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)

Most individuals realise that we have a moral obligation to avoid the evils of war. But this realization raises a host of difficult questions when we, as responsible individuals, witness harrowing injustices such as ""ethnic cleansing"" in Bosnia or starvation in Somalia. With millions of lives at stake, is war ever justified? And, if so, for what purpose? In this book, Richard J. Regan confronts these controversial questions by first considering the basic principles of just-war theory and then applying (...) those principles to historical and ongoing conflicts. Part One presents two opposing viewpoints: first, that war is not subject to moral norms and, second, that war is never morally permissible. The author rejects both perspectives, and moves to define the principles of just-war theory. He evaluates the roles of the president, Congress and, most importantly, the UN Security Council in determining when long-term US military involvement is justified. The moral limits of war conduct and the moral problem of using, or threatening to use, nuclear weapons are also discussed. On the just cause to wage war, Regan argues that defense of nations and nationals - whether in self-defense or in defense of others - remains the ""only"" classical cause that in the modern world would justify resorting to war. With respect to military intervention in secessionist and revolutionary wars, he contends that such intervention might be justified, but that prudence dictates extreme caution. In considering acceptable war conduct, Regan elaborates the specific principle of discrimination and proportionality; he maintains that civilians uninvolved in the enemy's war should not be directly targeted and that the costs of military action must be proportionate to the anticipated benefits of destroying military targets. The second part of the book presents case studies of eight historical wars - World War I, the Vietnam War, the Falklands War, the revolution and civil war in Nicaragua, the civil war in El Salvador, the Gulf War, the intervention in Somalia, and the Bosnian War - and poses several provocative questions about each. It invites readers and students to apply just-war principles to complex war-related situations and to understand the factual contingencies involved in moral judgements about war decisions. The book should be of particular interest to students of the moral issues of international relations and to readers interested more generally in philosophy, theology and political science. (shrink)

Many bodily sensations are connected quite closely with specific actions: itches with scratching, for example, and hunger with eating. Indeed, these connections have the feel of conceptual connections. With the exception of D. M. Armstrong, philosophers have largely neglected this aspect of bodily sensations. In this paper, I propose a theory of bodily sensations that explains these connections. The theory ascribes intentional content to bodily sensations but not, strictly speaking, representational content. Rather, the content of these sensations is an imperative: (...) in the case of itches, 'Scratch!' The view avoids non-intentional qualia and hence accords with what could be called, generalizing Lycan slightly, the 'hegemony of intentionality'. (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)

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)

Philosophers perennially debate the nature of the good for humans. Is it subjective or objective? That is to say, do the things that are intrinsically good for an agent, good for their own sakes and apart from further consequences, acquire this status only in virtue of how she happens to regard them? Or are there things that are good in themselves for an individual independently of her desires and attitudes toward them? The issue sounds recondite, but has been thought to (...) be pregnant with implications for politics as it ought to be. Plato vigorously insists that knowledge of the good is precious and the person who has it is uniquely fit to rule: "In the world of knowledge, the last thing to be perceived and only with great difficulty is the essential Form of Goodness. Once it is perceived, the conclusion must follow that, for all things, this is the cause of whatever is right and good; in the visible world it gives birth to the light and to the lord of light, while it is itself sovereign in the intelligible world and the parent of wisdom and truth. Without having had a vision of this Form no one can act with wisdom, either in his own life or in matters of state.". (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)

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)

Introduction i This book is about how we study history, how we research and write about it, and how we read it. In the postmodern age, historians are being ...

This essay reexamines the idea of paternalism and the basis for finding it objectionable in light of recent writings on “libertarian paternalism.” Suggestion: to qualify as paternalistic, an interference that restricts someone’s liberty or interferes with her choice-making with the aim of helping the individual must be contrary to that very individual’s will. A framework for determining the justifiability of paternalistic action is proposed, under the assumption that the individual has a personal prerogative, up to a point, to engage in (...) less than maximally beneficial action. Beyond that point, the content of the will of the individual disposed against interference can extinguish the presumptive wrongness of paternalism. (shrink)

"A fascinating and timely treatment of the objectivism versus relativism debates occurring in philosophy of science, literary theory, the social sciences, ...

