Signaling by the Epidermal Growth Factor Receptor (EGFR) and related ErbB family receptor tyrosine kinases can be deregulated in human malignancies as the result of mutations in the genes that encode these receptors. The recent identification of EGFR mutations that correlate with sensitivity and resistance to EGFR tyrosine kinase inhibitors in lung and colon tumors has renewed interest in such activating mutations. Here we review current models for ligand stimulation of receptor dimerization and for activation of receptor signaling by receptor (...) dimerization. In the context of these models, we discuss ErbB receptor mutations that affect ligand binding and those that cause constitutive receptor phosphorylation and signaling as a result of constitutive receptor dimerization. We discuss mutations in the cytoplasmic regions that affect enzymatic activity, substrate specificity and coupling to effectors and downstream signaling pathways. Finally, we discuss how emergent mechanisms of ErbB receptor mutational activation could impact the search for clinically relevant ErbB receptor mutations. BioEssays 29:558–565, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Ethics and the Clinical Encounter explores the moral dimensions of clinical medicine and the phenomenon of illness, to determine what ethics must be in order to be fully responsive to clinical encounters. Written in a lively and conversational style with minimal technical terminology, and enhanced by actual experience or real clinical situations, this volume lays out a clinical ethics methodology both in practical and theoretical terms. Here's what the experts had to say: Professor Zaner has provided us with a remarkably (...) lucid and trenchant discussion of the interface of philosophy and the field of medicine. He brings into play an extraordinary range of historial knowledge, extensive observations based on firsthand experience with medical practices, and an acute sense of philosophical argumentation. This is a work that will be an exemplary and indispensable text in the philosophy of medicine for years to come. -- Calvin Schrag... it is a highly original contribution usable in a number of fields.... It really has no competition.... The genius of Zaner's approach is to ground ethics from the 'bottom up' and to direct us to the concrete particulars of therapeutic encounters wherein lie moral and ethical matters... meaty, challenging, and ultimately rewarding.... -- Paul R. Dokecki Richard M. Zaner founded the Center for Clinical and Research Ethics at Vanderbilt University Medical Center. Having established Vanderbilt's first Hospital Ethics Committee (1985), he served as co-chair of VUMC's Ethics Committee since its inception in 1990. Zaner has published five original books, edited ten, and translated four more, and has published more than 100 sections of books and professional journals. (shrink)

Early in the first volume of his Ideen zu einer reinen Phiinomeno logie und phiinomenologischen Philosophie, Edmund Husserl stated concisely the significance and scope of the problem with which this present study is concerned. When we reflect on how it is that consciousness, which is itself absolute in relation to the world, can yet take on the character of transcendence, how it can become mundanized, We see straightaway that it can do that only by means of a certain participation in (...) transcendence in the first, originary sense, which is manifestly the transcendence of material Nature. Only by means of the experiential relation to the animate organism does consciousness become really human and animal (tierischen), and only thereby does it achieve a place in the space and in the time of Nature. l Consciousness can become "worldly" only by being embodied within the world as part of it. In so far as the world is material Nature, consciousness must partake of the transcendence of material Nature. That is to say, its transcendence is manifestly an embodiment in a material, corporeal body. Consciousness, thus, takes on the characteristic of being "here and now" (ecceity) by means of experiential (or, more accurately, its intentive) relation to that corporeal being which embodies it. Accordingly, that there is a world for consciousness is a conse quence in the first instance of its embodiment by 2 that corporeal body which is for it its own animate organism. (shrink)

Early in the first volume of his Ideen zu einer reinen Phiinomeno logie und phiinomenologischen Philosophie, Edmund Husserl stated concisely the significance and scope of the problem with which this present study is concerned. When we reflect on how it is that consciousness, which is itself absolute in relation to the world, can yet take on the character of transcendence, how it can become mundanized, We see straightaway that it can do that only by means of a certain participation in (...) transcendence in the first, originary sense, which is manifestly the transcendence of material Nature. Only by means of the experiential relation to the animate organism does consciousness become really human and animal (tierischen), and only thereby does it achieve a place in the space and in the time of Nature. l Consciousness can become "worldly" only by being embodied within the world as part of it. In so far as the world is material Nature, consciousness must partake of the transcendence of material Nature. That is to say, its transcendence is manifestly an embodiment in a material, corporeal body. Consciousness, thus, takes on the characteristic of being "here and now" (ecceity) by means of experiential (or, more accurately, its intentive) relation to that corporeal being which embodies it. Accordingly, that there is a world for consciousness is a conse quence in the first instance of its embodiment by 2 that corporeal body which is for it its own animate organism. (shrink)

The essays in this collection examine developments in three fundamental biological disciplines--embryology, evolutionary biology, and genetics--in conflict with each other for much of the twentieth century. They consider key methodological problems and the difficulty of overcoming them. Richard Burian interweaves historical appreciation of the settings within which scientists work, substantial knowledge of the biological problems at stake and the methodological and philosophical issues faced in integrating biological knowledge drawn from disparate sources.

This honest, forthright, and beautifully-written book introduces readers to the human variations on medical topics spoken of in abstract in the daily news--euthanasia, assisted suicide, abortion, "extreme procedures", genetic testing, experimental surgeries--and to the people who must agonize over those decisions regarding themselves and their loved ones.

