This book has its origin in my experience as a teacher of pharmacokinetics in many universities in four different continents. It was not my intention to write a popular book; what distinguishes this one from many others on the same subject is its large use of algebra and calculus. For this I make no apologies; in fact a serious study of pharmacokinetics without the help of mathematics is, in my opinion, impossible. The exact definition of many pharmacokinetic quantities, even the most common, and the correct use of many equations, even the most simple, requires the constant use of mathematical language. On the other hand I have made a considerable effort to use only elementary algebra and elementary calculus, as commonly taught in most introductory university courses. For the few exceptions, when less common mathematical concepts were needed, I have supplied the necessary explanations in four appendices. The first three chapters are a general introduction to the scientific method. Chapters 4 to 12 show different specific methods to deal with pharmacokinetic pr- lems. There is considerable overlap among those chapters; this is intentional and its p- pose is to convince the reader that every problem can be solved in more than one way, including ways that were not mentioned in this book and that intelligent readers can find for their own pleasure. Chapters 13 to 17 show how different parameters of importance in pharmacokinetics can be exactly defined and measured.

This book, written by a multidisciplinary team of authors comprising scientists, artists and communicators, explores one of the most pressing issues of our time - the menace plastics pose to marine environments and organisms. It takes readers on a journey that begins on the beaches of Galicia, where the beach litter formed the starting point for an exhibition that combines art and science to alert the audience to the urgent need for action. The journey culminates with a short "plastic story", which reveals a disturbing vision of the future significance of plastics for humans, and an example of how comics can deliver information to a younger audience. Along the way there is plenty of fascinating science, such as insights into the impacts of plastics and microplastics; the new marine ecosystem, known as the "plastisphere"; and the current status of the oceans, from the Arctic to the Mediterranean. The book also explores the historical developments; sustainable solutions, including the use of circular economy methodologies; and protective measures, like those being tried in China and the Far East. Lastly, it describes the role played by rivers as transport vectors for plastic, with special reference to the Danube, and to complete the picture, since most of the plastic is of terrestrial origin, it investigates problems related to microplastics in soils.

Physiologists have long been interested in the interaction, or coupling, between the heart and the vasculature. The early literature consists mainly of phenomenological descriptions of cardiac alterations resulting from specific interventions in the vasculature. Hundreds of studies, for example, describe functional aspects of hypertrophied myocardium associated with the excessive vascular loading produced by various types of experimental hypertension. Recently, the concepts of ventricular/vascular interaction have found important clinical application. The widespread use of vaso dilators and of intraaortic counterpUlsation balloons for unloading an ov erburdened, diseased heart is a prime example. Despite the interest in this field, until as recently as 20 years ago we were not able to describe ventricular or vascular function in a framework suitable for quantitatively expressing the interaction between these two complex systems. Three major developments-description of ventricular function in terms of both the time-varying elastance and the pump function graph and quantification of vascular function in terms of impedance have changed this. These functional descriptions now enable systems en gineers, bioengineers, physiologists, and clinicians to address very specific quantitative aspects of ventricular/vascular interaction and have resulted in a flurry of papers and symposia devoted to this subject."

As is true with most areas of Artificial Intelligence, there is real need for a symbiotic relationship between the biological and artificial - a need for problems to be viewed from many different angles, and particularly so in the study of vision. The INSIGHT consortium is taking steps in this direction. In a traditional sense, the papers in this volume are represented by the areas of neuroscience, psychophysics and traditional computer vision. However, to gain deeper insight into vision processes, it is the interaction of scientific ideas from these areas that is essential. The scope of the topics discussed has a definite interdisciplinary flavour: at one end of the spectrum we have experiments performed and direct measurement of the responses of neurons to visual stimuli; at the other end we have the mathematical and computational aspects of optical flow (the relative motion between observer and object) and approaches of tackling vision through binocular disparities (stereopsis). Traditional edge detection (essential for the initial classification of shape) is also covered as is the study of natural texture patterns that occur on object surfaces. A fundamental aim of the Basic Research part of the ESPRIT programme is the pro duction and maintenance of a pool of research expertise in Europe, from which both fur ther research and industry can draw. As the authors state in their preface, this project has not only succesfully merged the talents of senior researchers from different backgrounds, but also brought many young ones along."

