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)

These essays by some of the most prominent figures in linguistics, artificial intelligence, and psychology explore the problems involved in creating a general cognitive science that will treat language, thought, and behavior in an integrated fashion. They address the fundamental questions of the relations between linguistic structures and cognitive processes, between cognitive processes and language behavior, and between language behavior and linguistic structure. Contents: Introduction, Thomas G. Bever (Columbia University), John M. Carroll and Lance A. Miller (IBM Thomas J. Watson (...) Research Center). "Philosophy and "Linguistics: An Outline of Platonist Grammar, Jerrold J. Katz (CUNY). Sense and Reference in a Psychologically Based Semantics, Ray Jackendoff (Brandeis University). Some Thoughts on the Boundaries and Components of Linguistics, Charles J. Fillmore (University of California, Berkeley). Psychology: Approaches to the Study of the Psychology of Language, Walter Kintsch (University of Colorado). Toward An Abstract Performance Grammar, Charles E. Osgood (University of Illinois). Upgrading a Mind, David Premack (University of Pennsylvania). Computational "Models: "Memory, Meaning, and Syntax, Roger Schank (Yale University) and Lawrence Birnbaum (Yale University). Some Inadequate Theories of Human Language Processing, Mitchell P. Marcus (AT&T Bell Laboratories). (shrink)

Assessments of animal experience and consciousness are embedded in all issues of animal welfare policy, and the field of animal welfare science has been developed to make these evaluations. In light of modern studies of the social construction of scientific knowledge, it is surprising how little attention has been paid to date on how crucial evaluations about animals are made. In this paper, I begin to fill that gap by presenting a historical case study of the attempt to define the (...) pain and distress of one common practice in animal research-the use of the tabletop guillotine to decapitate laboratory rodents. I describe the negotiations involved in reaching consensus on the meaning of the available data and caution animal care and use committees that they should always work with the realization that our scientific knowledge of what animals experience is partial and provisional knowledge at best. (shrink)

In Justice for Hedgehogs, Dworkin defends a one-system understanding of law. According to this view, law is morality…more exactly, law is a branch of political morality. I have a special interest in the claim, because Dworkin argues that one of its principal consequences is that it undermines arguments I have made about the valid legal status of precepts that are not properly enforceable by courts. In this chapter, I look critically at both Dworkin’s defense of the one system view and (...) his claim that one can embrace the idea of judicially underenforced legal norms only by rejecting any moralized view of law and embracing positivism. (shrink)

Some ambiguities in the verb ‘to know’ are analyzed, and it is argued that “undefeatably justified true belief” is the meaning of most philosophical interest with respect to specifying truth conditions for ‘S knows that p’. Two general conditions for an adequate definition of ‘S knows that p’ are discussed. Then a proposal for a quasi-causal theory of knowledge is introduced and defended.

Some ambiguities in the verb ‘to know’ are analyzed, and it is argued that “undefeatably justified true belief” is the meaning of most philosophical interest with respect to specifying truth conditions for ‘S knows that p’. Two general conditions for an adequate definition of ‘S knows that p’ are discussed. Then a proposal for a quasi-causal theory of knowledge is introduced and defended.

This Is A New Release Of The Original 1910 Edition.

Sensorimotor learning refers to improvements that occur through practice in the performance of sensory-guided motor behaviors. Leveraging novel technical capabilities of an immersive virtual environment, we probed the component kinematic processes that mediate sensorimotor learning. Twenty naïve subjects performed a simulated marksmanship task modeled after Olympic Trap Shooting standards. We measured movement kinematics and shooting performance as participants practiced 350 trials while receiving trial-by-trial feedback about shooting success. Spatiotemporal analysis of motion tracking elucidated the ballistic and refinement phases of hand (...) movements. We found systematic changes in movement kinematics that accompanied improvements in shot accuracy during training, though reaction and response times did not change over blocks. In particular, we observed longer, slower, and more precise ballistic movements that replaced effort spent on corrections and refinement. Collectively, these results leverage developments in immersive virtual reality technology to quantify and compare the kinematics of movement during early learning of full-body sensorimotor orienting. (shrink)

