Since oxygen is mainly transported by diffusion within tissue, the oxygen pressure field reflects the local balance between oxygen supply and oxygen consumption and characterizes the state of oxygen supply. Despite large physiological varia- tions (e. g. , hypo-and hyperoxia, hypo-and hypertension, change of energy de- mand), this oxygen pressure field can remain remarkably constant, demonstrating that very effective mechanisms must exist that guarantee the adequacy of oxygen supply. Today, it is possible to describe in detail the responsible effector mecha- nisms that produce such a stable state of oxygen supply, but our knowledge of the reactions that sense tissue oxygen supply and trigger the regulatory responses is still incomplete. Since such knowledge is essential for understanding the system of oxygen supply and the way in which it has developed during evolution, even small progress is important. In this book the important O sensor reactions are discussed as they occur in 2 cells, organs, and organ systems. This broad approach gives an excellent picture of the actual state of knowledge in this field. Professor Dr. D. W. Lubbers Contributors Acker, H. Max-Planck-Institut fUr Systemphysiologie, Rheinlanddamm 201, 4600 Dortmund 1, FRG Bassenge, E. Institut fUr Angewandte Physiologie der Universitat Freiburg, Hermann-Herder-Stral3e 7, 7800 Freiburg, FRG Bingmann, D. Poliklinik fUr zahnarztliche Chirurgie, Universitat Mainz, Augustusplatz 2, 6500 Mainz, FRG Bauer, C. Physiologisches Institut, Universitat Zurich, Winterthurerstral3e 190, 8057 Zurich, Switzerland Busse, R. Institut fUr Angewandte Physiologie, Universitat Freiburg, Hermann-Herder-Stral3e 7, 7800 Freiburg, FRG Delpiano, M. A.

This book was written by many outstanding investigators who have spent decades to study different aspects of blood-tissue barrier function. They have summarized some of the latest and fascinating development in their fields of research including the blood-brain barrier, the blood-retinal barrier, the gut barrier, the blood-biliary barrier, the blood-follicle barrier, the blood-epididymis barrier, the blood-testis barrier, the tight junction barrier in general as well as barriers in the female reproductive tract. Included are also chapters that focus on topics that are physiologically applicable to all blood-tissue barriers. Many of these chapters also include information on specific human diseases, such as pathological changes of the gut barrier that cause bowel disorders resulting from inflammation of the epithelial lining in the intestine, and infertility in men as a result of disruption of the blood-epididymal and/or blood-testis barriers; and on new therapeutic approaches (e.g., drug delivery across the blood-brain and the blood-retinal barriers).

The craniofacial musculature, including the extraocular muscles, muscles associated with the

auditory system, the masseter, the tongue, and the laryngeal and pharyngeal muscles, all

participate in functions that are critical to life: vision, intact of nutrition, breathing, and hearing.

Despite their critical importance, the majority of research on skeletal muscle basically has

ignored this collection of muscles. This is most likely due to their complexity in form,

development, fiber types, physiology, and disease profiles. All these make these muscles

extremely difficult to study.

Vision depends on voluntary and reflexive eye movements initiated by the oculomotor system.

The effector arm of this motor system includes the extraocular muscles and their motor neurons.

Mastication, and therefore food intake, depends on the complex movements of the masseter and

tongue musculature. The effector arm of this motor system includes the masseter and tongue

muscles and their motor neurons. Respiration, human phonation, as well as gestation, depend on

the laryngeal and pharyngeal musculature. The effector arm of these motor systems includes the

intrinsic and extrinsic laryngeal muscles and the pharyngeal muscles and their motor neurons.

Recently there has been a renewed interest in understanding the basic cell biology and

pathologies associated with these unusual skeletal muscles. This book will highlight novel

findings on the development of these muscles and their innervation, metabolic design, functional

consequences of their structural organization, and potential reasons for their differential response

to various neuromuscular diseases. In addition, critical areas for future studies will be identified.

