Variations in levels of apolipoprotein E have been tied to the risk and progression of Alzheimer's disease . Our group has previously compared and contrasted the promoters of the mouse and human ApoE gene promoter sequences and found notable similarities and significant differences that suggest the importance of the APOE promoter's role in the human disease. We examine here three specific single-nucleotide polymorphisms within the human APOE promoter region, specifically at -491 , -427 , and at -219 upstream from the (...) +1 transcription start site. The -219 and -491 polymorphic variations have significant association with instance of AD, and -491AA has significant risk even when stratified for the APOEepsilon4 allele. We also show significant effects on reporter gene expression in neuronal cell cultures, and, notably, these effects are modified by species origin of the cells. The -491 and -219 polymorphisms may have an interactive effect in addition to any independent activity. DNA-protein interactions differ between each polymorphic state. We propose SP1 and GATA as candidates for regulatory control of the -491 and -219 polymorphic sites. This work's significance lies in drawing connection among APOE promoter polymorphisms' associations with AD to functional promoter activity differences and specific changes in DNA-protein interactions in cell culture-based assays. Taken together, these results suggest that APOE expression levels are a risk factor for AD irrespective of APOEepsilon4 allele status. (shrink)

Based on ten years of research, The Touch of the Past considers how historically traumatic events uniquely summon forgetting and remembrance. Within a specific focus on events of systemic mass violence, Roger Simon examines how testimonies of historic events influence learning as communities struggle with "difficult histories." The Touch of the Past is a serious and compelling contribution to research in education, historical consciousness, and memory/trauma studies.

The most pressing issues of the twenty-first century—climate change and persistent hunger in a world of food surpluses, to name only two—are not problems that can be solved from within individual disciplines, nation-states, or cultural perspectives. They are predicaments that can only be resolved by generating sustained and globally robust coordination across value systems. The scale of the problems and necessity for coordinated global solutions signal a world historical transit as momentous as the Industrial Revolution: a transition from the predominance (...) of technical knowledge to that of ethical deliberation. This volume brings together leading thinkers from around the world to deliberate on how best to correlate worth (value) with what is worthwhile (values), pairing human prosperity with personal, environmental, and spiritual flourishing in a world of differing visions of what constitutes a moral life. Especially in the aftermath of what is now being called the Great Recession, awareness has mounted of the imperative to question the modern divorce of economics from ethics. While the domains of economics and ethics were from antiquity through at least the eighteenth century understood in many cultures to be coterminous and mutually entailing, the modern assumption has been that the goal of maximizing human prosperity and the aim of justly enhancing our lives as persons and as communities were functionally and practically distinct. Working from a wide array of perspectives, the contributors to this volume offer a set of challenges to the assumed independence of the quantitative and qualitative dimensions of human and planetary well-being. Reflecting on the complex interrelationship among economics, justice, and equity, the book resists "one size fits all" approaches and struggles to revitalize the marriage of economics and ethics by activating cultural differences as the basis of mutual contribution to shared human flourishing. The publication of this important collection will stimulate or extend critical debates among scholars and students working in a number of disciplines in the social sciences and humanities, including philosophy, history, environmental studies, economics, and law. Contributors: Roger T. Ames, James Behuniak Jr., Steve Bein, Nalini Bhushan, Purushottama Bilimoria, Steven Burik, Amita Chatterjee, Baoyan Cheng, Gordon Davis, Jay L. Garfield, Steven F. Geisz, Peter D. Hershock, Larry A. Hickman, Kathleen M. Higgins, Heidi M. Hurd, Thomas P. Kasulis, Workineh Kelbessa, Lori Keleher, Oliver Leaman, James McRae, Jin Y. Park, James Peterman, Naoko Saito, May Sim, Robert Smid, Paul Standish, Kenneth W. Stikkers, Karsten J. Struhl, Meera Sushila Viswanathan, Wu Shiu- Ching, Xu Di, T. Yamauchi, Yang Liuxin. (shrink)

