Membrane Receptors, Channels and Transporters in Pulmonary Circulation is a proceeding of the 2008 Grover Conference (Lost Valley Ranch and Conference Center, Sedalia, Colorado; September 3-7, 2008), which provided a forum for experts in the fields of those receptors, channels and transporters that have been identified as playing key roles in the physiology and pathophysiology of the pulmonary circulation. The book rigorously addresses: i) recent advances in our knowledge of receptors, channels and transporters and their role in regulation of pulmonary vascular function; ii) how modulation of expression and function of receptors, channels and transporters and their interrelationships contribute to the pathogenesis of pulmonary vascular disease; and iii) the therapeutic opportunities that may be revealed by enhancing our understanding of this area. The overall goal was to explore the mechanisms by which specific receptors, channels and transporters contribute to pulmonary vascular function in both health and disease, and how this knowledge may lead to novel interventions in lung dysplasia, pulmonary edema, lung injury, and pulmonary and systemic hypertension to reduce and prevent death from lung disease. Membrane Receptors, Channels and Transporters in Pulmonary Circulation is divided into six parts. Part 1 (Ion Channels in the Pulmonary Vasculature: Basics and New Findings) is designated for basic knowledge and recent findings in the research field of ion channels in pulmonary circulation. There are five chapters in Part I discussing the function, expression, distribution and regulation of various ion channels present in pulmonary vascular smooth muscle cells and how these channels are integrated to regulate intracellular Ca2+ and cell functions. Part II (TRP Channels in the Pulmonary Vasculature: Basics and New Findings) is composed of five chapters that are exclusively designed to discuss the role of a recently identified family of cation channels, transient receptor potential (TRP) channels, in the regulation of pulmonary vascular tone and arterial structure. Part III (Pathogenic Role of Ion Channels in Pulmonary Vascular Disease) includes four chapters that discuss how abnormal function and expression of various ion channels contribute to changes in cell functions and the development of pulmonary hypertension. Part IV (Receptors and Signaling Cascades in Pulmonary Arterial Hypertension) consists of five chapters devoted to the role of bone morphogenetic protein receptors, Notch receptors, serotonin receptors, Rho kinase and vascular endothelial growth factor receptors in the development of pulmonary arterial hypertension. Part V (Receptors and Transporters: Role in Cell Function and Hypoxic Pulmonary Vasoconstriction) includes four chapters designed to illustrate the potential mechanisms involved in oxygen sensing and hypoxia-induced pulmonary vasoconstriction and hypertension. Part VI (Targeting Ion Channels and Membrane Receptors in Developing Novel Therapeutic Approaches for Pulmonary Vascular Disease) consists five chapters which discuss the translational research involving on membrane receptors, channels and transporters, including their potential as novel drug targets. We hope that Membrane Receptors, Channels and Transporters in Pulmonary Circulation will allow readers to foster new concepts and new collaborations and cooperations among investigators so as to further understand the role of receptors, channels and transporters in lung pathophysiology. The ultimate goal is to identify new mechanisms of disease, as well as new therapeutic targets for pulmonary vascular diseases. An additional outcome should be enhanced understanding of the role of these entities in systemic vascular pathophysiology, since the conference will include researchers and clinicians with interests in both pulmonary and systemic circulations.

Membrane Receptors, Channels and Transporters in Pulmonary Circulation is a proceeding of the 2008 Grover Conference (Lost Valley Ranch and Conference Center, Sedalia, Colorado; September 3-7, 2008), which provided a forum for experts in the fields of those receptors, channels and transporters that have been identified as playing key roles in the physiology and pathophysiology of the pulmonary circulation. The book rigorously addresses: i) recent advances in our knowledge of receptors, channels and transporters and their role in regulation of pulmonary vascular function; ii) how modulation of expression and function of receptors, channels and transporters and their interrelationships contribute to the pathogenesis of pulmonary vascular disease; and iii) the therapeutic opportunities that may be revealed by enhancing our understanding of this area. The overall goal was to explore the mechanisms by which specific receptors, channels and transporters contribute to pulmonary vascular function in both health and disease, and how this knowledge may lead to novel interventions in lung dysplasia, pulmonary edema, lung injury, and pulmonary and systemic hypertension to reduce and prevent death from lung disease. Membrane Receptors, Channels and Transporters in Pulmonary Circulation is divided into six parts. Part 1 (Ion Channels in the Pulmonary Vasculature: Basics and New Findings) is designated for basic knowledge and recent findings in the research field of ion channels in pulmonary circulation. There are five chapters in Part I discussing the function, expression, distribution and regulation of various ion channels present in pulmonary vascular smooth muscle cells and how these channels are integrated to regulate intracellular Ca2+ and cell functions. Part II (TRP Channels in the Pulmonary Vasculature: Basics and New Findings) is composed of five chapters that are exclusively designed to discuss the role of a recently identified family of cation channels, transient receptor potential (TRP) channels, in the regulation of pulmonary vascular tone and arterial structure. Part III (Pathogenic Role of Ion Channels in Pulmonary Vascular Disease) includes four chapters that discuss how abnormal function and expression of various ion channels contribute to changes in cell functions and the development of pulmonary hypertension. Part IV (Receptors and Signaling Cascades in Pulmonary Arterial Hypertension) consists of five chapters devoted to the role of bone morphogenetic protein receptors, Notch receptors, serotonin receptors, Rho kinase and vascular endothelial growth factor receptors in the development of pulmonary arterial hypertension. Part V (Receptors and Transporters: Role in Cell Function and Hypoxic Pulmonary Vasoconstriction) includes four chapters designed to illustrate the potential mechanisms involved in oxygen sensing and hypoxia-induced pulmonary vasoconstriction and hypertension. Part VI (Targeting Ion Channels and Membrane Receptors in Developing Novel Therapeutic Approaches for Pulmonary Vascular Disease) consists five chapters which discuss the translational research involving on membrane receptors, channels and transporters, including their potential as novel drug targets. We hope that Membrane Receptors, Channels and Transporters in Pulmonary Circulation will allow readers to foster new concepts and new collaborations and cooperations among investigators so as to further understand the role of receptors, channels and transporters in lung pathophysiology. The ultimate goal is to identify new mechanisms of disease, as well as new therapeutic targets for pulmonary vascular diseases. An additional outcome should be enhanced understanding of the role of these entities in systemic vascular pathophysiology, since the conference will include researchers and clinicians with interests in both pulmonary and systemic circulations.

