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)

Avoiding whinges from various and potentially conflicting stakeholders is a major challenge for sustainable development and for the identification of sustainability scenarios or policies for biodiversity and ecosystem services. It turns out that independently complying with whinge thresholds and constraints of these stakeholders is not sufficient because dynamic ecological-economic interactions and uncertainties occur. Thus more demanding no whinge standards are needed. In this paper, we first argue that these new boundaries can be endogenously exhibited with the mathematical concepts of viability (...) kernel and viable controls. Second, it is shown how these no whinge kernels have components, such as harvesting of resources, that should remain within safe corridor while some other components, in particular biodiversity, have only lower conservation limits. Thus, using radar charts, we show how this no whinge kernels can take the shape of a tree that we name viability tree. These trees of viability capture the idea that the unbounded renewal potential of biodiversity combined with a bounded use of the different ecosystem services are crucial ingredients for the sustainability of socio-ecosystems and the design of no whinge policies reconciling the different stakeholders involved. (shrink)

Science is remarkably reliable. It puts people on the moon, performs laser eye surgery, tells us about ancient civilisations and species, and predicts the future of our climate. What underwrites this reliability? This book argues that the standard answers—the scientific method, rigour, and objectivity—are insufficient for the job. Here we propose a new model of science that places its products front and centre. This is the ‘Tangle of Science’. In this book we show how any reliable piece of science is (...) underpinned by a vast, diverse, and thick network of other scientific products. In doing so we bring back into focus areas of science that have been long neglected, emphasising how every product, from the screws that hold the space shuttle together to ways of measuring the consumer price index to Einstein’s theory of general relativity, work together to support results we can trust. (shrink)

Plants are considered as archetypes of the ramification phenomenon but numerous elementary processes occur in the elaboration of the shaping of each species. This paper aims to identify the part ascribed to different mechanisms in the morphogenesis of a Thallophyte, the red alga Antihamnion plumula.Agonistic-antagonistic models (Bernard-Weil, 1988) can be applied to this alga whose thallus includes two different kinds of whorls, pleuridian and cladomian. In each whorl the agonistic and antagonistic effects are expressed by the full development (S) of (...) the two branches and by their symmetry rate (R) respectively. Variations in S and R show the existence of particular pleuridian whorls having an intermediary dissymmetry and a rhythmic arrangement similarly to that of the cladomian whorls. A unilateral change of the system (removal of a lateral cladome) induces a transitory destabilisation mainly manifested by the stimulating ascendant flow throughout the thallus. (shrink)

Multi-stakeholder initiatives for biodiversity conservation on working landscapes often necessitate strategies to facilitate learning in order to foster successful collaboration. To investigate the learning processes that both undergird and result from collaborative efforts, this case study employs the concept of boundary work as a lens to examine learning between rice growers and conservation professionals in California’s Central Valley, who were engaged in a collaborative research project focused on migratory bird conservation. Through analysis of workshop observations, project documents, and interviews with (...) rice growers and conservation professionals, we identified five distinct factors of the collaborative research process that influenced learning amongst these two groups: having mutually beneficial goals, sharing ownership of the collaborative research process, building trust, integrating knowledge, and institutional alignment. We also examined and identified learning outcomes for both rice growers and conservation professionals, which included new knowledge of the social-ecological system, new practices around farming and collaboration, and shifting identities. Our findings suggest that applying these factors and outcomes for learning when structuring collaborative research, and other multi-stakeholder initiatives, can foster learning amongst diverse stakeholder groups to support new approaches for balancing resource use and adaptive management. (shrink)

I give some reason for accepting a form of the view that there is some logical, And not just contingent, Connection between publicly observable behavior and a person's psychological states. If my contentions are sound, They open the way to the enterprise of delineating a stratification of psychological state concepts. This involves determining which mental concepts are logically connected to observable behavior and how the other categories of mental states are specified on the basis of these.

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)

This is a study of Aristotle's moral philosophy as it is contained in the Nicomachean Ethics. Hardie examines the difficulties of the text; presents a map of inescapable philosophical questions; and brings out the ambiguities and critical disagreements on some central topics, inclduing happiness, the soul, the ethical mean, and the initiation of action.

