Calpain (Cp) is a calcium (Ca2+)‐dependent cysteine protease. Activation of the major isoforms of Cp, CpI and CpII, are required for a number of important cellular processes including adherence, shape change and migration. The current concept that cytoplasmic Cp locates and associates with its regulatory subunit (Rs) and substrates as well as translocates throughout the cell via random diffusion is not compatible with the spatial and temporal constraints of cellular metabolism. The novel finding that Cp and Rs function relies upon (...) tenacious hydrophobic interactions with organelle membranes offers a unifying explanation for the paradoxical and puzzling features of Cp activation and regulation such as how nM concentrations of intracellular Ca2+ can activate Cp molecules requiring μM to mM concentrations of Ca2+ for in vitro activation, and how this protease can spatially and temporally locate specific substrates and translocate throughout the cell. We hypothesize that Cp and its regulatory moieties associate with organelles to facilitate the activation of this protease resulting in the cleavage of substrates and aid in its translocation throughout the cell. BioEssays 28: 850–859, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Political societies frequently regard philosophers as potential threats to morality and religion, and those who speak for politics often demand a defense of philosophy. This book will address philosophy as a mode of existence put into question.

This text is an ideal introduction for students to the basic mathematics of operations research as well as a valuable source of references to early literature ...

_The Laws_, Plato's longest dialogue, has for centuries been recognized as the most comprehensive exposition of the _practical_ consequences of his philosophy, a necessary corrective to the more visionary and utopian _Republic_. In this animated encounter between a foreign philosopher and a powerful statesman, not only do we see reflected, in Plato's own thought, eternal questions of the relation between political theory and practice, but we also witness the working out of a detailed plan for a new political order that (...) embodies the results of Plato's mature reflection on the family, the status of women, property rights, criminal law, and the role of religion and the fine arts in a healthy republic. "Because it succeeds in being both literal and comprehensive, it is by far superior to any translation available. By reproducing dramatic detail often omitted, such as oaths, hesitations, repetitions, and forms of address, Pangle allows the reader to follow the dialogue's interplay between argument and dramatic context.... Pangle's translation captures the excitement and the drama of Plato's text."—Mary P. Nichols, _Ancient Philosophy_ "Pangle's achievement is remarkable.... The accompanying interpretive essay is an excellent distillation of a dialogue three times its size. The commentary is thoughtful, even profound; and it amply demonstrates the importance of reading Plato carefully and from a translation that is true to his language."—Patrick Coby, _American Political Science Review_. (shrink)

The Spirit of the Laws —Montesquieu’s huge, complex, and enormously influential work—is considered one of the central texts of the Enlightenment, laying the foundation for the liberally democratic political regimes that were to embody its values. In his penetrating analysis, Thomas L. Pangle brilliantly argues that the inherently theological project of Enlightenment liberalism is made more clearly—and more consequentially— in Spirit than in any other work. _ In a probing and careful reading, Pangle shows how Montesquieu believed that rationalism, (...) through the influence of liberal institutions and the spread of commercial culture, would secularize human affairs. At the same time, Pangle uncovers Montesquieu’s views about the origins of humanity’s religious impulse and his confidence that political and economic security would make people less likely to sacrifice worldly well-being for otherworldly hopes. With the interest in the theological aspects of political theory and practice showing no signs of diminishing, this book is a timely and insightful contribution to one of the key achievements of Enlightenment thought. (shrink)

Introduction -- Nazi philosophy -- The expulsion of the invaders -- Philosophical method : virtue vs. vice -- The virtuous tradition : analysis, liberalism, englishness -- Epilogue.

