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Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

Understanding how people comprehend visual narratives (including picture stories, comics, and film) requires the combination of traditionally separate theories that span the initial sensory and perceptual processing of complex visual scenes, the perception of events over time, and comprehension of narratives. Existing piecemeal approaches fail to capture the interplay between these levels of processing. Here, we propose the Scene Perception & Event Comprehension Theory (SPECT), as applied to visual narratives, which distinguishes between front-end and back-end cognitive processes. Front-end processes occur (...) during single eye fixations and are comprised of attentional selection and information extraction. Back-end processes occur across multiple fixations and support the construction of event models, which reflect understanding of what is happening now in a narrative (stored in working memory) and over the course of the entire narrative (stored in long-term episodic memory). We describe relationships between front- and back-end processes, and medium-specific differences that likely produce variation in front-end and back-end processes across media (e.g., picture stories vs. film). We describe several novel research questions derived from SPECT that we have explored. By addressing these questions, we provide greater insight into how attention, information extraction, and event model processes are dynamically coordinated to perceive and understand complex naturalistic visual events in narratives and the real world. (shrink)

It was, until recently, accepted that the two classes of acetylcholine (ACh) receptors are distinct in an important sense: muscarinic ACh receptors signal via heterotrimeric GTP binding proteins (G proteins), whereas nicotinic ACh receptors (nAChRs) open to allow flux of Na+, Ca2+, and K+ ions into the cell after activation. Here we present evidence of direct coupling between G proteins and nAChRs in neurons. Based on proteomic, biophysical, and functional evidence, we hypothesize that binding to G proteins modulates the activity (...) and signaling of nAChRs in cells. It is important to note that while this hypothesis is new for the nAChR, it is consistent with known interactions between G proteins and structurally related ligand‐gated ion channels. Therefore, it underscores an evolutionarily conserved metabotropic mechanism of G protein signaling via nAChR channels.Also watch the Video Abstract. (shrink)

It was, until recently, accepted that the two classes of acetylcholine (ACh) receptors are distinct in an important sense: muscarinic ACh receptors signal via heterotrimeric GTP binding proteins (G proteins), whereas nicotinic ACh receptors (nAChRs) open to allow flux of Na+, Ca2+, and K+ ions into the cell after activation. Here we present evidence of direct coupling between G proteins and nAChRs in neurons. Based on proteomic, biophysical, and functional evidence, we hypothesize that binding to G proteins modulates the activity (...) and signaling of nAChRs in cells. It is important to note that while this hypothesis is new for the nAChR, it is consistent with known interactions between G proteins and structurally related ligand‐gated ion channels. Therefore, it underscores an evolutionarily conserved metabotropic mechanism of G protein signaling via nAChR channels.Also watch the Video Abstract. (shrink)

Gyula Klima’s distinctive work recovering medieval philosophy has inspired a generation of scholars. Klima’s attention to the distinctive terms, problems, and assumptions that constitute alternative historical conceptual frameworks has informed work in philosophy of language and logic, cognition and philosophical psychology, and metaphysics and theology. This volume celebrates Klima’s project by collecting new essays by colleagues, collaborators, and former students. Covering a wide range of thinkers (Plotinus, Anselm, Aquinas, Buridan, Ockham, and others) and various specifc questions (e.g., about language, cognition, (...) the soul, and God), it is unifed by a common interest in applying historically sensitive, hermeneutically sophisticated, and logically rigorous philosophical interpretation to recover, and appreciate, lost perspectives. (shrink)

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants’ locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant’s real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by (...) a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas. (shrink)

Aim of this paper was to fi nd and explicate similarities between science and religion with respect to classical criteria of scientifi cognition. The discourse was led within the following aspects: knowledge, method, language, institution and limits. The derived conclusion is that religion can be interpreted as satisfying all general conditions of scientific enterprise. Such a conclusion is interpreted as supporting two possible thesis: (1) religion as a scientifi c discipline ought to be implemented into scientific enterprise in the way (...) of interdisciplinary cooperation; (2) the presented similarity remains constructed, not discovered – there is no sense in comparing religion to science, since these two notions are too general and vague. Regardless which interpretation one would prefer, it shows, that anti-theistic arguments based on showing religion as opposed to science, does not sounds. (shrink)

The study area was a small lowland river valley (the Łęg river) located in the south-east of Poland. The object of investigation was the macrophytes of 10 river lakes with corresponding active river channel stretches of the same length as the cut-offs. The aim was to check the difference in species diversity between cut-off and active river channels. The second aim was to test the following hypothesis: vegetation of river lake has been shaped under the influence of contiguous river stretch (...) which has left a measurable mark in species abundance and composition. To test this, we checked whether a cut-off channel’s flora is more similar to flora of the contiguous river stretch, than to flora of a farther river stretch. During the course of the study it was found that the average species richness was approximately two times higher in the cut-off channels than in the river stretches. The number of the species exclusive for the river lakes was nine times higher in comparison with the river’s exclusives (not found in the cut-offs). The Shannon diversity index definitely spoke in favor of the river lakes. These results clearly show the significance of river lakes in maintaining biodiversity of aquatic ecosystems in a small river valley. We did not confirm our hypothesis concerning floristic relation between an active channel and its cut-offs. The floristic similarity between a given cut-off channel and the contiguous active river channel stretch is not stronger than the similarity between this lake and more distant river stretches. The cause of such a state of affairs may be high natural dynamics of investigated habitats and anthropogenic transformation of the river valley. (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)

