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)

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)

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)

This book compares Chinese thought to that of the West. With recent Western interest in Chinese Buddhism (also known as Zen) and Daoism an understanding of their underlying ways of thinking is crucial for approaching them properly. The topics treated include worldview, world -- man relation, and mind and consciousness. A unique feature of the book is the comparison between Daoism and Chinese Buddhism on the one hand, and the Greek schools of Epicureanism and Stoicism on the other. A remarkable (...) similarity as well as a significant difference is found between these ways of life. In both China and Greece they learned how to live in the 'Now'. But in China this is centred around the body, while in Greece this was a strictly rational pursuit. The main differences between the Chinese and Western ways can be summarised in the words 'accord' and 'separation'. Clearly, in East and West different roads have been, and still are walked. Yet, these roads do not inevitably entail different ways of life. 'Walking two roads at once' (Zhuangzi) it is possible to go beyond accord and separation. (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)

For countable structure, "Scott rank" provides a measure of internal, model-theoretic complexity. For a computable structure, the Scott rank is at most [Formula: see text]. There are familiar examples of computable structures of various computable ranks, and there is an old example of rank [Formula: see text]. In the present paper, we show that there is a computable structure of Scott rank [Formula: see text]. We give two different constructions. The first starts with an arithmetical example due to Makkai, and (...) codes it into a computable structure. The second re-works Makkai's construction, incorporating an idea of Sacks. (shrink)