New and exciting biological functions are still being discovered for vitamin A derivatives, including the vast number of physiological activities of retinoids. In Retinoids: Methods and Protocols, expert researchers in the field present the most recent technical tools with diverse techniques for both in vitro and in vivo studies. Combining biochemical, biophysical, and cell biological techniques, the book addresses topics such as the detection and quantitation of retinoids using HPLC, mass spectrometry, and fluorescence, fluorescence anisotropy of retinol binding protein, cell culture models for studying retinoid transport and the role of retinol in embryonic stem cell culture, as well as many other detailed procedures. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective subjects, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes highlighting tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Retinoids: Methods and Protocols seeks to aid beginning and experienced researchers from widely varied fields in the search to uncover even more vital aspects of vitamin A's impact on the human body.

Advances in methodologies and experimental models are pivotal to furthering our understanding of central nervous system (CNS) functions in mammals. "Isolated Central Nervous System Circuits" examines the application a variety of technologies to mostly active "in vitro" preparations from basically different CNS regions with a diversity of functions. From patch-clamp, multiphoton imaging, live fluorescent protein expression, or immunohistochemistry techniques to acute or 'organotypic' slices and "en bloc" preparations, this detailed volume features key protocols and examples for exciting results from the labs of renowned experts. Written for the popular "Neuromethods" series, chapters include the kind of thorough implementation advice that is vital for achieving successful results.

Comprehensive and cutting-edge, "Isolated Central Nervous System Circuits" will greatly aid scientists to further improve models and to develop corresponding models of not yet intensively studied structures such as "nucleus ruber," "superior colliculus," or basal ganglia."

This book illuminates that physiology, shining a bright light on the impact of trauma on the body and the phenomenon of somatic memory. It is now thought that people who have been traumatized hold an implicit memory of traumatic events in their brains and bodies. That memory is often expressed in the symptomatology of posttraumatic stress disorder-nightmares, flashbacks, startle responses, and dissociative behaviors. In essence, the body of the traumatized individual refuses to be ignored. While reducing the chasm between scientific theory and clinical practice and bridging the gap between talk therapy and body therapy, Rothschild presents principles and non-touch techniques for giving the body its due. With an eye to its relevance for clinicians, she consolidates current knowledge about the psychobiology of the stress response both in normally challenging situations and during extreme and prolonged trauma. This gives clinicians from all disciplines a foundation for speculating about the origins of their clients' symptoms and incorporating regard for the body into their practice. The somatic techniques are chosen with an eye to making trauma therapy safer while increasing mind-body integration. Packed with engaging case studies, The Body Remembers integrates body and mind in the treatment of posttraumatic stress disorder. It will appeal to clinicians, researchers, students, and general readers.

At the Mie International Symposium held in Japan in April 1994, leading scientists reviewed recent advances in the understanding of the contractile mechanism in smooth muscle. The present volume collects the papers presented at the symposium, summarizing the latest advances in smooth muscle function and emphasizing important components of the contraction-relaxation cycle. Topics include a discussion of the smooth muscle cell membrane, with emphasis on its ion channels; the regulation of cytosolic Ca2+ levels and the relationship to force in smooth muscle; aspects of the two key regulatory enzymes involved with myosin phosphorylation-dephosphorylation; the molecular basis for pharmacomechanical coupling in smooth muscle; developments in the basic contractile mechanisms involving the crossbridge cycle of tonic and phasic muscle; the role of myosin light chains; and many others. The approach is broad and presents contemporary opinions in pharmacology, physiology, and biochemistry as they relate to smooth muscle function. The book will appeal not only to those working in these disciplines, but to vascular clinicians, obstetric-gynecological physicians, and gastroenterologists as well.

A timely symposium entitled Body-Fluid Homeostasis: Transduction and Integration was held at Araraquara, Sao Paulo, Brazil in 2011. This meeting was convened as an official satellite of a joint gathering of the International Society for Autonomic Neuroscience (ISAN) and the American Autonomic Society (AAS) held in Buzios, Rio de Janeiro. Broad international participation at this event generated stimulating discussion among the invited speakers, leading to the publication of Neurobiology of Body Fluid Homeostasis: Transduction and Integration. Drawn from the proceedings and filled with rich examples of integrative neurobiology and regulatory physiology, this volume: Provides updated research using human and animal models for the control of bodily fluids, thirst, and salt appetite Explores neural and endocrine control of body fluid balance, arterial pressure, thermoregulation, and ingestive behavior Discusses recent developments in molecular genetics, cell biology, and behavioral plasticity Reviews key aspects of brain serotonin and steroid and peptide control of fluid consumption and arterial pressure The book highlights research conducted by leading scientists on signal transduction and sensory afferent mechanisms, molecular genetics, perinatal and adult long-term influences on regulation, central neural integrative circuitry, and autonomic/neuroendocrine effector systems. The findings discussed by the learned contributors are relevant for a basic understanding of disorders such as heat injury, hypertension, and excess salt intake. A unique reference on the neurobiology of body fluid homeostasis, this volume is certain to fuel additional research and stimulate further debate on the topic.

