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)

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.

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)

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)

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)

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.

This book measures the current institutional and political realities surrounding globalization against philosophical ideals.

Richard Brandt is one of the most eminent and influential of contemporary moral philosophers. His work has been concerned with how to justify what is good or right not by reliance on intuitions or theories about what moral words mean but by the explanation of moral psychology and the description of what it is to value something, or to think it immoral. His approach thus stands in marked contrast to the influential theories of John Rawls. The essays reprinted in (...) this collection span a period of almost 30 years and include many classic pieces in metaethical and normative ethical theory. The collection is aimed at both those moral philosophers familiar with Brandt's work and at those philosophers who may be largely unfamiliar with his work. The latter group will be struck by the lucid unpretentious style and the cumulative weight of Brandt's contributions to topics that remain at the forefront of moral philosophy. (shrink)

Richard Brandt is one of the most influential moral philosophers of the second half of the twentieth century. He is especially important in the field of ethics for his lucid and systematic exposition of utilitarianism. This new book represents in some ways a summation of his views and includes many useful applications of his theory. The focus of the book is how value judgments and moral belief can be justified. More generally, the book assesses different moral systems and theories (...) of justice, and considers specific problems such as the optimal level of charity and the moral tenability of the criminal law. This book will be essential reading for all professional philosophers concerned with ethics, and will prove helpful to students as well. (shrink)

Clouser and Gert’s 'A Critique of Principlism’ (1990) has ignited debate over the adequacy of substituting principlism for moral theory as a means for dealing with biomedical dilemmas. Clouser and Gert argue that this sort of substitution is not adequate to the task. I examine their argument in light of recent defences of principlism on this score, those of B. Andrew Lustig (1992), David Degrazia (1992), and Beauchamp and Childress (1994). I argue that both sides in the debate have assumed (...) differing conceptions of a moral theory that virtually guarantee their respective conclusions. These differing conceptions are motivated by antecedent epistemological commitments. The present debate over principlism is therefore inconclusive. Future discussion should focus on the underlying epistemological issues. (shrink)

The article explains a rule-Utilitarian normative thesis about when actions are morally excused; that an act otherwise morally objectionable in some way is excused if a moral system, The acceptance of which in the agent's society would be utility-Maximizing, Would not condemn it. What is meant by a "moral system condemning" an action is explained. The parallel between this moral thesis and the benthamite theory of criminal justice is developed. It is argued that this rule-Utilitarian thesis implies that an action (...) is morally excused (not blameworthy) if it does not manifest a defective trait of character. (shrink)

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)

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)

Scholars of ethics, and of human behavior more generally, will find this book consistently stimulating and rewarding.

The actions and decisions taken by the present generation will affect not only the welfare but also the composition of future generations. A number of authors have used this fact to bolster the conclusion that the present is only weakly obligated to provide for future welfare since in choosing between futures of poverty and abundance, we are not deciding the welfare of a well-defined group of future persons but instead deciding which set of potential persons – the poor or the (...) rich – will become actual. Provided that future generations have lives that are worth living, they will be grateful to us for bringing them into existence – or so the argument goes. In this paper, I argue that this position overlooks an important aspect of the intergenerational problem. We are obligated to provide for the actual children of today, who will in turn be obligated to provide for their children, and so forth from generation to generation. A chain of obligation is thus defined that stretches from the present into the indefinite future, and unless we ensure conditions favourable to the welfare of future generations, we wrong our existing children in the sense that they will be unable to fulfill their obligation to their children while enjoying a favourable way of life themselves. (shrink)