This book interprets Thomas Hardy’s Tess of the D’Urbervilles with the openness toward experience recommended by John Dewey’s Art as Experience . The characters of Tess are considered as real people with sexual bodies and complex minds. Efron identifies the “experience blockers” that the critical tradition has stumbled upon, and defends Hardy’s involvement in telling his story. Efron offers a new way of evaluating literature inspired by Dewey’s pragmatist aesthetics.

There are important studies that have directly focused on how, in times of conflict, it is possible for previously law abiding people to commit the most atrocious acts of cruelty and violence. The work of Erich Fromm, Hannah Arendt, Zygmunt Bauman and Ernest Becker have all contemplated the driving force of aggression and mass violence to further our understanding of how people are capable of engaging in extreme forms of cruelty and violence. This paper specifically addresses these issues by focusing (...) on C. P. Taylor’s play Good. This provocative play examines how a seemingly ‘good’ and intelligent university professor can gradually become caught up in the workings of the Third Reich. Taylor highlights the importance of appreciating how people can be steadily incorporated into an ideologically destructive system. I argue that the theatre is a powerful medium to explore these complex issues. The audience of Good find themselves confronted with the following question—‘What would you have done?’. (shrink)

Ssu-ma Ch'ien's hih chi is one of the most influential of Chinese histories, but its organization reflects a historiography quite different from that of traditional Western history. Ssu-ma divided his account of the past into five overlapping sections: basic annals , chronological tables, treatises, hereditary houses , and biographies. One result of this fragmented arrangement is that stories may be told more than once, from different perspectives, and these accounts may not be entirely consistent. From a Western perspective this would (...) seem to indicate a certain disregard for the truth, but in many hih chi passages Ssu-ma Ch'ien demonstrates a passionate concern for accuracy.In this article I examine in detail one typical set of multiple narrations--the five versions of Wei Pao's defection in c. 205 B.C.--and argue that in some ways Ssu-ma's conflicting accounts reflect the past more accurately than the unified narrative we expect from Western histories. Although Ssu-ma's methods might seem amenable to the constructivist theories of Louis Mink and Hayden White, in the end this type of analysis is inadequate to explain a work which is rooted in a non-Western tradition of historiography. Ssu-ma Ch'ien's own conception of history recognized the limitations of historians and evidence, held out the possibility of multiple interpretations, and focused on moral insight. It is a mix unfamiliar to Westerners, but it does provide a coherent picture of Ssu-ma Ch'ien's historical methodology, and it may serve as an interesting example for modern historians who seek to escape traditional modes of historical writing. (shrink)

En philosophie du droit, on a coutume d’opposer juspositivisme et jusnaturalisme et de placer Jeremy Bentham dans la première catégorie. Plusieurs auteurs tiennent même Bentham pour le père du juspositivisme. Je prétends pour ma part que cette façon de classer Bentham est inadéquate et nécessite une importante mise au point. S’il est vrai que Bentham était un adversaire des doctrines du droit naturel, il ne s’ensuit pas pour autant qu’il appartient au positivisme juridique; et les raisons qui pourraient justifier le (...) classement de Bentham parmi les juspositivistes militent aussi pour son association au jusnaturalisme. Que faut-il entendre exactement par « positivisme juridique », et en quel sens Bentham y adhère-t-il? C’est à cette double question que le présent article est consacré. (shrink)

Résistance(s) réunit un ensemble de contributions scientifiques originales émanant de chercheurs en sciences humaines et sociales et consacré à la ou aux résistance(s). La résistance décrit les capacités de refus, d'évitement et d'adaptation développées par les acteurs lorsqu'ils sont confrontés à une imposition externe ou à une injonction institutionnelle. Elle se présente comme une interprétation des refus, des éventuelles ruses voire des conflits ouverts qui s'expriment dans une telle situation ; cette interprétation diffère cependant de sa simple manifestation dans la (...) mesure où elle recadre la rationalité et le bien-fondé de l'action ou de la réaction. Il n'est plus question d'y voir l'immaturité d'une population ou le sous-développement d'une nation incapable d'offrir une réponse adéquate à une tension du monde ou à une décision dont elles seraient l'objet. Au contraire, cette réponse est analysée comme pertinente dans le cadre précis de cette population ou de cette nation: ramener l'interaction à son cadre, intégrer dans sa perception les logiques endogènes qui ont présidé à son élaboration, affirmer la simple présence de telles logiques, c'est-à-dire d'une telle cohérence, revient à accepter l'idée même de cette résistance qui, intrinsèquement, exprime ainsi l'existence et la reconnaissance d'une réelle diversité."--Page 4 of cover. (shrink)