Since the epochal discovery of the radical and highly toxic gas nitric oxide (NO) as a signaling molecule, two other no less toxic gases - carbon monoxide (CO) and hydrogen sulfide (H2S) - have been found to also be involved in a plethora of physiological and pathophysiological functions. The gases termed gasotransmitters play an increasingly important role in understanding how signalling into and between cells is modulated and fine-tuned. The advent of gasotransmitters has profoundly changed our way of thinking about biosynthesis, liberation, storage and action mechanisms in cellular signaling. In recent years an impressive amount of new data, distributed throughout the existing literature, has been generated. For this book the editors have recruited distinguished colleagues in the field to summarize and review important biological, pharmacological and medical functions and their implications, as well as methods for the detection of gasotransmitters.

Neuroproteomics: Methods and Protocols presents experimental details for applying proteomics to the study of the central nervous system (CNS) and its dysfunction through trauma and disease. The target audience includes clinical or basic scientists who look to apply proteomics to the neurosciences. Often researchers hear of proteomics without an adequate explanation of the methodology and inherent limitations. This volume conveys where proteomic methodology is in its application to CNS research and what results can be expected. We also address clinical translation of neuroproteomics, specifically in the area of biomarker research. The inception of neuroproteomics capitalized on rapid progress in large-molecule mass spectrometry over the last decade. Two seminal advances have spurred research - development of reliable polypeptide ionization processes and bioinformatics to rapidly process tandem mass spectra for peptide identification and quantification. What has followed is the exponential application of mass spectrometry to proteome characteri- tion across biological and biomedical disciplines. Arguably, the most elaborate proteomic implementation is in studying the CNS, the most enigmatic and complex animal system. Neuroscience is characterized by grandiose questions - what is consciousness, how does thought or memory work. Neuroproteomics researchers, however, have pri- rily involved themselves dysfunction, based on a pressing need (and invariably funding), in answering questions on CNS dysfunction, based on a pressing need (and invariably funding), and because such questions hold more accessible answers. Dysfunction is readily contrasted against normal function and presumably produces a lasting differential protein signature.

This collection of reviews will be of considerable interests to biologists and MDs working on any aspect of cardiovascular function. With state-of-the-art reviews written by competent experts in the field, the content is also of interest for MSc and PhD students in most fields of cardiovascular physiology.

A good knowledge of renal physiology is essential to the understanding of many disease states. The purpose of the book is to set out the principles of renal physiology and normal renal function. Now in its 30th year of continuous publication, this new edition offers a logical progression through renal physiology and pathophysiology. In addition, the anatomy, physiology, pharmacology and pathology of the kidney are covered -- making it highly suitable for system based courses. This 5th edition has been extensively revised and features a wealth of new and widely accepted information about kidney function. This includes our understanding of the role of the glycocalyx and structural proteins in glomerular filtration; details of tubular transport, tight junctions and paracellular transport; and an update of the loops of Henle functioning. Principles of Renal Physiology, 5th Edition is a concise and easily readable text ideal for undergraduate medical and medical science students.

Age is a nonreversible risk factor for atherosclerosis. The atherosclerotic process begins early in life, progresses during the middle years, and usually culminates in clinical disease towards the later years of the life span. Since atherosclerosis is a multifactorial disease, and many of the "risk factors" are time- and age related, it has been difficult to sort out intrinsic aging from environmental factors that operate over many years. Furthermore, the role of genetic factors remains unknown. This workshop has produced much worthwhile information that is helping elucidate the impact of age on atherogenesis. Important strides have been made in understanding the role of changes in the arterial wall and of lipoproteins, platelets, and monocyte-derived macrophages in the disease process. In parallel, our understanding of the biology of aging has increased sufficiently so that these two areas of interest can now profitably intersect. The proceedings of this successful workshop emphasize that there is much to be gained by continued interaction between those scientists interested in the biology of aging at all levels and those interested in the atherosclerotic process. Hopefully, we may eventually progress in our understanding and reach the stage when atherosclerosis will no longer be an inexorable concomitant of human aging. Edwin L. Bierman, M. D. Contents Foreword V Contributors IX Participants in the Workshop XV Introduction and Statement of Research Recommendations Sandra R."