In her recent, provocative essay “What Is the Point of Equality?”, Elizabeth Anderson argues against a common ideal of egalitarian justice that she calls “ luck egalitarianism” and in favor of an approach she calls “democratic equality.”1 According to the luck egalitarian, the aim of justice as equality is to eliminate so far as is possible the impact on people’s lives of bad luck that falls on them through no fault or choice of their own. In the ideal luck egalitarian (...) society, there are no inequalities in people’s life prospects except those that arise through processes of voluntary choice or faulty conduct, for which the agents involved can reasonably be held responsible. Anderson asserts that the adherents of luck egalitarianism, which can be elaborated in many different ways, include John Roemer, Erik Rakowski, Thomas Nagel, Ronald Dworkin, Gerald Cohen, Richard Arneson, and Philippe Van Parijs.2 In contrast, according to the democratic equality conception, justice as equality requires an end to oppressive social relationships. In the ideal society of democratic equality, the social conditions of everyone’s freedom are secured, each stands to every other in a relationship of fundamental equality, including equal respect, and all have real freedom to participate in democratic self-government. (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)

Jean Baudrillard is one of the most famous and controversial of writers on postmodernism. But what are his key ideas? Where did they come from and why are they important? This book offers a beginner's guide to Baudrillard's thought, including his views on technology, primitivism, reworking Marxism, simulation and the hyperreal, and America and postmodernism. Richard Lane places Baudrillard's ideas in the contexts of the French and postmodern thought and examines the ongoing impact of his work. Concluding with an (...) extensively annotated bibliography of the thinker's own texts, this is the perfect companion for any student approaching the work of Jean Baudrillard. (shrink)

What is the good for human persons? If I am trying to lead the best possible life I could lead, not the morally best life, but the life that is best for me, what exactly am I seeking?This phrasing of the question I will be pursuing may sound tendentious, so some explanation is needed. What is good for one person, we ordinarily suppose, can conflict with what is good for other persons and with what is required by morality. A prudent (...) person seeks her own good efficiently; she selects the best available means to her good. If we call the value that a person seeks when she is being prudent “prudential value,” then an alternative rendering of the question to be addressed in this essay is “What is prudential value?” We can also say that an individual flourishes or has a life high in well-being when her life is high in prudential value. Of course, these common-sense appearances that the good for an individual, the good for other persons, and the requirements of morality often are in conflict might be deceiving. For all that I have said here, the correct theory of individual good might yield the result that sacrificing oneself for the sake of other people or for the sake of a morally worthy cause can never occur, because helping others and being moral always maximize one's own good. But this would be the surprising result of a theory, not something we should presuppose at the start of inquiry. When a friend has a baby and I express a conventional wish that the child have a good life, I mean a life that is good for the child, not a life that merely helps others or merely respects the constraints of morality. After all, a life that is altruistic and perfectly moral, we suppose, could be a life that is pure hell for the person who lives it—a succession of horrible headaches marked by no achievements or attainments of anything worthwhile and ending in agonizing death at a young age. So the question remains, what constitutes a life that is good for the person who is living it? (shrink)

Individual differences in emotional reactivity or affective style can be decomposed into more elementary constituents. Several separable of affective style are identified such as the threshold for reactivity, peak amplitude of response, the rise time to peak and the recovery time. latter two characteristics constitute components of affective chronometry The circuitry that underlies two fundamental forms of motivation and and withdrawal-related processes-is described. Data on differences in functional activity in certain components of these are next reviewed, with an emphasis on (...) the nomological network of surrounding individual differences in asymmetric prefrontal The relevance of such differences for understanding the nature affective dysfunction in affective disorders is then considered. The ends by considering what the prefrontal cortex “does” in certain of affective style and highlights some of the important questions for future research. (shrink)

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