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)

IN the heroic Latin hexameter, after the essential alternation of long and short syllables, by far the most important feature is unquestionably the caesura. Nevertheless, ancient writers on metre dismiss it with the most cursory notice; all we get from them is that the chief caesura is the penthemimeral, the trochaic and hephthemimeral coming next; the fourth trochaic and the bucolic are usually rejected, and the trihemimeral is mentioned only by Ausonius, Modern writers, among whom are Müller and Winbolt, deal (...) with the question at greater length, but do not agree even on fundamental points, and often base their statements on an insufficient analysis of the extant remains of Latin hexameter verse. The purpose of the following paper is to attempt a more complete analysis, at least in the case of Virgil, the acknowledged master of the Latin hexameter. But before we proceed further there are two preliminaries which must be settled—what are the main types of caesura, and how many caesurae are admissible in one verse? (shrink)

Nature of the problem: Testimony from scientists. Reflex action and theism (1881) by W. James. The organization of thought (1916) by A.N. Whitehead. The changing scientific scene 1900-1950 (1952) by J.B. Conant. A note on methods of analysis (1943) by H.J. Muller. The way things are (1959) by P.W. Bridgman. A definition of style (1948) by J.R. Oppenheimer.--Consequences of the problem: Testimony from artists and writers. Existentialism (1947) by J.-P. Sartre. The testimony of modern art (1957) by W. Barrett. (...) Parts of speech and punctuation (1935) by G. Stein. The waves (1931) by V. Woolf. The imperfect paradise, by W. Stevens. A note on style and the limits of language, by W. Gibson. (shrink)

Gert H. Müller The growth of the number of publications in almost all scientific areas,· as in the area of (mathematical) logic, is taken as a sign of our scientifically minded culture, but it also has a terrifying aspect. In addition, given the rapidly growing sophistica tion, specialization and hence subdivision of logic, researchers, students and teachers may have a hard time getting an overview ofthe existing literature, partic ularly if they do not have an extensive library available in their (...) neighbourhood: they simply do not even know what to ask for! More specifically, if someone vaguely knows that something vaguely connected with his interests exists some where in the literature, he may not be able to find it even by searching through the publications scattered in the review journals. Answering this challenge was and is the central motivation for compiling this Bibliography. The Bibliography comprises (presently) the following six volumes (listed with the corresponding Editors): I. Classical Logic W. Rautenberg II. Non-c1assical Logics W. Rautenberg IH. Model Theory H. -D. Ebbinghaus IV. Recursion Theory P. G. Hinman V. Set Theory A. R. Blass VI. ProofTheory; Constructive Mathematics J. E. Kister; D. van Dalen & A. S. Troelstra. (shrink)

May lethal autonomous weapons systems—‘killer robots ’—be used in war? The majority of writers argue against their use, and those who have argued in favour have done so on a consequentialist basis. We defend the moral permissibility of killer robots, but on the basis of the non-aggregative structure of right assumed by Just War theory. This is necessary because the most important argument against killer robots, the responsibility trilemma proposed by Rob Sparrow, makes the same assumptions. We show that the (...) crucial moral question is not one of responsibility. Rather, it is whether the technology can satisfy the requirements of fairness in the re-distribution of risk. Not only is this possible in principle, but some killer robots will actually satisfy these requirements. An implication of our argument is that there is a public responsibility to regulate killer robots ’ design and manufacture. (shrink)

The principles of the 3Rs—replacement, refinement, and reduction—strongly shape discussion of methods for performing more humane animal research and the regulation of this contested area of technoscience. This special issue looks back to the origins of the 3Rs principles through five papers that explore how it is enacted and challenged in practice and that develop critical considerations about its future. Three themes connect the papers in this special issue. These are the multiplicity of roles enacted by those who use and (...) care for animals in research, the distribution of “feelings that matter” across species and spaces of laboratory animal practice, and the growing importance of “cultures of care” in animal research. (shrink)

Recent advances in neuroscience lead to a wider realm for philosophy to include the science of the Darwinian-evolved computational brain, our inner world producing organ, a non-recursive super- Turing machine combining 100B synapsing-neuron DNA-computers based on the genetic code. The whole system is a logos machine offering a world map for global context, essential for our intentional grasp of opportunities. We start from the observable contrast between the chaotic universe vs. our orderly inner world, the noumenal cosmos. So far, philosophy (...) has been rehearsing our thoughts, our human-internal world, a grand painting of the outer world, how we comprehend subjectively our experience, worked up by the logos machine, but now we seek a wider horizon, how humans understand the world thanks to Darwinian evolution to adapt in response to the metaphysical gap, the chasm between the human animal and its environment, shaping the organism so it can deal with its variable world. This new horizon embraces global context coded in neural structures that support the noumenal cosmos, our inner mental world, for us as denizens of the outer environment. Kant’s inner and outer senses are fundamental ingredients of scientific philosophy. Several sections devoted to Heidegger, his lizard debunked, but his version of the metaphysical gap & his doctrine of the logos praised. Rorty and others of the behaviorist school discussed also. (shrink)

Mill's feminism has been attacked as being logically incoherent. The general verdict has been that Mill can easily be defended from the charge. However, both sides in the debate have ignored the fact that his feminism is part of a broader theory of liberal empiricism. Placing The Subjection of Women in this context re–opens the question of its logical credentials and reveals a basic weakness in Millian feminism.

This volume is a critical edition of the eight-year correspondence between Gottfried Wilhelm Leibniz and Burcher de Volder, professor of philosophy and mathematics at Leiden University. Containing the surviving correspondence between Leibniz and De Volder, the volume also presents a generous selection from the letters between Leibniz and his friend Johann Bernoulli, through whose intercession the correspondence began. Bernoulli acted as intermediary throughout, and the often candid discussions between Leibniz and Bernoulli provide illuminating background to the correspondence proper. Each of (...) the selections appears both in the original Latin and in English translation. (shrink)