Most studies on autonomic innervation of smooth muscle have focused on the short-term mechanisms involved in neurotransmission in physiological and pathophysiological conditions. However recent obser vations of the long-term plasticity of this system, i. e. its capacity for regeneration and for compensatory change in pattern of innervation and expression of cotransmitters and receptors in ageing, following surgery, trauma or in disease, have indicated that an understanding of the mechanisms involved could influence the design of therapeutic regimes. There is increasing evidence for long-term communication between nerves and smooth muscle cells during development and throughout adult life. To date, the trophic interactions between nerves and airway musculature have attracted little interest, consequently, much of the information presented here is drawn from studies using other smooth muscles. However, the questions posed about trophic interactions dur ing development apply as much to airways smooth muscle neuroeffector systems as to other autonomic neuroeffector systems. These are: i) How do developing nerve fibres know where to go and how do they reach their target sites? ii) What determines the density and pattern of inner vation at reaching the effector? iii) How do the nerves survive and maintain their position once established? iv) What factors influence neurochemical differentiation such that genetically multipotential neu rones are triggered to synthesize one or combinations of neurotransmit ters? v) What influence do nerves have on the structure, function and receptor expression of their effector cells? vi) How do diseases interrupt these processes? - see 1]."

Red blood cells in humans-and most other mammals-have a tendency to form aggregates with a characteristic face-to-face morphology, similar to a stack of coins. Known as rouleaux, these aggregates are a normally occurring phenomenon and have a major impact on blood rheology. What is the underlying mechanism that produces this pattern? Does this really happen in blood circulation? And do these rouleaux formations have a useful function? The first book to offer a comprehensive review of the subject, Red Blood Cell Aggregation tackles these and other questions related to red blood cell (RBC) aggregates. The book covers basic, clinical, and physiological aspects of this important biophysical phenomenon and integrates these areas with concepts in bioengineering. It brings together state-of-the-art research on the determinants, mechanisms, and measurement and effects of RBC aggregation as well as on variations and comparative aspects. After an introductory overview, the book outlines factors and conditions that affect RBC aggregation. It presents the two hypotheses-the bridging model and the depletion model-that provide potential mechanisms for the adhesive forces that lead to the regular packing of the cells in rouleaux formations. The book also reviews the methods used to quantify RBC aggregation in vitro, focusing on their importance in clinical practice. Chapters discuss the effect of RBC aggregation on the in vitro rheology of blood as well as on tube flow. The book also looks at what happens in the circulation when red blood cells aggregate and examines variations due to physiological and pathophysiological challenges. The concluding chapter explores the formation of red blood cell aggregates in other mammals. Written by leading researchers in the field, this is an invaluable resource for basic science, medical, and clinical researchers; graduate stu

This book provides a comprehensive account of the proteins involved in blood coagulation, fibrinolysis and the complement system. A major section of the book is devoted to each of these three systems, with separate chapters dealing in detail with structural aspects and different functional processes. Topics covered in the blood coagulation section include the activation of factors IX and X and prothrombin, and the formation and stabilisation of fibrin. The fibrinolysis section includes the activation of plasminogen, the degradation of fibrin and the regulation of fibrinolysis. The complement system itself is covered in chapters dealing with classical activation, alternative activation, the lytic complex and the regulatory processes involved. In addition, one section deals with special topics, including the kinin system, signal peptides, haemostasis, and the evolution of protein structure. This volume will be of use to researchers and advanced students in the fields of haematology, immunology and clinical chemistry.

