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)

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.

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)

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)

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)

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 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...

Ecological theory is built upon assumptions about the fundamental nature of organism-environment interactions. We argue that two mutually exclusive sets of such assumptions are available and that they have given rise to alternative approaches to studying ecology. The fundamentally different premises of these approaches render them irreconcilable with one another. In this paper, we present the first logical formalisation of these two paradigms.The more widely-accepted approach - which we label the demographic paradigm - includes both population ecology and community ecology (...) (synecology). Demographic ecology assumes that the environment is relatively stable and that biotic processes, governed predominantly by resource availability, are the most important of ecological and evolutionary influences. Moreover, ecological processes are assumed to translate into directional selection pressures that drive significant evolutionary change on a local scale through the process of optimisation. (shrink)

We present a meta-analytic review on the processing of negations in conditional reasoning about affirmation problems (Modus Ponens: "MP", Affirmation of the Consequent "AC") and denial problems (Denial of the Antecedent "DA", and Modus Tollens "MT"). Findings correct previous generalisations about the phenomena. First, the effects of negation in the part of the conditional about which an inference is made, are not constrained to denial problems. These inferential-negation effects are also observed on AC. Second, there generally are reliable effects of (...) a negation in the clause referred to by the categorical premise, and these referred-negation effects are constrained to the logically fallacious AC and DA inferences. All findings are presented and discussed in relation to contemporary mental model (MM) and mental logic (ML) theories. It is argued that a double-negation elimination hypothesis provides a sufficient explanation of inferential-negation effects within both MM theory and ML theory, if the latter is extended by a validating search for counter examples. Both MM and ML theories adhere to a processing scheme that allows them to incorporate an account of referred-negation effects based on the thesis that counter-example frequency is modulated by the scope of a contrast class delineated by a false affirmative. We conclude that MM and ML theories provide adequate processing schemes to accommodate for the explanatory hypotheses, at least in principle. In practice, both approaches remain equivocal as regards the connectivity and interactivity with long-term memory knowledge invoked in generating, manipulating, and testing the mental representations of negative state of affairs. (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)

Amid public health concerns over climate change, “precision public health” is emerging in next generation approaches to practice. These novel methods promise to augment public health operations by using ever larger and more robust health datasets combined with new tools for collecting and analyzing data. Precision strategies to protecting the public health could more effectively or efficiently address the systemic threats of climate change, but may also propagate or exacerbate health disparities for the populations most vulnerable in a changing climate. (...) How PPH interventions collect and aggregate data, decide what to measure, and analyze data pose potential issues around privacy, neglecting social determinants of health, and introducing algorithmic bias into climate responses. Adopting a health justice framework, guided by broader social and climate justice tenets, can reveal principles and policy actions which may guide more responsible implementation of PPH in climate responses. (shrink)