Unraveling the molecular detail of insulin receptor activation has proved challenging, but a major advance is the recent determination of crystallographic structures of insulin in complex with its primary binding site on the receptor. The current model for insulin receptor activation is that two distinct surfaces of insulin monomer engage sequentially with two distinct binding sites on the extracellular surface of the insulin receptor, which is itself a disulfide‐linked (αβ)2 homodimer. In the process, conformational changes occur both within the hormone (...) and the receptor, the latter resulting in the disruption of the intracellular interactions that hold the kinase domains in their basal state and in the initiation of the phosphorylation events that drive insulin signaling. The purpose of this paper is to summarize the extant structural data relating to hormone binding and how it effects receptor activation, as well as to discuss the issues that remain unresolved. (shrink)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

This book explores the recovery of Socratic philosophy in 19th century political thought of G.W.F. Hegel, Soren Kierkegaard, John Stuart Mill, and Friedrich Nietzsche. For Kierkegaard the Socratic indivdual in modern times is the person of faith, for Mill the idiosyncratic public intellectual, and for Nietzsche the Dionysian artist.

Since its publication in 1965, Brian Barry's seminal work has occupied an important role in the revival of Anglo-American political philosophy. A number of ideas and terms in it have become part of the standard vocabulary, such as the distinction between "ideal-regarding" and "want-regarding" principles and the division of principles into aggregative and distributive. The book provided the first precise analysis of the concept of political values having trade-off relations and its analysis of the notion of the public interest has (...) also been significant. (shrink)

(No abstract is available for this citation).

Professor Strawson's paper is refreshing in content as well as refreshingly intemperate. It is salutary to be reminded that even the Type Identity Theory does not entail physicalism as that doctrine is usually understood (since c-fiber firings are not by definition purely physical). And it's fun to consider versions of panpsychism. I can see why Strawson finds his position hard to classify (p. 7), and I sympathize. In my title I have cast my own vote for '?-ism' on the grounds (...) that any familiar label would be either misleading or unwieldy. My main purpose here is to assess Strawson's case for panpsychism and then to offer some objections to panpsychism, but first I want to answer an interesting and serious charge he makes against me. (shrink)

This volume is a critical edition of the eight-year correspondence between Gottfried Wilhelm Leibniz and Burcher de Volder, professor of philosophy and mathematics at Leiden University. Containing the surviving correspondence between Leibniz and De Volder, the volume also presents a generous selection from the letters between Leibniz and his friend Johann Bernoulli, through whose intercession the correspondence began. Bernoulli acted as intermediary throughout, and the often candid discussions between Leibniz and Bernoulli provide illuminating background to the correspondence proper. Each of (...) the selections appears both in the original Latin and in English translation. (shrink)

Neo-Darwinian theories of cultural evolution are apt to be criticized on the grounds that they merely borrow from the theory of natural selection concepts that are then metaphorically applied to conventional historical narratives to which they add no more, if anything, than an implicit presupposition of progress from one predetermined stage to the next. Such criticisms, of which a particularly forceful example is a recent article in this journal by Fracchia and Lewontin, can however be shown to be seriously misconceived. (...) The fundamental process of heritable variation and competitive selection of information affecting phenotype underlies both biological and cultural evolution despite the obvious differences between the mechanisms of information transfer by genetic inheritance and by exosomatic imitation and learning. Information transfer is in neither case a metaphor standing for any other thing, and in neither case does change over time proceed in accordance with developmental laws from which the future evolution of either species or cultures could be predicted in advance. For all the unresolved questions that remain, neo-Darwinian evolutionary theory has demonstrated the mutual compatibility of idiographic and nomothetic explanation in the study of species and of cultures alike. (shrink)