Many factors may influence the release of neurotransmitters from airway nerves 1]. This is likely to be important in physiological control of airway functions and may be particularly relevant in airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Neural elements in airways interact in a complex manner and the activation of certain neural pathways may profoundly influence the release of transmitters from other neural pathways. Similarly inflamma tory mediators released from inflammatory cells in the airways may also modulate neurotransmitter release. There are marked differences be tween species in airway innervation and in neuromodulatory effects and, wherever possible, studies in human airways have been emphasised, although information on neuromodulation in human airways is some what limited at present. Release of neurotransmitters from nerve terminals occurs via a Ca2+ dependent secretion evoked by a nerve action potential, but may also be evoked experimentally by a high extracellular K + concentration which directly depolarises the nerve terminal membrane. Modulation refers to the alteration of neurotransmitter release, which may either be increased (facilitation) or reduced (inhibition) by the action of a particular agent, thus changing the magnitude of the neurally-mediated response. Such agents would normally act on receptors on the nerve terminal which are referred to as pre-junctional (or presynaptic) receptors, in contrast to post-junctional (or post-synaptic) receptors located on the target cells which are influenced by that particular transmitter."

Cardiac ion channels and mechanisms for protection against atrial fibrillation. Intrinsically photosensitive retinal ganglion cells. Quantifying and modeling the temperature-dependent gating of TRP channels.

The skin, the body's largest organ, is strategically located at the interface with the external environment where it detects, integrates and responds to a diverse range of stressors, including solar radiation. It has already been established that the skin is an important peripheral neuroendocrine-immune organ that is closely networked with central regulatory systems. These capabilities contribute to the maintenance of peripheral homeostasis. Specifically, epidermal and dermal cells produce and respond to classical stress neurotransmitters, neuropeptides and hormones, production which is stimulated by ultraviolet radiation (UVR), biological factors (infectious and non-infectious) and other physical and chemical agents. Examples of local biologically active products are cytokines, biogenic amines (catecholamines, histamine, serotonin and N-acetyl-serotonin), melatonin, acetylocholine, neuropeptides including pituitary (proopiomelanocortin-derived ACTH, b-endorphin or MSH peptides, thyroid stimulating hormone) and hypothalamic (corticotropin-releasing factor and related urocortins, thyroid-releasing hormone) hormones, as well as enkephalins and dynorphins, thyroid hormones, steroids (glucocorticoids, mineralocorticoids, sex hormones, 7- steroids), secosteroids, opioids and endocannabinoids. The production of these molecules is hierarchical, organized along the algorithms of classical neuroendocrine axes such as the hypothalamic pituitary adrenal axis (HPA), hypothalamic-thyroid axis (HPT), serotoninergic, melatoninergic, catecholaminergic, cholinergic, steroid/secosteroidogenic, opioid and endocannabinoid systems. Disruptions of these axes or of communication between them may lead to skin and/or systemic diseases. These local neuroendocrine networks also serve to limit the effect of noxious environmental agents to preserve local and consequently global homeostasis. Moreover, the skin-derived factors/systems can also activate cutaneous nerve endings to alert the brain to changes in the epidermal or dermal environments, or alternatively to activate other coordinating centers by direct (spinal cord) neurotransmission without brain involvement. Furthermore, rapid and reciprocal communications between epidermal and dermal and adnexal compartments are also mediated by neurotransmission including antidromic modes of conduction. Lastly, skin cells and the skin as an organ coordinate and/or regulate not only peripheral but also global homeostasis.

Divided into two convenient sections, Protein Kinase Technologies collects contributions from experts in the field examining recent methodologies and techniques generally applicable to protein kinase research as well as to individual protein kinases which require special attention in neuroscience. These chapters will not only be practical instructions useful for readers' daily work in setting up and performing research but also thought-provoking and enjoyable reviews of recent advancements of individual protein kinases in neuroscience. Written for the highly successful Neuromethods series, this work contains the kind of detailed description and implementation advice that is crucial for getting optimal results. Authoritative and accessible, Protein Kinase Technologies seeks to foster cross-talk among investigators who study different protein kinases, and will also be beneficial for the entry of new investigators into this pivotal field.

