Activators of RNA polymerase II transcription possess distinct and separable DNA‐binding and transcriptional activation domains. They are thought to function by binding to specific sites on DNA and interacting with proteins (transcription factors) binding near to the transcriptional start site of a gene. The ability of these proteins to activate transcription is a highly regulated process, with activation only occurring under specific conditions to ensure proper timing and levels of target gene expression. Such regulation modulates the ability of transcription factors (...) either to bind DNA or to interact with the transcriptional machinery. Here we discuss recent advances in our understanding of these mechanisms of transcriptional regulation in yeast. (shrink)

Girotto and Legrenzi's 1993 facilitation effect for their SARS version of Wason s THOG problem a disjunctive reasoning task was examined. The effect was not replicated when the standard THOG problem instructions were used in Experiments 1 and 2. However, in Experiment 3 when Girotto and Legrenzi's precise instructions were used, facilitation was observed. Experiment 4 further investigated the role of the type of instructions in the observed facilitation. The results suggest that such facilitation may result from attentional factors rather (...) than the use of a combinatorial analysis in the problem. (shrink)

Understanding the components of clinical care that work best is a cornerstone of improving health care. And yet, the more we improve the quality of quality improvement and move to continuous learning about clinical care more broadly, the more we find ourselves in a regulatory environment that makes evaluation more difficult, expensive, and, in some situations, impossible. In their paper on the ethical underpinnings of the distinction between research and treatment, Ruth Faden and colleagues raise important implications for a wide (...) array of situations. These points give reason to rethink the definition of routine clinical operations to include evaluation of the processes and outcomes of care and dissemination of findings. We concur with the assertion by Faden and colleagues, and with previous work from The Hastings Center, that conducting continuous improvement activities such as these is an obligation of health systems and clinicians. We believe that rigorous, systematic evaluation should be considered part of normal, expected operations, rather than exceptional behavior that requires extraordinary regulatory control. (shrink)

In 2012, a U.S. Institute of Medicine report called for a different approach to health care: “Left unchanged, health care will continue to underperform; cause unnecessary harm; and strain national, state, and family budgets.” The answer, they suggested, would be a “continuously learning” health system. Ethicists and researchers urged the creation of “learning health organizations” that would integrate knowledge from patient‐care data to continuously improve the quality of care. Our experience with an ongoing research study on atrial fibrillation—a trial known (...) as IMPACT‐AFib—gave us some insight into one of the challenges that will have to be dealt with in creating these organizations. Although the proposed educational intervention study placed no restrictions on what providers and health plans could do, the oversight team argued that the ethical principle of beneficence did not allow the researchers to be “bystanders” in relation to a control group receiving suboptimal care. In response, the researchers designed a “workaround” that allowed the project to go forward. We believe the experience suggests that what we call “bystander ethics” will create challenges for the kinds of quality improvement research that LHOs are designed to do. (shrink)

In 2012, a U.S. Institute of Medicine report called for a different approach to health care: “Left unchanged, health care will continue to underperform; cause unnecessary harm; and strain national, state, and family budgets.” The answer, they suggested, would be a “continuously learning” health system. Ethicists and researchers urged the creation of “learning health organizations” that would integrate knowledge from patient‐care data to continuously improve the quality of care. Our experience with an ongoing research study on atrial fibrillation—a trial known (...) as IMPACT‐AFib—gave us some insight into one of the challenges that will have to be dealt with in creating these organizations. Although the proposed educational intervention study placed no restrictions on what providers and health plans could do, the oversight team argued that the ethical principle of beneficence did not allow the researchers to be “bystanders” in relation to a control group receiving suboptimal care. In response, the researchers designed a “workaround” that allowed the project to go forward. We believe the experience suggests that what we call “bystander ethics” will create challenges for the kinds of quality improvement research that LHOs are designed to do. (shrink)

"Cluster randomized trials," in which groups of patients are randomly assigned to different therapeutic interventions, provide a powerful way of evaluating drugs. CRTs have not been widely used, in good part because of concerns about whether patients must give informed consent to participate in them. A better understanding of how CRTs fit into clinical practice resolves the concerns.

Mr. Richards is justified in saying that S0009838800006017_inline1 is here indefensible, but he does not much mend matters by reading S0009838800006017_inline2. Iocasta may have been a paragon of all the virtues, but what has that to do with it? No, the real correction is S0009838800006017_inline3. ‘ To whom should I tell even greater things than this rather than to thee ?’.

This second edition of the book contains a new chapter on the notions of natural-kind words and natural kinds.

The Exchange of Words is a philosophical exploration of human testimony, specifically as a form of intersubjective understanding in which speakers communicate by making themselves accountable for the truth of what they say. This account weaves together themes from philosophy of language, moral psychology, action theory, and epistemology, for a new approach to this basic human phenomenon.

The paper argues for the centrality of believing the speaker (as distinct from believing the statement) in the epistemology of testimony, and develops a line of thought from Angus Ross which claims that in telling someone something, the kind of reason for belief that a speaker presents is of an essentially different kind from ordinary evidence. Investigating the nature of the audience's dependence on the speaker's free assurance leads to a discussion of Grice's formulation of non-natural meaning in an epistemological (...) light, concentrating on just how the recognition of the speaker's self-reflexive intention is supposed to count for his audience as a reason to believe P. This is understood as the speaker's explicitly assuming responsibility for the truth of his statement, and thereby constituting his utterance as a reason to believe. (shrink)

In this volume Rorty offers a Deweyan account of objectivity as intersubjectivity, one that drops claims about universal validity and instead focuses on utility for the purposes of a community. The sense in which the natural sciences are exemplary for inquiry is explicated in terms of the moral virtues of scientific communities rather than in terms of a special scientific method. The volume concludes with reflections on the relation of social democratic politics to philosophy.