We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey, which is part of the Sloan Digital Sky Survey III. Our results come from the Data Release 11 sample, containing nearly one million galaxies and covering approximately 8500 square degrees and the redshift range 0.2 < z < 0.7. We also compare these results with those from the publicly released (...) DR9 and DR10 samples. Assuming a concordance Λ cold dark matter cosmological model, the DR11 sample covers a volume of 13 Gpc3 and is the largest region of the Universe ever surveyed at this density. We measure the correlation function and power spectrum, including density-field reconstruction of the BAO feature. The acoustic features are detected at a significance of over 7σ in both the correlation function and power spectrum. Fitting for the position of the acoustic features measures the distance relative to the sound horizon at the drag epoch, rd, which has a value of rd,fid = 149.28 Mpc in our fiducial cosmology. We find DV = at z = 0.32 and DV = at z = 0.57. At 1.0 per cent, this latter measure is the most precise distance constraint ever obtained from a galaxy survey. Separating the clustering along and transverse to the line of sight yields measurements at z = 0.57 of DA = and H =. Our measurements of the distance scale are in good agreement with previous BAO measurements and with the predictions from cosmic microwave background data for a spatially flat CDM model with a cosmological constant. © 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society. (shrink)

This paper has two central aims. First, we motivate a puzzle. The puzzle features four independently plausible but jointly inconsistent claims. One of the four claims is the sufficiency leg of the knowledge norm of assertion (KNA-S), according to which one is properly epistemically positioned to assert that p if one knows that p. Second, we propose that rejecting (KNA-S) is the best way out of the puzzle. Our argument to this end appeals to the epistemic value of intellectual humility (...) in social-epistemic practice. (shrink)

A scholarly edition of a work by Adam Smith. The edition presents an authoritative text, together with an introduction, commentary notes, and scholarly apparatus.

The standard use of the propositional calculus ('P.C.?) in analyzing the validity of inferences involving conditionals leads to fallacies, and the problem is to determine where P.C. may be ?safely? used. An alternative analysis of criteria of reasonableness of inferences in terms of conditions of justification rather than truth of statements is proposed. It is argued, under certain restrictions, that P. C. may be safely used, except in inferences whose conclusions are conditionals whose antecedents are incompatible with the premises in (...) the sense that if the antecedent became known, some of the previously asserted premises would have to be withdrawn. (shrink)

Nazi ideology was premised on a belief in the superiority of the Germanic race. However, the idea of a superior Germanic race was not invented by the Nazis. By the beginning of the 20th century this idea had already gained not only popular but also mainstream scientific support in England, Germany, the U.S., Scandinavia, and other parts of the world in which people claimed Germanic origins (p. xiii). Yet how could this idea, which is now recognised as ideology of the (...) most dangerous kind, be given the appearance of scientific legitimacy by some of the leading physical anthropologists of the day? (shrink)

I describe a way of handling comparative adjectives "a is P-er than b", in terms of degrees "a has P to degree d". I defend this approach against attacks due to C J F Williams in an article in the same issue of *Analysis*, by tracing his objections to the assumption that degrees must be linearly ordered. Since this abstract is written years later, I can mention that some of the ideas were taken further in my Hypercomparatives. Synthese 111, 1997, (...) 97-114 . (shrink)

We describe the three place relation of contrastive knowledge, which holds between a person, a target proposition, and a contrasting proposition. The person knows that p rather than that q. We argue for three claims about this relation. (a) Many common sense and philosophical ascriptions of knowledge can be understood in terms of it. (b) Its application is subject to fewer complications than non-contrastive knowledge is. (c) It applies over a wide range of human and nonhuman cases.

