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)

Mitochondria contain a molecular genetic system to express the 13 protein components of the electron transport system encoded in the mitochondrial genome (mtDNA). Defects in the function of this system result in some diaseases, many of which are multisystem disorders, prominently involving highly aerobic, postmitotic tissues. These defects can be caused by large‐scale rearrangements of mtDNA, by point mutations, or by nuclear gene mutations resulting in abnormalities in mtDNA. Although any of these mutations would be expected to produce a similar (...) clinical phenotype by compromising oxidative phosphorylation, the surprising and puzzling result is that different clinical phenotypes are generally associated with specific mtDNA mutations. Moreover, the same mutation can produce a distinct clinical phenotype in different individuals or pedigrees. MtDNA rearrangements are also found in aged individuals, but at a subclinical level, suggesting that normal and pathological processes can differ by the effect of genetic or environmental factors on the error rate of mtDNA replication. (shrink)

El nuevo libro de Xavier de Planhol, L'Islam et la mer es el primer intento, por parte de un especialista occidental, de evaluar el papel del mar en el mundo islámico. No es un libro que se dedique a describir acontecimientos sino a establecer paradigmas culturales e intelectuales, llegando a la conclusión de que «el islam es incompatible con el mar». En consecuencia, explora las implicaciones de esta antipatía a lo largo de la historia islámica desde tiempos pre-islámicos hasta el (...) presente. Su tesis, sin embargo, puede ser cuestionada desde diversas perspectivas, y este artículo, a la vez reseña y estado de la cuestión, sugiere aspectos en los que, tanto las fuentes que él cita, como otras no utilizadas en el libro, pueden ser interpretadas para llegar a conclusiones muy diferentes. (shrink)

This collection of interdisciplinary essays on a unique work by a physician and political figure in 12th-century Spain and North Africa casts important light on the social and intellectual history of the period and breaks new ground in the critical assessment of medieval Arabic literary works.

Insect molting is elicited by a class of polyhydroxylated steroids, ecdysteroids, that originate in the prothoracic glands. Ecdysteroid synthesis in the prothoracic glands is controlled in large measure by a peptide hormone from the brain, prothoracicotropic hormone (PTTH), which exists in two forms and is released into the general circulation as a result of environmental and developmental cues. The means by which PTTH activates the prothoracic glands has been examined at the cellular level and the data reveal the involvement of (...) cAMP, calcium, calmodulin, cAMP‐dependent protein kinase and the ultimate phosphorylation of a 34 kDa protein tentatively identified as ribosomal protein S6. (shrink)

Logic and Computation is concerned with techniques for formal theorem-proving, with particular reference to Cambridge LCF (Logic for Computable Functions). Cambridge LCF is a computer program for reasoning about computation. It combines methods of mathematical logic with domain theory, the basis of the denotational approach to specifying the meaning of statements in a programming language. This book consists of two parts. Part I outlines the mathematical preliminaries: elementary logic and domain theory. They are explained at an intuitive level, giving references (...) to more advanced reading. Part II provides enough detail to serve as a reference manual for Cambridge LCF. It will also be a useful guide for implementors of other programs based on the LCF approach. (shrink)

We show the existence of Lorentz invariant Berry phases generated, in the Stueckelberg–Horwitz–Piron manifestly covariant quantum theory (SHP), by a perturbed four dimensional harmonic oscillator. These phases are associated with a fractional perturbation of the azimuthal symmetry of the oscillator. They are computed numerically by using time independent perturbation theory and the definition of the Berry phase generalized to the framework of SHP relativistic quantum theory.