Objectivity can be effectively described as striving for detachment -a capacity to achieve some distance from one's own spontaneous perceptions and convictions, to experimentally adopt perspectives that do not come naturally. Novick's treatment of objectivity satisfies the requirements of objectivity, while on a rhetorical level he rejects the notion as unrealistic. Detachment enables an intellectual, specifically an historian, to operate with self-reflexivity and simultaneously socializes him or her. The ultimate power in a community of detached intellectuals striving for objectivity is (...) a powerful argument. Under Novick's notion of objectivity, the conflict for historians between scholarly integrity and political alliance is unresolvable. Removing neutrality from the definition of objectivity resolves this conflict, enabling historians to strive for detachment and fairness, not disengagement from life. Postmodern disclaimers, such as Novick's on the futility of objectivity, fail, through being overly dismissive, to help us establish criteria for evaluating individual historical accounts. Having objectivity as a goal enables us to establish those criteria. (shrink)

Few moral questions have greater bearing on the conduct of our everyday lives than questions about the morality of lying. These questions are also important for ethical theory. An important test of any theory of right and wrong is whether it gives an adequate account of the morality of lying. Conceptual questions about the nature of lying are prior to questions about the moral status of lying. Any theory about the moral status of lying presupposes an account of what lying (...) is. (shrink)

While many (perhaps most) of those engaged in the study of philosophy would accept the continued reality and importance of an analytic/continental divide in the discipline, there has been no serious examination of the political dimensions of this rift. Here a series of political assumptions are revealed to be widely held among the British analytic philosophers who were active during the period in which the analytic/continental divide was being established. This paper will approach demonstrating the analysts’ beliefs about the political (...) affiliations of continental philosophy in three ways. Firstly, it will produce direct evidence of the analysts’ belief in the relationship between 19th century continental philosophy and various politically undesirable regimes. Secondly, it will examine in detail one illustrative example, that of Hegel. Thirdly, it will illustrate how the political beliefs already canvassed permeated beyond the limited political critique of continental philosophy into the analysts’ writing on the history of philosophy. (shrink)

Marr's levels of analysis—computational, algorithmic, and implementation—have served cognitive science well over the last 30 years. But the recent increase in the popularity of the computational level raises a new challenge: How do we begin to relate models at different levels of analysis? We propose that it is possible to define levels of analysis that lie between the computational and the algorithmic, providing a way to build a bridge between computational- and algorithmic-level models. The key idea is to push the (...) notion of rationality, often used in defining computational-level models, deeper toward the algorithmic level. We offer a simple recipe for reverse-engineering the mind's cognitive strategies by deriving optimal algorithms for a series of increasingly more realistic abstract computational architectures, which we call “resource-rational analysis.”. (shrink)

For as long as humans have pondered philosophical issues, they have contemplated the good life. Yet most suggestions about how to live a good life rest on assumptions about what the good life actually is. Thomas Carson here confronts that question from a fresh perspective. Surveying the history of philosophy, he addresses first-order questions about what is good and bad as well as metaethical questions concerning value judgments. Carson considers a number of established viewpoints concerning the good life. He (...) offers a new critique of Mill's and Sidgwick's classic arguments for the hedonistic theory of value, employing thought experiments that invite us to clarify our preferences by choosing between different kinds of lives. He also assesses the desire- or preference-satisfaction theory of value in detail and takes a fresh look at both Nietzsche's Übermensch ideal and Aristotle's theory of the good life. In exploring foundational questions, Carson observes that many established theories rest on undefended assumptions about the truth of moral realism. Arguing against this stand, he defends the view that good means desirable and presents a divine-preference version of the desire-satisfaction theory. In this he contends that, if there exists a kind and omniscient God who created the universe, then what is good or bad is determined by His preferences; if such a God does not exist, what is good or bad depends on what we as rational humans desire. Value and the Good Life is the only book that defends a divine-preference theory of value as opposed to a divine-command theory of right and wrong. It offers a masterfully constructed argument to an age-old question and will stimulate all who seek to know what the good life truly is. (shrink)

. What distinguishes Pangle's study from the dozens of books which have challenged or elaborated upon the republican revision is the sharpness with which he ...

