Deamination of adenosine in RNA to form inosine has wide ranging consequences on RNA function including amino acid substitution to give proteins not encoded in the genome. What determines which adenosines in an mRNA are subject to this modification reaction? The answer lies in an understanding of the mechanism and substrate recognition properties of adenosine deaminases that act on RNA (ADARs). Our recent publication of X‐ray crystal structures of the human ADAR2 deaminase domain bound to RNA editing substrates shed considerable (...) light on how the catalytic domains of these enzymes bind RNA and promote adenosine deamination. Here we review in detail the deaminase domain‐RNA contact surfaces and present models of how full length ADARs, bearing double stranded RNA‐binding domains (dsRBDs) and deaminase domains, could process naturally occurring substrate RNAs. (shrink)

The translational research community, in general, and the Clinical and Translational Science Awards (CTSA) community, in particular, share the vision of repurposing EHRs for research that will improve the quality of clinical practice. Many members of these communities are also aware that electronic health records (EHRs) suffer limitations of data becoming poorly structured, biased, and unusable out of original context. This creates obstacles to the continuity of care, utility, quality improvement, and translational research. Analogous limitations to sharing objective data in (...) other areas of the natural sciences have been successfully overcome by developing and using common ontologies. This White Paper presents the authors’ rationale for the use of ontologies with computable semantics for the improvement of clinical data quality and EHR usability formulated for researchers with a stake in clinical and translational science and who are advocates for the use of information technology in medicine but at the same time are concerned by current major shortfalls. This White Paper outlines pitfalls, opportunities, and solutions and recommends increased investment in research and development of ontologies with computable semantics for a new generation of EHRs. (shrink)

The classic theory of Common Law is based on the idea of a law derived from immemorial customs that guide judges’ decisions and contribute to the continuity and stability of the legal order. Hobbes, in his criticism of Edward Coke, questions the legal principles that characterize the “spirit of Common Law”. In his view, it is authority and not use that makes the law. This Hobbesian criticism, which can be considered as one of the ­sources of positivist interpretation of customary (...) law, first raises the question of the legal validity of custom but also leads to an original analysis of the court decisions and precedents. Two forms of rationality of law are opposed: one based on custom and knowledge of which is an “artificial reason”, the other based on natural law and the prescriptions of the judges’ individual reason. (shrink)

Thomas Spence was a native of Newcastle upon Tyne who is best known for his political writings, and more particularly for his radical `Plan' for social reform involving common ownership of the land. One hitherto neglected aspect of Spence's Plan was his proposal to extend the benefits of reading and of `correct' pronunciation to the lower classes by means of a phonetic script of his own devising, first set out and used in Spence's Grand Repository of the English Language. (...) The Grand Repository was one of many English pronouncing dictionaries produced in the late eighteenth century to satisfy the growing demands for a clear guide to `correct' pronunciation. It differs from its contemporaries firstly in that it was intended primarily for the lower classes, and secondly in that it is the only eighteenth-century pronouncing dictionary of English to use a truly `phonetic' script in the sense of one sound = one symbol. In this fascinating and unique account, Beal pays particular attention to the actual pronunciations advocated by Spence and his contemporaries with a view to reconstructing what was felt to be `correct' pronunciation in eighteenth-century Britain. With broad appeal to linguists and historians alike, this study highlights the importance of pronouncing dictionaries as a resource for the historical phonologist, and provides a valuable addition to the limited body of knowledge on eighteenth-century pronunciation. (shrink)

The Reverend Dr John Beale, FRS, DD, and chaplain to Charles II, carried out a vigorous campaign in the early Royal Society for the reform of agriculture, trade, and public education-reforms which signalled his continuing commitment to the ideas not only of Bacon, but of Hartlib and Comenius as well. In addition to promoting orchard plantations and expanded commercial horticulture, he collaborated with Evelyn, Oldenburg, and Houghton to publish or publicize items on the improvement of agriculture and the national (...) economy. His later writings, including the unfinished manifesto ‘From Utopia’, also identify the ‘mercantilist’ thought of Thomas Mun as a crucial link in Beale's alignment of technology, socioeconomic reform, and the religious and ethical values of Christian humanism. (shrink)