Membrane Receptors, Channels and Transporters in Pulmonary Circulation is a proceeding of the 2008 Grover Conference (Lost Valley Ranch and Conference Center, Sedalia, Colorado; September 3-7, 2008), which provided a forum for experts in the fields of those receptors, channels and transporters that have been identified as playing key roles in the physiology and pathophysiology of the pulmonary circulation. The book rigorously addresses: i) recent advances in our knowledge of receptors, channels and transporters and their role in regulation of pulmonary vascular function; ii) how modulation of expression and function of receptors, channels and transporters and their interrelationships contribute to the pathogenesis of pulmonary vascular disease; and iii) the therapeutic opportunities that may be revealed by enhancing our understanding of this area. The overall goal was to explore the mechanisms by which specific receptors, channels and transporters contribute to pulmonary vascular function in both health and disease, and how this knowledge may lead to novel interventions in lung dysplasia, pulmonary edema, lung injury, and pulmonary and systemic hypertension to reduce and prevent death from lung disease. Membrane Receptors, Channels and Transporters in Pulmonary Circulation is divided into six parts. Part 1 (Ion Channels in the Pulmonary Vasculature: Basics and New Findings) is designated for basic knowledge and recent findings in the research field of ion channels in pulmonary circulation. There are five chapters in Part I discussing the function, expression, distribution and regulation of various ion channels present in pulmonary vascular smooth muscle cells and how these channels are integrated to regulate intracellular Ca2+ and cell functions. Part II (TRP Channels in the Pulmonary Vasculature: Basics and New Findings) is composed of five chapters that are exclusively designed to discuss the role of a recently identified family of cation channels, transient receptor potential (TRP) channels, in the regulation of pulmonary vascular tone and arterial structure. Part III (Pathogenic Role of Ion Channels in Pulmonary Vascular Disease) includes four chapters that discuss how abnormal function and expression of various ion channels contribute to changes in cell functions and the development of pulmonary hypertension. Part IV (Receptors and Signaling Cascades in Pulmonary Arterial Hypertension) consists of five chapters devoted to the role of bone morphogenetic protein receptors, Notch receptors, serotonin receptors, Rho kinase and vascular endothelial growth factor receptors in the development of pulmonary arterial hypertension. Part V (Receptors and Transporters: Role in Cell Function and Hypoxic Pulmonary Vasoconstriction) includes four chapters designed to illustrate the potential mechanisms involved in oxygen sensing and hypoxia-induced pulmonary vasoconstriction and hypertension. Part VI (Targeting Ion Channels and Membrane Receptors in Developing Novel Therapeutic Approaches for Pulmonary Vascular Disease) consists five chapters which discuss the translational research involving on membrane receptors, channels and transporters, including their potential as novel drug targets. We hope that Membrane Receptors, Channels and Transporters in Pulmonary Circulation will allow readers to foster new concepts and new collaborations and cooperations among investigators so as to further understand the role of receptors, channels and transporters in lung pathophysiology. The ultimate goal is to identify new mechanisms of disease, as well as new therapeutic targets for pulmonary vascular diseases. An additional outcome should be enhanced understanding of the role of these entities in systemic vascular pathophysiology, since the conference will include researchers and clinicians with interests in both pulmonary and systemic circulations.