Languages are transmitted from person to person and generation to generation via a process of iterated learning: people learn a language from other people who once learned that language themselves. We analyze the consequences of iterated learning for learning algorithms based on the principles of Bayesian inference, assuming that learners compute a posterior distribution over languages by combining a prior (representing their inductive biases) with the evidence provided by linguistic data. We show that when learners sample languages from this posterior (...) distribution, iterated learning converges to a distribution over languages that is determined entirely by the prior. Under these conditions, iterated learning is a form of Gibbs sampling, a widely-used Markov chain Monte Carlo algorithm. The consequences of iterated learning are more complicated when learners choose the language with maximum posterior probability, being affected by both the prior of the learners and the amount of information transmitted between generations. We show that in this case, iterated learning corresponds to another statistical inference algorithm, a variant of the expectation-maximization (EM) algorithm. These results clarify the role of iterated learning in explanations of linguistic universals and provide a formal connection between constraints on language acquisition and the languages that come to be spoken, suggesting that information transmitted via iterated learning will ultimately come to mirror the minds of the learners. (shrink)

There is a consensus that post-war British analytic philosophy was politically neutral. This view has been affirmed by the post-war analysts themselves, and by their critics. This paper argues that this consensus-view is false. Many central analytic philosophers claimed that their empirical philosophy had liberal outcomes, either through cultivating liberal habits of mind, or by revealing truths about the world that supported liberal conclusions. These beliefs were not subject to significant scrutiny or attempts at justification, but they do help us (...) to explain the otherwise puzzling disinclination to engage with questions of political philosophy on the part of these politically active individuals. (shrink)

The recent accounting scandals at Enron, WorldCom, and other corporations have helped to fuel a massive loss of confidence in the integrity of American business and have contributed to a very sharp decline in the U.S. stock market. Inasmuch as these events have brought ethical questions about business to the forefront in the media and public consciousness as never before, they are of signal importance for the field of business ethics. I offer some observations and conjectures about the bearing of (...) the recent scandals on the literature on business ethics. I defend the following contentions: 1. Recent events reveal serious weaknesses of the stakeholder theory about the social responsibilities of business which lacks prohibitions against fraud and deception. This is a glaring deficiency of standard versions of the stakeholder theory, but it is easily remedied by adding explicit prohibitions against fraud and deception. In addition, recent events highlight the stakeholder theory's very naive and unrealistic hopes and expectations for business executives as moral arbiters and agents of social improvement. 2. Recent events do not constitute an objection to the shareholder theory about the social responsibilities of business, however, these events make evident the implausibility of strong versions of the invisible hand theory. 3. Schemes of payment and reward often create perverse incentives for individuals to engage in unethical conduct. 4. Both the shareholder theory and the stakeholder theory need to add a constraint that requires executives to respect the professional obligations of employees. (shrink)

What is freedom? In this study, Thomas Dumm challenges the conventions that have governed discussions and debates concerning modern freedom by bringing the work of Michel Foucault into dialogue with contemporary liberal thought. While Foucault has been widely understood to have characterized the modern era as being opposed to the realization of freedom, Dumm shows how this characterization conflates Foucault’s genealogy of discipline with his overall view of the practices of being free. Dumm demonstrates how Foucault’s critical genealogy does (...) not shrink from understanding the ways in which modern subjects are constrained and shaped by forces greater than themselves, but how it instead works through these constraints to provide, not simply a vision of liberation, but a joyous wisdom concerned with showing us, in his words, that we “are much freer than we feel.” Both as an introduction to Foucault and as an intervention in liberal theory, Michel Foucault and the Politics of Freedom is bound to change how we think about the limits and possibilities of freedom in late modernity. (shrink)