The contents of this volume derive loosely from an EMBO worksh9P held at EMBL (Heidelberg) towards the end of 1989. The topic of Patterns in Protein Sequence and Structure attracted a wide range of participants, from biochemists to computer scientists, and that diversity has, to some extent, remained in the contributions to this volume. The problems of interpreting biological sequence data are to an increasing extent forcing molecular biologists to learn the language of computers, including at times, even the abstruse language of the computer scientists themselves. While, on their side, the computer scientists have discovered a veritable honey-pot of real data on which to test their algorithms. This enforced meeting of two otherwise alien fields has resulted in some difficulties in communication and it was an aim of the EMBO workshop to help resolve these. By the end, most biologists at the meeting had, at least, heard the terms Dynamic Programming and Regular Expression while for their part the computer programmers began to realise that protein sequences might be more than simple Markov chains in a 20-letter alphabet. Thanks to the modern facilities at EMBL, the three day meeting was video-taped and from this a transcript was taken and offered to the speakers as the basis for a contribution to this volume.

This book is more than a standard proceedings volume, although it is an almost direct result of the workshop on "Nonlinear Analysis of Physiologi cal Time Series" held in Freital near Dresden, Germany, in October 1995. The idea of the meeting was, as for previous meetings devoted to related topics, such as the conference on dynamical diseases held near Montreal in February 1994 (see CHAOS Vol. 5(1), 1995), to bring together experts on the techniques of nonlinear analysis and the theory of chaos and applicants from the most fascinating field where such methods could potentially be useful: the life sciences. The former group consisted mainly of physicists and mathe maticians, the latter was represented by physiologists and medical researchers and practitioners. Many aspects of this workshop were unusual and not previously expe rienced. Also, the hosting institution, the Max Planck Institute for Physics of Complex Systems (MPIPKS), at this time was brand new. The organiz ers' rather unconventional intention was to bring specialists of both groups together to really work together. Therefore, there was an excessive availabil ity of computers and the possibility to numerically study time series data sets practitioners had supplied from their own fields, e. g. electrocardiogram (ECG) data, electroencephalogram (EEG) data, data from the respiratory system, from human voice, human posture control, and several others. These data formed a much stronger link between theoreticians and applicants than any of the common ideas."

Insects as a group occupy a middle ground in the biosphere between bacteria and viruses at one extreme, amphibians and mammals at the other. The size and general nature of insects present special problems to the student of entomology. For example, many commercially available instruments are geared to measure in grams, while the forces commonly encountered in stUdying insects are in the milligram range. Therefore, techniques developed in the study of insects or in those fields concerned with the control of insect pests are often unique. Methods for measuring things are common to all sciences. Advances sometimes depend more on how something was done than on what was measured; indeed a given field often progresses from one technique to another as new methods are discovered, developed, and modified. Just as often, some of these techniques find their way into the classroom when the problems involved have been sufficiently ironed out to permit students to master the manipulations in a few laboratory periods. Many specialized techniques are confined to one specific research laboratory. Although methods may be considered commonplace where they are used, in another context even the simplest procedures may save considerable time. It is the purpose of this series (1) to report new developments in methodology, (2) to reveal sources of groups who have dealt with and solved particular entomological problems, and (3) to describe experiments which may be applicable for use in biology laboratory courses.

Biologic System Evaluation with Ultrasound is a reference book for engineers in the field of ultrasonics and is intended to inform those unfamiliar with current methods of ultrasonic analysis. Explaining the mathematical and physical principles of ultrasound imaging of living tissue with effective precision, the book encompasses the following topics: relationships between the biological and scattering hierarchies; graphic description of scattering; class 1,2,3,4 scattering and their association with the biological hierarchy; instruments used for biologic system evaluation; computed tomographic methods of imaging. The authors have provided an effective explanation of the ultrasound scattering of image and image acquisition that will benefit engineers, physicists, and radiologists alike.

The past two decades have witnessed an unprecedented growth in the field ofneuroendocrinology. The conjoint research contributions by clinicians and basic scientists have promulgated revolutionary concepts at a breakneck speed. This first volume in Clinical Surveys in Endocrinology, The Pituitary Gland, has been written with but one purpose in mind: to integrate the current knowledge in this dynamic field with the existing body of information already available to the clinician. The chapters in this book attempt to portray current research information seen through the eyes of a clinician. The contributions of pioneers in each field have been placed in a perspective relevant to the practicing endocrinologist. The selection of the almost 1500 references from a bewil of literature has been inftuenced by the degree to which these dering body articles-original as weil as review papers-contributed to the growth of pi tuitary endocrinology. Despite the most scrutinizing attempts, it is inevitable and regrettable that works of importance must be excluded due to the practical limitations of any comprehensive work. Nevertheless, to the researcher these references are complete enough to serve as a significant resource. To the reader who wishes to gain an indepth clinical perspective of pituitary disor ders, this work is written precisely from that vantage point. The single authorship of this work notwithstanding, several friends have been instrumental in the completion of this work. I deeply appreciate the incessant zeal and excellent assistance of Ms."

