Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Intro -- Title -- Contents -- Publisher's Acknowledgment -- Introduction -- Madhyamaka's Promise as Philosophy -- 1. Trying to Be Fair -- 2. How Far Can a Mādhyamika Reform Customary Truth? Dismal Relativism, Fictionalism, Easy-Easy Truth, and the Alternatives -- Logic and Semantics -- 3. How Do Mādhyamikas Think? Notes on Jay Garfield, Graham Priest, and Paraconsistency -- 4. "How Do Mādhyamikas Think?" Revisited -- 5. Prasaṅga and Proof by Contradiction in Bhāviveka, Candrakīrti, and Dharmakīrti -- 6. Apoha Semantics: What (...) Did Bhāviveka Have to Do with It? -- 7. What Happened to the Third and Fourth Lemmas in the Tibetan Madhyamaka? -- Ethics and the Spiritual Path -- 8. Madhyamaka Buddhist Ethics -- 9. Reason, Irrationality, and Akrasia (Weakness of the Will) in Buddhism: Reflections upon Śāntideva's Arguments with Himself -- 10. Yogic Perception, Meditation, and Enlightenment: The Epistemological Issues in a Key Debate between Madhyamaka and Chan -- Madhyamaka in Contemporary Debates -- 11. On Minds, Dharmakīrti, and Madhyamaka -- 12. Serious, Lightweight, or Neither: Should Madhyamaka Go to Canberra? -- Notes on the Articles -- Abbreviations -- Bibliography -- Index -- About the Author -- Studies in Indian and Tibetan Buddhism Titles Previously Published -- About Wisdom Publications -- Copyright. (shrink)

Avez-vous remarqué que dans le monde tout ce qui compte va par quatre? La musique : timbre, harmonie, rythme et mélodie. Le repérage : altitude, latitude, longitude et datation. Les quatre aspects de la cause: pour quoi, avec quoi, par quoi et selon quoi? Les forces de la nature : interactions faible, forte, électromagnétique et gravitationnelle... Les vingt-quatre particules élémentaires qui constituent la matière une famille de six leptons associée à trois familles de quarks. Et aussi la logique d'un discours (...) nuancé : oui, non, oui et non, ni oui ni non. Pourquoi quatre est-il partout? La notion de quaternité apporte une réponse à la fois simple et surprenante à cette question. A partir d'exemples tirés de l'expérience humaine, les auteurs en dégagent les aspects structurels et s'en servent pour approfondir le sens des mathématiques et de divers autres domaines liés à la genèse de la connaissance. Il s'agit d'une nouvelle épistémologie, fondée sur un modèle logique qui complète celui d'Aristote. (shrink)

Draws on examples ranging from prehistoric cave art to modern pop music to discuss the nature and purpose of art and its use by powerful social and cultural forces.

Ook al staan de beelden van Confucius, Lao Zi en Boeddha in sommige Chinese tempels weer broederlijk bijeen op het altaar, hun verschillende wegen tot zelfcultivering worden zelden in onderlinge samenhang beschreven. Dit boek benadert confucianisme, daoïsme en het Chinese boeddhisme in zijn vroege ontwikkeling vanuit hun visie op de praktijk van de zelfcultivering. Hoewel ze een volstrekt ander doel hebben dan de westerse zelfverwerkelijking, mogen de Chinese wegen zich in onze contreien toch in een grote populariteit verheugen. Omdat de (...) zelfcultivering in China primair gericht is op de emoties, vormt de emotiecultivering de rode draad in dit boek. Het begrip Qi, levenskracht, speelt een grote rol in alle cultiveringspraktijken en staat centraal in het klassieke Chinese denken. Het eerste hoofdstuk biedt een inleiding in dit begrip, waardoor de lezer een overzicht krijgt van een aantal Chinese kernconcepten en theorieën en daarmee ook van de context van de emotiecultivering. Naast de beschrijving daarvan in confucianisme, daoïsme en boeddhisme biedt het boek verder een beschouwing van de Chinese landschapsschilderkunst als "filosoferen met het penseel". Het slothoofdstuk vat de verschillende cultiveringspraktijken samen en presenteert ze onder de noemer van Wegen naar het Midden. (shrink)

The eclipse of interest in Joseph Butler's analysis of the relation of conscience and action and the dismissal of his ethics on the grounds that the argument is flawed by circularity and/or the naturalistic fallacy are both a consequence of the failure of scholars to attend to the complex design of his work considered as a whole. The seldom studied Sermon XV is pivotal to understanding Butler's conception of failure and possibility. While it builds on the familiar arguments of Sermons (...) I-III, the last sermon sets aside the analogy of the watch to explore the problem of virtue in light of Old Testament wisdom narratives that establish the vanity of human endeavor and the limitations of the human condition. Sermon XV not only alters our reading of those that precede it but also binds Butler's reflections on ethics to his later reflections on religious truth. (shrink)

Is it possible to interfere with individual decision-making while preserving freedom of choice? The purpose of this article is to assess whether ‘libertarian paternalism’, a set of political and ethical principles derived from the observations of behavioural sciences, can form the basis of a viable framework for the ethical analysis of public health interventions. First, the article situates libertarian libertarianism within the broader context of the law and economics movement. The main tenets of the approach are then presented and particular (...) attention is given to its operationalization through the notion of a ‘nudge’. Essentially, a ‘nudge’ consists in an intervention, which aims to suggest one choice over another by gently steering individual choices in welfare-enhancing directions yet without imposing any significant limit on available choices. Finally, the article concludes that, while it fails as an overreaching framework of ethical analysis, libertarian paternalism nonetheless constitutes a valuable addition to the conceptual toolbox of public health ethics. (shrink)

_The Budapest School: Beyond Marxism_ develops a systematic reconstruction of the post-Marxist projects of the Budapest School. It charts the evolution of these thinkers from their beginnings in the ‘renaissance of Marxism’ through to their contemporary critical theories of modernity.

For a computable structure A\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathcal{A}}$$\end{document}, there may not be a computable infinitary Scott sentence. When there is a computable infinitary Scott sentence φ\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi}$$\end{document}, then the complexity of the index set I\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${I}$$\end{document} is bounded by that of φ\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\varphi}$$\end{document}. There are results giving “optimal” Scott sentences for (...) structures of various familiar kinds. These results have been driven by the thesis that the complexity of the index set should match that of an optimal Scott sentence. In this note, it is shown that the thesis does not always hold. For a certain subgroup of Q\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathbb{Q}}$$\end{document}, there is no computable d-Σ2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\Sigma_2}$$\end{document} Scott sentence, even though the index set is d-Σ20\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\Sigma^0_2}$$\end{document}. (shrink)

In this paper the authors argue that ethical considerations are relevant for evaluating animal production systems and that in consequence agrologists should seriously consider the arguments of animal welfare supporters. Furthermore, the authors point out the ethical basis for some (though not all) of the conclusions proposed by supporters of animal welfare. In consequence it is necessary to determine the nature of animal welfare and methods of evaluating the welfare of animals and to recognize when production systems fail to satisfy (...) the needs of animals. (shrink)