Leo Strauss's controversial writings have long exercised a profound subterranean cultural influence. Now their impact is emerging into broad daylight, where they have been met with a flurry of poorly informed, often wildly speculative, and sometimes rather paranoid pronouncements. This book, written as a corrective, is the first accurate, non-polemical, comprehensive guide to Strauss's mature political philosophy and its intellectual influence. Thomas L. Pangle opens a pathway into Strauss's major works with one question: How does Strauss's philosophic thinking contribute (...) to our democracy's civic renewal and to our culture's deepening, critical self-understanding? This book includes a synoptic critical survey of writings from scholars who have extended Strauss's influence into the more practical, sub-philosophic fields of social and political science and commentary. Pangle shows how these analysts have in effect imported Straussian impulses into a "new" kind of political and social science. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Books ReceivedThe Ambitions of Curiosity: Understanding the World in Ancient Greece and China. By G.E.R. Lloyd. Cambridge: Cambridge University Press, 2002. Pp. xvi + 175. Price not given.The Art of the Han Essay: Wang Fu's Ch'ien-Fu Lun. By Anne Behnke Kinney. Tempe: Center for Asian Studies, Arizona State University, 1990. Pp. xi + 154. Paper $10.00.The Autobiography of Jamgön Kongtrul: A Gem of Many Colors. By Jamgön Kongtrul Lodrön (...) Thayé and translated by Richard Barron (Chökyi Nyima). Ithaca, New York: Snow Lion Publications, 2003. Pp. xxii + 549. Price not given.Awesome Nightfall: The Life, Times, and Poetry of Saigyō. By William R. LaFleur. Boston: Wisdom Publications, 2003. Pp. xiii + 173. Paper $14.95.Becoming the Compassion Buddha: Tantric Mahamudra for Everyday Life. By Lama Thubten Yeshe, edited by Robina Courtin, and foreword by Geshe Lhundub Sopa. Boston: Wisdom Publications, 2003. Pp. xi + 194. Paper $14.95.Between Two Worlds East and West: An Autobiography. By J. N. Mohanty. New Delhi: Oxford University Press, 2002. Pp. ix + 134. Hardcover RS 525.00.The Chinese Face of Jesus Christ. Edited by Roman Malek, S.V.D. Sankt Augustin, Germany: Institut Monumenta Serica and China-Zentrum; and Nettetal, Germany: Steyler Verlag, 2002. Pp. 391. EUR 40.00.Chinese Medicine in Contemporary China: Plurality and Synthesis. By Volker Scheid. Durham and London: Duke University Press, 2002. Pp. xiv + 407. Hardcover $69.95. Paper $23.95.Confucian Feminist: Memoirs of Zeng Baosun (1893-1978). Translated and adapted by Thomas L. Kennedy. Philadelphia: American Philosophical Society, 2002. Pp. xxi + 170. Price not given.Consciousness Studies: Cross-Cultural Perspectives. By K. Ramakrishna Rao. Jefferson (North Carolina) and London: McFarland and Company, 2002. Pp. 367. Hardcover $65.00.Constituting Communities: Theravāda Buddhism and the Religious Cultures of South and Southeast Asia. Edited by John Clifford Holt, Jacob N. Kinnard, and Jonathan S. Walters. Albany: State University of New York Press, 2003. Pp. viii + 224. Hardcover $65.50. Paper $21.95.Developments in Indian Philosophy from Eighteenth Century Onwards: Classical and Western. By Daya Krishna. Volume X Part 1 of History of Science, Philosophy and Culture in Indian Civilization, edited by D. P. Chattopadhyaya. New [End Page 110] Delhi: Centre for Studies in Civilizations, 2001. Pp. xxiii + 417. Hardcover RS 1200.East and West: Identità e dialogo interculturale. By Giangiorgio Pasqualotto. Venezia: Marsilo Editori, 2003. Pp. 210. EUR 16.00.Effortless Action: Wu-wei as Conceptual Metaphor and Spiritual Ideal in Early China. By Edward Slingerland. New York: Oxford University Press, 2003. Pp. xii + 352. Price not given.Encountering Kā lī: In the Margins, at the Center, in the West. Edited by Rachel Fell McDermott and Jeffrey J. Kripal. Berkeley and Los Angeles: University of California Press, 2003. Pp. xviii + 321. Hardcover $55.00, £37.95. Paper $21.95, £15.95.Encyclopedia of Chinese Philosophy. Edited by Antonio S. Cua. New York and London: Routledge, 2003. Pp. xx + 1020. Hardcover $150.00.Essays on Indian Philosophy. By J. N. Mohanty and edited by Purushottama Bilimoria. New Delhi: Oxford University Press, 2002. Pp. xxxvii + 347. Paper RS 525.00.Faith, Humor, and Paradox. By Ignacio L. Götz. Westport, Connecticut: Praeger Publishers, 2002. Pp. 136. Hardcover $61.95.Four Illusions: Candrakīrti's Advice for Travelers on the Bodhisattva Path. Translated by Karen C. Lang. New York: Oxford University Press, 2003. Pp. xv + 240. Price not given.The Great Awakening: A Buddhist Social Theory. By David R. Loy. Boston: Wisdom Publications, 2003. Pp. 223. Paper $16.95.The Hidden History of The Tibetan Book of the Dead. By Bryan J. Cuevas. New York: Oxford University Press, 2003. Pp. xi + 328. Price not given.Huang Di nei jing su wen: Nature, Knowledge, Imagery in an Ancient Chinese Medical Text. By Paul U. Unschuld. Berkeley and Los Angeles: University of California Press, 2003. Pp. xii + 520. Hardcover $75.00, £52.00.In Dewey's Wake: Unfinished Work of Pragmatic Reconstruction. Edited by William J. Gavin. Albany: State University of New York Press, 2003. Pp. vi + 249. Hardcover $71.50. Paper $23.95.Knowledge and Freedom in Indian Philosophy. By Tara Chatterjea. Lanham, Maryland: Lexington Books, 2002. Pp. xvi + 159. Hardcover... (shrink)