Various kinds of mineralization have been found in many biological systems. Investigations made at a microscopical level using various sophisticated analytical methods and using principles developed in different fields have clarified their mechanisms very much. Sometimes, very similar phenomena have been found in the mineralized tissues of completely different biological systems. Compilation and comparative investigations of such findings obtained from the many specimens systematically collected contribute a great deal to an understanding of the crucial mechanisms and significance of biominerali zation which originated in very primitive organisms and remain in advanced ones. Previously, the functional significance of mineralized tissues was considered mainly from an anatomical point of view based upon their morphological and structural features. However, the recent advance of investigations has made it possible to interpret the func tional significance of biomineralization not only from local and mechanical points of view, but also from a systemic and phylogenetic point of view. It is also well-known that biomineralization has contributed in various ways to geological and oceanographical conditions of the environment in which the organisms were living. During this process, the mechanisms of biomineralization may have evolved to maintain harmony between organisms and their environments."

Recently, there have been significant advances in the fields of high-enthalpy hypersonic flows, high-temperature gas physics, and chemistry shock propagation in various media, industrial and medical applications of shock waves, and shock-tube technology. This series contains all the papers and lectures of the 19th International Symposium on Shock Waves held in Marseille in 1993. They are published in four topical volumes, each containing papers on related topics, and preceded by an overview written by a leading international expert. The volumes may be purchased independently.

This Advanced Study Institute was arranged to discuss in depth the physical and technical basis of the latest developments in methods of measurement and image analysis suitable for determining the prop erties of cells and tissues and for evaluating medical structures. All topics under consideration have benefitted dramatically from an injection of new ideas during the past 10 years, and some have developed even more recently. The Institute brought together lecturers and participants from 14 different countries, and the subject matter recorded in this volume may be considered under two general headings. The first part of the meeting concentrated on techniques that are most appropriate at the cellular level. One major area of develop ment has been centered on attempts to classify cells by computerized ex traction of visual features, and here, it was notable how different techniques frequently complement each other. This part of the meeting also examined mechanisms of damage at the cellular level caused by different forms of radiation, and the contrasting effects of ionizing radiation, ultraviolet light and ultrasound were highlighted.

Advances in Comparative and Environmental Physiology helps biologists, physiologists, and biochemists keep track of the extensive literature in the field. Providing comprehensive, integrated reviews and sound, critical, and provocative summaries, this series is a "must" for all active researchers in environmental and comparative physiology.

Many novel cooperative phenomena found in a variety of systems studied by scientists can be treated using the uniting principles of synergetics. Examples are frustrated and random systems, polymers, spin glasses, neural networks, chemical and biological systems, and fluids. In this book attention is focused on two main problems. First, how local, topological constraints (frustrations) can cause macroscopic cooperative behavior: related ideas initially developed for spin glasses are shown to play key roles also for optimization and the modeling of neural networks. Second, the dynamical constraints that arise from the nonlinear dynamics of the systems: the discussion covers turbulence in fluids, pattern formation, and conventional 1/f noise. The volume will be of interest to anyone wishing to understand the current development of work on complex systems, which is presently one of the most challenging subjects in statistical and condensed matter physics.

The concept of this book was developed during the Winter Seminar held in the Austrian mountains at the Alpengasthof Zeinisjoch, Tirol-Vorarlberg, from February 27 to March 3, 1988. Leading experts and advanced students in math ematics, physics, chemistry and computer science met to present and discuss their most recent results in an informal seminar. These were the circumstances that led to the idea of compiling some of the essential contributions presented at this seminar together with others describing basic features of "optimal struc tures in heterogeneous reaction systems". The aim of this book is to present the scientific results of the intensive work carried out in each of the specific fields of research. Each contribution therefore presents the current state of the art together with a deeper treatment enabling a more comprehensive understanding of that particular field of work. The common ideas which unite all the different contributions are already ex pressed in the title of this book. The nature of heterogeneous reaction systems is quite varied. An example is provided by the chemical systems such as noble metal particles which may act as heterogeneous catalysts for gaseous chemical compounds. Under these circumstances the metal particles and/or their sur faces may undergo phase transitions during reaction. Imbihl and Plath report on special catalytic systems of this kind, which are of industrial importance.