Jnanasrimitra (975-1025) was regarded by both Buddhists and non-Buddhists as the most important Indian philosopher of his generation. His theory of exclusion combined a philosophy of language with a theory of conceptual content to explore the nature of words and thought. Jnanasrimitra's theory informed much of the work accomplished at Vikramasila, a monastic and educational complex instrumental to the growth of Buddhism. His ideas were also passionately debated among successive Hindu and Jain philosophers. This volume marks the first English translation (...) of Jnanasrimitra's Monograph on Exclusion, a careful, critical investigation into language, perception, and conceptual awareness. Featuring the rival arguments of Buddhist and Hindu intellectuals, among other thinkers, the Monograph reflects more than half a millennium of competing claims while providing an invaluable introduction to a crucial philosopher. Lawrence J. McCrea and Parimal G. Patil familiarize the reader with the author, themes, and topics of the text and situate Jnanasrimitra's findings within his larger intellectual milieu. Their clear, accessible, and accurate translation proves the influence of Jnanasrimitra on the foundations of Buddhist and Indian philosophy. (shrink)

The Tree of Life hypothesis frames the evolutionary process as a series of events whereby lineages diverge from one another, thus creating the diversity of life as descendent lineages modify properties from their ancestors. This hypothesis is under scrutiny due to the strong evidence for lateral gene transfer between distantly related bacterial taxa, thereby providing extant taxa with more than one parent. As a result, one argues, the Tree of Life becomes confounded as the original branching structure is gradually superseded (...) by reticulation, ultimately losing its ability to serve as a model for bacterial evolution. Here we address a more fundamental issue: is there a Tree of Life that results from bacterial evolution without considering such lateral gene transfers? Unlike eukaryotic speciation events, lineage separation in bacteria is a gradual process that occurs over tens of millions of years, whereby genetic isolation is established on a gene-by-gene basis. As a result, groups of closely related bacteria, while showing robust genetic isolation as extant lineages, were not created by an unambiguous series of lineage-splitting events. Rather, a temporal fragmentation of the speciation process results in cognate genes showing different genetic relationships. We argue that lineage divergence in bacteria does not produce a tree-like framework, and inferences drawn from such a framework have the potential to be incorrect and misleading. Therefore, the Tree of Life is an inappropriate paradigm for bacterial evolution regardless of the extent of gene transfer between distantly related taxa. (shrink)

The last several years have seen vibrant debates among policymakers and scholars on whether to craft new human rights (or novel interpretations of existing ones) around neurotechnologies. These con...

Graphical AbstractHow exactly specific biological pathways and eventually life arise from the crowded molecular environment of the cell is a problem that has long vexed humanity and will require a paradigm shift toward mechanistic experimental and computational approaches that probe intracellular diversity and complexity more directly. More details can be found in article number 1800244 by Nils G. Walter. DOI: 10.1002/bies.201800244.

"The Fragility of Consciousness is the first published collection of his essays and contains several of his best known writings as well as unpublished work. The essays in this volume exhibit a long interdisciplinary engagement with the relationship between faith and reason in the context of the crisis of culture that has marked twentieth- and twenty-first century thought and practice. Frederick G. Lawrence, with his profound and generous commitment to the intellectual life of the church, has produced a body (...) of work that engages with Heidegger, Gadamer, Habermas, Ricoeur, Strauss, Voegelin, and Benedict XVI among others. These essays also explore various themes such as the role of religion in a secular age, political theology, economics, neo-Thomism, Christology, and much more. In an age marked by social, cultural, political, and ecclesial fragmentation, Lawrence models a more generous way--one that prioritizes friendship, conversation, and understanding above all else."--. (shrink)

With almost incredible rapidity Marxist socialism has spread throughout the world and other forms of socialism have penetrated societies on all continents. Communist governments have not only come to dominate the U.S.S.R. and China but also eastern Europe and Cuba; Africa has not only non-Marxist forms of socialism but is the contending ground for world powers; and Latin America has seen duly elected socialist governments overthrown by rightist forces with the collusion of multinational corporations based in the U.S.A. Socialism has (...) proved itself to be not a monolithic world movement. It is its history of theory and practice. With respect to the future it depends on what organized men and women will make of it. (shrink)