This book is intended as an equivalent to or substitute for that "more reflective reading" which Rousseau considered essential to an understanding of his ideas. It is designed to complement perusal of the texts themselves, and the arrangement is such that chapters on each of Rousseau's major writings can be consulted separately or the commentary may be read through in sequence. The author's purpose is not to present a "key" to Rousseau's political philosophy, but rather to explore the works themselves (...) in an effort to reveal Rousseau's "system," from which the reader may then draw his own conclusions. Originally published in 1976. The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These editions preserve the original texts of these important books while presenting them in durable paperback and hardcover editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905. (shrink)

Ralph Waldo Emerson's theory of rhetoric has been the subject of ongoing inquiry that has moved Emerson further and further outside a line of Platonic thinkers in order to make his discussion of rhetoric applicable to contemporary discussions about civic discourse and the public sphere. Such accounts, however, subtly undermine the complexity of Emerson's attempts to reconcile transcendentalism with democracy. Understanding Emerson as involved in a project to not only democratize language and rhetorical theory but also Plato, the representative of (...) truth seeking and idealism, clarifies precisely how Emerson understands the power of rhetoric and philosophy to shape and enact democracy. Emerson was trying to find a place for Platonic idealism in the shaping of a young country, and in doing so, he reconfigured what might seem today to be irreconcilable dualities. For Emerson the split between the spiritual and the material world does not implicitly prioritize one domain over the other. Instead, Emerson negotiates the terrain between the worlds and suggests ultimately that language and action are means of straddling them and realizing real change in society. If ideals are in some way external in Emerson's metaphysics, they are no less accessible by every person who attends to his or her own experience in the world. Rhetoric, for Emerson, brings those poles together. (shrink)

My article provides a systematic interpretation of the transformation of capitalist society in the neo-liberal era as a form of what Karl Polanyi called ‘cultural catastrophe’. I substantiate this claim by drawing upon Erich Fromm’s theory of social character. Fromm’s notion of social character, I argue, offers a plausible, psychodynamic explanation of the processes of social change and the eventual class composition of neo-liberal society. I argue, further, that Fromm allows us to understand the psychosocial basis of the process that (...) Polanyi calls cultural catastrophe. This requires an elucidation of the major social forces of financialization and emancipation which, I argue, proved to be important formative factors in the emergence of neo-liberal society. The cultural catastrophe of neo-liberalism concerns the working class, whose prevailing social character has become misaligned with the new expectations and requirements of neo-liberal society. (shrink)

Environmental ethics has traditionally focused on a defense of the intrinsic value of animals and wild habitats. However, this ethical project needs to be supplemented by a consideration of the kind of culture that can take such an ethical point of view seriously. This essay argues that one component of an environmentally responsible culture is its domesticated environment. How we construct the domesticated environment has an impact on our perception of our own identities and our relations to wild nature. If (...) we care about wild nature, we must also care about the domesticated environment in which we live our lives. This essay contributes to an ethical reflection on the need to overcome the traditional dualism between domesticated and wild, built and natural that permeates environmental ethical thinking. (shrink)

In an influential recent paper, Hawthorne, Rothschild, and Spectre (“HRS”) argue that belief is weak. More precisely: they argue that the referent of believe in ordinary language is much weaker than epistemologists usually suppose; that one needs very little evidence to be entitled to believe a proposition in this sense; and that the referent of believe in ordinary language just is the ordinary concept of belief. I argue here to the contrary. HRS identify two alleged tests of weakness – the (...) neg-raising and weak upper bounds tests, as I call them – which they claim believe and think pass. But I identify several other expressions in ordinary English for attributing belief, all of which fail both tests. Therefore, even if HRS are correct that believe and think refer to a weak attitude, it does not follow that the ordinary concept of belief is weak. I conclude by raising some problems for the accounts of belief as guessing, building on HRS's arguments, due to Kevin Dorst, Matt Mandelkern, and Ben Holguín. (shrink)

