Here we review concepts related to an ensemble description of G-protein-coupled receptors. The ensemble is characterized by both inactive and active states, whose equilibrium populations and exchange rates depend sensitively on ligand, environment, and allosteric factors. This review focuses on the adenosine A2 receptor, a prototypical class A GPCR. 19F Nuclear Magnetic Resonance studies show that apo A2AR is characterized by a broad ensemble of conformers, spanning inactive to active states, and resembling states defined earlier for rhodopsin. In keeping with (...) ideas associated with a conformational selection mechanism, addition of agonist serves to allosterically restrict the overall degrees of freedom at the G protein binding interface and bias both states and functional dynamics to facilitate G protein binding and subsequent activation. While the ligand does not necessarily “induce” activation, it does bias sampling of states, increase the cooperativity of the activation process and thus, the lifetimes of functional activation intermediates, while restricting conformational dynamics to that needed for activation. GPCRs represent a ubiquitous class of transmembrane receptors, responsible for cell signaling and cell homeostasis. Their activation gives rise to conformational changes that allow the receptor to engage downstream partners. Activation can be thought of in terms of a free energy landscape associated with distinct conformers, responsible for the process. Here, the action of ligands is seen to alter this landscape by enabling transitions between key intermediates. (shrink)

Information can be public among a group. Whether or not information is public matters, for example, for accounts of interdependent rational choice, of communication, and of joint intention. A standard analysis of public information identifies it with (some variant of) common belief. The latter notion is stipulatively defined as an infinite conjunction: for p to be commonly believed is for it to believed by all members of a group, for all members to believe that all members believe it, and so (...) forth. This analysis is often presupposed without much argument in philosophy. Theoretical entrenchment or intuitions about cases might give some traction on the question, but give little insight about why the identification holds, if it does. The strategy of this paper is to characterize a practical-normative role for information being public, and show that the only things that play that role are (variants of) common belief as stipulatively characterized. In more detail: a functional role for “taking a proposition for granted” in non-isolated decision making is characterized. I then present some minimal conditions under which such an attitude is correctly held. The key assumption links this attitude to beliefs about what is public. From minimal a priori principles, we can argue that a proposition being public among a group entails common commitment to believe among that group. Later sections explore partial converses to this result, the factivity of publicity and publicity from the perspective of outsiders to the group, and objections to the aprioricity of the result deriving from a posteriori existential presuppositions. (shrink)

The ability to feel pain is a property of human beings that seems to be based entirely in our biological natures and to place us squarely within the animal kingdom. Yet the experience of pain is often used as an example of a mental attribute with qualitative properties that defeat attempts to identify mental events with physiological mechanisms. I will argue that neurophysiology and psychology help to explain the interwoven biological and subjective features of pain and recommend a view of (...) pain which differs in important respects from the one most commonly accepted. (shrink)

Experience with electronic communication in ethics committees at two hospitals is reviewed and discussed. A listserver of ethics committee members transmitted a synopsis of the ethics consultation shortly after the consultation was initiated. Committee comments were sometimes incorporated into the recommendations. This input proved to be most useful in unusual cases where additional, diverse inputs were informative. Efforts to ensure confidentiality are vital to this approach. They include not naming the patient in the e-mail, requiring a password for access to (...) the listserver, and possibly encryption. How this electronic communication process alters group interactions in ethics committees is a fruitful area for future investigation. (shrink)

This treatise on aesthetics begins by showing that the word "art" is used as a name not only for "art proper" but also for certain things which are "art falsely so called." These are craft or skill, magic, and amusement, each of which, by confusion with art proper, generates a false aesthetic theory. In the course of attacking these theories the author criticizes various psychological theories of art, offers a new theory of magic, and reinterprets Plato's so-called "attack on art," (...) showing that it has been entirely misunderstood. Finally, he draws important inferences concerning the position of art in human society. (shrink)

This original and lively book uses texts from ancient medicine, epic, lyric, tragedy, historiography, philosophy, and religion to explore the influence of Greek ideas on health and disease on Greek thought. Fundamental issues are deeply implicated: causation and responsibility, purification and pollution, the mind-body relationship and gender differences, authority and the expert, reality and appearances, good government, and good and evil themselves.

