The rapid rise of international collaborative science has enabled access to genomic data. In this article, it is argued that to move beyond mapping genomic variation to understanding its role in complex disease aetiology and treatment will require extending data sharing for the purposes of clinical research translation and implementation.

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

Achieving space situational awareness requires, at a minimum, the identification, characterization, and tracking of space objects. Leveraging the resultant space object data for purposes such as hostile threat assessment, object identification, and conjunction assessment presents major challenges. This is in part because in characterizing space objects we reference a variety of identifiers, components, subsystems, capabilities, vulnerabilities, origins, missions, orbital elements, patterns of life, operational processes, operational statuses, and so forth, which tend to be defined in highly heterogeneous and sometimes inconsistent (...) ways. The Space Domain Ontologies are designed to provide a consensus-based realist framework for formulating such characterizations in a way that is both consistent and computable. Space object data are aligned with classes and relations in a suite of ontologies built around the existing Space Object Ontology. They are stored in a dynamically updated Resource Description Framework triple store, which can be queried to support space situational awareness and the needs of spacecraft operators and analysts. This paper provides an overview of the Space Domain Ontologies and their development and use. It presents the motivation for and advantages of the Space Domain Ontologies, including the benefits they provide for enhancing and maintaining long-term space situational awareness. (shrink)

Contrary to the usual interpretation of Locke, Cox argues that Locke's political philosophy has a strong Hobbesian flavor. The state of nature is really a state of war, and the law of nature turns out to be a "con- struct of the mind." To justify this interpretation, Cox carefully analyzes Locke's two Treatises. He suggests that Locke accommodated his philosophic argument to the prevailing political, philosophical, and religious atmosphere of the day, but that this is only a device for presenting (...) a much more radical position. The reader may not be completely persuaded by Cox's forceful arguments, but he will discover insights and difficulties which must be taken into account for an adequate understanding of Locke's political philosophy.--R. J. B. (shrink)

Oxidative damage to DNA has been associated with neurodegenerative diseases. Developmental exposure to lead has been shown to elevate the Alzheimer's disease related beta-amyloid peptide , which is known to generate reactive oxygen species in the aging brain. This study measures the lifetime cerebral 8-hydroxy-2'-deoxyguanosine levels and the activity of the DNA repair enzyme 8-oxoguanine DNA glycosylase in rats developmentally exposed to Pb. Oxo8dG was transiently modulated early in life , but was later elevated 20 months after exposure to Pb (...) had ceased, while Ogg1 activity was not altered. Furthermore, an age-dependent loss in the inverse correlation between Ogg1 activity and oxo8dG accumulation was observed. The effect of Pb on oxo8dG levels did not occur if animals were exposed to Pb in old age. These increases in DNA damage occurred in the absence of any Pb-induced changes in copper/zinc-superoxide dismutase , manganese-SOD , and reduced-form glutathion . These data suggest that oxidative damage and neurodegeneration in the aging brain could be impacted by the developmental disturbances. (shrink)

