell the unit of society, marking the beginning of its asocial behaviour, is most frequently a malignant alteration. This process is not abrupt, nor is it based on a single event. It is, rather, a long-term process characterized mainly by mutation, competition and natural selection operating within the population of cells. The basic mechanisms controlling the cell sociability represent the first defence line against the altered cells, while the second line of defence is supposed to be made up of the immune system cells.Speaking in Darwinian terms, within the ecosystem of an organism, cells of the immune system operate as predators of the altered and mutated cells or cells infected by the intracellular parasites. The biological phenomena whose mechanisms are, at present, explored and largely understood, certainly had their own evolution. Searching for the origin and details of the evolution of advanced solutions as well as selection pressures that might justify their emergence and existence, we often fail to see that many such phenomena are, in fact, co-evolutionary by-products of evolutionary innovations. In other words, the evolutionary emergence of advanced solutions is sometimes, if not always, accompanied by certain by-products and by the co-evolution of compensatory mechanisms acting as a counterbalance to these. An example of the evolution of advanced solutions is the evolution of adoptive immunity, and co-evolution of auto-immunity and alloimmunity. Alongside the diversification of the mechanisms of adoptive immunity, auto-immunity and alloimmunity gain attributes of the evolutionary by-products and become sources of selection pressure.To that effect, alloimmunity could be a source of very strong selection pressure in mammals, simply because it is directly connected with the reproductive efficacy. At the same time, new forms of selection pressure that are connected with adoptive immunity gave rise to new mechanisms controlling killer machinery of the immune system. Finally, the last in a line of by-products in the processes of evolutionary modelling and re-modelling of vertebrate immune systems can be regarded as the failure of anti-tumor immunity. There is now much evidence that tumors can be immunogenic. Tumor cells very often express antigens in a form recognizable by the host immune system, but most frequently without consequences on tumor progression. This has been shown in many experimental models and different experimental conditions. Immediate mechanisms for the escape of tumors from the immune response are very similar to mechanisms for the escape of the fetoplacental unit (as allograft) from the maternal immune response. The similarity between these two mechanisms is so significant that any randomness must be banished.Mechanisms of anti-tumor immunity in mammals are probably substantially different from mechanisms of anti-tumor immunity in other classes of vertebrates. Moreover, the type of most frequent tumors in non-mammalian vertebrates is also significantly different. Finally, the incidence of malignant tumors in non-mammalian vertebrates is significantly lower than the incidence of malignant tumors in mammals. These facts indicate that the mammalian immune system during the anti-tumor immune response is tricked by the similarity between tumor cells and trophoblast or other placental cells. From this aspect, anti-tumor immunity failure in mammals can be defined as an immunoreproductive phenomenon, which is developed under the evolutionary pressure of auto-immunity and alloimmunity/reproductive effectiveness. It may be a specific evolutionary approach in the rendering of anti-tumor immunity failure in mammals, and a new possibility for anti-tumor immunotherapy.

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.

How does the brain code and process incoming information, how does it recog nize a certain object, how does a certain Gestalt come into our awareness? One of the key issues to conscious realization of an object, of a Gestalt is the attention de voted to the corresponding sensory input which evokes the neural pattern underly ing the Gestalt. This requires that the attention be devoted to one set of objects at a time. However, the attention may be switched quickly between different objects or ongoing input processes. It is to be expected that such mechanisms are reflected in the neural dynamics: Neurons or neuronal assemblies which pertain to one object may fire, possibly in rapid bursts at a time. Such firing bursts may enhance the synaptic strength in the corresponding cell assembly and thereby form the substrate of short-term memory. However, we may well become aware of two different objects at a time. How can we avoid that the firing patterns which may relate to say a certain type of move ment (columns in V5) or to a color (V 4) of one object do not become mixed with those of another object? Such a blend may only happen if the presentation times be come very short (below 20-30 ms). One possibility is that neurons pertaining to one cell assembly fire syn chronously. Then different cell assemblies firing at different rates may code different information."

Scientific advances over the past two decades have afforded unprecedented oppor tunities to understand the structure and function of receptors, receptor-ligand interactions, and receptor signaling. The extent ofprogress in this area is underscored by the recent Nobel Prize for Medicine and Physiology to Alfred Gilman and Martin Rodbell, both of whose work in understanding receptorlG-protein interactions has redefined the way in which we think of how hormones and neurochemicals exert their activity on cellular function. This book is replete with examples of current research approaches to help us better understand the cellular roles in which the renin-angiotensin system and the angiotensin receptors participate. Clearly, defining the structure of angiotensin receptor subtypes is an important first step in cJarifying the mechanisms by which these receptors take part in cellular function. However, the chapters within this book range far beyond structural studies and encompass research on tissue specific expression of the angiotensin receptor subtypes, the genetic regulation ofthese receptors, and the unique function ofvarious angiotensin subtypes in different organ systems, such as the brain, the reproductive system, adipose tissue, the heart, and the kidneys."

'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.

