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 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.

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)

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)

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)

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.

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

In the past decade, debates about the status and character of ‘race’ within philosophy have been dominated by philosophers of language, of biology, and of science, and metaphysicians. I here propose a viewpoint on the race debate arising from within social philosophy and the sociohistorical study of race.

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)

In The Sovereignty of Good Iris Murdoch suggests that the central task of the moral agent involves a true and loving perception of an- other individual, who is seen as a particular reality external to the agent. Writing in the 1960s she claimed that this dimension of morality had been "theorized away" in contemporary ethics. I will argue today that 20 years later, this charge still holds true of much contemporary ethical theory.

The words ‘racist’ and ‘racism’ have become so overused that they nowconstitute obstacles to understanding and interracial dialogue about racial matters. Insteadof the current practice of referring to virtually anything that goes wrong or amiss withrespect to race as ‘racism,’ we should recognize a much broader moral vocabulary forcharacterizing racial ills – racial insensitivity, racial ignorance, racial injustice, racialdiscomfort, racial exclusion. At the same time, we should fix on a definition of ‘racism’ thatis continuous with its historical usage, and avoids (...) conceptual inflation. I suggest two basic,and distinct, forms of racism that meet this condition – antipathy racism and inferiorizingracism. We should also recognize that not all racially objectionable actions are done froma racist motive, and that not all racial stereotypes are racist. (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)

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)

In The Righteous Mind, Jonathan Haidt claims that liberals have a narrower moral outlook than conservatives—they are concerned with fairness and relief of suffering, which Haidt sees as individualistic values, while conservatives care about authority and loyalty too, values concerned with holding society together. I question Haidt’s methodology, which does not permit liberals to express concerns with social bonds that do not fit within an ‘authority’ or ‘loyalty’ framework and discounts people who support liberal positions but do not self-ascribe as (...) liberals. I also argue that of the six ‘moral foundations’, fairness and relief of suffering are more fundamental values than authority and loyalty, which are virtues only if their objects are worthy. Moral education programs must also encourage students to recognize some values as more urgent than others, and permit inquiry into the actual reasons for political behavior other than professed value commitments. (shrink)

This two-volume collection of essays brings together major contemporary theoretical works on freedom of speech. Volume I, begins with a theoretical overview of freedom of speech and then turns to the topics of what justifies freedom of speech and what kinds of acts raise free speech concerns. Volume II, examines the distinctions among content regulations and between content and content-neutral regulations. It also analyses the concept of the public forum, inciting and hateful speech and lastly the tension between the subsidizing (...) activities of the affirmative state and the negative liberty of freedom of speech. (shrink)

Laplace once argued that if one could “comprehend all the forces by which nature is animated,” it would be possible to predict the future and explain the past. The advent of analysis of large-scale data sets has been accompanied by newfound concerns about “Laplace’s Demon” as it relates to certain fields of science as well as management, evaluation, and audit. I begin by asking how statistical data are constructed, illustrating the hermeneutic acts necessary to create a variable. These include attributing (...) a certain characteristic to a particular phenomenon, isolating the characteristic of interest, and assigning a value to it. In addition, a population must be identified and a sample must be “taken” from that population. Next, I examine how statistical analyses are conducted, examining the interpretive acts there as well. In each case, I show how big data add new challenges. I then show how statistics are incorporated into audits and evaluations, emphasizing how alternative interpretations are concealed in the audit process. I conclude by noting that these issues cannot be “resolved” as Laplace suggested. His Demon, already banished from physics, needs to be banished from other fields of science, management, audits, and evaluations as well. (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.

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 describe cases of moral blackmail as cases where A is told by B that if A does not commit an otherwise immoral act, B will commit an immoral act of equal or greater gravity. I describe cases of moral dilemma as cases where A must commit an otherwise immoral act to avert a natural disaster of equal or greater gravity. I then argue that cases of moral blackmail are structurally identical to cases of moral dilemma in (...) all respects but one: In cases of moral blackmail, A is predicting the free actions of a moral agent (B), whereas in cases of moral dilemma, A is predicting natural events. I conclude that cases of moral blackmail are more problematic than otherwise similar cases of moral dilemma for this reason alone. (shrink)

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)

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)

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)

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)

Roughly speaking all economists can be divided into two groups--those who agree with Milton Friedman and those who do not. Both groups, however, espouse the view that science is a series of approximations to a demonstrated accord with reality. Methodological controversy in economics is now merely a Conventionalist argument over which comes first--simplicity or generality. Furthermore, this controversy in its current form is not compatible with one important new and up and coming economic (welfare) theory called "the theory of the (...) Second Best." In this paper I offer a Second Best meta-theory that says that (1) any compromise between simplicity and generality must yield a theory which is "third best" by these Conventionalist criteria; and (2) there exists a better way than a compromise. (shrink)

In this paper I describe cases of moral blackmail as cases where A is told by B that if A does not commit an otherwise immoral act, B will commit an immoral act of equal or greater gravity. I describe cases of moral dilemma as cases where A must commit an otherwise immoral act to avert a natural disaster of equal or greater gravity. I then argue that cases of moral blackmail are structurally identical to cases of moral dilemma in (...) all respects but one: In cases of moral blackmail, A is predicting the free actions of a moral agent (B), whereas in cases of moral dilemma, A is predicting natural events. I conclude that cases of moral blackmail are more problematic than otherwise similar cases of moral dilemma for this reason alone. (shrink)

John Rawls’ Difference Principle, which requires that primary goods--income, wealth, and opportunities--be distributed so as to maximize the primary goods of the least advantaged class, has both a libertarian and a welfarist interpretation. The welfarist interpretation, which fits somewhat more easily with Rawls’ method for deriving principles of justice--rational contractors choosing principles behind the veil of ignorance--and with Rawls’ contention that there is a natural affirmative duty to aid others and to help establish and maintain just institutions, is the orthodox (...) interpretation. But there is scattered, fragmentary evidence for the libertarian interpretation as well. In this article I examine a recent version of the libertarian interpretation put forward by Jeffrey Reiman and discuss its implications as a standard for justice in cooperative arrangements. (shrink)