A mysterious remark to Friedrich Waismann on 30 December 1929 marks the only occasion where Wittgenstein refers to both Heidegger and Kierkegaard. Yet although this has generated much controversy, little attention has been paid to the charge of nonsense that Wittgenstein here appears to bring against Heidegger; thus, the supporting argument that may be latent has not been unearthed. Through analysis of this remark, Wittgenstein's arguments in the Tractatus and 'A Lecture on Ethics', and Heidegger's account of anxiety (Angst) in (...) Being and Time, I argue that we can extract an argument against the central question of Heidegger's philosophy: the question of being. To understand this, I examine the Kierkegaardian ideas employed by Wittgenstein and Heidegger and attempt to show that this argument can be partly understood in Kierkegaardian terms. I further argue that examining what Heidegger means by 'being' (Sein) shows that Wittgenstein's argument does not meet its target. (shrink)

Issues of reliability are claiming center-stage in the epistemology of machine learning. This paper unifies different branches in the literature and points to promising research directions, whilst also providing an accessible introduction to key concepts in statistics and machine learning – as far as they are concerned with reliability.

Big Ideas for Little Kids includes everything a teacher, a parent, or a college student needs to teach philosophy to elementary school children from picture books. Written in a clear and accessible style, the book explains why it is important to allow young children access to philosophy during primary-school education. Wartenberg also gives advice on how to construct a "learner-centered" classroom, in which children discuss philosophical issues with one another as they respond to open-ended questions by saying whether they agree (...) or disagree with what others have said. (shrink)

Cette étude essaye d’établir qu’il y a deux notions très différentes de « fondation » à l’œuvre dans les Recherches logiques de Husserl. Dans la IIIème Recherche, où le terme est formellement introduit, lorsqu’il se demande quels sont les contenus qui peuvent exister d’une manière autonome (indépendants) et lesquels peuvent exister uniquement en tant que moments d’autre chose (dépendants), Husserl suit ce que j’appelle un « modèle ontologique ». Selon ce modèle, le concret possède une priorité sur à l’abstrait qui (...) est fondé en lui. Dans la VIème Recherche, en revanche, Husserl s’oriente principalement sur un « modèle gnoséologique » qui voit le complexe comme fondé sur ce qui est relativement simple, étant donné que les expériences d’ordre supérieur (telles les perceptions de types d’objets plus complexes) sont « fondées sur » des expériences plus simples, bien qu’elles ne puissent pas y être réduites. L’exemple principal ici est celui des intuitions catégoriales : fondées sur les intuitions sensibles, elles n’y sont pas réductibles. Mais cette distinction entre deux sens différents du terme de « fondation » peut également nous aider à mieux comprendre de nombreuses thèses husserliennes plutôt controversées. Par exemple, elle peut nous permettre de mieux comprendre dans quelle mesure faire l’expérience d’un être humain comme un tout se fonde sur l’expérience d’un corps physique, et cela même si l’étant que nous rencontrons inclut à la fois des aspects corporels et des aspects spirituels – les deux étant vus, d’une manière essentielle, comme des moments de cette unique personne qui fait l’objet de notre expérience. (shrink)

v. 1. Editorial introduction -- v. 2. The English and Latin texts (i) -- v. 3. The English and Latin texts (ii).