This paper addresses the following three claims that Frankfurt makes about the concept of bullshit:1. Bullshit requires the intention to deceive others.2. Bullshit does not constitute lying.3. The essence of bullshit is lack of concern with the truth of what one says.I offer counterexamples to all three claims. By way of defending my counterexamples, I examine Cohen’s distinction between bullshiting and bullshit and argue that my examples are indeed cases of bullshiting that Frankfurt’s analysis is intended to cover. My examples (...) of bullshitters who are very concerned to say only things that are true show that Frankfurt is mistaken in claiming that the “essence” of bullshit is lack of concern with the truth of what one says. (shrink)

People are adept at inferring novel causal relations, even from only a few observations. Prior knowledge about the probability of encountering causal relations of various types and the nature of the mechanisms relating causes and effects plays a crucial role in these inferences. We test a formal account of how this knowledge can be used and acquired, based on analyzing causal induction as Bayesian inference. Five studies explored the predictions of this account with adults and 4-year-olds, using tasks in which (...) participants learned about the causal properties of a set of objects. The studies varied the two factors that our Bayesian approach predicted should be relevant to causal induction: the prior probability with which causal relations exist, and the assumption of a deterministic or a probabilistic relation between cause and effect. Adults’ judgments (Experiments 1, 2, and 4) were in close correspondence with the quantitative predictions of the model, and children’s judgments (Experiments 3 and 5) agreed qualitatively with this account. (shrink)

My interest in the issues considered here arose out of my great frustration in trying to attack the all-pervasive relativism of my students in introductory ethics courses at Virginia Polytechnic Institute and State University. I am grateful to my students for forcing me to take moral relativism and skepticism seriously and for compelling me to argue for my own dogmatically maintained version of moral objectivism. The result is before the reader. The conclusions reached here (which can be described either as (...) a minimal objectivism or as a moderate verson of relativism) are considerably weaker than those that I had expected and would have liked to have defended. I have arrived at these views kicking and screaming and have resisted them to the best of my ability. The arguments of this book are directed at those who deny that moral judgments can ever be correct (in any sense that is opposed to mistaken) and who also deny that we are ever rationally com pelled to accept one moral judgment as opposed to another. I have sought to take their views seriously and to fight them on their own grounds without making use of any assumptions that they would be unwilling to grant. My conclusion is that, while it is possible to refute the kind of extreme irrationalism that one often encounters, it is impossible to defend the kind of objectivist meta-ethical views that most of us want to hold, without begging the question against the non-objectivist. (shrink)