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.

Although death by neurologic criteria is legally recognized throughout the United States, state laws and clinical practice vary concerning three key issues: the medical standards used to determine death by neurologic criteria, management of family objections before determination of death by neurologic criteria, and management of religious objections to declaration of death by neurologic criteria. The American Academy of Neurology and other medical stakeholder organizations involved in the determination of death by neurologic criteria have undertaken concerted action to address variation (...) in clinical practice in order to ensure the integrity of brain death determination. To complement this effort, state policymakers must revise legislation on the use of neurologic criteria to declare death. We review the legal history and current laws regarding neurologic criteria to declare death and offer proposed revisions to the Uniform Determination of Death Act and the rationale for these recommendations. (shrink)

Recent brain imaging studies using functional magnetic resonance imaging (fMRI) have implicated insula and anterior cingulate cortices in the empathic response to another’s pain. However, virtually nothing is known about the impact of the voluntary generation of compassion on this network. To investigate these questions we assessed brain activity using fMRI while novice and expert meditation practitioners generated a loving-kindness-compassion meditation state. To probe affective reactivity, we presented emotional and neutral sounds during the meditation and comparison periods. Our main hypothesis (...) was that the concern for others cultivated during this form of meditation enhances affective processing, in particular in response to sounds of distress, and that this response to emotional sounds is modulated by the degree of meditation training. The presentation of the emotional sounds was associated with increased pupil diameter and activation of limbic regions (insula and cingulate cortices) during meditation (versus rest). During meditation, activation in insula was greater during presentation of negative sounds than positive or neutral sounds in expert than it was in novice meditators. The strength of activation in insula was also associated with self-reported intensity of the meditation for both groups. These results support the role of the limbic circuitry in emotion sharing. The comparison between meditation vs. rest states between experts and novices also showed increased activation in amygdala, right temporo-parietal junction (TPJ), and right posterior superior temporal sulcus (pSTS) in response to all sounds, suggesting, greater detection of the emotional sounds, and enhanced mentation in response to emotional human vocalizations for experts than novices during meditation. Together these data indicate that the mental expertise to cultivate positive emotion alters the activation of circuitries previously linked to empathy and theory of mind in response to emotional stimuli.. (shrink)

Offering an inside look at the hidden dimensions of teaching, this provocative text presents insight into, and analysis of, the work of teaching--from preparing ...

The value of any kind of data is greatly enhanced when it exists in a form that allows it to be integrated with other data. One approach to integration is through the annotation of multiple bodies of data using common controlled vocabularies or ‘ontologies’. Unfortunately, the very success of this approach has led to a proliferation of ontologies which itself creates obstacles to integration. The Open Biomedical Ontologies (OBO) consortium has set in train a strategy to overcome this problem. Existing (...) OBO ontologies, including the Gene Ontology, are undergoing a process of coordinated reform and new ontologies being created on the basis of an evolving set of shared principles governing ontology development. The result is an expanding family of ontologies designed to be interoperable, logically well-formed, and to incorporate accurate representations of biological reality. We describe the OBO Foundry initiative, and provide guidelines for those who might wish to become involved. (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)

Recently, Richard Healey and Simon Friederich have each advocated a pragmatist interpretation of quantum mechanics as a way to dissolve its foundational problems. The idea is that if we concentrate on the way quantum claims are used, the foundational problems of quantum mechanics cannot be formulated, and so do not require solution. Their central contention is that the content of quantum claims differs from the content of non-quantum claims, in that the former is prescriptive whereas the latter is descriptive. (...) Healey also argues that claims about non-decoherent systems are largely devoid of content. I consider various objections to these claims, noting in particular the ways in which the application of pragmatism to quantum mechanics differs from previous examples of pragmatist therapy. I conclude that a pragmatist dissolution of the foundational difficulties of quantum mechanics is promising, but requires fairly radical changes to our understanding of the content of propositions and the extent of physical explanation. (shrink)