This chapter outlines ways in which Wittgenstein’s opposition to scientism is manifest in his later conception of philosophy and the negative attitude he held toward his times. The chapter tries to make clear how these two areas of Wittgenstein’s thought are connected and reflect an anti-scientistic worldview he held, one intimated in Philosophical Investigations §122. -/- It is argued that the later Wittgenstein’s metaphilosophy is marked out against two scientistic claims in particular. First, the view that the scientific method is (...) superior to all other means of learning or gaining knowledge. Second, the view that scientific knowledge is superior to all other kinds of knowledge and understanding. Wittgenstein’s opposition to these claims is brought out through examining a fundamental aim of his later philosophy, producing the ‘kind of understanding which consists in “seeing connections”’ (PI §122), and his attempts to expose certain philosophical confusions. It is argued that these reflect his antiscientistic worldview. -/- Through discussion of Oswald Spengler’s influence on Wittgenstein, the chapter outlines how Wittgenstein’s opposition to scientism underwrites his negative cultural outlook and how this is connected with the anti-scientistic elements of his later philosophy discussed. The work of Ray Monk (1999; 1990) and Hans-Johann Glock (1996) is instrumental in what follows. (shrink)

Wittgenstein criticised prevailing attitudes toward the sciences. The target of his criticisms was ‘scientism’: what he described as ‘the overestimation of science’. This collection is the first study of Wittgenstein’s anti-scientism - a theme in his work that is clearly central to his thought yet strikingly neglected by the existing literature. The book explores the philosophical basis of Wittgenstein’s anti-scientism; how this anti-scientism helps us understand Wittgenstein’s philosophical aims; and how this underlies his later conception of philosophy and the kind (...) of philosophy he attacked. An outstanding team of international contributors articulate and critically assess Wittgenstein’s views on scientism and anti-scientism, making Wittgenstein and Scientism essential reading for students and scholars of Wittgenstein’s work, on topics as varied as the philosophy of mind and psychology, philosophical practice, the nature of religious belief, and the place of science in modern culture. (shrink)

In this book, T. M. Scanlon offers new answers to these questions, as they apply to the central part of morality that concerns what we owe to each other.

Thomas Reid , the Scottish natural and moral philosopher, was one of the founding members of the Aberdeen Philosophical Society and a significant figure in the Scottish Enlightenment. Reid believed that common sense should form the foundation of all philosophical inquiry. He criticised the sceptical philosophy propagated by his fellow Scot David Hume and the Anglo-Irish bishop George Berkeley, who asserted that the external world did not exist outside the human mind. Reid was also critical of the theory of (...) ideas propagated by Locke and Descartes, arguing that it was incompatible with physical and experiential facts. For Reid, our senses demonstrate that the external world must exist, and this work is organised in chapters examining each of the senses in turn. The book, based on his lectures, was first published in 1764 when Reid was a regent professor at King's College, Aberdeen, and was reissued in 1818. (shrink)

This paper is an exposition and evaluation of the Agustín Rayo's views about the epistemology and metaphysics of mathematics, as they are presented in his book The Construction of Logical Space.

In recent years an increasing number of psychologists have begun to explore the prevalence, causes and effects of ordinary people’s intuitions about moral realism. Many of these studies have lacked in construct validity, i.e., they have failed to measure moral realism. My aim in this paper accordingly is to motivate and guide methodological improvements. In analysis of prominent existing measures, I develop general recommendations for overcoming ten prima facie serious worries about research on folk moral realism. G1 and G2 require (...) studies’ answer choices to be as metaethically comprehensive as methodologically feasible. G3 and G4 prevent fallacious inferences from intuitions about related debates. G5 and G6 limit first-order moral and epistemic influences. G7 address studies’ instructions. And G8 and G9 suggest tests of important psychological presuppositions. (shrink)

This volume is a study of the influence of Timaeus on the development of Western cosmology in three axial periods of European culture: Late Antiquity, Middle Ages and Renaissance.

