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)

BackgroundParanoia is associated with a multitude of social cognitive deficits, observed in both clinical and subclinical populations. Empathy is significantly and broadly impaired in schizophrenia, yet its relationship with subclinical paranoia is poorly understood. Furthermore, deficits in emotion recognition – a very early component of empathic processing – are present in both clinical and subclinical paranoia. Deficits in emotion recognition may therefore underlie relationships between paranoia and empathic processing. The current investigation aims to add to the literature on social cognition (...) and paranoia by: (1) characterizing the relationship between paranoia and empathy, and (2) testing whether there is an indirect effect of emotion recognition on the relationship between empathy and paranoia.MethodsParanoia, empathy, and emotion recognition were assessed in a non-clinical sample of adults (n= 226) from the Nathan Kline Institute-Rockland (NKI-Rockland) dataset. Paranoia was measured using the Peters Delusions Inventory-21 (PDI-21). Empathy was measured using the Interpersonal Reactivity Index (IRI), a self-report instrument designed to assess empathy using four subscales: Personal Distress, Empathic Concern, Perspective Taking, and Fantasy. Emotion recognition was assessed using the Penn Emotion Recognition Test (ER-40). Structural equation modeling (SEM) was used to estimate relationships between paranoia, the four measures of empathy and emotion recognition.ResultsParanoia was associated with the Fantasy subscale of the IRI, such that higher Fantasy was associated with more severe paranoia (p< 0.001). No other empathy subscales were associated with paranoia. Fantasy was also associated with the emotion recognition of fear, such that higher Fantasy was correlated with better recognition of fear (p= 0.008). Paranoia and emotion recognition were not significantly associated. The Empathic Concern subscale was negatively associated with emotion recognition, with higher empathic concern related to worse overall emotion recognition (p= 0.002). All indirect paths through emotion recognition were non-significant.DiscussionThese results suggest that imaginative perspective-taking contributes to paranoia in the general population. These data do not, however, point to robust global relationships between empathy and paranoia or to emotion recognition as an underlying mechanism. Deficits in empathy and emotion recognition observed in schizophrenia may be associated with the broader pathology of schizophrenia, and therefore not detectable with subclinical populations. (shrink)

When people make judgments about the effects of a perturbation on populations of species in a food web, their judgments exhibit the dissipation effect: a tendency to judge that effects of the perturbation weaken or dissipate as they spread out through the food web from the locus of the perturbation. In the present research evidence for two more phenomena is reported. Terminal locations are points in the food web with just a single connection to the rest of the web. Judged (...) changes tended to be higher for species at terminal locations than for species the same distance from the perturbation but at nonterminal locations. Branches are points in the web where a route splits into two or more routes. Judged changes tended to be lower for species following branching points than for species the same distance from the perturbation but not following branching points. It is proposed that the findings can be explained as effects of a mental model employing concepts of influence and resistance. Under this model a perturbation is a change in energy level at a point in the system that acts as an influence affecting the rest of the system. The basic concepts in this model are domain‐general and on that basis it is predicted that the dissipation effect should be found in judgments of any physical system to which notions of influence and resistance can be applied. (shrink)

In the past few decades, scholars have offered positive, normative, and most recently, interpretive theories of contract law. These theories have proceeded primarily from deontological and consequentialist premises. In A Theory of Contract Law: Empirical Understandings and Moral Psychology, Professor Peter A. Alces confronts the leading interpretive theories of contract and demonstrates their interpretive doctrinal failures. Professor Alces presents the leading canonical cases that inform the extant theories of Contract law in both their historical and transactional contexts and, argues (...) that moral psychology provides a better explanation for the contract doctrine than do alternative comprehensive interpretive approaches. (shrink)

It was a little over ten years ago, 1967–8, that H. D. Lewis delivered the first series of Gifford lectures, The Elusive Mind, in the University of Edinburgh. It was my privilege that year to be an auditor in the Seminar at King's College that Professor Lewis was conducting with his students in the area of this topic. I had already read the works in which, in the midst of neo-orthodox and existentialist religious movements, he had devoted himself to critical (...) valuation of those doctrines - witness his Morals and the New Theology, and Morals and Revelation. This earlier work prepared for a comprehensive interpretation of religious experience in his book in 1960: Our Experience of God. (shrink)

