DNA gyrase, an enzyme unique to prokaryotes, has been implicated in almost all processes that involve DNA. Although efficient inhibitors of this protein have been known for more than 20 years, none of them have enjoyed prolonged pharmaceutical success. It is only recently that the mechanisms of inhibition for some of these classes of drugs have been established unequivocally by X‐ray crystallography. It is hoped that this detailed structural information will assist the design of novel, effective inhibitors of DNA gyrase.

It is known that, on average, people adapt their choice of memory strategy to the subjective utility of interaction. What is not known is whether an individual's choices are boundedly optimal. Two experiments are reported that test the hypothesis that an individual's decisions about the distribution of remembering between internal and external resources are boundedly optimal where optimality is defined relative to experience, cognitive constraints, and reward. The theory makes predictions that are tested against data, not fitted to it. The (...) experiments use a no-choice/choice utility learning paradigm where the no-choice phase is used to elicit a profile of each participant's performance across the strategy space and the choice phase is used to test predicted choices within this space. They show that the majority of individuals select strategies that are boundedly optimal. Further, individual differences in what people choose to do are successfully predicted by the analysis. Two issues are discussed: the performance of the minority of participants who did not find boundedly optimal adaptations, and the possibility that individuals anticipate what, with practice, will become a bounded optimal strategy, rather than what is boundedly optimal during training. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

This book is a collection of secondary essays on America's most important philosophic thinkers—statesmen, judges, writers, educators, and activists—from the colonial period to the present. Each essay is a comprehensive introduction to the thought of a noted American on the fundamental meaning of the American regime.

Arguments are advanced that a theory of possible worlds cannot be a theory of meaning for modal statements, And lewis's version of the theory in his "counterfactuals" is used as a particular stalking-Horse. (a) 'possible world', Though used referentially, Is defined in a way that makes it non-Referential, And moreover, The theory does not supply or validate proposals for criteria that individuate worlds; hence the theory seems incomprehensible. (b) the theory yields no useable account of truth-Conditions for modal statements. (...) (c) a conceptualist version of the theory cannot overcome these problems. (d) lewis's similarity theory of possible worlds as a semantics for counterfactuals sustains in many cases (including one he cites) intuitively untrue counterfactuals and rejects many intuitively correct ones. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Controversy Between Schelling and Jacobi LEWIS S. FORD SCHELLING, ALONGWITH FICHTE, has suffered the fate of being labelled one of tIegel's predecessors. Richard Kroner provides the classic expression of this viewpoint in his monumental study, Von Kant bis Hegel, which examines Schelling's thought primarily for its contribution to Hegel's final synthesis.I In English we have Josiah Royce's sympathetic and lively account of Schelling's early romantic exuberance, (...) regarded as a transitional stage in the development of German idealism. 2 But this emphasis on the early ScheUing has led to an unfortunate neglect of his work subsequent to the break with Hegel in 1807. Schelling's romanticism, so ably documented by E. D. Hirsch, Jr., 3 can only be regarded as one phase in the total sweep of his thought, for, after the break with Hegel, Schelling produced at least three major works: the essay •ber das Wesen der menschlichen Freiheit,4 wrestling with the problem of evil and human freedom, the fragmentary Weltalter, 5 which in scope and dialectical intricacy should be compared with Hegel's Logic, and the Philosophie der Mythologie und Offenbarung, 6 furnishing a fundamental critique of the whole dialectical enterprise. Save for the essay on human freedom, however, none of these works were published during his lifetinm, as Schelling withdrew from the public eye after his controversies with Hegel and Jacobi. Thus the publishing histories of Schelling and Hegel are exactly reverse. Schelling rushed into print his early speculative gropings, while Hegel suppressed his/making the Ph~nomenologic des Geistes his first major publication. Then while Hegel's Logic and Encyclopedia were being publicly acclaimed, Schelling remained silent. This accident of history is largely responsible for the illusion that Schelling is the older of the two x (Tiibingen: J. C. B. Mohr, 1921-24),2 vols. 2The Spirit of Modern Philosophy (Boston: Houghton Mifflin, 1892), Lecture VI, 164-189. Wordsworth and ScheUing, A Typological Study of Romanticism (New Haven: Yale University Press, 1960),Yale Studies in English, Vol. CXLV. 4Friedrich Wilhelm Joseph yon Sehelling, Philosophische Untersuchungen i~berdas Wesen der menschlichen Freyheit und die damit zusaramenhdngenden Gegenstdnde, 1809. Reprinted in the Sdmmtliche Werke, Erste Abtheilung, VII. Band (Stuttgart und Augsburg: J. G. Cotta, 1856), 331-416. English translation by James Gutmann: Of Human Freedom (Chicago: Open Court, 1936). 5Three fragmentary versions of the Weltalter have been published. The Urfassungen of 1811 and 1813were edited by Manfrcd SehrSter and published as a separate Naehlassband to the M~nchener Jubildumsausgabe of the collected works: Die Weltalter, Fragmente (Munich: Biederstein, Leibniz, 1946). A later version is published in S.W. I: 8, pp. 195-344,which has been translated by Frederick de Wolfe Bolman, Jr. : The Ages of the World (NewYork: Columbia University Press, 1942). 6Philosophie der Mythologie is published in S.W. II: 1-2; Philosophie der Offenbarung in S.W. II: 3-4. These essays were first collected and published by Herman Nohl in Hegels theologische Jugendschriften (Tiibingen: 1907).T. M. Knox translated them into English, with an introduction by Richard Kroner: GeorgWilhelm Friedrich Hegel, Early Theological Writings (Chicago: University of Chicago Press, 1948). [75] 76 HISTORY OF PHILOSOPHY thinkers (actually he was five years Hegel's junior), who retired from the philosophical scene after making his contribution to the Hegelian synthesis. Paul Tillich's doctoral dissertations s and Ernst Cassirer's studies in post-Kantian thought 9 made serious inroads on this conception, yet the iIInsion persisted. Their insistence on the importance of the later Schelling has been brilliantly sustained by two recent studies: Horst Fuhrmans's Schellings Philosophie der Weltalter1~and Walter Schulz's Die Vollendung des deutschen Idealismus in der Spdtphilosophie Schellings, ~ and we may hope that the conventional estimate of Schelling will be drastically revised. Fuhrmans has demonstrated that the split between the early and the later Schelling must be placed in the year 1806 when he came in contact with Franz yon Bander in Munich, who encouraged him to delve deeper into the theological and cosmological ramifications of Jacob Boehme's thought. TM The reorientation this caused is apparent in the essay on human freedom, published in 1809, but it was not fully exploited until the... (shrink)

