Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

The book includes 13 contributions that deal with the first attempts of opposition to the of Aristotle's thought. From Theophrastus to Epicurus, and to Plotinus. The best specialists have collaborated (among others: M. Mignucci, E. Berti, K. Ierodiakonou, C. Natali, S. Maso, F. Ferrari, D. Taormina, A. Falcon, A. Schiaparelli).

The papers presented in this volume in honour of Alfonso Maieru cover some of the major topics of his research area. The institutional and intellectual life of university training in the Middle Ages, including the peculiar tradition of related works, is the focus of the papers by Louis Jacques Bataillon, William J. Courtenay, Jacqueline Hamesse, Zenon Kaluza, Loris Sturlese and Olga Weijers. Three papers, by Jacopo Costa, Pasquale Porro and Thomas Ricklin, deal with philosophical problems in Dante'sMonarchia and Convivio. The (...) complex interrelations between logic and the other main aspects of medieval philosophy, with a particular attention to theology, metaphysics and natural philosophy, are the core of the other papers by Stefano Caroti, Sten Ebbesen, Barbara Faes de Mottoni, Simo Knuuttila, Alain de Libera, Olga Lizzini, Costantino Marmo, Claude Panaccio, Ivan Bendwell, Irene Rosier-Catach, Lambert Marie de Rijk, Leonardo Sileo, Luisa Valente, and Albert Zimmermann. A larger number of friends and colleagues of Alfonso Maieru than those who appear as contributors and editors of this volume have warmly welcomed its publication. We could say, therefore, that it is absolutely contingent that the Editors are: Stefano Caroti (Universita degli Studi di Parma), Ruedi Imbach (Universite de Paris-Sorbonne), Zenon Kaluza (Centre d'Etudes des Religions du Livre, C.N.R.S), Loris Sturlese (Universita degli Studi di Lecce) and Giorgio Stabile(Universita degli Studi di Roma "La Sapienza"). (shrink)

Cet article réexamine la documentation sur le sanctuaire extra-urbain d’Asklépios et le temple ionique de la terrasse du théâtre à Pergame. Ces deux cas d’étude permettent d’étudier les développements diachroniques du paysage sacré de la cité et de ses alentours pendant la « longue période hellénistique » (fin du ive s. av. J.-C. – début du iiie ap. J.-C.). Cette analyse interdisciplinaire combine les sources textuelles, archéologiques et numismatiques pour étudier la distribution topographique des cultes pour les dieux et les (...) chefs politiques, leurs relations et changements à travers le temps. Pour ce faire, plusieurs questions méthodologiques sont examinées : les critères permettant de distinguer la présence du temple d’un dieu des traces diffuses de son culte à travers le paysage urbain ; la topographie de la dissémination et du remploi des textes et des artéfacts anciens et le type d’information qu’elle livre sur leur situation et fonction originaires ; l’équilibre entre continuité et innovation dans les modèles d’intégration des cultes pour les chefs politiques dans l’espace et le temps sacrés de la communauté. L’article apporte un nouveau soutien à la thèse selon laquelle Pergame n’abrita jamais un deuxième Asklépieion à l’intérieur de ses murs. (shrink)

God and the City, based on the Aquinas Lecture delivered at the University of Dallas in 2022, aims to think about politics ontologically. In other words, it seeks to reflect on, not some political theory or other, nor on the legitimacy of political action or the distinctiveness of particular regimes, but on the nature of political order as such, and how this order implicates the fundamental questions of existence, those concerning man, being, and God. Aristotle, and Aquinas after him, identified (...) metaphysics and politics as "architectonic" sciences, since each concerns in some respect the whole of reality, of which the particular sciences study a part. Chapter one of this book argues that, just as metaphysics, in studying being as a whole, cannot but address the question of God in some respect, so too does politics, the ordering of human life as a whole, necessarily implicate the existence of God. In this regard, the modern liberal project has deluded itself in attempting to render religion a private, rather than a genuinely political, matter. We cannot organize human existence without making some claim, whether implicitly or explicitly, about the nature of God and God's relation to the world. The second chapter approaches this theme from the anthropological dimension. As Plato affirmed, the "city is the soul writ large": if man is religious by nature, he cannot be properly understood, and the human good cannot be properly secured and fostered, if the "God question" is "bracketed out" of the properly political order. Moreover, if we fail to recognize the essentially political dimension of relation to God, we will be unable properly to grasp the presence of God in the (ecclesial and sacramental) Body of Christ: God cannot be real in the Church as Church unless he is also real in the city as city (and vice versa). In his De regno, Aquinas famously affirms that "the king is to be in the kingdom what the soul is in the body and what God is in the world." Chapter three offers a careful study of the body-soul relationship in order to illuminate, on the one hand, the nature of political authority, and, on the other, the precise way that God is present in human community. (shrink)

