C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non‐coding RNAs that have been long known to perform 2′‐O‐methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader‐Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre‐mRNA alternative splicing, mRNA abundance, activate enzymes, and (...) be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD can form both methylating and non‐methylating ribonucleoprotein complexes, providing an indication of the likely physical basis for such diverse new functions. Thus, SNORDs are more structurally and functionally diverse than previously thought, and their role in gene expression is under‐appreciated. The action of SNORDs in non‐methylating complexes can be substituted with oligonucleotides, allowing devising therapies for diseases like Prader‐Willi syndrome. (shrink)

"This edition, which replaces the original Loeb edition..., offers text, translation, and annotation that are fully current with modern scholarship"--Front flap of dust jacket, volume 1.

Background Inadequate knowledge among health care providers (HCPs) and parents of affected children limits the understanding and utility of secondary genetic findings (SFs) in under-represented populations in genomics research. SFs arise from deep DNA sequencing done for research or diagnostic purposes and may burden patients and their families despite their potential health importance. This study aims to evaluate the perspective of both groups regarding SFs and their choices in the return of results from genetic testing in the context of orofacial (...) clefts.Methods Using an online survey, we evaluated the experiences of 252 HCPs and 197 parents across participating cleft clinics in Ghana and Nigeria toward the return of SFs across several domains.Results Only 1.6% of the HCPs felt they had an expert understanding of when and how to incorporate genomic medicine into practice, while 50.0% agreed that all SFs should be returned to patients. About 95.4% of parents were willing to receive all the information from genetic testing (including SFs), while the majority cited physicians as their primary information source (64%).Conclusions Overall, parents and providers were aware that genetic testing could help in the clinical management of diseases. However, they cited a lack of knowledge about genomic medicine, uncertain clinical utility, and lack of available learning resources as barriers. The knowledge gained from this study will assist with developing guidelines and policies to guide providers on the return of SFs in sub-Saharan Africa and across the continent. (shrink)

A study in philosophical logic of the meaning of 'true'. Dr Williams demonstrates the shortcomings of various analyses which interpret 'true' as a predicate or truth as a relational property, and clears up a number of important points about propositions, quantification, definite descriptions and correspondence. This 'deflationary metaphysics' is interwoven with a positive theory of his own, which seeks to develop ideas about the late Arthur Prior. The work is marked throughout by great clarity, precision and thoroughness.

A study in philosophical logic of the meaning of 'true'. Dr Williams demonstrates the shortcomings of various analyses which interpret 'true' as a predicate or truth as a relational property, and clears up a number of important points about propositions, quantification, definite descriptions and correspondence. This 'deflationary metaphysics' is interwoven with a positive theory of his own, which seeks to develop ideas about the late Arthur Prior. The work is marked throughout by great clarity, precision and thoroughness.

In this paper, I discuss whether different interpretations of the ‘aim’ of belief—both the teleological and normative interpretations—have the resources to explain certain descriptive and normative features of suspended belief (suspension). I argue that, despite the recent efforts of theorists to extend these theories to account for suspension, they ultimately fail. The implication is that we must either develop alternative theories of belief that can account for suspension, or we must abandon the assumption that these theories ought to be able (...) to account for suspension. To close, I briefly consider some of the reasons we have in favour of pursing each of these options, and I suggest that it is worth exploring the possibility that suspension is best understood as its own attitude, independently of theories of belief’s ‘aim’. (shrink)

Kengo Miyazono, in his work Delusions and Beliefs, defends a teleo-functional account of delusions. In my contribution to this symposium, I question one of Miyazono’s motivations for appealing to teleo-functionalism over its main rival, dry-functionalism. Miyazono suggests that teleo-functionalism, unlike dry-functionalism, can account for the compatibility of the theses (i) that delusions are genuine doxastic states (doxasticism about delusions) and (ii) that delusions do not perform the typical causal roles of beliefs (the causal difference thesis). I argue, however, that there (...) are also ways for dry-functionalism to account for this compatibility. If what I have to say is correct, then Miyazono is perhaps too hasty—at least in one important respect—to opt for teleo-functionalism over dry-functionalism. Dry-functionalism has an equally good chance of satisfying some of Miyazono’s explanatory goals. (shrink)

Belief in substance dualism, the idea that mind and matter are two different kinds of substances, has been found to be a strong predictor of belief in free will. Why? Here, we test whether believing that mind and matter are different kinds of substance correlates with differences in how people think of free will and/or differences in how people interpret the scenarios used to test their conceptions. We provided participants (N = 515) with two hypothetical scenarios where the world was (...) presented either as deterministic or not and asked them whether they thought that a given decision could be free in that world. Incompatibilist free will requires that determinism, the idea that at any instant only one possible future can follow from the state of the world, is false. Compatibilists hold that free will is possible even if determinism is true. In this study, we investigate if substance dualists are more compatibilist. We find that they are not, and that both dualists and physicalists agree that free will is incompatible with determinism. In addition, we show that dualists and physicalists are equally likely to commit bypassing, i.e., to misinterpret determinism as excluding mental causation. We also show that dualists have a stronger tendency to commit intrusion, i.e., to misinterpret determinism by importing indeterministic metaphysics into their interpretation of deterministic descriptions. (shrink)