There is a widely acknowledged, albeit still imprecisely defined, connection between the ‘calculatory’ analyses of local motion developed within the fourteenth century ‘Merton School’ and Galileo Galilei's later treatment of natural motion. The present essay is intended to cast some light on the possible sources and significance of Galileo's putative familiarity with the medieval discussions through a study of the fortunes of the most typical representative of the School, Richard Swineshead. Particular attention is paid to the writings of such (...) scholastic philosophers of Galileo's day as Francisco Toledo, Francesco Piccolomini, Iacopo Zabarella, Francesco Buonamico and Scipione Chiaramonte. Somewhat unexpectedly, it emerges that such authors possessed only the most fragmentary and attenuated knowledge of Swineshead's ideas. The implications of this circumstance, especially insofar as it renders Galileo's familiarity with the Merton tradition even more problematical, are discussed briefly. (shrink)

Présentation de cinq grands intellectuels catholiques. Réflexion sur la foi et la raison. Essai engagé et sujet à débat.

"[This book] is a fascinating look at the fantasy and philosophy of C. S. Lewis and J. R. R. Tolkien. The two men were friends and fellow professors at Oxford, renowned Christian thinkers who both 'found it necessary to create for the purposes of their fiction other worlds—not utopias or dystopias, but different worlds.'" --.

The twenty-sixth volume in the highly acclaimed Library of Living Philosophers series is devoted to the work of British philosopher of logic and metaphysician, P. F. Strawson. Following the Library of Living Philosophers series format, the volume contains an intellectual autobiography, twenty critical and descriptive essays by leading philosophers from around the world, Strawson's replies to the essays, and a bibliography of Strawson's works. Born in 1919, Strawson was a leading proponent of ordinary language philosophy. He is the author of (...) the early and extremely influential paper "On Referring" in which he criticized Russell's theory of definite descriptions. His most influential book, Individuals, helped to raise the status of metaphysics as a philosophical enterprise. Themes first addressed in this book continued to be of concern to him in his later work, including the possibility of objective knowledge, the subject-predicate distinction, the ontological status of persons, and the problem of individuation. Contributors to the book include: Ruth Garrett Millikan, Susan Haack, E. M. Adams, Panayot Butchvarov, Richard Behling, John McDowell, Simon Blackburn, Tadeusz Szubka, David Frederick Haight, Joseph S. Wu, Andrew G. Black, David Pears, Robert Boyd, Hilary Putnam, Paul F. Snowdon, Arindam Chakrabarti, Wenceslao J. Gonzalez, Ernest Sosa, Chung-M. Tse, John R. Searle, P. F. Strawson. (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)

While Plato recommended expelling poets from the ideal society, W. H. Auden famously declared that poetry makes nothing happen. The 19 contributions to the present book avoid such polarized views and, responding in different ways to the “ethical turn” in narrative theory, explore the varied ways in which narratives encourage readers to ponder matters of right and wrong. All work from the premise that the analysis of narrative ethics needs to be linked to a sensitivity to esthetic form. The ethical (...) issues are accordingly located on different levels. Some are clearly presented as thematic concerns within the text considered, while others emerge through the presentation of character and event by means of particular narrative techniques. The objects of analysis include such well-known or canonical texts as Biblical Old Testament stories, Mark Twain’s Huckleberry Finn , J. R. R. Tolkien’s The Lord of the Rings , Vladimir Nabokov’s Lolita , Jonathan Littell’s The Kindly Ones , Ann Radcliffe’s The Italian and Matthew Lewis’s The Monk . Others concentrate on less-well-known texts written in languages other than English. There are also contributions that investigate theoretical issues in relation to a range of different examples. (shrink)