The preface paradox does not show that it can be rational to have inconsistent beliefs, because preface writers do not have inconsistent beliefs. I argue, first, that a fully satisfactory solution to the preface paradox would have it that the preface writer's beliefs are consistent. The case here is on basic intuitive grounds, not the consequence of a theory of rationality or of belief. Second, I point out that there is an independently motivated theory of belief – sensitivism – which (...) allows such a solution. I sketch a sensitivist account of the preface writer's doxastic state. (shrink)

Available for the first time in English, Roger's masterwork of intellectual history situates the life sciences within the larger context of French Enlightenment thought and the history of institutions.

In her book Michel de Montaigne: Accidental Philosopher, Ann Hartle argues that Montaigne’s thought is dialectical in the Hegelian sense. Unlike Hegel’s progressive dialectic, however, Montaigne’s thought is, according to Hartle, circular in that the reconciliation of opposed terms comes not in the form of a newly emergent term, but in a return to the first term, where the meaning of the first is transformed as a result of its dialectical interaction with the second. This analysis motivates Hartle’s claim that (...) Montaigne is not a skeptic at all, let alone a Pyrrhonian skeptic. In this paper, I argue that Hartle’s circular-dialectical interpretation of Montaigne is not only compatible with Pyrrhonism, but is in fact an ideal model for understanding Sextus Empiricus’s skeptical therapy. (shrink)

This paper is a plea for hedonism to be taken more seriously. It begins by charting hedonism's decline, and suggests that this is a result of two major objections: the claim that hedonism is the ‘philosophy of swine’, reducing all value to a single common denominator, and Nozick's ‘experience machine’ objection. There follows some elucidation of the nature of hedonism, and of enjoyment in particular. Two types of theory of enjoyment are outlined–internalism, according to which enjoyment has some special ‘feeling (...) tone’, and externalism, according to which enjoyment is any kind of experience to which we take some special attitude, such as that of desire. Internalism–the traditional view–is defended against current externalist orthodoxy. The paper ends with responses to the philosophy of swine and the experience machine objections. (shrink)

Description: The common western understanding of Buddhism today envisions this major world religion as one of compassion and tolerance. But as the author Droit reveals, this view bears little resemblance to one broadly held in the nineteenth-century European philosophical imagination that saw Buddhism as a religion of annihilation calling for the destruction of the self. The Cult of Nothingness traces the history of the western discovery of Buddhism. In so doing, the author shows that such major philosophers as Schopenhauer, Nietzsche, (...) Hegel, Cousin, and Renan imagined Buddhism as a religion that was, as Nietzsche put it, a negation of the world. In fact, says the author, such portrayals were more a reflection of what was happening in Europe at the time-when the collapse of traditional European hierarchies and values, the specter of atheism, and the rise of racism and social revolts were shaking European societies-than an accurate description of Buddhist thought. The author also reflects on how this history continues to echo in contemporary western understanding of Buddhism. The book includes a comprehensive bibliography on books on Buddhism published in the west between 1638 and 1890. (shrink)

Journal of Philosophy of Education, Volume 56, Issue 2, Page 342-355, April 2022.

Thompson Clarke’s seminal paper “The Legacy of Skepticism” (1972) is notoriously difficult in both substance and presentation. Despite the paper’s importance to skepticism studies in the nearly half-century since its publication, no attempt has been made in the secondary literature to provide an account, based on a close reading of the text, of just what Clarke’s argument is. Furthermore, much of the existing literature betrays (or so it seems to me) fundamental misunderstandings of Clarke’s thought. In this essay, I attempt (...) to explain—concisely but comprehensively—Clarke’s overall argument in “The Legacy of Skepticism.”. (shrink)

Non language-using animals cannot have beliefs, because believing entails the ability to distinguish true from false beliefs and also the ability to distinguish changes in belief from changes in the world. For these abilities we need both the fixation of belief and counter-factual thought, for both of which language is necessary. The argument of the paper extends Davidson's argument to the same conclusion. But denying beliefs to animals has no moral implications.