This monograph is the result of a course given to graduate students and to the faculty of the Dept. of Medical Physics and Biophysics of Nijmegen University, Nijmegen, The Netherlands, in the fall of 1984 and 1985. The course was intended to put together experi ment, theory, and analysis methods in order to study neural in teraction and coding in the brain. The following pages give a survey of neural interaction and its experimental substrate: cor related neural activity. The basic reason for restricting myself to vertebrate brains was to keep the material concise. As the text developed, however, it became more of a review, than a research monograph, in the attempt to balance theoretical and experimen tal aspects in brain research. Consequently, the book can be read from various points of view: that of requiring an overview of theories and theoretical principles, or an overview of experimental studies in neural interaction and the methods that can be used, or with the conviction that theory and experiment cannot be separat ed. In the latter case the book should be read from beginning to end. A way to read through the theoretical sections and the ex perimental sections of the book is presented in the following flow chart; Theory: /Chap. 2 -Chap. 4 -Chap. 5 ___ ~ Introduction -+ Chap. 1 \, Chap. 10 -+ Chap. 14 Experim~Chap. 3 -Chap. 6 -Chap. 7 -Chap. 8 ~ Chap.

This book is a survey of some aspects of current knowledge on regional Cerebral Blood Flow (rCBF), mainly as studied by the isotope clearance method. Although both theoretical and methodological problems are discussed, attention is mainly dedicated to data obtained from clinical studies. The papers which make up this book were presented at the International Symposium on the Clinical Applications of Isotope Clearance Measurement of Cerebral Blood Flow, held in Mainz, Western Germany, on April 10-12, 1969. The previous meetings on Cerebral Blood Flow, held in Lund in 1964* and in Lund and Copenhagen 1968**, had shown that the moment had come to concentrate on the possibilities of introducing rCBF measurements into clinical routine. This is why in the Mainz Symposium attention was initially focused on methodological aspects. This is also why theoretical problems of physiology of CBF were not emphasized. Finally, this explains why such topics as cerebrovascular disease, head trauma, coma, carotid surgery, brain tumors and intracranial pressure were given pride of place. However a survey of the clinical aspects of rCBF measurements would not be complete without an account of the application of such measurements to monitor cerebral circulatory changes during anesthesia and therapeutic procedures like, for instance, hyperventilation and hyperbaric treatment. Furthermore, it is now possible to obtain data from correlative rCBF studies per formed before, during and after surgical operations on the human brain."

Recent research, especially in fields of orthopaedic surgery and rehabilita tion, point to the importance of periodic, moderate stress for maintaining normal structure and function of tissues. Moreover, growth and healing of load-bearing tissues such as bone, cartilage, and intervertebral disc are especially dependent upon stress-related stimuli. Extreme levels of stress, however, are usually detrimental to tissue integrity, and most treatment regimens today address problems related to trauma and other conditions of abnormally high stress. Therefore, the purpose of this book is to bring together experts in fields of tissue nutrition and growth in order to review previous work and examine new ideas and results concerning the importance of mechanical stress in tissues. This book is unique in that the topic of tissue nutrition and growth, especially related to possible benefits of periodic moderate stress, has never been addressed comprehensively, drawing together experts on vari ous tissues and organs. One objective is to focus attention on tissue nutrition where controversy still exists regarding basic mechanisms of metabolite transport and fluid homeostasis within the interstitium. An other objective is to examine the pathophysiology of tissue compression and discuss strategies to improve viability. Tissues which are treated in this book include bone, cartilage, intervertebral disc, lung, nerve, skeletal muscle, umbilical cord, synovium, skin, and subcutaneous tissues. Based upon these objectives, this book is primarily addressed to students, inves tigators, and teachers in fields of physiology, biochemistry, biomechan ics, exercise, orthopaedic surgery, rehabilitation, and sports medicine."

"Function dictates structure" is a classic paradigm reaffirmed in Wolff's law of the skeletal system. A major question being addressed by current research in biomechanics is whether this doctrine also holds true for the cardiovascular system and connective tissues. Taking a multidisciplinary approach to this question has produced new insights into the sensors, signals, and activators that produce remodeling and functional adaptation in cardiac muscle, blood vessels, and bone, including important new findings on the response of vascular endothelial cells to shear stress. Other work focuses on the extent of remodeling and adaptation processes in tendons, ligaments, and intervertebral discs. Together with two companion volumes, "Computational Biomechanics" and the "Data Book on Mechanical Properties of Living Cells, Tissues, " "and Organs," this monograph will prove invaluable to those working in fields ranging from medical science and clinical medicine to biomedical engineering and applied mechanics.