The Pragmatism Reader is the essential anthology of this important philosophical movement. Each selection featured here is a key writing by a leading pragmatist thinker, and represents a distinctively pragmatist approach to a core philosophical problem. The collection includes work by pragmatism's founders, Charles Peirce, William James, and John Dewey, as well as seminal writings by mid-twentieth-century pragmatists such as Sidney Hook, C. I. Lewis, Nelson Goodman, Rudolf Carnap, Wilfrid Sellars, and W.V.O. Quine. This reader also includes the most (...) important work in contemporary pragmatism by philosophers like Susan Haack, Cornel West, Hilary Putnam, Richard Rorty, Cheryl Misak, and Robert Brandom. Each selection is a stand-alone piece--not an excerpt or book chapter--and each is presented fully unabridged. The Pragmatism Reader challenges the notion that pragmatism fell into a midcentury decline and was dormant until the advent of "neopragmatism" in the 1980s. This comprehensive anthology reveals a rich and highly influential tradition running unbroken through twentieth-century philosophy and continuing today. It shows how American pragmatist philosophers have contributed to leading philosophical debates about truth, meaning, knowledge, experience, belief, existence, justification, and freedom. Covers pragmatist philosophy from its origins to today Features key writings by the leading pragmatist thinkers Demonstrates the continuity and enduring influence of pragmatism Challenges prevailing notions about pragmatism Includes only stand-alone pieces, completely unabridged Reflects the full range of pragmatist themes, arguments, concerns, and commitments. (shrink)

Nanay (2015; 2016) revives manner or attitude accounts of aesthetic experience. While manner-based accounts are promising, Nanay's claim that certain kinds of aesthetic experiences require attention to be focused on one object, but distributed across many properties of that object, that 'aesthetic attention' is necessary for 'Proustian experience', is false. Attention to objects of aesthetic experience frequently involves attention to intra-objects, objects that are proper perceptual parts of the attended objects.

Most people interested in the problems of ethics aspire to two kinds of knowledge, one systematic, the other historical. They wish a systematic understanding of the field: knowledge of what are the various problems and their interrelations and knowledge of what has been done toward the solution of these problems. They also wish to learn what the great historical philosophers -- particularly those who have had the most important ideas about values and conduct -- have said about the subject. This (...) book is intended to enable the reader to approximate the achievement of these twin goals at once. (shrink)

What system of morals should rational people select as the best for society? Using a contemporary psychological theory of action and of motivation, Richard Brandt's Oxford lectures argue that the purpose of living should be to strive for the greatest good for the largest number of people. Brandt's discussions range from the concept of welfare to conflict between utilitarian moral codes and the dictates of self-interest. Copyright © Libri GmbH. All rights reserved.

According to an old saying, "We make a living by what we get, but we make a life by what we give." In 22 brief and insightful essays, Richard B. Gunderman shows us that the key to more rewarding giving can be found by looking beyond mere donations of money. Exploring the ethical core of sharing and examining its importance for both those who receive and those who give, here is a book to deepen our understanding of what it (...) means to share. (shrink)

The ancient critics are well known—some might say notorious—for their readiness to read literature, and particularly Homer, through moral spectacles. Their interpretations of Homeric epic are philosophical, not only in the more limited sense that they identified specific doctrines in the speeches of Homer's characters, making the poet or his heroes spokesmen for the views of Plato or Epicurus, but also in a wider sense: the critics demand from Homer not merely entertainment but enlightenment on moral and religious questions, on (...) good and evil, on this life and the after-life. When they fail to find what they seek, they follow Plato and find him wanting. (shrink)

This article assays Paul Ramsey's influential attempt to conceive possible nuclear deterrents within the confines of just war tenets. I look first at Ramsey's construction of just war ideas according to a protection paradigm, one in which agape is deontically defined. I also note a subtle sub-theme in Ramsey's construction of just war ideas, what I call a preservation motif. I then assess Ramsey's discussion of nuclear deterrence, closing with a critique of his treatments of intention and proportionality. I conclude (...) by arguing that Ramsey's argument falters, and that the weaknesses of his argument can be rendered intelligible by noting how the full implications of the protection paradigm are attenuated by the preservation motif. (shrink)

This is the text of The Lindley Lecture for 1963, given by Richard B. Brandt (1910-1997), an American philosopher.

The book is philosophical psychology somewhat after the manner of Hume. It contains much helpful phenomenology of thinking, analysis, definitions of basic concepts, the outlines of a theory, and an account of how thinking so conceived can be knowledge. Again like Hume, Price aims to provide an empiricist account, that is, one the basic concepts in which can be "cashed" in terms of experience. Those interested in the problem of intentionality, in particular, should read the book.