The metre of Olympian II is still a matter of some difficulty. It has commonly been recognized as differing from Pindar's other metres, but many opinions have been held of its character. An understanding of it is, however, not merely essential to any general theory of Pindar's metric but vital to the textual criticism of the poem. Without some coherent theory we cannot say where ‘Responsionsfreiheiten’ are allowed and some important cruces remain unsolved. In recent years three theories have been (...) put forward. In his Res Metrica pp. 153–5 W. R. Hardie put forward the view that it is an example of a μτρον μονοεδές composed in Cretic verse. He holds that it is written in Cretics or their recognized metrical equivalent, Paeons. This kind of verse is known from the Delphic Paean to Apollo and the Paean of Limenius, and so far as the equivalence of Cretics and Paeons is concerned, there is no difficulty in it. But as Hardie himself admitted, his theory does not account for all the facts. It may be said to suffer from the following defects. n In Str. 1, 3, 5, 7 and Ep. 1, 4, 5 he has to assume the existence of an extra single syllable at the beginning of the line. Since all attempts to defend ‘Anacrusis’ are extremely doubtful, this can hardly be maintained here. 2. The clausula of the Strophe cannot be reduced to Cretics or Paeons. 3. He has to admit that in Ep. 2 and 3 there is ‘some Trochaic movement’ and presumably he would have to admit that in Str. 3 there is either an Iambic, or, as he would prefer, a Trochaic movement with Anacrusis in το πσα μεν. There is certainly some truth in Hardie's theory, but since it does not consider all the facts or co-ordinate them into a whole, it is not really satisfactory. (shrink)

The metre of Olympian II is still a matter of some difficulty. It has commonly been recognized as differing from Pindar's other metres, but many opinions have been held of its character. An understanding of it is, however, not merely essential to any general theory of Pindar's metric but vital to the textual criticism of the poem. Without some coherent theory we cannot say where ‘Responsionsfreiheiten’ are allowed and some important cruces remain unsolved. In recent years three theories have been (...) put forward. In his Res Metrica pp. 153–5 W. R. Hardie put forward the view that it is an example of a μέτρον μονοεɩδές composed in Cretic verse. He holds that it is written in Cretics or their recognized metrical equivalent, Paeons. This kind of verse is known from the Delphic Paean to Apollo and the Paean of Limenius, and so far as the equivalence of Cretics and Paeons is concerned, there is no difficulty in it. But as Hardie himself admitted, his theory does not account for all the facts. It may be said to suffer from the following defects. n In Str. 1, 3, 5, 7 and Ep. 1, 4, 5 he has to assume the existence of an extra single syllable at the beginning of the line. Since all attempts to defend ‘Anacrusis’ are extremely doubtful, this can hardly be maintained here. 2. The clausula of the Strophe cannot be reduced to Cretics or Paeons. 3. He has to admit that in Ep. 2 and 3 there is ‘some Trochaic movement’ and presumably he would have to admit that in Str. 3 there is either an Iambic, or, as he would prefer, a Trochaic movement with Anacrusis in ἤτοɩ πɩσα μεν. There is certainly some truth in Hardie's theory, but since it does not consider all the facts or co-ordinate them into a whole, it is not really satisfactory. (shrink)

