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)

The earliest Analects yet discovered, this work provides us with a new perspective on the central canonical text that has defined Chinese culture--and clearly illuminates the spirit and values of Confucius.

The Zhuangzi is a deliciously protean text: it is concerned not only with personal realization, but also with social and political order. In many ways the Zhuangzi established a unique literary and philosophical genre of its own, and while clearly the work of many hands, it is one of the finest pieces of literature in the classical Chinese corpus. It employs every trope and literary device available to set off rhetorically charged flashes of insight into the most unrestrained way to (...) live one's life, free from oppressive, conventional judgments and values. The essays presented here constitute an attempt by a distinguished community of international scholars to provide a variety of exegeses of one of the Zhuangzi's most frequently rehearsed anecdotes, often referred to as "the Happy Fish debate." The editors have brought together essays from the broadest possible compass of scholarship, offering interpretations that range from formal logic to alternative epistemologies to transcendental mysticism. Many were commissioned by the editors and appear for the first time. Some of them have been available in other languages—Chinese, Japanese, German, Spanish—and were translated especially for this anthology. And several older essays were chosen for the quality and variety of their arguments, formulated over years of engagement by their authors. All, however, demonstrate that the Zhuangzi as a text and as a philosophy is never one thing; indeed, it has always been and continues to be, many different things to many different people. (shrink)

THE OBJECTIVITY OF REALITY Reality and Mind We cannot talk or think about reality without talking or thinking about it. This is a truism which seems almost ...

From Thomas Hobbes to Jeremy Bentham, 'British Moralists' have questioned whether being virtuous makes you happy. Roger Crisp elucidaties their views on happiness and virtue, self-interest and sacrifice, and well-being and morality, and highlights key themes such as psychological egoism, evaluative hedonism, and moral reason in their thought.

(1) is an example of an adjectival comparative. In it, the adjective important is flanked by more and a comparative clause headed by than. This article is a survey of recent ideas about the interpretation of comparatives, including (i) the underlying semantics based on the idea of a threshold; (ii) the interpretation of comparative clauses that include quantifiers (brighter than on many other days); (iii) remarks on differentials such as much in (1) above: what they do in the comparative and (...) what they do elsewhere in the language; (iv) the relationship between comparatives and other Degree constructions (e.g. as important, too impor- tant); and (v) the types of phrases in which comparatives are found (adjective: tighter versus noun: more water). Given the nature and purpose of this essay, I have tried not to presuppose background in formal semantics and I have departed from standard practice in journal articles by, as much as possible, not interrupting the flow with footnotes and references. There are two appendices. The first provides more analytical detail and there I do rely on formal techniques of natural language semantics. The second covers the sources for the ideas surveyed here. (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.

Starting from an examination of foundational issues, the book covers a range of topics, including animals, agency, enjoyment, the good life, contemplation, ...

Parkinson's disease (PD) is characterized by the loss of the dopaminergic nigrostriatal pathway which has led to the successful development of drug therapies that replace or stimulate this network pharmacologically. Although these drugs work well in the early stages of the disease, over time they produce side effects along with less consistent clinical benefits to the person with Parkinson's (PwP). As such there has been much interest in repairing this pathway using transplants of dopamine neurons. This work which began 50 (...) years ago this September is still ongoing and has now moved to first in human trials using human pluripotent stem cell‐derived dopaminergic neurons. The results of these trials are eagerly awaited although proof of principle data has already come from trials using human fetal midbrain dopamine cell transplants. This data has shown that developing dopamine cells when transplanted in the brain of a PwP can survive long term with clinical benefits lasting decades and with restoration of normal dopaminergic innervation in the grafted striatum. In this article, we discuss the history of this field and how this has now led us to the recent stem cell trials for PwP. (shrink)

The classical Greeks give us a substance ontology grounded in ‘being qua being’ or ‘being per se’ (to on he on) that guarantees a permanent and unchanging subject as the substratum for the human experience. With the combination of eidos and telos as the formal and final cause of independent things such as persons, this ‘substance’ necessarily persists through change. This substratum or essence includes its purpose for being, and is defining of the ‘what-it-means-to-be-a-thing-of-this-kind’ of any particular thing in setting (...) a closed, exclusive boundary and the strict identity necessary for it to be this, and not that.In the Yijing 易經 or Book of Changes we find a vocabulary that makes explicit cosmological assumptions that are a stark alternative to this substance ontology, and provides the interpretive context for the Confucian canons by locating them within a holistic, organic, and ecological worldview. To provide a meaningful contrast with this fundamental assumption of on or ‘being’ we might borrow the Greek notion of zoe or ‘life’ and create the neologism ‘zoe-tology’ as ‘the art of living’. This cosmology begins from ‘living’ (sheng 生) itself as the motive force behind change, and gives us a world of boundless ‘becomings’: not ‘things’ that are, but ‘events’ that are happening, a contrast between an ontological conception of the human ‘being’ and a process conception of what I will call human ‘becomings’. (shrink)

