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)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

Despite pervasive variation in the content of laws, legal theorists and anthropologists have argued that laws share certain abstract features and even speculated that law may be a human universal. In the present report, we evaluate this thesis through an experiment administered in 11 different countries. Are there cross‐cultural principles of law? In a between‐subjects design, participants (N = 3,054) were asked whether there could be laws that violate certain procedural principles (e.g., laws applied retrospectively or unintelligible laws), and also (...) whether there are any such laws. Confirming our preregistered prediction, people reported that such laws cannot exist, but also (paradoxically) that there are such laws. These results document cross‐culturally and –linguistically robust beliefs about the concept of law which defy people's grasp of how legal systems function in practice. (shrink)

Among the most outstanding discoveries of the last century is one that is not quite as momentous as the theory of relativity or cybernetics. It may even still be enigmatic. It has no one single author, it is not expressed in a single formula, conception, or invention. Nonetheless it is worth all the others combined.

This is a collection of the key articles written by renowned Wittgenstein scholar, G.P. Baker, on Wittgenstein’s later philosophy, published posthumously. Following Baker’s death in 2002, the volume has been edited by collaborator and partner, Katherine Morris. Contains articles previously only available in other languages, and one previously unpublished paper. Completely distinct from the widely-known work Baker did with P.M.S. Hacker in the Analytical Commentary on the Philosophical Investigations.

The title of this article will perhaps seem excessively contentious to the reader. What solitude of Vladimir Ivanovich Vernadskii, he might ask, if he has even the slightest familiarity with the scientist's biography?

This collection of thirty-one cases and commentaries addresses ethical problems commonly encountered by the average health care professional, not just those working on such high-tech specialties as organ transplants or genetic engineering. It deals with familiar issues that are rarely considered in ethics casebooks, including such fundamental matters as informed consent, patient decision-making capacity, the role of the family, and end-of-life decisions. It also provides resources for basic but neglected ethical issues involving placement decisions for elderly or technologically dependent patients, (...) rehabilitation care, confidentiality regarding AIDS, professional responsibility, and organizational and institutional ethics. The authors describe in detail the perspectives of each party to the case, the kind of language that ethicists use to discuss the issues, and the outcome of the case. A short bibliography suggests useful articles for further reading or curriculum development. Easily understood by readers with no prior training in ethics, this book offers guidance on everyday problems from across the broad continuum of care. It will be valuable for health-care professionals, hospital ethics committees, and for students preparing for careers in health-care professions. (shrink)

In ‘Wittgenstein on Language and Rules’, Professor N. Malcolm took us to task for misinterpreting Wittgenstein's arguments on the relationship between the concept of following a rule and the concept of community agreement on what counts as following a given rule. Not that we denied that there are any grammatical connections between these concepts. On the contrary, we emphasized that a rule and an act in accord with it make contact in language. Moreover we argued that agreement in judgments and (...) in definitions is indeed necessary for a shared language. But we denied that the concept of a language is so tightly interwoven with the concept of a community of speakers as to preclude its applicabilty to someone whose use of signs is not shared by others. Malcolm holds that ‘This is an unwitting reduction of Wittgenstein's originality. That human agreement is necessary for “shared” language is not so striking a thought as that it is essential for language simpliciter.’ Though less striking, we believe that it has the merit of being a true thought. We shall once more try to show both that it is correct, and that it is a correct account of Wittgenstein's arguments. (shrink)

In this paper, we have considered a dynamical model of Chlamydia disease with varying total population size, bilinear incidence rate and pulse vaccination strategy. We have defined two positive numbers $$R_{0}$$ R 0 and $$R_{1}$$ R 1. It is proved that there exists an infection-free periodic solution which is globally attractive if $$R_{0} 1.$$ R 1 > 1. The important mathematical findings for the dynamical behaviour of the Chlamydia disease model are also numerically verified using MATLAB. Finally epidemiological implications of (...) our analytical findings are addressed critically. (shrink)

This chapter contains sections titled: The Tractatus and rules of logical syntax From logical syntax to philosophical grammar Rules and rule‐formulations Philosophy and grammar The scope of grammar Some morals.

The word, first attested in writers of the fifth century B.C., belongs to a large group of possessive adjectives in which are formed from ethnic names. A few of these occur in Homer () and in the early lyric poets, but examples become increasingly common in the fifth century and later; their characteristic function is to denote something as belonging to a people or city as a whole, as distinct from ethnic adjectives which are applied to persons.

The word , first attested in writers of the fifth century B.C., belongs to a large group of possessive adjectives in which are formed from ethnic names. A few of these occur in Homer () and in the early lyric poets , but examples become increasingly common in the fifth century and later; their characteristic function is to denote something as belonging to a people or city as a whole, as distinct from ethnic adjectives which are applied to persons.

The dictum ‘“ought” implies “can”’ has a status in moral philosophy in some respects like that of ‘a good player needs good co-ordination’ in talk about ball-games. Clearly, you say something important but not conclusive about proficiency in playing a ball-game when you say that it requires good co-ordination: similarly, you say something important but not conclusive about obligation when you say that it implies a certain possibility or power or ability. Each dictum is a reminder: the one about such (...) courses of physical instruction, the other about such exhortations to duty, as are worth persevering with. It would be hopeless to keep on teaching a boy the moves and tricks of rugby football if he could never co-ordinate well enough to get his eye in, so to speak. Correspondingly, it would be meaningless to recommend that someone ought to do something the specification of which involved a contradiction, and pointless to suggest that he ought to do something which, for quite general reasons, was not, and was certain to remain not, within his power. So each dictum expresses a bluff, no-nonsense wisdom which we should count on before involving ourselves in certain more detailed commitments. But probably this is as far as the comparison between the two sayings can well be taken. (shrink)