This dissertation examines the general problem of how to give a philosophical account of the nature of representation by looking at three specific philosophies of language and the philosophic treatment of fictional discourse. I argue that Edmund Husserl, Ludwig Wittgenstein, and J. L. Austin all try to give accounts of meaning by arguing for what I call a "closure of meaning" in language. The closure thesis is the claim that some set of criteria can exhaustively determine the ways in which (...) language can be meaningful. This thesis is implicit in Husserl's theory of expressive meaning in the Logical Investigations, in Wittgenstein's picture theory, and in J. L. Austin's pragmatic account of meaning in speech act theory. My general thesis is that the three philosophers in question do not successfully defend the closure thesis for linguistic representation. Since fictional discourse is a source of counterexamples to the closure thesis, I look specifically at two recent philosophical accounts of fiction by David Lewis and John Searle. I criticize these attempts to account for fictional discourse within referential and pragmatic theories of language. Since such attempts are usually part of a closure thesis, my discussion of fiction provides further reasons for doubting the general possibility of accounting for a closure of meaning in language. (shrink)

All humans have an equal basic moral status. They possess the same fundamental rights, and the comparable interests of each person should count the same in calculations that determine social policy. Neither supposed racial differences, nor skin color, sex, sexual orientation, ethnicity, intelligence, nor any other differences among humans negate their fundamental equal worth and dignity. These platitudes are virtually universally affirmed. A white supremacist racist or an admirer of Adolf Hitler who denies them is rightly regarded as beyond the (...) pale of civilized dialogue. However, a very simple line of argument developed by Peter Singer challenges our understanding of these platitudes and forces us to rethink the basis and nature of the moral equality of all humans. What I call the “Singer Problem” arises if one accepts that the morally significant cognitive capacities that are relevant to the determination of the fundamental moral status of a being vary from individual to individual by degree. The problem is to specify a moral principle determining fundamental moral status that assigns a superior status to humans compared to other animals on the basis of the superior cognitive capacities of humans but also assigns all human persons an equal fundamental moral status regardless of their differing cognitive capacities. More broadly posed, the problem is to specify moral principles that yield intuitively satisfactory implications for the treatment of human individuals and other individual animals given that cognitive capacities differ across species and individuals. A search for a resolution of the Singer problem leads to disappointing results. (shrink)

In recent years some moral philosophers and political theorists, who have come to be called “luck egalitarians,” have urged that the essence of social justice is the moral imperative to improve the condition of people who suffer from simple bad luck. Prominent theorists who have attracted the luck egalitarian label include Ronald Dworkin, G. A. Cohen, and John Roemer.1 Larry Temkin should also be included in this group, as should Thomas Nagel at the time that he wrote Equality and Partiality.2 (...) However, each of these theorists asserts a different position. The common ground, if any, is obscure. The idea of luck that is invoked is not transparently clear. Anyway, the term “luck egalitarianism” was coined by a critic of the doctrine, and tendentiously defined to denote an extreme version of the view that looks implausible from the start.3 With some justice Ronald Dworkin, perhaps the chief architect of the luck egalitarian position, has denied that he is a luck egalitarian. (shrink)

This essay surveys varieties of the luck egalitarian project in an exploratory spirit, seeking to identify lines of thought that are worth developing further and that might ultimately prove morally acceptable. I do not attend directly to the critics and assess their concerns; I have done that in other essays. 7 I do seek to identify some large fault lines, divisions in ways of approaching the task of constructing a theory of justice or of conceiving its substance. These are controversial (...) in the sense that in the present state of discussion it is unclear how best to view them or to which side it is better to scramble. But in the end of course I’m not a moral geographer and map-maker, just an involved spectator/tourist offering yet another view of the cathedral. (shrink)

This essay examines several possible rationales for the egalitarian judgment that justice requires better-off individuals to help those who are worse off even in the absence of social interaction. These rationales include equality (everyone should enjoy the same level of benefits), moral meritocracy (each should get benefits according to her responsibility or deservingness), the threshold of sufficiency (each should be assured a minimally decent quality of life), prioritarianism (a function of benefits to individuals should be maximized that gives priority to (...) the worse off), and mixed views. A case is made for adopting either prioritarianism or a mixed view that gives priority both to the worse off and to the more responsible and deserving. (shrink)