This is an engaging book on a subject which most people in our culture assume went out of fashion long ago. The book had its genesis in one of a series of symposia convened by the Church Society for College Work of Cambridge to explore certain themes and ideas which have great import for our time. The various authors of the essays eschew the habit of viewing Transcendence as the traditional content of metaphysical arguments or revelatory statements about the nature (...) of God outside or independent of the world and seek for signs of the possibility of achieving a renewed sense of Transcendence in the domains of inner experience, history, culture, language, science, technology, and the arts. Huston Smith suggests two options of human fulfillment: psychological and ontological, both providing a kind of transcendence of self and society. He refuses to accept one and reject the other but instead to convince us that both are legitimate. M. Murphy claims that the experience of psychological and social transcendence can be fostered by educational projects such as encounter groups, gestalt therapy workshops and sensitivity training programs. In his "Manifesto for a Dionysian Theology," Sam Keen analyzes the Apollonian way of reasoning and planning which has come to dominate in Western culture and makes a plea for a reassertion of the Dionysian principle in religion which might be expressive of life as dance, centrality of feelings and sensations, a pantheistic conception of God and a theology of play. Harvey Cox asserts that our society has lost its capacity for utopian fantasy resulting in the inability to conceive of any world which is not a mere modification or extension of our own world. He suggests that we consciously become "fools for Christ" again and give full rein to our powers of creative fantasizing even at the risk of contracting "religious madness." Donald Schon urges post-modern man to give up hope for achieving a stable political order and to develop an "ethic for change" appropriate to the demands of our society where change is all-pervasive. Essays by R. Bellah and H. Richardson explore myths of transcendence as ordering structures in society and plead for increased attention to correspondences among the disciplines of theology, sociology, and psychology. E. Fackenheim and W. Kaufman seek to clarify the notion of transcendence in Judaism and Christianity respectively and to "clear the way for a positive revelation." In keeping with the shared notion that transcendent reality is present and active within the human process, two eminent process philosophers, Wieman and Hartshorne discuss the "implications for a concept of transcendence that follows from affirming the creative freedom of man." The essays singly and together reject the notion that the existence and nature of transcendent reality can be arrived at by pursuing a single line of argumentation to its bitter end and instead they work together from various points of view to reinforce our sense of man's renewed thirst for the Divine and the subsequent rediscovery of God's uninterrupted presence within the world of "Immanent Possibility."--J. B. L. (shrink)

This book is available either individually, or as part of the specially-priced Arguments of the Philosphers Collection.

The New Evil Demon problem has been hotly debated since the case was introduced in the early 1980’s (e.g. Lehrer and Cohen 1983; Cohen 1984), and there seems to be recent increased interest in the topic. In a forthcoming collection of papers on the New Evil Demon problem (Dutant and Dorsch, forthcoming), at least two of the papers, both by prominent epistemologists, attempt to resist the problem by appealing to the distinction between justification and excuses. My primary aim here is (...) to critically evaluate this new excuse maneuver as a response to the New Evil Demon problem. -/- Their response attempts to give us reason to reject the idea that victims of the New Evil Demon have justification for believing as they do. I shall argue that this approach is ultimately unsuccessful, however much of value can be learned from these attempts. In particular, progress in the debate can be made by following those who advance the excuse maneuver and make explicit the connection between epistemic justification and epistemic norms. By doing so, the questions being debated are clarified, as is the methodology being used to attempt to answer them. (shrink)

In this article I argue that the value of epistemic justification cannot be adequately explained as being instrumental to truth. I intend to show that false belief, which is no means to truth, can nevertheless still be of epistemic value. This in turn will make a good prima facie case that justification is valuable for its own sake. If this is right, we will have also found reason to think that truth value monism is false: assuming that true belief does (...) have value, there is more of final epistemic value than mere true belief. (shrink)

Modern science developed in the interflow of culture between west and east. Combing of pratice technology with philosophic thoughts formed experimental method. Holistic views contacting atomism produced system theory. System thoughts are applicated in the science and engineering of biosystems, and the cencepts of system biomedicine (Kamada T.1992), systems biology (Zieglgansberger W, Tolle TR.1993), system bioengineering and system genetics (Zeng BJ. 1994) were established. From positive to synthetic thoughts, philosophy have been developed ontology, cosmology, organism theories. Structurity is structure logic (...) system founded on entity, develop, exist axioms, tolerance, adaptation, fluctuate, interweave, transform theorems and integrate, adaptation, construct laws. Structurity be discussed on the cosmos, life, culture system, creation, hologram theories of structure ontology, construct mutation, simi-structure organism and entity emergence, symbol implication. From the relation of structure, function and development, the structurity put forward the cycle, spiral, triangle structure stability patterns of self-organization in structure complement each other and stratification, functional couple and interflow bounds growth, coordinativetransformation and holographic symmetry. (shrink)