El debate que se gestó alrededor del concepto de existencia en manos de Willard Van Orman Quine y Rudolf Carnap, dio al siglo XX un cúmulo de aportes significativos a la ontología. La postura realista, con algunas variantes, de Quine y el criterio anti-realista de Carnap, otorga insumos para pensar de mejor forma cómo se intenta dar descripciones acerca del inmobiliario del mundo. Conocer este debate es importante, ya que, se expone los alcances y limitaciones que implican las explicaciones ontológicas (...) acerca de la realidad que deben ser tenidas en cuenta en la actualidad. Este trabajo cumple esa función, la de explicar sintéticamente uno de los debates más importantes para la ontología. (shrink)

Prior research has demonstrated that antisocial behavior, substance-use disorders, and personality dimensions of aggression and impulsivity are indicators of a highly heritable underlying dimension of risk, labeled externalizing. Other work has shown that individual trait constructs within this psychopathology spectrum are associated with reduced self-monitoring, as reflected by amplitude of the error-related negativity (ERN) brain response. In this study of undergraduate subjects, reduced ERN amplitude was associated with higher scores on a self-report measure of the broad externalizing construct that links (...) these various indicators. In addition, the ERN was associated with a response-locked increase in anterior theta (4–7 Hz) oscillation; like the ERN, this theta response to errors was reduced among high-externalizing individuals. These findings suggest that neurobiologically based deficits in endogenous action monitoring may underlie generalized risk for an array of impulse-control problems. (shrink)

Dietrich Bonhoeffer’s thinking about ethics and Christianity in his famous book Ethics, an unfinished and posthumously published work representing his most mature thought on the subject, is a fascinating attempt to combine different, and often conflicting, strands in the Christian intellectual tradition. In this article, I outline his thinking therein, analyse the advantages and disadvantages in his approach, and relate it to developments in contemporary philosophy. His critique of an excessive stress upon principles and abstraction in opposition to a concern (...) for concrete circumstances is, I argue, best seen as a necessary critique of what I call moralism rather than morality. It is also related to recent philosophical theories of particularism and the debates about ‘emergency ethics’ in current philosophy. On the negative side, Bonhoeffer has a tendency to treat non-Christian ethics as necessarily relativist and at times is excessively influenced by the elements in Christian theological tradition that are hostile to the natural and to non-Christian philosophy. In addition, his invocation of ‘the Divine mandates’ seems to have undesirable implications for some genuine values in liberal democratic theory and practice. (shrink)

The concept of conscience continues to play a central role in our ethical reasoning as well as in public and philosophical debate over medical ethics, religious freedom, and conscientious objection in many fields, including war. Despite this continued relevance the nature of conscience itself has remained a relatively neglected topic in recent philosophical literature. In this paper I discuss some historical background to the concept and outline the essential features required for any satisfactory account of conscience and its significance for (...) a coherent moral psychology. It will become clear that conscience is a complex concept resisting reduction to any one of its component features. In doing so I critique recent accounts of conscience which have been insufficiently attentive to these complexities and as a consequence have drawn mistaken conclusions about the legitimate role of conscience in moral reasoning. I also discuss the significance of various distortions of conscience such what I call “the fanaticised conscience”. Clarifying our concept of conscience helps us avoid both conceptual confusion in moral psychology and misapplications of the concept in our understanding of conscientious objection both theoretically and in practice. (shrink)

Business Ethics: A European Review, EarlyView.

Literal meaning is often identified with conventional meaning. In A Nice Derangement of Epitaphs Donald Davidson argues (1) that literal meaning is distinct from conventional meaning, and (2) that literal meaning is identical to what he calls first meaning. In this paper it is argued that Davidson has established (1) but not (2), that he has succeeded in showing that there is a distinction between literal meaning and conventional meaning but has failed to see that literal meaning and first meaning (...) are also distinct. This failure is somewhat surprising, since it is through a consideration of Davidson's notion of radical interpretation that the distinction between literal meaning and first meaning becomes apparent. (shrink)

The first solid bit of argumentation you get in Plato's Phaedo goes something like this: Whatever comes to be, comes to be from its opposite . If at a certain time t a given thing a begins to be F , before that time t it must have been non- F . Wherever a pair of predicates, F and G , are genuine contradictories; where, that is, they stand to each other in the same relation as F stands in to (...) non- F ; it is necessarily true that if a began to be F at t before then a was G . The only trouble comes from the difficulty of finding substitutes for F and G that people will allow to be genuine contradictories. It the butter began to be soft at four o'clock, we may suggest, before four it was hard. A tiresome opponent will retort that there is a state in which butter cannot properly be called either hard or soft. We try again: If Ann began to be asleep at eight, before eight she was awake; if my shirt became dirty on Tuesday, before Tuesday it was clean; if Bonzo died last week, before last week he was alive. And when the advocate of the borderline state reminds us of the various twilight areas of consciousness or cleanliness, we are reduced to legislation: “asleep” shall henceforth apply to every mental state short of complete wakefulness, “alive” to every condition of the body before the onset of putrefaction, “clean” to every shirt incapable of producing a certain measurable discoloration in the water in which it is washed. “Let F and G be contradictories”, we still guardedly maintain: “then if a comes to be F at time t , before time t a was G ”. (shrink)

There are different ways of looking at the achievements of outstanding personalities. In reading this book, the reader will be in touch with some of Jung's best insights into artistic and literary creation. The essays are on Paracelsus, Freud, Richard Wilhelm, Picasso, and Joyce's _Ulysses_. There are also two chapters on poetry and literature.