I defend the doctrine of double effect and a so-called ‘strict’ definition of intention: A intends an effect if and only if A has it as an end or believes that it is a state of affairs in the causal sequence that will result in A's end. Following Kamm's proposed ‘doctrine of triple effect’, I distinguish an intended effect from an effect that motivates an action, and show that this distinction is morally significant. I use several contrived cases as illustrations, (...) but my position does not depend on intuitive judgements about them. Instead, it follows from the view that the moral permissibility of an action depends at least partly on how it forms the agent's character. I also respond to some objections presented by Harris, Bennett, McIntyre, Thomson and Scanlon to the doctrine of double effect. (shrink)

I argue that physicians can save women from life-threatening pregnancies by performing a craniotomy, placentectomy, or salpingotomy without intending death or harm. To support this conclusion, I defend the relevance thesis about intentions (a person intends X only if X explains the action). I then criticize the identity thesis (if a person intends X and knows X is Y then the person intends Y) and three mistakenly strict moral principles: (1) one may not intend something that is a serious harm (...) for an innocent person, (2) one may not intend to terminate pregnancy before viability, which would prohibit, and (3) one may not act on a person’s body in a harmful way in order to benefit another person. (1) would prohibit procuring organs from living donors, (2) would prohibit treating hepatic pregnancies and other ectopic pregnancies, and (3) would prohibit procuring organs from living donors and performing many prenatal surgeries. (shrink)

Critics have charged that Heidegger's account of authenticity is morally nihilistic, that his fundamental ontology is either egocentric or chauvinistic; and many see Heidegger's turn to Nazism in 1933 as following logically from an indifference, and even hostility, to "otherness" in the premises of his early philosophy. In_ The Fragile "We": Ethical Implications of Heidegger's "Being and Time,"_ Lawrence Vogel presents three interpretations of authentic existence--the existentialist, the historicist, and the cosmopolitan--each of which is a plausible version of the (...) personal ideal depicted in _Being and Time._ He then draws parallels between these interpretations and three moments in the contemporary liberal-communitarian debate over the relationship of the "I" and the "We." His book contributes both to a diagnosis of what there is about _Being and Time_ that invites moral nihilism and to a sense of how fundamental ontology might be recast so that "the other" is accorded an appropriate place in an account of human existence. (shrink)

The scientific consensus regarding anthropogenic climate change is firmly established yet climate change denialism, a species of what I call pseudoskepticism, is on the rise in industrial nations most responsible for climate change. Such denialism suggests the need for a robust ethics of inquiry and public discourse. In this paper I argue: (1) that ethical obligations of inquiry extend to every voting citizen insofar as citizens are bound together as a political body. (2) It is morally condemnable for public officials (...) to put forward assertions contrary to scientific consensus when such consensus is decisive for public policy and legislation. (3) It is imperative upon educators, journalists, politicians and all those with greater access to the public forum to condemn, factually and ethically, pseudoskeptical assertions made in the public realm without equivocation. (shrink)

Manuel Velasquez and F. Neil Brady apply the doctrine of double effect to business ethics and conclude that the doctrine allows a pharmaceutical company to sell a drug with potentially fatal side effects only if it also has the good effect of saving lives. This forbidsthe sale of many common products, such as automobiles and alcohol. My account preserves the virtues of the doctrine of double effectwithout making it too restrictive. I apply the doctrine to a pharmaceutical company’s decision to (...) market a drug with dangerous side effects and argue that free markets often offer the best way to compare the good and bad effects of business decisions. I conclude that the doctrine does allow a business to sell a potentially fatal product that does not save lives, provided that it warns consumers about the danger. (shrink)

I propose that primary conscious awareness arises from synchronized activity in dendrites of neurons in dorsal thalamic nuclei, mediated particularly by inhibitory interactions with thalamic reticular neurons. In support, I offer four evidential pillars: consciousness is restricted to the results of cortical computations; thalamus is the common locus of action of brain injury in vegetative state and of general anesthetics; the anatomy and physiology of the thalamus imply a central role in consciousness; neural synchronization is a neural correlate of consciousness.