This paper attempts a defense of John Stuart Mill’s absolute ban against paternalistic restrictions on liberty. Mill’s principle looks more credible once we recognize that some instances of what are thought to be justified instances of paternalism are not instances of paternalism at all—e.g. anti-duelling laws. An interpretation of Mill’s argument is advanced which stresses his commitment to autonomy and his suggestion that exactly the same reasons which favor absolute freedom of speech also favor an absolute prohibition of paternalism. Alternative (...) expositions and appraisals of Mill by Gerald Dworkin and Joel Feiriberg are criticized. Finally, consideration is given to two arguments that render Mill’s principle trivial via the denial that there are any significant self-regarding actions. (shrink)

Some theorists hold that there is no serious, significant issue concerning cosmopolitanism. They hold that cosmopolitanism is either the anodyne doctrine that we have some duties to distant strangers merely on the ground of shared humanity or the absurd doctrine that we have no special moral duties based on special-ties such as those of friendship, family, and national community. This essay argues against this deflationary position by defending (1) a very extreme cosmopolitan doctrine that denies special-tie moral duties altogether and (...) (2) a slightly milder but still extreme form of cosmopolitanism that allows that there might be special-tie moral duties to intimate associates such as friends and family members but denies that broader social group associations such as those of subjection to a national state or national or ethnic community memberships ever constitute special ties that ground special moral duties. The defense proceeds by rebutting bad arguments leveled against extreme cosmopolitanisms. (shrink)

Prioritarianism holds that improvements in someone's life are morally more valuable, the worse off the person would otherwise be. The doctrine is impartial, holding that a gain in one person's life counts exactly the same as an identical gain in the life of anyone equally well off. If we have some duty of beneficence to make the world better, prioritarianism specifies the content of the duty. Unlike the utilitarian, the prioritarian holds that we should not only seek to increase human (...) well-being, but also distribute it fairly across persons, by tilting in favor of the worse off. A variant version adds that we should also give priority to the morally deserving – to saints over scoundrels. The view is a standard for right choice of individual actions and public policies, offering a distinctive alternative to utilitarianism, sufficiency and egalitarianism. (shrink)

At present, there is an enormous gulf between the visibility of evil and the paucity of our intellectual resources for coming to grips with it. We have been flooded with images of death camps, terrorist attacks and horrendous human suffering. Yet when we ask what we mean by radical evil and how we are to account for it, we seem to be at a loss for proper responses. Bernstein seeks to discover what we can learn about the meaning of evil (...) and human responsibility. He turns to philosophers such as Kant, who coined the expression 'radical evil', as well as to Hegel and Schelling. He also examines more recent explorations of evil, namely the thinking of Freud and Nietzsche on the moral psychology of evil. Finally, he looks at the way in which three post-Holocaust thinkers - Emmanuel Levinas, Hans Jonas, and Hannah Arendt - have sought to come to grips with evil "after Auschwitz." Bernstein's primary concern throughout this challenging book is to enrich and deepen our understanding of evil in the contemporary world, and to emphasize the vigilance and personal responsibility required for combating it. Radical Evil will be essential reading for students and scholars of philosophy, social and political theory, and religious studies. (shrink)