This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.

The main goal of this book is to form a high-quality platform in which well-known and emerging pioneering basic, translational and clinical scientists can present their latest, exciting findings in the studies of redox signaling in the pulmonary vasculature. Content from outstanding investigators with unique expertise and skills of molecular and cell biology, biochemistry, physiology, pharmacology, biophysics, biotechnology and medicine will update our current out-of-date concepts with new knowledge. Rapidly increasing scientific studies have gathered a large volume of novel and important information on redox signaling in healthy and diseased pulmonary vasculature. This volume covers the need for a cohesive book to display state-of-the-art advances in the field. The second major aim of this book is to help direct future research. Redox signaling is a major molecular process involved in almost every physiologic cellular response in the pulmonary vasculature including energy metabolism, host defense, gene expression, contraction, proliferation, and migration. Aberrancy in this important signaling pathway leads to a critical role in the development of nearly all pulmonary diseases, such as pulmonary hypertension, cor pulmonale, pulmonary edema, and vasculitis, among others.

An introduction to how neuroethology can inform the development of robots controlled by synaptic networks instead of algorithms, from a pioneer in biorobotics. The trait most fundamental to the evolution of animals is the capability to adapt to novel circumstances in unpredictable environments. Recent advances in biomimetics have made it feasible to construct robots modeled on such unsupervised autonomous behavior, and animal models provide a library of existence proofs. Filling an important gap in the field, this introductory textbook illuminates how neurobiological principles can inform the development of robots that are controlled by synaptic networks, as opposed to algorithms. Joseph Ayers provides a comprehensive overview of the sensory and motor systems of a variety of model biological systems and shows how their behaviors may be implemented in artificial systems, such as biomimetic robots. Introduces the concept of biological intelligence as applied to robots, building a strategy for autonomy based on the neuroethology of simple animal models Provides a mechanistic physiological framework for the control of innate behavior Illustrates how biomimetic vehicles can be operated in the field persistently and adaptively Developed by a pioneer in biorobotics with decades of teaching experience Proven in the classroom Suitable for professionals and researchers as well as undergraduate and graduate students in cognitive science and computer science

Cancer remains a major challenge for modern society. Not only does cancer rank among the first three causes of mortality in most population groups but also the therapeutic options available for most tumor types are limited. The existing ones have limited efficacy, lack specificity and their administration carry major side effects. Hence the urgent need for novel cancer therapies. One of the most promising avenues in research is the use of specific immunotherapy. The notion that the immune system may have important anti-tumor effects has been around for more than a century now. Every major progress in microbiology and immunology has been immediately followed by attempts to apply the new knowledge to the treatment of cancer. Progress has reached a point where it is well established that most cancer patients mount specific T cell responses against their tumors. The molecular identity of the antigens recognized by anti-tumor T cells has been elucidated and several hundreds of tumor-derived antigenic peptides have been discovered. Upon recognition of such peptides presented by self MHC molecules, both CD8 and CD4 T cells are activated, expand to high numbers and differentiate into effective anti-tumor agents. CD8 T cells directly destroy tumor cells and can cause even large tumors to completely regress in experimental mouse models. These observations have spurred intense research activity aimed at designing and testing cancer vaccines. Over 100 years ago Coley successfully used intratumoral injection of killed bacteria to treat sarcomas. The important anti-tumor effects observed in a fraction of these patients fueled major research efforts. These led to major discoveries in the 80s and the 90s. It turns out that bacterial lipopolysaccharides stimulate the production of massive amounts of a cytokine still known today as tumor necrosis factor (TNF-a). They do so by engagement of a rather complex set of interactions culminating in the ligation of a Toll-like receptor, TLR -4. Ensuing signaling through this receptor initiates potent innate immune responses. Unfortunately the clinical use of both TNF-a and LPS can not be generalized due to their very narrow therapeutic margin. Importantly, synthetic Lipid A analogs have been identified that retain useful bioactivity and yet possess only mild toxicity. The relatively large body of information accumulated thus far on the molecular and cellular interactions set in motion by administration of LPS as well as by the synthetic lipid A analogs allow to place this family of bacterially-derived molecules at the crossroads between innate and adaptive immunity. By virtue of this key position, the therapeutic applications being pursued aim at using these compounds either as direct anti-tumor agents or as vaccine adjuvants. The clinical experience acquired so far on these two avenues is asymmetric. Few clinical trials using Lipid A analogs as single anti-cancer agents involving less than 100 patients with advanced cancer have been reported. In contrast, lipid A has been tested in over 300,000 individuals in various vaccines trials, including therapeutic cancer vaccines. Clearly most of the work needed to develop lipid A as effective anti-cancer agents and/or as vaccine adjuvant lies ahead in the near future. This book is a timely contribution and provides a much needed up-to-date overview of the chemical, biological and physiological aspects of lipid A. It should be a beacon to all those involved in this field of research.