W. V. Quine was quite simply the most distinguished analytic philosopher of the later half of the twentieth century. His celebrated attack on the analytic/synthetic tradition heralded a major shift away from the views of language descended from logical positivism. His most important book, Word and Object, introduced the concept of indeterminacy of radical translation, a bleak view of the nature of the language with which we ascribe thoughts and beliefs to ourselves and others. Quine is also famous for the (...) view that epistemology should be naturalized, that is conducted in a scientific spirit with the object of investigating the relationship between the inputs of experience and the outputs of belief. The eleven essays in this volume cover all the central topics of Quine's philosophy: the underdetermination of physical theory, analycity, naturalism, propositional attitudes, behaviorism, reference and ontology, positivism, holism and logic. (shrink)

The aim of this article is to demonstrate the respects in which private schools are unfair, and why they pose a threat to the well-being of not only those who are excluded on financial grounds, but to democratic equality and social cohesion in general. The shortcomings associated with relying on a form of educational provision that is merely ‘adequate’ are rendered explicit, and the article concludes with a consideration of a variety of measures that might go some way towards nullifying (...) the harmful effects of private schools, the objections to which are sufficiently strong as to warrant a prima facie case for the abolition of such schools. (shrink)

Key ideas in the work of Michel Foucault are explored and applied to the organized pursuit of knowledge in higher education. His association of power and knowledge accounts for deeply rooted practices in higher education that would need to be mediated or overcome for there to be a revolution in inquiry to occur, such as the one advanced by Nicholas Maxwell. Foucault’s concepts of disciplinary power and bio-power, and how they act to manage the behavior of free citizens, are described. (...) These concepts are then applied to free inquiry, to show how the activity of individual inquirers is managed and how critical inquiry is controlled. The management of inquiry involving four norms, two of them intrinsic to inquiry and the other two extrinsic, is explained. The potential of Foucault’s concept of discursive formations is introduced as a means of reconceiving inquiry to overcome these impediments to a revolution in inquiry. (shrink)

Uses a comparative hermeneutical method to explain the most important terms in the classical Confucian philosophical texts, in an effort to allow the tradition to speak on its own terms.

Speciesism defended against common misrepresentations of what people actually believe about human moral status.

Animal liberationists call speciesism their enemy, but speciesism, perspicuously specified, says only that being human is sufficient for having our moral status. No one thinks it necessary. Throughout history, people have imagined alter-specifics, like the crowd at a Star Wars cantina, whom they’d recognize as their moral equals. Speciesism says nothing about our treatment of nonhumans. Speciesism’s historic popularity justifies presuming it true, a presumption buttressed by the absence of sound objections to it when properly understood. Its rationality is explained (...) by combining two ideas. First, universalizations of our reasons require some category of self-identification. Second, our primary category of self-identification is our key concept for understanding ourselves biologically, metaphysically, psychologically and socially, namely our species concept. We’re rationally bound to conspecifics by the relational “accident” of their essence being our own. (shrink)

Psychological terms, such as ‘mind’, ‘memory’, ‘emotion’ and indeed ‘psychology’ itself, have a history. This history, I argue, supports the view that basic psychological categories refer to historical and social entities, and not to ‘natural kinds’. The case is argued through a wide ranging review of the historiography of western psychology, first, in connection with the field’s extreme modern diversity; second, in relation to the possible antecedents of the field in the early modern period; and lastly, through a brief introduction (...) to usage of the words ‘soul’, ‘mind’, ‘memory’ and ‘emotion’. The discussion situates the history of psychology within a large historical context, questions assumptions about the continuity of meaning, and draws out implications for the philosophical and social constitution of ‘psychology’ and ‘the psychological’ from the existing literature. The historical evidence, this paper concludes, does not support the conventional presumption that modern psychological terms describe ‘natural kinds’. (shrink)