A record of the words and teachings of Confucius, _The Analects_ is considered the most reliable expression of Confucian thought. However, the original meaning of Confucius's teachings have been filtered and interpreted by the commentaries of Confucianists of later ages, particularly the Neo-Confucianists of the Song dynasty, not altogether without distortion.In this monumental translation by Professor D. C. Lau, an attempt has been made to interpret the sayings as they stand. The corpus of the sayings is taken as an organic (...) whole and the final test of the interpretation rests on the internal consistency it exhibits. In other words, _The Analects_ is read in the light of _The Analects._This results in a truer understanding of Confucius' thought than the traditional interpretation and paves the way for a re-assessment of its importance in the history of Chinese thought and its relevance to the present day world.This volume also contains an introduction to the life and teachings of Confucius, and three appendices on the events in the life of Confucius, on his disciples, and on the composition of _The Analects._. (shrink)

Mencius, who lived in the 4th century B.C., is second only to Confucius in importance in the Confucian tradition. The _Mencius_ consists of sayings of Mencius and conversations he had with his contemporaries. When read side by side with the _Analects_, the _Mencius_ throws a great deal of light on the teachings of ConfuciusMencius developed many of the ideas of Confucius and at the same time discussed problems not touched upon by Confucius. He drew out the implications of Confucius' moral (...) principles and reinterpreted them for the conditions of his time. As the fullest of the four great Confucian texts, the _Mencius_ has been the required reading amongst Chinese scholars for two thousand years, and it still throws considerable light on the character of the Chinese people. (shrink)

Mencius, who lived in the 4th century B.C., is second only to Confucius in importance in the Confucian tradition. The _Mencius_ consists of sayings of Mencius and conversations he had with his contemporaries. When read side by side with the _Analects_, the _Mencius_ throws a great deal of light on the teachings of ConfuciusMencius developed many of the ideas of Confucius and at the same time discussed problems not touched upon by Confucius. He drew out the implications of Confucius' moral (...) principles and reinterpreted them for the conditions of his time. As the fullest of the four great Confucian texts, the _Mencius_ has been the required reading amongst Chinese scholars for two thousand years, and it still throws considerable light on the character of the Chinese people. (shrink)

In over thirty lines of the Agamemnon I think I discern lurking in the apparatus of modern editions truths unnoticed by recent editors, and needing for the most part merely redivision, repunctuation, or reaccentuation to become recognizable. At a few points I offer alternative interpretations of readings that have been accepted by some at least among modern editors.

This article discusses the adequacy of Rawls’ theory of justice as a tool for racial justice. It is argued that critics like Charles W Mills fail to appreciate both the insights and limits of the Rawlsian framework. The article has two main parts spread out over several different sections. The first is concerned with whether the Rawlsian framework suffices to prevent racial injustice. It is argued that there are reasons to doubt whether it does. The second part is concerned with (...) whether a Rawlsian framework has the resources to rectify past racial injustice. It is argued that it has more resources to do this than Mills allows. This second part of the article centers on two Rawlsian ideas: ideal theory and the fair equality of opportunity principle. It is argued that ideal theory is essential for the kind of rectificatory work that Mills wants nonideal theory to do, and that where there is a socioeconomic legacy of past injustice, it is hard to see how FEO could be implemented if it did no rectificatory work, a result which means that there is less need to turn to nonideal theory at all. (shrink)

... the topic of 'meaning' is the one topic discussed in philosophy in which there is literally nothing but 'theory' - literally nothing that can be labelled or even ridiculed as the 'common sense view'. Putnam, 'The Meaning of Meaning' This book explores some truths behind the truism that experimentation is a hallmark of scientific activity. Scientists' descriptions of nature result from two sorts of encounter: they interact with each other and with nature. Philosophy of science has, by and large, (...) failed to give an account of either sort of interaction. Philosophers typically imagine that scientists observe, theorize and experiment in order to produce general knowledge of natural laws, knowledge which can be applied to generate new theories and technologies. This view bifurcates the scientist's world into an empirical world of pre-articulate experience and know how and another world of talk, thought and argument. Most received philosophies of science focus so exclusively on the literary world of representations that they cannot begin to address the philosophical problems arising from the interaction of these worlds: empirical access as a source of knowledge, meaning and reference, and of course, realism. This has placed the epistemological burden entirely on the predictive role of experiment because, it is argued, testing predictions is all that could show that scientists' theorizing is constrained by nature. Here a purely literary approach contributes to its own demise. The epistemological significance of experiment turns out to be a theoretical matter: cruciality depends on argument, not experiment. (shrink)

In this paper we will offer a few examples to illustrate the orientation of contemporary research in data analysis and we will investigate the corresponding role of mathematics. We argue that the modus operandi of data analysis is implicitly based on the belief that if we have collected enough and sufficiently diverse data, we will be able to answer most relevant questions concerning the phenomenon itself. This is a methodological paradigm strongly related, but not limited to, biology, and we label (...) it the microarray paradigm. In this new framework, mathematics provides powerful techniques and general ideas which generate new computational tools. But it is missing any explicit isomorphism between a mathematical structure and the phenomenon under consideration. This methodology used in data analysis suggests the possibility of forecasting and analyzing without a structured and general understanding. This is the perspective we propose to call agnostic science, and we argue that, rather than diminishing or flattening the role of mathematics in science, the lack of isomorphisms with phenomena liberates mathematics, paradoxically making more likely the practical use of some of its most sophisticated ideas. (shrink)