Richard M Weaver, a thinker and writer celebrated for his unsparing diagnoses and realistic remedies for the ills of our age, is known largely through a few of his works that remain in print. This new collection of Weaver's shorter writings, assembled by Ted J Smith III, Weaver's leading biographer, presents many long-out-of-print and never-before-published works that give new range and depth to Weaver's sweeping thought. Included are eleven previously unpublished essays and speeches that were left in near-final form (...) at the time of Weaver's death in 1963. In all, there are some one hundred and twenty-six essays, speeches, book reviews, and editorials. (shrink)

The ideas of Martin Heidegger, one of the most important philosophers of the twentieth century, have had a profound influence on work in literary theory and aesthetics, as well as on mainstream philosophy. This book offers a clear and concise guide to Heidegger's notoriously complex writings, while giving special attention to his major work Being and Time. Richard McDonough adds historical context by exploring Heidegger's intellectual roots in German idealism and ancient Greek philosophy, and introduces readers to the key (...) themes in Heidegger's work including Dasein, Existenz, time, conscience, death, and phenomenology. This book, which also considers Heidegger's controversial ethics and politics, would make an excellent text for both introductory and advanced undergraduate courses on existentialism, phenomenology, continental philosophy, and Heidegger himself. (shrink)

This 2004 book is an accessible introduction to the full range of the philosophy of William James. It portrays that philosophy as containing a deep division between a Promethean type of pragmatism and a passive mysticism. The pragmatist James conceives of truth and meaning as a means to control nature and make it do our bidding. The mystic James eschews the use of concepts in order to penetrate to the inner conscious core of all being, including nature at large. (...) class='Hi'>Richard Gale attempts to harmonize these pragmatic and mystical perspectives. This introduction is drawn from and complements the author's much more comprehensive and systematic study The Divided Self of William James, a volume that has received the highest critical praise. With its briefer compass and non-technical style this introduction should help to disseminate the key elements of one of the great modern philosophies to an even wider readership. (shrink)

Introduction -- Part I: Growth, inquiry, and unity -- Problems with inquiry -- Aesthetic inquiry -- Inquiry, inquiry, inquiry -- Why unification? -- Part II: The metaphysics of unity -- The quest for being QUA being -- Time and individuality -- The Humpty-Dumpty intuition -- The mystical.

The Argument of the "Tractatus" presents a single unified interpretation of the Tractatus based on Wittgenstein's own view that the philosophy of logic is the real foundation of his philosophical system.

Originally published in 1983, the purpose of this book was to discuss the relations between philosophy and developmental psychology, as those relations existed over the course of the history of the discipline and as they existed at that time. Although not all portions of developmental psychology are surveyed, major proponents of several key areas are represented. In addition, discussion of many currently prominent issues are included. The diversity of approaches and of interests present in the book are representative of the (...) breadth of theoretical and empirical interests found in developmental psychology at the time. (shrink)

_Archetypal Expressions_ is a fresh approach to one of Jung's best-know and most exciting concepts. Richard M. Gray uses archetypes as the basis for a new means of interpreting the world and lays the foundations of what he terms an "archetypal sociology". Jung's ideas are combined with elements of modern biology and systems theory to explore the basic human experiences of life, which recur through the ages. Revealing the implicitly cross-cultural and interdisciplinary nature of Jungian Psychology, _Archetypal Explorations_ represents (...) a significant contribution to the literature of archetypes and integrative approaches to human behaviour. (shrink)

The present study seeks to lay out the most basic elements of the ontology of classical Aš‘arite theology. In several cases this requires a careful examination of the traditional and the formal lexicography of certain key expressions. The topics primarily treated are: how they understood “Being/ existence” and “being/existent” and essential natures; the systematic exploitation of the equivocities of certain expressions within a general context in which other than words there are no universals proves to be elegant as well as (...) insightful; the basic categories of primary entities: independant beings and nonindependant beings, created and uncreated, the equivocity of “being/existent” as predicated of contingent entities on the one hand and of God and His attributes on the other, and certain problems that arise because of the rigid application of the system's underlying analytic principles. Nous essayons ici de presenter les éléments fondamentaux de l'ontologie de l'aš‘arisme classique. Pour quelques expressions, il a fallu examiner la lexicographie et ordinaire et technique pour bien comprendre leur emploi et leur signification. Les sujets examinés sont: le sens de “Etre/existence” et de “être/existant” et le concept de réalité essentielle; l'emploi nuancé des équivocités de quelques expressions dans un contexte où les seuls universaux sont des mots, emploi qui se révèle philosophiquement élégant; les catégories fondamentales des êtres: êtres indépendants et êtres non-indépendants, soit créés soit incréés, l'équivocité de “être/existant” dit des êtres contingents d'une part, de Dieu et ses attributs d'autre part, et enfin quelques difficultiés qui résultent de l'application rigide des principes analytiques du système. (shrink)

This paper examines the ten-year history of somaesthetics – describing the field's origins and genealogical roots, explaining its terminology, analyzing its structure, tracing its reception, exploring its most interesting applications, and responding to the most important criticisms that have been directed at it. Somaesthetics, as the paper shows, emerges from the framework of my work in pragmatist aesthetics which sought to revive aesthetics by bringing art closer to life and bridging the presumed divide between the aesthetic and the practical while (...) also advocating an idea of ethics as an art of living. One way to bring more life to aesthetics is to emphasize the role of the living body in art and aesthetic experience. Another strategy of revival is to expand the field of aesthetics to make it more relevant to more people by including practices of somatic stylization and enhanced somatic perception (aisthesis). Somaesthetics, a discipline of both theory and practice, deploys these means of revival, and seems to have had some positive influence. It has been applied by diverse authors in many different fields – from performance art and computer design, to sports, feminist issues of identity, and the use of technological body enhancements in the art of living. The three main branches of somaesthetics are introduced, and the complex structure of the field is used in refuting some of the typical criticisms made against it. Somaesthetics is not a blanket apology for the dangerous excesses of our body culture, but rather a site for the ideological critique of the dominant somatic ideals. Its interest in the body is not a celebration of irrationality or the abandoning of critical reflection. (shrink)