What makes an intellectual virtue a virtue? A straightforward and influential answer to this question has been given by virtue-reliabilists: a trait is a virtue only insofar as it is truth-conducive. In this paper I shall contend that recent arguments advanced by Jack Kwong in defence of the reliabilist view are good as far as they go, in that they advance the debate by usefully clarifying ways in how best to understand the nature of open-mindedness. But I shall argue that (...) these considerations do not establish the desired conclusions that open-mindedness is truth-conducive. To establish these much stronger conclusions we would need an adequate reply to what I shall call Montmarquet’s objection. I argue that Linda Zagzebski’s reply to Montmarquet’s objection, to which Kwong defers, is inadequate. I conclude that it is contingent if open-mindedness is truth-conducive, and if a necessary tie to truth is what makes an intellectual virtue a virtue, then the status of open-mindedness as an intellectual virtue is jeopardised. We either need an adequate reliabilist response to Montmarquet’s objection, or else seek alternative accounts of what it is that makes a virtue a virtue. I conclude by briefly outlining some alternatives. (shrink)

In this paper I wish to propose and defend a form of the Representative Theory of Perception. According to this version of the theory, when a subject perceives some object x to be in a state P1 he does so by being aware of some modfication M1 of some object E. The subject's way of perceiving any one of a range of objects x,y,z, … is that of being aware of some modification of E. It will be a necessary condition (...) of someone's perceiving x to have property P1 that E be modified in some way. And in order for the modifications of E to be representations, a given property P1 will need to be causally related, characteristically, to one or more specific modifications, M1,M2, … Mn, of E. symbolized by ‘X'.). (shrink)

In common with traditional forms of epistemic internalism, epistemological disjunctivism attempts to incorporate an awareness condition on justification. Unlike traditional forms of internalism, however, epistemological disjunctivism rejects the so-called New Evil Genius thesis. In so far as epistemological disjunctivism rejects the New Evil Genius thesis, it is revisionary. -/- After explaining what epistemological disjunctivism is, and how it relates to traditional forms of epistemic internalism / externalism, I shall argue that the epistemological disjunctivist’s account of the intuitions underlying the New (...) Evil Genius thought experiment is at best incomplete. As presented, therefore, epistemological disjunctivism is unable to accommodate the core guiding intuitions of epistemic internalism. Given the stated aim of not being revisionary on this score, the view is at a dialectical disadvantage over the traditional forms of epistemic internalism the position is meant to replace. Unfortunately, therefore, at present, the impasse between internalism and externalism remains. (shrink)

One thing nearly all epistemologists agree upon is that Gettier cases are decisive counterexamples to the tripartite analysis of knowledge; whatever else is true of knowledge, it is not merely belief that is both justified and true. They now agree that knowledge is not justified true belief because this is consistent with there being too much luck present in the cases, and that knowledge excludes such luck. This is to endorse what has become known as the 'anti-luck platitude'. <br /><br (...) />But what if generations of philosophers have been mistaken about this, blinded at least partially by a deeply entrenched professional bias? There has been another, albeit minority, response to Gettier: to deny that the cases are counterexamples at all. <br /><br />Stephen Hetherington, a principal and vocal proponent of this view, advances what he calls the 'Knowing Luckily Proposal'. If Hetherington is correct, this would call for a major re-evaluation and re-orientation of post-Gettier analytic epistemology, since much of it assumes the anti-luck platitude both in elucidating the concept of knowledge, and in the application of such accounts to central philosophical problems. It is therefore imperative that the Knowing Luckily Proposal be considered and evaluated in detail. <br /><br />In this paper I critically assess the Knowing Luckily Proposal. I argue that while it draws our attention to certain important features of knowledge, ultimately it fails, and the anti-luck platitude emerges unscathed. Whatever else is true of knowledge, therefore, it is non-lucky true belief. For a proposition to count as knowledge, we cannot arrive at its truth accidentally or for the wrong reason. (shrink)

This chapter first surveys general issues in the epistemic internalism / externalism debate: what is the distinction, what motivates it, and what arguments can be given on both sides. -/- The second part of the chapter will examine the internalism / externalism debate as regards to the specific case of the epistemology of memory belief.