In the Fifth Meditation, Descartes makes a remarkable claim about the ontological status of geometrical figures. He asserts that an object such as a triangle has a 'true and immutable nature' that does not depend on the mind, yet has being even if there are no triangles existing in the world. This statement has led many commentators to assume that Descartes is a Platonist regarding essences and in the philosophy of mathematics. One problem with this seemingly natural reading is that (...) it contradicts the conceptualist account of universals that one finds in the Principles of Philosophy and elsewhere. In this paper, I offer a novel interpretation of the notion of a true and immutable nature which reconciles the Fifth Meditation with the conceptualism of Descartes' other work. Specifically, I argue that Descartes takes natures to be innate ideas considered in terms of their so-called 'objective being'. (shrink)

The East Asian family-oriented principle is defensible in theory as a shared decision making model and thus a viable alternative to individual-oriented decision making in bioethics. There are two crucial problems with the family-oriented principle, i.e., family-oriented paternalism and conflicts of interests between a patient and his family. These obstacles may appear formidable but they are not insurmountable in practice.

In this paper, I want eventually to get around to proposing a criterion of identity for events which are changes in physical objects, where events are construed as comprising a distinct metaphysical category of thing. The proposal will be preceded by a discussion of what I take to be a mistaken suggestion for such a criterion; I will do that because I think that seeing what it takes to show why that suggestion fails helps to motivate a theory about what (...) it is to be an event; and that theory wi II supply the conceptual foundations for my proposal concerning the criterion of identity for events. Before that suggestion is discussed, however, I want to discuss briefly an aspect of the question, Why do we have to give a criterion of identity for events, or for objects of any sort whatsoever? I want to have a brief look at the connection between identity criteria and the idea of a kind of object. (shrink)

This commentary on Rossi’s The Ethical Commonwealth in History will address three points of interpretation related to Kant’s conception of the ethical community/commonwealth. First, I will raise a number of concerns related to Rossi’s use of Kant’s concept of the highest good. Second, I will examine the relevance of the overall project of Kant’s Religion within the Boundaries of Mere Reason to his discussion of the ethical community, a matter that Rossi does not take up. Third, I will challenge the (...) optimism that Rossi assigns to Perpetual Peace in light of its closing “antinomy between politics and morals.”. (shrink)

The report of the President's Council on Bioethics, Human Cloning and Human Dignity, addresses the central ethical, political, and policy issue in human embryonic stem cell research: the moral status of extracorporeal human embryos. The Council members were in sharp disagreement on this issue and essentially failed to adequately engage and respectfully acknowledge each others' deepest moral concerns, despite their stated commitment to do so. This essay provides a detailed critique of the two extreme views on the Council (i.e., embryos (...) have full moral status or they have none at all) and then gives theoretical grounding for our judgment about the intermediate moral status of embryos. It also supplies an account of how to address profound moral disagreements in the public arena, especially by way of constructing a middle ground that deliberately pays sincere respect to the views of those with whom it has deep disagreements. (shrink)

This article enlarges classical syllogistic logic with assertions having to do with comparisons between the sizes of sets. So it concerns a logical system whose sentences are of the following forms: Allxareyand Somexarey, There are at least as manyxasy, and There are morexthany. Herexandyrange over subsets (not elements) of a giveninfiniteset. Moreover,xandymay appear complemented (i.e., as$\bar{x}$and$\bar{y}$), with the natural meaning. We formulate a logic for our language that is based on the classical syllogistic. The main result is a soundness/completeness theorem. (...) There are efficient algorithms for proof search and model construction. (shrink)

Recent advances in Artificial Intelligence and their application within the field of mental health provision raise issues that cross social, economic, and philosophical boundaries. While Therapeutic A.I. promises to disrupt the current provision of mental health services to reach populations without access to adequate mental health care there are risks. This paper addresses the philosophical problems posed by Therapeutic A.I. I suggest that in the absence of legal guidelines there is a need for philosophical guidance that prioritizes the dignity of (...) clients/consumers. To that end, I advance Rosen’s concept of dignity-as-respectfulness as the most appropriate philosophical principle to guide the application of Therapeutic A.I. (shrink)