This book consists of papers presented at an international symposium spon sored and organised by The Rank Prize Funds and held at The Royal Society, London, on 27-29 September, 1982. Since the inception of the Funds, the Trustees and their Scientific Advi sory Committee on Opto-e1ectronics have considered that the scope of opto electronics should extend to cover the question of how the eye transduces and processes optical information. The Funds have aimed to organise symposia on topics which, because of their interdisciplinary nature, were not well cov ered by other regular international scientific meetings. It was therefore very appropriate that the 1982 symposium should be on Physical and Biologi cal Processing of Images. The purpose of the symposium was to bring together scientists working on the physiology and psychology of visual perception with those developing ma chine systems for image processing and understanding. The papers were planned in such a way as to emphasise questions of how image-analysing systems can be organised, as well as the principles underlying them, rather than the detailed biophysics and structure of sensory systems or the specific design of hardware devices. As far as possible, related topics in biological and artificial sys tems were considered side by side."

Scientists challenging dominant paradigms are either ignored or attacked by the scientific mainstream. This book, however, contains a selection of scientific papers presented at the two last GIRI meetings (International Research Group on Very Low Dose and High Dilution Effects). The majority of these papers present results performed with succussed high dilutions (homeopathic dilutions), even beyond the Avogrado number. All presented models are classified, and their interpretation is possible either in the mechanistic paradigm or in an information paradigm. This new field of research introduces new scientific concepts which are supported by experimental results. Furthermore, this nascent science is totally concerned with living organisms and, as such, it becomes necessary to define `information' brought by non-molecular high dilutions. This book presents brain-storming work of this research group and is one of the starting points of a scientific evolution.

There are probably few people who do not dream of the good old times, when do ing science often meant fascination, excitement, even adventure. In our time, do ing science involves often technology and, perhaps, even business. But there are still niches where curiosity and fascination have their place. The subject of this book, technological as its title may sound, is one of the fortunate examples. It will report on lasers generating the coldest places in the Universe, and on table top laser microtools which can produce a heat "inferno" as it prevails in the interior of the Sun, or simulate, for specific plant cells, microgravity of the space around our plan et Earth. There will be some real surprises for the reader. The applications range from basic studies of the driving forces of cell division (and thus life) via genetic modification of cells (for example, for plant breeding) to medical applications such as blood cell analysis and finally in vitro fertilization. What are these instruments: laser microbeams and optical tweezers? Both are lasers coupled with a fluorescence microscope. The laser microbeam uses a pulsed ultraviolet laser. Light is focused, as well as possible, in space and time, in order to obtain extremely high light intensities - high enough to generate, for a very short instant, extremely hot spots which can be used to cut, fuse or perforate biological material."

Because of their ability to differentiate and develop into functional vasculature, stem cells hold tremendous promise for therapeutic applications. However, the scientific understanding and the ability to engineer these cellular systems is still in its early stages, and must advance significantly for the therapeutic potential of stem cells to be realized. Stem cell differentiation and function are exquisitely tuned by their microenvironment. This book will provide a unique perspective of how different aspect of the vasculature microenvironment regulates differentiation and assembly. Recent efforts to exploits modern engineering techniques to study and manipulate various biophysical cues will be described including: oxygen tension during adult and embryonic vasculogenesis (Semenza and Zandstra), extracellular matrix during tube morphogenesis and angiogenesis (Wirtz, Davis, Ingber), surface topography and modification (Chen and Gerecht), shear stress and cyclic strain effect on vascular assembly and maturation (Vunjak-Novakovic and Niklason), and three dimensional space for angio-andvasculogensis (Ferreria and Fischbach).

"Methods in Protein Sequence Analysis - 1988" - contains selected contributions on modern protein- analytical techniques as presented by speakers at the Seventh International Conference on "Methods in Protein Sequence Analysis," held from July 3rd to July 8th, 1988 in Berlin. The book contains information on new methodologies for sensitive amino acid analysis, N- and C-terminal sequence analysis, and protein and peptide purification. In addition recent mass spectrometric approaches are described, as an alter native technique to the common stepwise degradative sequence analysis of polypeptides by the Edman method. The book presents new possibilities in the design of sequencers and sophisticated equipment for the structural analysis of peptides and proteins. It describes practical approaches for the investigation of protein domains and protein complexes, and contains review chapters on the crystallization of cell organelles as well as on recent theoretical aspects of protein folding mechanisms. The nature of protein folding is not yet understood, but further advances in this area would greatly enhance our present knowledge of protein structure and function. Further, the book gives examples of the application of gene technology to protein characterization and to the design of new proteins. This enables new studies on the structure and function of proteins to be made, and opens up efficient approaches to the design of drugs."