In order to study early human development while avoiding the burdens associated with human embryo research, scientists are redirecting their efforts towards so-called human embryo-like structures (hELS). hELS are created from clusters of human pluripotent stem cells and seem capable of mimicking early human development with increasing accuracy. Notwithstanding, hELS research finds itself at the intersection of historically controversial fields, and the expectation that it might be received as similarly sensitive is prompting proactive law reform in many jurisdictions, including the (...) Netherlands. However, studies on the public perception of hELS research remain scarce. To help guide policymakers and fill this gap in the literature, we conducted an explorative qualitative study aimed at mapping the range of perspectives in the Netherlands on the creation and research use of hELS. This article reports on a subset of our findings, namely those pertaining to (the degrees of and requirements for) confidence in research with hELS and its regulation. Despite commonly found disparities in confidence on emerging biotechnologies, we also found wide consensus regarding the requirements for having (more) confidence in hELS research. We conclude by reflecting on how these findings could be relevant to researchers and (Dutch) policymakers when interpreted within the context of their limitations. (shrink)

This volume is a critical edition of the ten-year correspondence between Gottfried Wilhelm Leibniz, one of Europe’s most influential early modern thinkers, and Bartholomew Des Bosses, a Jesuit theologian who was keen to bring together Leibniz’s philosophy and the Aristotelian philosophy and religious doctrines accepted by his order. The letters offer crucial insights into Leibniz’s final metaphysics and into the intellectual life of the eighteenth century. Brandon C. Look and Donald Rutherford present seventy-one of Leibniz’s and Des Bosses’s letters in (...) the original Latin and in careful English translation. Few of the letters have been translated into English before. The editors also provide extensive annotations, deletions, and marginalia from Leibniz’s various drafts, and a substantial introduction setting the context for the correspondence and analyzing the main philosophical issues. (shrink)

My discussion of this theme falls into two parts. In the first part, starting from the assumption that we do in fact tend to respond favourably to the idea, vague though it may be, that “persons are to be respected, simply as persons”, I endeavour to clear my mind a little about our warrant for speaking in this way; and to do this is at the same time to clarify in some measure our understanding of what such language means. But (...) of course, since it is the language of practical principle, or precept, there can be no full understanding of its meaning without a grasp of its “working value”, of its significance as a clue to the proper directing and assessing of conduct. The second, and briefer, part of the discussion, accordingly, which is reserved for a subsequent article, is devoted to the question of the practical import of the principle of respect, the sort of guidance that it may provide in the actual business of life. (shrink)

Introduction, W G Runciman Social Evolution in Primates: The Role of Ecological Factors and Male Behaviour, Carel P van Schaik Determinants of Group Size in Primates: A General Model, R I M Dunbar Function and Intention in the Calls of Non-Human Primates, Dorothy L Cheney & Robert M Seyfarth Why Culture is Common, but Cultural Evolution is Rare, Robert Boyd & Peter J Richerson An Evolutionary and Chronological Framework for Human Social Behaviour, Robert A Foley Friendship and the Banker?s Paradox: (...) Other Pathways to the Evolution of Adaptations for Altruism, John Tooby & Leda Cosmides The Early Prehistory of Human Social Behaviour: Issues of Archaeological Inference and Cognitive Evolution, Steven Mithen The Emergence of Biologically Modern Populations in Europe: A Social and Cognitive ?Revolution??, Paul Mellars Responses to Environmental Novelty: Changes in Men?s Marriage Strategies in a Rural Kenyan Community, Monique Borgerhoff Mulder Genetic Language Impairment: Unruly Grammars, M Gopnik, J Dalalakis, S E Fukuda, S Fukuda & E Kehayia The Emergence of Cultures among Wild Chimpanzees, Christophe Boesch Terrestriality, Bipedalism and the Origin of Language, Leslie C Aiello Conclusions, John Maynard Smith. (shrink)

In this lively and provocative book, W. G. Runciman shows where and why they fail, even after due allowance has been made for the different historical contexts in which they wrote.