Part I Introduction -/- Passion at a Distance (Don Howard) -/- Part II Philosophy, Methodology and History -/- Balancing Necessity and Fallibilism: Charles Sanders Peirce on the Status of Mathematics and its Intersection with the Inquiry into Nature (Ronald Anderson) -/- Newton’s Methodology (William Harper) -/- Whitehead’s Philosophy and Quantum Mechanics (QM): A Tribute to Abner Shimony (Shimon Malin) -/- Bohr and the Photon (John Stachel) -/- Part III Bell’s Theorem and Nonlocality A. Theory -/- Extending the Concept of an (...) “Element of Reality” to Work with Inefficient Detectors (Daniel M. Greenberger) -/- A General Proof of Nonlocality without Inequalities for Bipartite States (GianCarlo Ghirardi and Luca Marinatto) -/- On the Separability of Physical Systems (Jon P. Jarrett) -/- Bell Inequalities: Many Questions, a Few Answers (Nicolas Gisin) -/- B. Experiment -/- Do Experimental Violations of Bell Inequalities Require a Nonlocal Interpretation of Quantum Mechanics? II: Analysis a la Bell (Edward S. Fry, Xinmei Qu, and Marlan O. Scully) -/- The Physics of 2 = 1 + 1 (Yanhua Shih) -/- Part IV Probability, Uncertainty, and Stochastic Modifications of Quantum Mechanics -/- Interpretations of Probability in Quantum Mechanics: A Case of “Experimental Metaphysics” (Geoffrey Hellman) -/- “No Information Without Disturbance”: Quantum Limitations of Measurement (Paul Busch) -/- How Stands Collapse II (Philip Pearle) -/- Is There a Relation Between the Breakdown of the Superposition Principle and an Indeterminacy in the Structure of the Einsteinian Space-Time? (Andor Frenkel) -/- Indistinguishability or Stochastic Dependence? (D. Costantini and U. Garibaldi) -/- Part V Relativity -/- Plane Geometry in Spacetime (N. David Mermin) -/- The Transient nows (Steven F. Savitt) -/- Quantum in Gravity? (Michael Horne) -/- A Proposed Test of the Local Causality of Spacetime (Adrian Kent) -/- Quantum Gravity Computers: On the Theory of Computation with Indefinite Causal Structure (Lucien Hardy) -/- “Definability,” “Conventionality,” and Simultaneity in Einstein–Minkowski Space-Time (Howard Stein) -/- Part VI Concluding Words -/- Bistro Banter: A Dialogue with Abner Shimony and Lee Smolin -/- Unfinished Work: A Bequest (Abner Shimony) -/- Bibliography of Abner Shimony. (shrink)

In his 1947 British Academy lecture on Naturalistic Ethics, Mr. W. F. R. Hardie is concerned to ask himself whether a naturalistic theory of ethics can give a “satisfactory account of our moral knowledge or convictions,” or whether some form of non-naturalism is demanded by our moral experience. It will be remembered that after a careful sifting and examination of certain features of our moral knowledge or convictions, Mr. Hardie suspends judgment between naturalism and non-naturalism, observing that “on the one (...) hand philosophers who start from the ostensible facts of our moral experience and thinking, and are most careful and accurate in their rendering of these facts, have tended to be led to objectivist and anti-naturalistic conclusions. Where they least carry conviction is in the moral epistemology which they assume or defend. When we reflect, with the epistemological issue in mind, on the actual process in ourselves of moral reflection and decision, we are more inclined to sympathize with a ‘moral sentiment’ theory than we ought to be if the rationalists are wholly in the right.” In what follows I wish to consider another feature of our moral experience which Mr. Hardie did not examine in his lecture and which appears to be of considerable importance, namely the situation where, to put it very roughly for the moment, we find ourselves at variance with another person or persons on a moral issue, where, for instance, I hold that a certain course of conduct is right, and the other person or persons hold that it is wrong, or vice versa , and where further we may pursue divergent courses of action accordingly. I wish to ask myself whether the naturalistic commentary on this situation of ethical disagreement is altogether satisfactory when we consider it in the light of “the ostensible facts of our moral experience and thinking,” whether, in fact, to use another phrase of Mr. Hardie's, it squares altogether with “our fundamental moral convictions” in regard to such a situation. The naturalistic commentary with which I am primarily concerned is that which is now sometimes labelled “the emotive theory of ethics,” and is to be found admirably developed, for example, in Professor Stevenson's book Ethics and Language. (shrink)

Unlike its predecessors, this systematic survey of the law of Athens is based on explicit discussion of how the subject might be studies, incorporating topics such as the democratic political system and social structure. Technical and legal terms are explained in a comprehensive glossary.