Among theories which fit all of our data, we prefer the simpler over the more complex. Why? Surely not merely for practical convenience or aesthetic pleasure. But how could we be justified in this preference without knowing in advance that the world is more likely to be simple than complex? And isn’t this a rather extravagant a priori assumption to make? I want to suggest some steps we can take toward reducing this embarrassment, by showing that the assumption which supports (...) favouring simplicity is far more modest than it first seems. (shrink)

This is the first comprehensive biography of John Locke to be published in nearly a half century. Setting Locke's life within exciting historical and intellectual contexts, which included the English Civil War, religious persecution, and the Glorious Revolution of 1688, Roger Woolhouse interweaves an account of Locke's life with a summary and development of his ideas in theory of knowledge, philosophy of science, medicine, economics, philosophy of religion, and political philosophy. Systematic and encyclopedic in its coverage, Woolhouse's biography offers (...) both an account and explanation of Locke's ideas, while treating seriously his emotional relationship with Elinor Parry. Based on broad research and many years of study of Locke's philosophy, this volume is an authoritative biography on one of the most significant early modern philosophers. (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.

This unique collection of essays not only explores the complexity of ancient Greek thought, but also reveals Popper's engagement with Presocratic philosophy and the enlightenment he experienced in reading Parmenides. It includes writings on Greek science, philosophy and history, and demonstrates Popper's lifelong fascination and admiration of the Presocratic philosophers, in particular Parmenides, Xenophanes and Heraclitus.

Platon observe nos smartphones, croise nos migrants, découvre les attentats terroristes, scrute nos dirigeants politiques. Roger-Pol Droit lui fait rencontrer Teddy Riner, Bob Dylan, Thomas Pesquet, l'emmène à la COP 21, au MacDo, à Pôle Emploi, au Mémorial de la Shoah, l'incite à visionner House of Cards, à écouter Emmanuel Macron et Donald Trump. Entre autres. Pour jouer? Evidemment. Mais pas seulement. Cette promenade dans notre actualité du père fondateur de la philosophie permet de découvrir des traits essentiels de (...) sa pensée, en expérimentant des écarts entre nous et lui, en testant ce qu'il comprendrait aisément, ou pas du tout. Finalement, ce périple montre ce que Platon nous indique d'essentiel, que nous ne verrions pas sans lui. Rédigé sous la forme de trois carnets écrits au jour le jour, dans une langue accessible et élégante, ce livre se révèle peu à peu bien autre chose qu'un divertissement. L'air de rien, il développe une méditation vivante, personnelle et profonde sur les usages de la philosophie, ses impasses et ses zones d'ombre, sa nécessité et ses bienfaits. (shrink)