This study investigated the performance of boys with psychopathic tendencies and comparison boys, aged 9 to 17 years, on two tasks believed to be sensitive to amygdala and orbitofrontal cortex func- tioning. Fifty-one boys were divided into two groups according to the Psychopathy Screening Device (PSD, P. J. Frick & R. D. Hare, in press) and presented with two tasks. The tasks were the gambling task (A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994) and the Intradimensional/ (...) Extradimensional (ID/ED) shift task (R. Dias, T. W. Robbins, & A. C. Roberts, 1996). The boys with psychopathic tendencies showed impaired performance on the gambling task. However, there were no group differences on the ID/ED task either for response reversal or extradimensional set shifting. The implications of these results for models of psychopathy are discussed. (shrink)

Applied or practical ethics is perhaps the largest growth area in philosophy today, and many issues in moral, social, and political life have come under philosophical scrutiny in recent years. Taken together, the essays in this volume – including two overview essays on theories of ethics and the nature of applied ethics – provide a state-of-the-art account of the most pressing moral questions facing us today. Provides a comprehensive guide to many of the most significant problems of practical ethics Offers (...) state-of-the-art accounts of issues in medical, environmental, legal, social, and business ethics Written by major philosophers presently engaged with these complex and profound ethical issues. (shrink)

Business Ethics, the Environment & Responsibility, EarlyView.

This study investigates the ability of individuals with psychopathy to perform passive avoidance learning and whether this ability is modulated by level of reinforcement/punishment. Nineteen psychopathic and 21 comparison individuals, as defined by the Hare Psychopathy Checklist Revised (Hare, 1991), were given a passive avoidance task with a graded reinforcement schedule. Response to each rewarding number gained a point reward specific to that number (i.e., 1, 700, 1400 or 2000 points). Response to each punishing number lost a point punishment specific (...) to that number (i.e., the loss of 1, 700, 1400 or 2000 points). In line with predictions, individuals with psychopathy made more passive avoidance errors than the comparison individuals. In addition, while the performance of both groups was modulated by level of reward, only the performance of the comparison population was modulated by level of punishment. The results are interpreted with reference to a computational account of the emotional learning impairment in individuals with psychopathy. (shrink)

This full-length study of Plato's dialogue Phaedrus, now in paperback, is written in the belief that such concerted scrutiny of a single dialogue is an important part of the project of understanding Plato so far as possible 'from the inside' - of gaining a feel for the man's philosophy. The focus of this account is on how the resources both of persuasive myth and of formal argument, for all that Plato sets them in strong contrast, nevertheless complement and reinforce each (...) other in his philosophy. Not only is the dialogue in its formal structure a dovetail of myth and argument, but the philosophic life that it praises is also shaped by an acknowledgement of the limitations of argument and the importance of mythical understanding. By means of this correlation of form and content Plato invites his readers, through the very act of reading, to take a first step along the path of the philosophical life. (shrink)

A detailed study of the political organization in an important area of Tanzania shortly before Independence. Unyamwezi covers 35,000 square miles and has a population of 400,000. Dr Abrahams outlines the social and economic framework and examines the origins of the modern political system. He then discusses the internal organization of Nyamwezi chiefdoms and villages and the emergence of national politics. The theoretical and comparative implications of the study, which is based on extensive field work in the area, are also (...) considered. (shrink)

In discussing Disembodied Persons we need to confront two problems:A. Under what conditions would we consider that a person was present in the absence of the normal bodily cues?B. Could such circumstances arise?The first question may be regarded as epistemic and the second as metaphysical.