This paper argues that the concept and role of ‘institutional racism’ in contemporary discussions of race should be reconsidered. It starts by distinguishing between ‘intrinsic institutional racism’, which holds that institutions are racist in virtue of their constitutive features, and ‘extrinsic institutional racism’, which holds that institutions are racist in virtue of their negative effects. It accepts intrinsic institutional racism, but argues that a ‘disparate impact’ conception of extrinsic conception faces a number of objections, the most serious being that it (...) has no plausible account of what it is that makes extrinsically racist institutions racist. It also argues that claims about the explanatory indispensability of institutional racism are overstated (individual racism is at least as important), critiques structural approaches to racial inequality, and suggests that there is reason to doubt whether institutional reform can provide us with all that morality may require in the racial domain. (shrink)

Current thinking and talk about race uses ‘racist’ for virtually everything that goes wrong in the domain of race. This paper examines the relationship between racial justice, racial discrimination and racism to argue for a more pluralistic approach to race-related ills. Such an approach provides the tools we need to understand an important if relatively neglected source of racial injustice, and does much to illuminate some race-related disputes. It starts by arguing that racial justice is a surprisingly limited ideal, and (...) then suggests understanding ‘racial discrimination’ in a minimal way. From there it is argued that while racial discrimination is necessary for racial injustice, the same is not true for racism. (shrink)

I discuss the formal implementation, interpretation, and justification of likelihood attributions in cosmology. I show that likelihood arguments in cosmology suffer from significant conceptual and formal problems that undermine their applicability in this context.

This chapter presents and illustrates fundamental principles of the intuitionistic mathematics devised by L.E.J. Brouwer and then describes in largely nontechnical terms metamathematical results that shed light on the logical character of that mathematics. The fundamental principles, such as Uniformity and Brouwer’s Theorem, are drawn from the intuitionistic studies of logic and topology. The metamathematical results include Gödel’s negative and modal translations and Kleene’s realizability interpretation. The chapter closes with an assessment of anti-realism as a philosophy of intuitionism.

This article argues that blacks should reject integration on self-protective and solidarity grounds. It distinguishes two aspects of black devaluation: a ‘stigmatization’ aspect that has to do with the fact that blacks are subject to various forms of discrimination, and an aesthetic aspect (‘phenotypic devaluation’) that concerns the aesthetic devaluation of characteristically black phenotypic traits. It identifies four self-worth harms that integration may inflict, and suggests that these may outweigh the benefits of integration. Further, it argues that, while the integrating (...) process may reduce stigmatization, there is less reason to think that it can do the same for phenotypic devaluation. (shrink)

Revonsuo argues that the biological function of dreaming is to simulate threatening events and to rehearse threat avoidance behaviors. He views recurrent dreams as an example of this function. We present data and clinical observations suggesting that (1) many types of recurrent dreams do not include threat perceptions; (2) the nature of the threat perceptions that do occur in recurrent dreams are not always realistic; and (3) successful avoidance responses are absent from most recurrent dreams and possibly nightmares. [Hobson et (...) al.; Revonsuo]. (shrink)

We introduce a novel point of view on the “models as mediators” framework in order to emphasize certain important epistemological questions about models in science which have so far been little investigated. To illustrate how this perspective can help answer these kinds of questions, we explore the use of simplified models in high energy physics research beyond the Standard Model. We show in detail how the construction of simplified models is grounded in the need to mitigate pressing epistemic problems concerning (...) the uncertainty inherent in the present theoretical and experimental contexts. (shrink)

This paper suggests that empirical educational research has not, on the whole, been treated well by philosophers of education. A variety of criticisms have been offered, ranging from triviality, conceptual confusion and the impossibility of empirically studying normative processes. Furthermore, many of those who criticise, or dismiss, empirical research do so without subjecting any specific examples to careful scholarly scrutiny. It is suggested that both philosophy of education, and the empirical research enterprise, stand to profit if philosophers pay more attention (...) to real cases—and this attention is especially important at present, when research funding is being based on spurious scientistic criteria such as the use of ‘gold standard’ randomised experimental research designs. (shrink)

A diagonal version of the strong reflection principle is introduced, along with fragments of this principle associated with arbitrary forcing classes. The relationships between the resulting principles and related principles, such as the corresponding forcing axioms and the corresponding fragments of the strong reflection principle, are analyzed, and consequences are presented. Some of these consequences are “exact” versions of diagonal stationary reflection principles of sets of ordinals. We also separate some of these diagonal strong reflection principles from related axioms.

I present a recent historical case from cosmology—the story of inflationary cosmology—and on its basis argue that solving explanatory problems is a reliable method for making progress in science. In particular, I claim that the success of inflationary theory at solving its predecessor’s explanatory problems justified the theory epistemically, even in advance of the development of novel predictions from the theory and the later confirmation of those predictions.