On July 10, 1980, Kenneth S. Cole became 80 years old. In order to celebrate this landmark, a symposium in the form of a series of Monday evening lectures was held in his honor at the Marine Biological Labora tory throughout the summer of 1980. The selection of speakers was made from among those investigators who had been either his students or co-workers. One intent of the symposium was to examine the current status of knowledge of those areas of interest in excitable membrane structure and function that owe their initiation or encouragement to Kacy Cole. The papers assembled in this volume represent a large majority of the presentations given during the 1980 Cole Symposium. It seems clear on examination of these papers that Kacy's interests in membrane impedance, ion channel conductances, channel fluctuation phenomena, excitation, and the development of membrane biophysical methodology are all being actively pursued. It is also clear that many of his suggestions have borne fruit. Of these, his invention of the voltage v vi Preface clamp method has been most productive. It is hoped that these papers will provide new directions for investigations into the nature of excitable membrane phenomena. The organizers of the symposium and the editors of this volume wish to express their thanks to the Marine Biological Laboratory for making available the facilities for the symposium. They also wish to thank Dr.

This volume, The Adrenal Gland, is the second in the Clinical Surveys in Endo crinology series. Like its predecessor on the pituitary gland, this work is written with one purpose in mind-to view the vast, relevant adrenal literature through a clinician's eyes. The intricate, and often complex, interrelationship between the clinical and research perspectives of "adrenology" poses a challenge. This is, in part, due to the commonly held belief that the milieux of steroid hormone research and clinical medicine are parallel phenomena, not destined to meet. But the twain do meet, and often with relative ease, when viewed as twin facets of the same gem. The view presented in this work is from the vantage point of the clinical endocrinologist who applies the research literature to understand adre nal diseases more clearly. Adrenal pathology is arguably the most fascinating of all endocrinopathies. The images of patients suffering from adrenal diseases are of kaleidoscopic quality: the newborn child with ambiguous genitalia, in whom the very first ritual of assigning sex becomes shrouded with uncertainty; the revitalized pa tient with hitherto undiagnosed Addison's disease, who but for the cognitive powers of the endocrinologist would have ultimately succumbed, undiagnosed; the virilized female with adrenal tumor and its attendant onslaught on the body and mind; the febrile patient with pheochromocytoma masquerading as fever of undetermined origin for months."

This book attempts to combine many different threads into a comprehensible whole. Since the subject is the Gamma Knife and the author is a neurosurgeon, the field of clinical interest is restricted to intracranial pathology. The discipline of radiosurgery now applies to patients who may reasonably be referred by internists, neurologists, otolaryngologists, endocrinologists and several others. Some of the topics, touched upon, such as stereotaxy and the construction of a radio surgical instrument are unfamiliar to the majority of medical men. Other topics, such as those pertaining to the reactions between radiation and living tissue, are not exactly unfamiliar and yet, for most of us, they are not comfortable areas of expertise: in that we have some basic knowledge but not enough to draw conclusions and interpret. In particular, it is not easy to answer the very sensible questions that patients ask, when being considered for this particular form of treatment. The author has attempted to describe the basic relevant phenomenology in terms that should be readily understandable to a non-specialist physician. To do this, he has been heavily dependent on the expertise of a number of mathematically sophisticated collaborators, who have checked his manuscript. They are named in the acknowledgments section. The relevance of the different sections of this book will naturally be assessed differently, according to the experience and interest of the reader. To simplifY access to the information that is required, the book is divided into three main sections.

Biophysical Chemistry: Molecules to Membranes is a one-semester textbook for graduate and senior undergraduate students. Developed over several years of teaching, the approach differs from that of other texts by emphasizing thermodynamics of aqueous solutions, by rigorously treating electrostatics and irreversible phenomena, and by applying these principles to topics of biochemistry and biophysics. The main sections are: (1) Basic principles of equilibrium thermodynamics. (2) Structure and behavior of solutions of ions and molecules. The discussions range from properties of bulk water to the solvent structure of solutions of small molecules and macromolecules. (3) Physical principles are extended for the non-homogenous and non-equilibrium nature of biological processes. Areas included are lipid/water systems, transport phenomena, membranes, and bio-electrochemistry. This new textbook will provide an essential foundation for research in cellular physiology, biochemistry, membrane biology, as well as the derived areas bioengineering, pharmacology, nephrology, and many others.