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.

ABSTRACT:This manuscript develops the concept of organizational virtue orientation (OVO) and examines differences between family and non-family firms on the six organizational virtue dimensions of Integrity, Empathy, Warmth, Courage, Conscientiousness, and Zeal. Using content analysis of shareholder letters fromS&P 500companies, our analyses find that there are significant differences between family and non-family firms in their espoused OVO, with family firms generally being higher. Specifically, family firms were significantly higher on the dimensions of Empathy, Warmth, and Zeal, but lower on Courage. (...) Based on these findings we further develop the OVO concept through the discussion of implications and areas for future research. (shrink)

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)

The logic RM and its basic fragments (always with implication) are considered here as entire consequence relations, rather than as sets of theorems. A new observation made here is that the disjunction of RM is definable in terms of its other positive propositional connectives, unlike that of R. The basic fragments of RM therefore fall naturally into two classes, according to whether disjunction is or is not definable. In the equivalent quasivariety semantics of these fragments, which consist of subreducts of (...) Sugihara algebras, this corresponds to a distinction between strong and weak congruence properties. The distinction is explored here. A result of Avron is used to provide a local deduction-detachment theorem for the fragments without disjunction. Together with results of Sobociski, Parks and Meyer (which concern theorems only), this leads to axiomatizations of these entire fragments — not merely their theorems. These axiomatizations then form the basis of a proof that all of the basic fragments of RM with implication are finitely axiomatized consequence relations. (shrink)

Saul Kripke is one of the most original and creative philosophers writing today. His work has had a tremendous impact on the direction that philosophy has taken in the last thirty years and continues to dominate some of its most fundamental aspects. Given Kripke's importance it is perhaps surprising that there is no introduction to his philosophy available to the general student. This book fills that gap. As much of Kripke's work is highly technical, the book's central aim is to (...) provide clear exposition of Kripke's ideas in a form that is understandable to a beginning readership as well as a commentary on them that more advanced students will find useful. The book begins with a discussion of Kripke's early work on modal logic, which provides the foundation for many of his later philosophical contributions, before examining in detail Kripke's central ideas and arguments contained in Naming and Necessity. In further chapters, Kripke's work on semantic paradoxes and his theory of truth are outlined as well as his controversial interpretation of Wittgenstein's famous private language argument. Kripke's ideas are situated alongside those of his precursors and some of the most important and interesting responses to them are explored. The reader is thus able to appreciate the path-breaking nature of Kripke's contributions, how they have challenged fundamentally traditional interpretations, and how they have sparked some of the most important philosophical debates of recent years. (shrink)

This paper investigates connectionism's potential to solve the frame problem. The frame problem arises in the context of modelling the human ability to see the relevant consequences of events in a situation. It has been claimed to be unsolvable for classical cognitive science, but easily manageable for connectionism. We will focus on a representational approach to the frame problem which advocates the use of intrinsic representations. We argue that although connectionism's distributed representations may look promising from this perspective, doubts can (...) be raised about the potential of distributed representations to allow large amounts of complexly structured information to be adequately encoded and processed. It is questionable whether connectionist models that are claimed to effectively represent structured information can be scaled up to a realistic extent. We conclude that the frame problem provides a difficulty to connectionism that is no less serious than the obstacle it constitutes for classical cognitive science. (shrink)

(No abstract is available for this citation).

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)

In Part I of this discussion I considered the nature and validity of the principle of respect for persons as distinguished from its practical import and application. Before I proceed to that second topic let me draw together in summary fashion the main points of the view I have put forward.

This paper discusses the debate over whether emotional expressions are spontaneous or intentional actions. We describe a variety of empirical evidence supporting these two possibilities. But we argue that the spontaneous-intentional distinction fails to explain the psychological dynamics of emotional expressions. We claim that a complex systems perspective on intentions, as self-organized critical states, may yield a unified view of emotional expressions as a consequence of situated action. This account simultaneously acknowledges the embodied status of environment, evolution, culture and mind (...) in theories of emotion. (shrink)

The complex chaotic dynamics and multistability of financial system are some important problems in micro- and macroeconomic fields. In this paper, we study the influence of two-delay feedback on the nonlinear dynamics behavior of financial system, considering the linear stability of equilibrium point under the condition of single delay and two delays. The system undergoes Hopf bifurcation near the equilibrium point. The stability and bifurcation directions of Hopf bifurcation are studied by using the normal form method and central manifold theory. (...) The theoretical results are verified by numerical simulation. Furthermore, one feature of the proposed financial chaotic system is that its multistability depends extremely on the memristor initial condition and the system parameters. It is shown that the nonlinear dynamics of financial chaotic system can be significantly changed by changing the values of time delays. (shrink)