In recent years, a plethora of high-profile scientific publications has been reporting about machine learning algorithms outperforming clinicians in medical diagnosis or treatment recommendations. This has spiked interest in deploying relevant algorithms with the aim of enhancing decision-making in healthcare. In this paper, we argue that instead of straightforwardly enhancing the decision-making capabilities of clinicians and healthcare institutions, deploying machines learning algorithms entails trade-offs at the epistemic and the normative level. Whereas involving machine learning might improve the accuracy of medical (...) diagnosis, it comes at the expense of opacity when trying to assess the reliability of given diagnosis. Drawing on literature in social epistemology and moral responsibility, we argue that the uncertainty in question potentially undermines the epistemic authority of clinicians. Furthermore, we elucidate potential pitfalls of involving machine learning in healthcare with respect to paternalism, moral responsibility and fairness. At last, we discuss how the deployment of machine learning algorithms might shift the evidentiary norms of medical diagnosis. In this regard, we hope to lay the grounds for further ethical reflection of the opportunities and pitfalls of machine learning for enhancing decision-making in healthcare. (shrink)

Thomas Reid is now recognized as one of the towering figures of the Enlightenment. Best known for his published writings on epistemology and moral theory, he was also an accomplished mathematician and natural philosopher, as an earlier volume of his manuscripts edited by Paul Wood for the Edinburgh Reid Edition, Thomas Reid on the Animate Creation, has shown. The Correspondence of Thomas Reid collects all of the known letters to and from Reid in a fully annotated form. (...) Letters already published by Sir William Hamilton and others have been reedited, and roughly half of the letters included appear in print for the first time. Writing in 1802, Reid's disciple and biographer Dugald Stewart doubted that Reid's correspondence &"would be generally interesting.&" This collection proves otherwise, for the letters illuminate virtually every aspect of Reid's life and career and, in some instances, provide us with invaluable evidence about activities otherwise undocumented in his manuscripts or published works. Through his correspondence we can trace Reid's relations with contemporaries such as David Hume and his colleagues at both King's College, Aberdeen, and the University of Glasgow, as well as his engagement with the most controversial philosophical, scientific, and political issues of his day. If anything, the letters assembled here serve as the starting point for understanding Reid and his place in the Enlightenment. (shrink)

Income inequality in the US has now reached levels not seen since the 1920s. Management, as a field of scholarly inquiry, has the potential to contribute in significant ways to our understanding of recent inequality trends. We review and assess recent research, both in the management literature and in other fields. We then delineate a conceptual framework that highlights the mechanisms through which business practice may be linked to income inequality. We then outline four general areas in which management scholars (...) are uniquely positioned to contribute to ongoing research: data and description, organizational dynamics, collective action, and value flows and tradeoffs. To stimulate future research, we highlight a number of relevant research questions and link these questions to existing management research streams that could be leveraged to address them. (shrink)

Conciliatory theories of disagreement require that one lower one’s confidence in a belief in the face of disagreement from an epistemic peer. One question about which people might disagree is who should qualify as an epistemic peer and who should not. But when putative epistemic peers disagree about epistemic peerhood itself, then Conciliationism makes contradictory demands and paradoxes arise.

Feeling good: four ways -- Finding that feeling -- The place of pleasure -- Knowing what's what -- Making things happen -- Being good -- Love and friendship -- Putting it together.

This book is a fiftieth anniversary republication of Thomas Nagel's "What Is It Like to Be a Bat?", a classic in the philosophy of mind. Through its argument for the irreducible subjectivity of consciousness, it played an essential role in making the study of consciousness a central part of philosophy, psychology, and neuroscience. It also spurred the now flourishing scientific attention to the consciousness of non-human creatures: mammals, birds, fish, mollusks, and insects. The book also includes a second essay (...) offering Nagel's more recent thoughts on the most promising positive response to the mind-body problem, as posed in the original essay. (shrink)

Existing research suggests that people's judgments of actual causation can be influenced by the degree to which they regard certain events as normal. We develop an explanation for this phenomenon that draws on standard tools from the literature on graphical causal models and, in particular, on the idea of probabilistic sampling. Using these tools, we propose a new measure of actual causal strength. This measure accurately captures three effects of normality on causal judgment that have been observed in existing studies. (...) More importantly, the measure predicts a new effect ("abnormal deflation"). Two studies show that people's judgments do, in fact, show this new effect. Taken together, the patterns of people's causal judgments thereby provide support for the proposed explanation. (shrink)