In general, epistemic internalists hold that an individual’s justification for a belief is exhausted by her reflectively accessible reasons for thinking that the contents of her beliefs are true. Applying this to the epistemology of testimony, a hearer’s justification for beliefs acquired through testimony is exhausted by her reflectively accessible reasons to think that the contents of the speaker’s testimony is true. A consequence of internalism is that subjects that are alike with respect to their reflectively accessible reasons are alike (...) with respect to what they have justification to believe. Testimony should be thought no different: hearers that are alike with respect to reflectively accessible reasons to think that a speaker’s testimony is true are alike with respect to their justification for beliefs based upon that testimony. But it has been recently argued that this view faces powerful counterexamples. So the central question is this: assuming that a hearer can acquire justification to believe a proposition through the testimony of a speaker, can epistemic internalism provide the resources to explain how such justification is possible? My aim in this paper is to address these counterexamples, and in so doing, defend epistemic internalist accounts of testimony. (shrink)

Cross cultural ethical conflicts are a major challenge for managers of multinational corporations (MNEs) when an MNE''s business practices and a host country''s practices differ. We develop a set of decision principles to help MNE managers deal with these conflicts and illustrate with examples of ethical conflicts faced by MNEs doing business in contemporary Russia (DeGeorge, 1994). We discuss the generalizability of the principles by comparing them to the Donaldson (1989) and Buller and Kohls (1997) decision models. Finally we discuss (...) changes in the cross cultural ethical problems facing MNE managers and offer suggestions for future corporate and academic work on these problems. (shrink)

Epistemic internalism, by stressing the indispensability of the subject’s perspective, strikes many as plausible at first blush. However, many people have tended to reject the position because certain kinds of beliefs have been thought to pose special problems for epistemic internalism. For example, internalists tend to hold that so long as a justifier is available to the subject either immediately or upon introspection, it can serve to justify beliefs. Many have thought it obvious that no such view can be correct, (...) as it has been alleged that internalism cannot account for the possibility of the justification of beliefs stored in memory. -/- My aim in this paper is to offer a response that explains how memory justification is possible in a way that is consistent with epistemic internalism and an awareness condition on justification. Specifically, I will explore the plausibility of various options open to internalists, including both foundationalist and non-foundationalist approaches to the structure of justification. I intend to show that despite other difficult challenges that epistemic internalism might face, memory belief poses no special problems that the resources of internalism cannot adequately address. (shrink)

In this paper I consider a recent argument of Timothy Williamson’s that epistemic internalism and content externalism are indeed incompatible, and since he takes content externalism to be above reproach, so much the worse for epistemic internalism. However, I argue that epistemic internalism, properly understood, remains substantially unaffected no matter which view of content turns out to be correct. What is key to the New Evil Genius thought experiment is that, given everything of which the inhabitants are consciously aware, the (...) two worlds are subjectively indistinguishable for them, which is what matters on internalist accounts of epistemic justification. I argue that even if a standard moral of the New Evil Genius intuition is untenable due to considerations arising from content externalism, the case can be understood as supporting epistemic internalism in a way that is wholly compatible with content externalism. In short, epistemic internalism is committed to sameness of justificatory status between subjectively indistinguishable counterparts, not sameness of content of their justifiers. (shrink)

How do our brains make choices? How do factors such as Alzheimer's or depression impair decision-making? Presenting the latest research on 'hot' and 'cold' decision-making, Barbara Sahakian and Jamie Nicole LaBuzetta look at the therapeutic smart drugs now available, and raise concerns about their unregulated use to enhance mental performance.