In the last few years, the U.S. health care system has seemingly been gripped by “back to the nineties” fever. But there is a notable change in professional debates about how to better control health care costs. Discussion of health care rationing, which was hotly debated in the nineties, has become much more muted.Is health care rationing passé? I contend that debates about health care rationing have waned not because the need to ration has dwindled nor because ethical debates about (...) how or whether to ration have been resolved. They have declined because the word “rationing,” and unrelated concepts such as cost‐effectiveness analysis, have been replaced by terms—“parsimony,” “value,” and “CER”—that are not burdened by emotional and historical baggage.Sometimes the best way to promote healthy moral debate is to turn to new words that don't carry the burden of past debates. (shrink)

It is argued that causal understanding originates in experiences of acting on objects. Such experiences have consistent features that can be used as clues to causal identification and judgment. These are singular clues, meaning that they can be detected in single instances. A catalog of 14 singular clues is proposed. The clues function as heuristics for generating causal judgments under uncertainty and are a pervasive source of bias in causal judgment. More sophisticated clues such as mechanism clues and repeated interventions (...) are derived from the 14. Research on the use of empirical information and conditional probabilities to identify causes has used scenarios in which several of the clues are present, and the use of empirical association information for causal judgment depends on the presence of singular clues. It is the singular clues and their origin that are basic to causal understanding, not multiple instance clues such as empirical association, contingency, and conditional probabilities. (shrink)

ExcerptThe new world “order” is a complicated, emerging political “disorder” with remote historical roots in Cartesian and Enlightenment sophistry and secularized Protestant theology, not in philosophy.1 Because the “new world order” is complicated, understanding justice in the new world order is also complicated. Proximately, the new world order began as the brainchild of some well-meaning Western intellectuals just after the end of World War II, as a means to heal what at least one leading Catholic philosopher of the time, Jacques (...) Maritain, described to be a “world broken by postwar distress and the weight of rival economic, political, and ideological…. (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)

This work brings together three themes whose relationship has gone unexplored in the recent literature of philosophy: the transcendental phenomenology of Edmund Husserl, the phenomenological ontology of Martin Heidegger and the discipline of logic, especially formal logic. Part One and Two of the work present a detailed explication of Husserl's and Heidegger's philosophy of logic which are respectively characterized as an archeology of logic based upon transcendental phenomenological criticism and a radical phenomenology of logic based upon phenomenological criticism which issues (...) from a concern with the question of the meaning of Being. Part Three, then, offers a comparative analysis combined with a critical appraisal of these two philosophies of logic in order to achieve a more penetrating understanding of the relationship between Husserl and Heidegger. Thus, in one sense, this work takes the domain of logic and the varying approaches to it by Husserl and Heidegger as a clue to the similarities and dissimilarities within the thinking of these two phenomenologists, especially with regard to the understanding each has of the goal and method of phenomenology, and the results proper to phenomenological reflection. (shrink)

We discuss two inconsistencies between Levelt et al.'s model and existing theory about, and data from, picture-word experiments. These inconsistencies show that the empirical support for WEAVER ++ is much weaker than Levelt et al. suggest. We close with a discussion of the proposed explanation for phonological coactivation of near synonyms of a target word.

This book, written by well-known students of Etienne Gilson and especially dedicated to Armand A. Maurer, helps inaugurate a long-overdue special series in philosophy honoring Gilson's legendary scholarship. It presents wide-ranging expositions of Thomist realism in the tradition of Gilsonian humanism covering themes related to philosophy in general, historical method, aesthetics, metaphysics, epistemology, and politics.".