Hans Jonas accuses Heidegger of “never bring[ing] his question about Being into correlation with the testimony of our physical and biological evolution.” Neither the early nor later Heidegger has a “philosophy of nature,” Jonas charges, because Naturphilosophie demands a new concept of matter, a monistic account of cosmogony and evolution, and the grounding of ethical responsibility for future generations in an ontological “first principle.” Jonas’s ontological rethinking of Darwinism allows him to overcome the nihilism that a mechanistic interpretation of evolution (...) forces upon us: a nihilism allegedly shared by Heidegger. I imagine a Heideggerian response to Jonas, and ask whether the dream of recovering a synthesis between cosmogony and moral insight has been irrecoverably shattered by modern natural science. (shrink)

Alexander Raven Thomson was a British fascist philosopher, active from 1932 to 1955. I outline Thomson’s Spenglerian views on civilization and decline. I argue that Thomson in his first book is an orthodox Spenglerian who accepts that decline is inevitable and thinks that it is morally required to destroy civilization in its final stages. I argue that this suffers from conceptual issues which may have caused Thomson’s change to a revised form of Spenglerianism, which is more authentically fascist. This authentically (...) fascist view is then seen to fall prey into the problem inherent in the very idea of permanent rebirth. (shrink)

Chimpanzee behaviour with mirrors makes it plausible that they can recognise themselves as themselves in mirrors, and so have a 'self-concept'. I defend this claim, and argue that roughly similar behaviour in pigeons, as reported, does not in fact make it equally plausible that they also have this mental capacity. But for all that it is genuine, chimpanzee self-consciousness may differ significantly from ours. I describe one possibility I believe consistent with the data, even if not very plausible: that the (...) chimpanzee is aware of itself only as a material being, and not as a subject of any psychological states. As I try to make clear, this possibility exists even if the chimpanzee has psychological states, and is aware of some of them. (shrink)

CHAPTER I INTRODUCTION Liberty is perhaps the most praised of all social ideals. Rare is the modern political movement which has not inscribed "liberty," ...

I argue that Kant identifies the only principle that refutes war realism, or the view that warring nations should do whatever they can to win the war as quickly as possible. According to Kant, warring nations must follow principles that preserve the possibility of entering a peaceful condition, and the peaceful condition is not merely an end to hositilities.

I argue that Descartes intended the so-called ontological "argument" as a self-validating intuition, rather than as a formal proof. The textual evidence for this view is highly compelling, but the strongest support comes from understanding Descartes's diagnosis for why God's existence is not 'immediately' self-evident to everyone and the method of analysis that he develops for making it self-evident. The larger aim of the paper is to use the ontological argument as a case study of Descartes's nonformalist theory of deduction (...) and his method of analysis, showing how he conceives the latter as a form of philosophical therapy. (shrink)

Observers have noted a decline (in the US) in attributions of genetically-based inferiority (e.g. in intelligence) to Blacks, and a rise in attributions of culturally-based inferiority. Is this "culturalism" merely warmed-over racism ("cultural racism") or a genuinely distinct way of thinking about racial groups? The question raises a larger one about the relative place of biology and culture in racist thought. I develop a typology of culturalisms as applied to race: (1) inherentist or essentialist culturalism (inferiorizing cultural characteristics wrongly but (...) intelligibly regarded as inhering in the nature of racial groups). This view has an historical pedigree in the work of J.G. von Herder, and the tradition of "national racism." (2) non-inherentist culturalism (groups regarded as possessing changeable, malleable inferiorizing cultural characteristics). (3) colonalist culturalism (colonial subjects regarded as uncivilized but capable of becoming civilized under European tutelage). (4) neo-racism (cultures of former colonial subjects in or potentially immigrating to European countries are regarded in an inherentist manner and incompatible with but not inferior to European cultures). Non-inherentist culturalism (#2) can be put to either a racist or an anti-racist use. (shrink)

I argue that the contralife argument, which new natural law theorists have proposed as an argument against contraception, also would rule out altered nuclear transfer, which has been proposed as a way of procuring human stem cells without destroying human embryos.