I begin this paper by claiming that commentators who regard the Groundwork as Kant's final word on ethics inevitably misunderstand his moral theory. In support of this claim I focus on how Kant portrayed the role of inclinations in the morally virtuous life. A person who reads only the Groundwork will surely be struck by Kant's negative treatment of desires in that book: they are completely irrelevant to the rightness of our moral judgments, and the only specifically moral motive is (...) dutifulness, excluding all influence of the emotions, which function as the main rival to moral motivation.Kant left a thorough discussion of his division of duties for his Metaphysics of Morals, and there, when he discusses imperfect duties as well as morally permissible activities, we find that the categorical imperative is an indeterminate guide to the majority of our decisions. That is, in such matters, pure practical reason must be supplemented by both prudential judgments and motives grounded on inclinations. Then inclinations operate, not as a crutch to induce us to do our duty, but as a complement to the Categorical Imperative.The Categorical Imperative, therefore, has a more limited role in most of our decisions than appears to be the case in the Groundwork. Yet the all-encompassing role enjoyed by the moral law means that which permissible activities we engage in and exactly how we fulfil positive obligations still both need to be recognized as expressions of a person's character. Contrary a common misinterpretation, then, the criterion of effectiveness can therefore be both relevant to and even mandated by the moral law and so function as a moral category in Kant's theory. Instances in which practice goes amiss in these areas are failures of prudence, and such "faults," as Kant called them, are not necessarily incompatible with a person's ultimate moral commitment.We now can see how misled are those who describe Kant's moral theory as totally rule-bound and excessively rigoristic. That his theory leaves vast areas of our life open to prudential judgments is but another reflection of the way in which he was faitful to the thinking of ordinary people. Zu Beginn meines Beitrags behaupte ich, daß Autoren, die die Grundlegung zur Metaphysik der Sitten als sein letztes Wort zur Ethik ansehen, Kants Moraltheorie unvermeidlich mißverstehen. Um diese Behauptung zu begründen, richte ich meinen Blick in erster Linie auf die Frage, wie Kant die Rolle der sinnlichen Antriebe und Neigungen in einem moralisch tugendhaften Leben schildert. Demjenigen, der sich auf die Grundlegung beschränkt, wird die negative Behandlung dieser sinnlichen Antriebe und Neigungen in diesem Buch sicherlich auffallen. Für die Richtigkeit unserer moralischen Urteile spielen sie keine Rolle. Im Gegenteil: Die spezifisch moralische Triebfeder ist allein die Pflicht selbst. Die Gefühle sind von jedem Einfluß ausgeschlossen; statt dessen fungieren sie als die hauptsächlichen Rivalen eines eigentlich moralischen Antriebs.Kant hat die eingehende Erörterung der Einteilung der Pflichten auf die Metaphysik der Sitten verschoben, und wenn er dort sowohl unvollkommene Pflichten als auch moralisch erlaubte Handlungen diskutiert, dann sehen wir, daß der Kategorische Imperativ für die Mehrzahl unserer Entscheidungen nur eine unbestimmte Anleitung liefert. Das heißt, in diesen Bereichen bedarf die reine praktische Vernunft einer Ergänzung, durch Klugheitsurteile wie auch durch Motive, die von unseren Neigungen abhängig sind. Die Neigungen sind in der Metaphysik der Sitten nicht eine Krücke, um uns zu pflichtgemäßem Handeln zu bringen, vielmehr dienen sie der Vervollständigung des Kategorischen Imperativs.Die Rolle, die der Kategorische Imperativ bei den meisten unserer Entscheidungen spielt, ist deshalb viel eingeschränkter, als es in der Grundlegung erscheint. Das bedeutet, daß die Art und Weise, wie wir unsere positiven Verpflichtungen erfüllen, und die Auswahl der erlaubten Handlungen, auf die wir uns einlassen, immer noch als Ausdruck des Charakters unserer Person anerkannt werden müssen, obwohl und weil das moralische Gesetz über allem steht. Entgegen einem gewöhnlichen Mißverständnis kann auch das Kriterium der Effektivität für das moralische Gesetz relevant und vom moralischen Gesetz sogar vorgeschrieben sein und so in Kants Theorie als eine moralische Kategorie fungieren. Soweit diese Überlegungen reichen, erweisen sich Mängel in unserer Praxis als Fälle, in denen unsere Klugheit versagt hat, und derartige "Fehler", wie Kant sie nennt, sind nicht notwendigerweise unvereinbar mit einem Selbstverständnis, daß das moralische Gesetz für mich letztendlich die entscheidende Rolle spielt.Wir sehen nun, wie falsch eine Interpretation ist, die Kants Moraltheorie als vollständig an Regeln gebunden und übertrieben rigoristisch beschreibt. Daß seine Theorie große Bereiche unseres Lebens für Klugheitsentscheidungen offen läßt, ist nur ein anderer Aspekt seiner Bindung an die "gemeine Menschenvernunft". (shrink)

Ramon Llull hat das größte mittelalterliche Korpus von literarischen Dialogen in der Romania hinterlassen. Es steht im lateinischen, romanischen und arabischen Kontext der theologisch-philosophischen Diskussion. Die Arbeit untersucht sechs der 26 Dialoge Llulls eingehender im Hinblick auf ihre ideologische Ausrichtung und die literarischen Verfahren, die diese im Dialog transportieren. Llull entwickelt dabei bestimmte mittelalterliche Dialogtraditionen zu einem eigenen Modell weiter, das eine iberoromanische Linie lullistischer Dialoge begründet. Die Arbeit enthält die Erstedition der »Consolatio Venetorum«.

Essays on the relationship of theology and philosophy, the sciences and the arts.