Recently in the U.S. a near-consensus has formed around the idea that it would be desirable to "end welfare as we know it," in the words of President Bill Clinton.1 In this context, the term "welfare" does not refer to the entire panoply of welfare state provision including government sponsored old age pensions, government provided medical care for the elderly, unemployment benefits for workers who have lost their jobs without being fired for cause, or aid to the disabled. "Welfare" in (...) contemporary debates means "cash, food, or housing assistance to healthy nonaged persons with low incomes."2 In the U.S., the main policy that qualifies as welfare in this sense is Aid to Families with Dependent Children.3 Although contemporary attacks on welfare are identified with conservative policy analysts such as Charles Murray, in fact dissatisfaction with the policies Murray targets for criticism is widespread among liberal intellectuals. For example, in a sharply critical review essay on Murray's book Losing Ground, Christopher Jencks worries that "the social policies that prevailed from 1964 to 1980 often seemed to reward vice" instead of rewarding virtuous conduct by the poor. The problem as Jencks, following Murray, views it is not easy to repair, because "if you set out to help people who are in trouble, you almost always find that most of them are to some extent responsible for their present troubles. Few victims are completely innocent. Helping those who are not doing their best to help themselves poses extraordinarily difficult moral and political problems."4 David T. Ellwood writes that Murray “is almost certainly correct in stating that welfare does not reflect or reinforce our most basic values. He is also correct in stating that no amount of tinkering with benefit levels or work rules will change that.”. (shrink)

Richard J. Bernstein argues that many of the important themes in philosophy during the past 150 years are variations and developments of ideas that were prominent in the classical American pragmatists: Charles S. Peirce, William James, John Dewey, and George H. Mead. The pragmatic thinkers reject a sharp dichotomy between subject and object, mind-body dualism, the quest for certainty, and the spectator theory of knowledge. They seek to bring about a sea change in philosophy that highlights the social character (...) of human experience and normative social practices, the self-correcting nature of all inquiry, and the continuity of theory and practice. And they - especially James, Dewey, and Mead - emphasize the democratic ethical-political consequences of a pragmatic orientation. Many of the themes developed by the pragmatic thinkers were central to the work of major twentieth-century philosophers such as Wittgenstein and Heidegger, but the so-called analytic/Continental split obscures this underlying continuity. Bernstein develops an alternative reading of contemporary philosophy that brings out the persistence and continuity of pragmatic themes. He explains why the discussion of pragmatism is alive, varied, and widespread"--Jacket. (shrink)

In this major new work, Bernstein explores the ethical and political dimensions of the modernity/post-modernity debate. Bernstein argues that modernity / post-modernity should be understood as a kind of mood - one which is amorphous, shifting and protean but which exerts a powerful influence on our current thinking. Focusing on thinkers such as Heidegger, Derrida, Foucault, Habermas and Rorty, Bernstein probes the strengths and weaknesses of their work, and shows how they have contributed to the formation of a new mood, (...) a new and distinctive constellation of ideas. This new constellation has put ethical and political issues back on the philosophical agenda, forcing us to confront anew, the Socratic question 'How should I live?'. (shrink)

Would a just society or government absolutely refrain from shaming or humiliating any of its members? "No," says this essay. It describes morally acceptable uses of shame, stigma and disgust as tools of social control in a decent (just) society. These uses involve criminal law, tort law, and informal social norms. The standard of moral acceptability proposed for determining the line is a version of perfectionistic prioritarian consequenstialism. From this standpoint, criticism is developed against Martha Nussbaum's view that to respect (...) the dignity of each person, society absolutely must refrain from certain ways of shaming and humiliating its members and rendering them objects of communal disgust. (shrink)

Left-libertarianism is a version of Lockean libertarianism that combines the idea that each person is the full rightful owner of herself and the idea that each person should have the right to own a roughly equal amount of the world's resources. This essay argues against left-libertarianism. The specific target is an interesting form of left-libertarianism proposed by Michael Otsuka that is especially stringent in its equal world ownership claim. One criticism advanced is that there is more tension than Otsuka acknowledges (...) between private ownership of self and equal ownership of the world. This emerges once one notices that self-ownership should not be conceived merely in a thin, formal way but also as a thicker substantive insistence on wide individual freedom. A second criticism is that in other respects the formal idea of self-ownership that Otsuka and other left-libertarians embrace is an extreme doctrine that merits rejection. (shrink)