Recent progress in recombinant DNA technology and the availability of a number of nonpeptide subtype-specific receptor antagonists and of specific antibodies to components of prorenin-renin-angiotensin system (PRAS) have led to rapid advances in the under standing of the multifaceted role of angiotensin II, classically known as a peptide hormone of cardiovascular homeostasis. Accumulating evidence sug responsible for the regulation gests that, in addition to its role in salt and water metabolism, PRAS may control other physiological functions including neurosecretion, cellular proliferation, hypertrophy and/or differentiation, angiogenesis and gonadal function. At the same time, it is becoming evident that the specialized functions of endocrine glands are not only regulated by trophic hormones but also by locally produced paracrine/autocrine factors. The concept is emerging that tissue PRAS is one such locally active regulatory system. With more and more reproductive and endocrine organs being added to the list of tissues that contain a local tissue PRAS, questions are being raised by the reproductive biologists and endocrinologists as to the role of such systems in the tissues of their interest. On the other hand, the cardiovascular and renovascular physiologists are wondering about the relevance of PRAS in various peripheral tissues compared to those of the classical cardiovascular organs. It appeared, therefore, that the time was ripe for a meeting to consider a merger of interest in these two important but heretofore distinct areas of physiology."

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).

Here is the first effort in a single volume to cover all of the integrative functions of calcium signalling - how changes in intracellular calcium coordinate a variety of coherent cellular responses. Written by a team of internationally established researchers, Integrative Aspects of Calcium Signalling provides the latest experimental data and concepts, bringing together a detailed analysis of the events, processes, and functions regulated by calcium signalling. A unique resource for professionals and students of physiology, biophysics, neurobiology, biochemistry, and all related fields.

Although there is general agreement that exogenous electric and electromagnetic fields influence and modulate the properties of biological systems. there is no concensus regarding the mechanisms by which such fields operate. It is the purpose of this volume to bring together and examine critically the mechanistic models and concepts that have been proposed. We have chosen to arrange the papers in terms of the level of biological organization emphasized by the contributors. Some papers overlap categories. but the progression from ions and membrane surfaces. through macromolecules and the membrane matrix to integrated systems. establishes a mechanistic chain of causality that links the basic interactions in the relatively well understood simple systems to the complex living systems. where all effects occur simultaneously. The backgrounds of the invited contributors include biochemistry. biophysics. cell biology. electrical engineering. electrochemistry. electrophysiology. medicine and physical chemistry. As a result of this diversity. the mechanistic models reflect the differing approaches used by these disciplines to explain the same phenomena. Areas of agreement define the common ground. while the areas of divergence provide opportunities for refining our ideas through further experimentation. To facilitate the interaction between the different points of view, the authors have clearly indicated those published observations that they are trying to explain. i.e. the experiments that have been critical in their thinking. This should establish a concensus regarding important observations. In the discussion of theories.

Proteins are still gaining importance in the pharmaceutical world, where they are used to improve our arsenal of therapeutic drugs and vaccines and as diagnostic tools. Proteins are different from "traditional" low-molecular-weight drugs. As a group, they exhibit a number of biopharmaceutical and formulation problems. These problems have drawn considerable interest from both industrial and aca demic environments, forcing pharmaceutical scientists to explore a domain previ ously examined only by peptide and protein chemists. Biopharmaceutical aspects of proteins, e.g., low oral bioavailability, have been extensively investigated. Although all possible conventional routes of ad ministration have been examined for proteins, no real, generally applicable alter native to parenteral administration in order to achieve systemic effects has yet been discovered. Several of these biopharmaceutical options have been discussed in Volume 4 of this series, Biological Barriers to Protein Delivery. Proteins are composed of many amino acids, several of which are notorious for their chemical instability. Rational design of formulations that optimize the native structure and/or bioactivity of a protein is therefore of great importance when long shelf life is required, as it is for pharmaceutical products. This issue has also been examined in two prior volumes of this series: Volume 2: Stability of Protein Pharmaceuticals (Part A) and Volume 5: Stability and Characterization of Protein and Peptide Drugs.

Since programmed cell death was first described in insects in 1964 and apoptosis was described in 1972, rapid progress has been made in understanding the basic mechanisms and genes regulating programmed cell death and apoptosis. In addition, defects in various genes regulating programmed cell death have been delineated in several experimental models of human diseases. This volume surveys various aspects of these rapidly developing areas of research in programmed cell death/apoptosis. This volume should be of interest to basic immunologists and molecular biologists. The volume begins with a historical perspective of cell death. The remainder of the volume is divided into four different parts. Part I deals with the signaling pathways in apoptosis, including cell cycle control of apoptosis, role of ceramide in apoptosis, role of antibody signaling, and biochemical regulation of apoptosis. The mechanisms for recognition of apoptotic lymphocytes by macrophages are also reviewed. Part II examines the role of various genes that regulate apoptosis, including the role ofFas, FasL, and other TNF family members in apoptosis and homeostatic regulation of immune response. Recently described splice variants and their influence on apoptosis are also reviewed, and the role of the members of the Bcl-2 family in apoptosis is discussed in detail. Part III reviews various aspects of apoptosis in B lymphocytes, including mechanisms that regulate apoptosis/survival of B lymphocytes and the regulation of Fas-mediated apoptosis in B lymphocytes.