Reid thought that testimony possesses positive epistemic value. Epistemic autonomy is not necessarily the royal road to truth; nor is credulity a systematic epistemic fault and indeed, it can be an intellectual virtue. Even though the notion of epistemic virtue does not explicitly appear in Reid’s epistemology, it seems inherent to his views that what will give a heteronomous agent exercising the social operations of the mind the best chance to acquire and develop true beliefs is the epistemic virtues that (...) permit her to recognize reliable authorities. This is why it seems to me possible to associate Reid with to the virtue epistemology tradition. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:The Impact of Fingarette’s Confucius: The Secular as Sacred on Confucian StudiesRoger T. Ames (bio)Confucius: The Secular as Sacred. By Herbert Fingarette. Hannacroix: Apocryphile Press, 2023.Writing a review of this Apocryphile Press edition of Herb Fingarette’s 1972 publication of Confucius: Secular as Sacred with its new preface by my good friend Michael Nylan is deeply personal. Like Michael and the several other distinguished scholars who have written their endorsements (...) for this new reprint, this occasion gives me a long moment to reflect on how this little book has changed my life. The project has also given me a reason to go back and reread the review of this book written by my longtime friend and collaborator, Henry Rosemont, Jr., published almost 50 years ago in Philosophy East and West.My first memory is of Herb Fingarette himself. I met this gentleman, and gentle he was, early on in my tenure at the University of Hawai‘i when Herb, always accompanied by Leslie, would make regular visits to participate in our public lectures and conferences. I always marveled at how in his presentations he would begin from some seemingly simple and offhand fact about our everyday lives. He would then quite masterfully take this ordinary detail and, through a series of incrementally insightful reflections and then again through his sensitive responses to the questions raised by his audience, elevate the discussion to become an extraordinarily memorable event. I remember well how this seasoned teacher always began the question session by calling upon the graduate students, leaving his eager professional colleagues to wait their turn. And then, with the rigor and impeccable logic of the best kind of analytical philosopher, he would gently and always smilingly, win everyone over to his conclusions.When Herb retired from Santa Barbara, he was adamant that he was retired, and in spite of the many efforts we made to draw him back into the circuit, he would have none of it. My only success in my numerous attempts to corral him was in persuading him to write a chapter for a Festschrift I edited celebrating the career of a philosopher much in his own mold as an independent thinker, my colleague Eliot Deutsch. [End Page 516]Even though Herb’s withdrawal from professional events was unequivocal, he was always available for a Reuben sandwich and a good conversation. Over the ensuing years that saw a clear-headed and always happy Herb carry on until a few years short of his centenary, I would sometimes accompany Rosemont in his regular pilgrimages to sojourn with his best Berkeley friends, which included, along with Herb, David Keightley, Huston Smith, and of course, Michael Nylan.Turning then from the large-souled man to the little book that changed the world of Confucian studies, to say that it was not well received is an understatement. When this monograph published by HarperCollins, a trade press, first appeared in the bookstores, whispers ran through the sinological community about how this pretender had the temerity to engage a canonical text well beyond his reach. Without proper philological training, he was actually challenging what we all know to be the proper translations of important Chinese terms. Again, Herb’s philosophical colleagues who were baffled by his efforts to engage Chinese philosophy as philosophy, also had his number, and it was not a high one.As Rosemont pointed out in both a critical, and to my knowledge, the first truly appreciative review of Fingarette’s commentary on the Analects (a feature review that in its pages would constitute a goodly portion of Fingarette’s 79-page book), what made this book an important inflection point for Confucian studies is that a rigorously trained philosopher was writing a philosophical and philological exegesis on what he deemed a philosophically profound text. Even for Fingarette who was himself initially nonplussed by the idea that the Analects was good philosophy, it took a careful reading and an open mind to fathom both the depth and the worth of the Analects for reflecting on our lives as they are lived today.It is a commonplace that we often do not appreciate those teachers who have influenced... (shrink)

The problems of environmental ethics are so basic that the exploration of an alternative metaphysics or attendant ethical theory is not a sufficiently radical solution. In fact, the assumptions entailed in adefinition of systematic philosophy that gives us a tradition of metaphysics might themselves be the source of the current crisis. We might need to revision the responsibilities of the philosopher and think in terms of the artist rather than the “scientific of first principles.” Taoism proceeds from art rather than (...) science, and produces an ars contextualis: generalizations drawn from human experience in the most basic processes of making aperson, making a community and making a world. This idea of an “aesthetic cosmology” is one basis for redefining the nature of the relatedness that obtains between particular and world-between tao and te. (shrink)

John Earman's A Primer on Determinism treats the doctrine of Laplacian determinism by a careful look at a considerable variety of physical theories. This paper enriches Earman's discussion of chaos theory by considering in some detail the analysis of dripping faucets due to Robert Shaw. Shaw's analysis exhibits in a nice way some of the techniques used in chaos theory and gives a feel for research in this area. The paper concentrates on the tension between the determinism inherent in any (...) description involving differential equations and the in-practice unpredictability resulting from the extreme sensitivity to initial conditions of the non-linear differential equations characteristic of chaos theory. (shrink)