Impressions of Hume consists of an editorial Introduction and twelve original essays, most of which were earlier presented at the “Hume Studies in Britain” interdisciplinary workshops held in Cambridge, Edinburgh, and Oxford. This collection is a valuable one, especially for those interested in the intellectual contexts of Hume’s metaphysics and ethics. It might be shelved alongside—in parts it seems an extension of—M. A. Stewart and John P. Wright’s edited collection from 1994, Hume and Hume’s Connexions. Indeed, Impressions of Hume begins (...) with M. A. Stewart’s 47-page article, “The Intellectual Development of Hume, 1711–1752,” which covers Hume’s life of reading in detail from the curriculum at the College of Edinburgh through his bookish interests of 1725–1729, and then leaps ahead, in more summary fashion, to Hume’s professional interests in the decade after completing the Treatise, including his ongoing concern to distance himself from that work, culminating in the 1775 “Advertisement” and 1776 “My Own Life.” Rich in archival research and in full command of Hume’s intellectual and social milieus, Stewart’s article whets the appetite for the full-blown biography of which this seems a partial draft. According to this volume’s “Notes on Contributors,” however, Hume’s intellectual biography is now in the hands of James A. Harris, whose contribution here, “Hume’s Use of the Rhetoric of Calvinism,” marks him as a worthy successor to Stewart and the other scholars—Harris cites Roger Emerson and James Moore—who have set the understanding of Hume’s life on a whole new footing since E. C. Mossner’s second edition of The Life of David Hume. Harris argues that Hume used fideistic pronouncements, especially in the first Enquiry, to align himself strategically with the Calvinist opponents of the neo-Stoic moderates in church and university, including Hutcheson, who blocked Hume from securing the Edinburgh moral philosophy chair in 1745. Hume’s intention, according to Harris, “was to discredit by whatever means possible the revolution in moral philosophy being engineered by Hutcheson, and so to imply a need for a return to the time when moral philosophy was one thing, and the teaching of natural religion another”. (shrink)

Impressions of Hume consists of an editorial Introduction and twelve original essays, most of which were earlier presented at the “Hume Studies in Britain” interdisciplinary workshops held in Cambridge, Edinburgh, and Oxford. This collection is a valuable one, especially for those interested in the intellectual contexts of Hume’s metaphysics and ethics. It might be shelved alongside—in parts it seems an extension of—M. A. Stewart and John P. Wright’s edited collection from 1994, Hume and Hume’s Connexions. Indeed, Impressions of Hume begins (...) with M. A. Stewart’s 47-page article, “The Intellectual Development of Hume, 1711–1752,” which covers Hume’s life of reading in detail from the curriculum at the College of Edinburgh through his bookish interests of 1725–1729, and then leaps ahead, in more summary fashion, to Hume’s professional interests in the decade after completing the Treatise, including his ongoing concern to distance himself from that work, culminating in the 1775 “Advertisement” and 1776 “My Own Life.” Rich in archival research and in full command of Hume’s intellectual and social milieus, Stewart’s article whets the appetite for the full-blown biography of which this seems a partial draft. According to this volume’s “Notes on Contributors,” however, Hume’s intellectual biography is now in the hands of James A. Harris, whose contribution here, “Hume’s Use of the Rhetoric of Calvinism,” marks him as a worthy successor to Stewart and the other scholars—Harris cites Roger Emerson and James Moore—who have set the understanding of Hume’s life on a whole new footing since E. C. Mossner’s second edition of The Life of David Hume. Harris argues that Hume used fideistic pronouncements, especially in the first Enquiry, to align himself strategically with the Calvinist opponents of the neo-Stoic moderates in church and university, including Hutcheson, who blocked Hume from securing the Edinburgh moral philosophy chair in 1745. Hume’s intention, according to Harris, “was to discredit by whatever means possible the revolution in moral philosophy being engineered by Hutcheson, and so to imply a need for a return to the time when moral philosophy was one thing, and the teaching of natural religion another”. (shrink)

There have been many claims that quantum mechanics plays a key role in the origin and/or operation of biological organisms, beyond merely providing the basis for the shapes and sizes of biological molecules and their chemical affinities. These range from Schr¨odinger’s suggestion that quantum fluctuations produce mutations, to Hameroff and Penrose’s conjecture that quantum coherence in microtubules is linked to consciousness. I review some of these claims in this paper, and discuss the serious problem of decoherence. I advance some further (...) conjectures about quantum information processing in bio-systems. Some possible experiments are suggested. © 2004 Elsevier Ireland Ltd. All rights reserved. (shrink)

Institute of Theoretical Astronomy, University of Cambridge, Cambridge, UK 3fS. received 28th August 1970, in final revised form 1st July 1971..

This volume centers on debates about how far moral judgments bind across traditions and epochs. Nowadays such debates appear especially volatile, both in popular culture and intellectual discourse: although there is increasing agreement that the moral and political criteria invoked in human rights documents possess cross-cultural force, many modern and postmodern developments erode confidence in moral appeals that go beyond a local consensus or apply outside a particular community. Often the point of departure for discussion is the Enlightenment paradigm of (...) a common morality, in which it is assumed that certain unchanging beliefs inhere in the structure of human reason. Whereas some thinkers continue to defend this paradigm, others modify it in diverse ways without abandoning entirely the attempt to address a universal audience, and still others jettison virtually all of its distinguishing features. Exhibiting a range of positions Western participants take in these debates, this volume seeks to advance the substance of the debates themselves without prejudging the outcome. Rival assessments of the Enlightenment paradigm are offered from various philosophical and theological points of view. In addition to the editors, the contributors include Robert Merrihew Adams, Annette C. Baier, Alan Donagan, Margaret A. Farley, Alan Gewirth, David Little, Richard Rorty, Jeffrey Stout, and Lee H. Yearley. (shrink)