Many health care decisions depend not only upon medical facts, but also on value judgments—patient goals and preferences. Until recent decades, patients relied on doctors to tell them what to do. Then ethicists and others convinced clinicians to adopt a paradigm shift in medical practice, to recognize patient autonomy, by orienting decision making toward the unique goals of individual patients. Unfortunately, current medical practice often falls short of empowering patients. In this article, we reflect on whether the current state of (...) medical decision making effectively promotes patients' health care goals. We base our reflections, in part, on research in which we observed physicians making earnest efforts to partner with patients in making treatment decisions, but still struggling to empower patients—failing to communicate clearly to patients about decision-relevant information, overwhelming patients with irrelevant information, overlooking when patients' emotions made it hard to engage in choices, and making recommendations before discussing patients' goals. (shrink)

There is a debate in normative ethics about whether or not our moral obligations depend solely on either our evidence concerning, or our beliefs about, the world. Subjectivists maintain that they do and objectivists maintain that they do not. I shall offer some arguments in support of objectivism and respond to the strongest argument for subjectivism. I shall also briefly consider the significance of my discussion to the debate over whether one’s future voluntary actions are relevant to one’s current moral (...) obligations. (shrink)

We show that if A and $\widehat{A}$ are automorphic via Φ then the structures $S_{R}(A)$ and $S_{R}(\widehat{A})$ are $\Delta_{3}^{0}-isomorphic$ via an isomorphism Ψ induced by Φ. Then we use this result to classify completely the orbits of hhsimple sets.

OBJECTIVE: To describe the issues faced, and how they were addressed, by the University of Toronto Critical Care Medicine Program/Joint Centre for Bioethics Task Force on Appropriate Use of Life-Sustaining Treatment. The clinical problem addressed by the Task Force was dealing with requests by patients or substitute decision makers for life-sustaining treatment that their healthcare providers believe is inappropriate. DESIGN: Case study. SETTING: The University of Toronto Joint Centre for Bioethics/Critical Care Medicine Program Task Force on Appropriate Use of Life-Sustaining (...) Treatment. PARTICIPANTS: The 24-member Task Force included physician and nursing leaders from five critical care units, bioethicists, a legal scholar, a health administration expert, a social worker, and a hospital public relations professional. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our specific lessons learned include a) a policy focus on process; b) use of a negotiation and mediation model, rather than a hospital ethics committee model, for this process; and c) the policy development process is itself a negotiation, so we recommend equal involvement of interested groups including patients, families, and the public. CONCLUSIONS: This article describes the key issues faced by the Task Force while developing its policy. It will provide a useful starting point for other groups developing policy on appropriate use of life-sustaining treatment. (shrink)

A principle that many have found attractive is one that goes by the name “'Ought' Implies 'Can'.” According to this principle, one morally ought to do something only if one can do it. This essay has two goals: to show that the principle is false and to undermine the motivations that have been offered for it. Toward the end, a proposal about moral obligation according to which something like a restricted version of 'Ought' Implies 'Can' is true is floated. Though (...) no full-fledged argument for this proposal is offered, that it fits with a rather natural and intuitive picture of the structure of morality and seems to explain certain salient features of the debate over whether the principle is true, goes some way toward recommending it. (shrink)

Peter Schouls examines the role played by the concepts of freedom, mastery, and progress in Descartes' writings, arguing that these ideas express a vital and ...

This book is a devastating and anomalous critique of analytic philosophy. It is devastating, because of its detailed exposition of analytic philosophy as a failed project. It is anomalous, because the exposition involves writing a detailed history of the analytic movement, an activity that analysts have scrupulously avoided. According to Capaldi, while analytic philosophy pretends to express a timeless explanation about everything, the movement has always sought to justify its existence by ultimate appeal to a progressive historical account, and rests (...) on the presumption that science is the final historical form of a timeless truth, thereby subsuming the history of…. (shrink)

David Lewis has offered a reply to the standard argument for the claim that the truth of determinism is incompatible with anyone’s being able to do otherwise than she in fact does. Helen Beebee has argued that Lewis’s compatibilist strategy is untenable. In this paper I show that one recent attempt to defend Lewis’s view against this argument fails and then go on to offer my own defense of Lewis’s view.