There are many difficulties connected with the notion of punishment, but perhaps it is not disputed that it is at least a deliberate infliction of pain of one kind or another. Of course, that is not an adequate description of its nature, but so far as it goes it seems to be a true one.1 And the idea that it could be morally right deliberately tp inflict pain on another, unlike, for example, the idea that it is morally right to (...) tell the truth, is so manifestly intolerable unless we look beyond the infliction of pain itself that we are tempted to leap forward to the question, “What is the justification of such action?” before making quite explicit to ourselves what it is, over and above its being the deliberate infliction of pain, that constitutes the action punishment at all. The questions “Why hurt?” and “Why punish?” are confused with one another. No doubt some distinction between them is present vaguely in everyone's mind and the confusion may not be in fact serious: but anyhow it is a defect and should be remedied. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:BOOK REVIEWS 387 and contributed an important and helpful study. This dissertation is a model of its kind. One hopes the author will continue his scholarly efforts. The Catholic University of America Washington, D.C. WILLIAM E. MAY John Henry Newman: A Biography. By IAN KER. New York: Oxford University Press, 1990. Pp. xii + 764. $24.95 (paper). The Achievement of John Henry Newman. By IAN KER. Notre Dame: University (...) of Notre Dame Press, 1990. Pp. x + 209. $24.95 (cloth). Ian Ker has inherited the mantle of the late Charles Stephen Dessain as the finest textual expositor of the Newman corpus, and Ker's biography should become a standard reference tool in the field. Ker ap· prenticed under Dessain in the production of the monumental (31volume ) Letters and Diaries, and his biography shows his command of the materials of that as yet unfinished project. Ker's hook joins the biographies of W. Ward (1912) and M. Trevor (1962) as significant "lives of Newman" to consider, and it addresses their earlier shortcomings : Ward's inadequate appraisal of the Anglican Newman and Trevor's unconcern for Newman's theological writings. Of Newman's intellectual contribution, Ker's treatment is similar to Dessain's John Henry Newman, an exposition of the major themes and intellectual moves, and theologically-minded inquirers need read both. Ker offers the hook as a personal life, a literary appraisal, and an intellectual study. The personal life and literary analysis are ably carried off; Ker's background in English literature and his editorial work on the letters have served him well. The intellectual study takes the form of synopses of Newman's hooks and articles, which are woven into the chronological narrative of the life. This aspect of Ker's hook is by no means "the theological achievement of JHN" (cf. Tracy's work on Lonergan); such a project still awaits Newman studies and someone of the conceptual breadth of the late Jan Walgrave to achieve it. Ker provides accurate and readable summaries of Newman's writings, and if a biography is meant to introduce the sundry aspects of a person, especially a complex thinker like Newman, then Ker's treatment of the intellectual aspect offers a fine introduction. I shall consider these three dimensions of the biography, and first the personal life. Newman considered that a person's life is best told 888 BOOK REVIEWS through that person's correspondence. Ker's biography is approached chronologically, and Newman's published letters guide the tale. Newman 's advice is particularly apropos for his own biographer, since Newman 's hooks and articles often displayed a "reserve" in which his true feelings were couched and nuanced. His letters, especially to confidants, were candid and often hard-hitting, as when he described the Curia in these words: " And who is Propaganda? one sharp man of business, who works day and night, and dispatches his work quick off, to the East and West, a high dignitary, [perhaps an Archbishop], hut after all little more than a clerk... with two or.three clerks under him " (p. 519). (Ker displays some reserve himself, omitting Newman's episcopal aside.) Ker's use of the letters is most revealing during Newman's Roman Catholic period when he encountered opposition from Archbishop Manning and W. G. Ward in England, from Archbishop Cullen in Dublin, and from Cardinal Barnaho in Rome. One senses how the laity rallied round him. Some of Newman's most pungent thoughts on ·theological freedom, on the suspicious nature of the clergy toward educated laity, on the wherewithal to make an institution a genuine university, on the role of patience and.trust in God when authorities are hearing down, are to he found in Ker's choice of letters. With so much material to mine-Newman wrote 20,000 letters-it is understandable that Ker does not include, save rarely, what Newman's opponents were thinking. Ker's account of Newman's Anglican period is equally illuminating, and indeed it is a highlight of the biography. While the Apologia has provided the main lines of the story, Ker puts flesh and hones to Newman 's struggle with his conscience. In coming to Oxford, Newman... (shrink)