Richard Swinburne offers an original treatment of a question at the heart of epistemology: what makes a belief rational, or justified in holding? He maps the rival accounts of philosophers on epistemic justification ("internalist" and "externalist"), arguing that they are really accounts of different concepts. He distinguishes between synchronic justification (justification at a time) and diachronic justification (synchronic justification resulting from adequate investigation)--both internalist and externalist. He also argues that most kinds of justification are worth having because they are (...) indicative of truth; however, it is only justification of internalist kinds that can guide a believer's actions. Swinburne goes on to show the usefulness of the probability calculus in elucidating how empirical evidence makes beliefs probably true. (shrink)

This paper explores some aspects of the relation between different ways of achieving a consensus on the judgemental values of a group of indviduals; in particular, aggregation and deliberation. We argue firstly that the framing of an aggregation problem itself generates information that individuals are rationally obliged to take into account. And secondly that outputs of the deliberative process that this initiates is in tension with constraints on consensual values typically imposed by aggregation theory, at least when deliberation is modelled (...) as process of learning from others compatible with Bayesian updating principles. (shrink)

Atheism is a familiar kind of skepticism about religion. Moral error theory is an analogous kind of skepticism about morality, though less well known outside academic circles. Both kinds of skeptic face a "what next?" question: If we have decided that the subject matter (religion/morality) is mistaken, then what should we do with this way of talking and thinking? The natural assumption is that we should abolish the mistaken topic, just as we previously eliminated talk of, say, bodily humors and (...) unicorns. The fictionalist, however, offers a less obvious recommendation. According to the fictionalist, engaging in the topic in question provides pragmatic benefits that do not depend on its truth-in a way roughly analogous to engaging with a novel or a movie. The religious fictionalist maintains that even if we were atheists, we should carry on talking, thinking, and acting as if religion were true. The moral fictionalist maintains a similar view regarding moral talk, thought, and action. Both forms of fictionalism face serious challenges. Some challenges can be levelled at either form of fictionalism (or at any form of fictionalism), whereas others are problems unique to moral fictionalism or to religious fictionalism. There are important questions to be asked about the relationship between these two kinds of fictionalism. Could moral fictionalism be plausible even if religious fictionalism is not (or vice versa)? This is a volume of thirteen previously unpublished papers on the topics of religious fictionalism, moral fictionalism, and the relation between these views. (shrink)

This book brings together twenty articles giving a comprehensive view of the work of the Aristotelian commentators.... The importance of the commentators is partly that they represent the thought and classroom teaching of the Aristotelian and Neoplatonist schools and partly that they provide a panorama of a thousand years of anicient Greek philosophy, revealing many original quotations from lost works. Even more significant is the profound influence... that they exert on later philosophy, Islamic and Western. Not only did they preserve (...) anti-Aristotelian marterial which helped inspire Medieval and Renaissance science, but they presented Aristotle in a form that made him acceptable to the Christian Church. It is not Aristotle, but Aristotle transformed and embedded in the philosophy of the commentators, that so often lies behind the views of later thinkers. --From book jacket. (shrink)

Richard Swinburne presents a powerful new case for substance dualism and for libertarian free will. He argues that pure mental events are distinct from physical events and interact with them, and claims that no result from neuroscience or any other science could show that interaction does not take place. Swinburne goes on to argue for agent causation, and claims that it is we, and not our intentions, that cause our brain events. It is metaphysically possible that each of us (...) could acquire a new brain or continue to exist without a brain; and so we are essentially souls. Brain events and conscious events are so different from each other that it would not be possible to establish a scientific theory which would predict what each of us would do in situations of moral conflict. Hence, we should believe that things are as they seem to be: that we make choices independently of the causes which influence us. It follows that we are morally responsible for our actions. (shrink)

Philosophy and literature enjoy a close, complex relationship. Elucidating the connections between these two fields, this book examines the ways philosophy deploys literary means to advance its practice, particularly as a way of life that extends beyond literary forms and words into physical deeds, nonlinguistic expression, and subjective moods and feelings.

_Heidegger_ is a classic introduction to Heidegger's notoriously difficult work. Truly accessible, it combines clarity of exposition with an authoritative handling of the subject-matter. Richard Polt has written a work that will become the standard text for students looking to understand one of the century's greatest minds.

The book begins with an overview that introduces the Theorem and the issues surrounding it, and explores how the essays that follow contribute to our understanding of those issues.

Richard Kilvington (ca. 1302-1361) was one of the most original and influential thinkers among the Oxford Calculators. His impact on late medieval philosophy and theology remains unquestionable. His physical, logical, and ethical solutions were extensively debated and referred to, paving the way for new approaches in philosophy and theology. This volume presents a critical edition of question 4 from Kilvington's Quaestiones super libros Sententiarum, complete with an introduction to the edition and a guide to Kilvington's theological concepts.

The sixteen essays in this volume confront the current debate about the relationship between philosophy and its history. On the one hand intellectual historians commonly accuse philosophers of writing bad - anachronistic - history of philosophy, and on the other, philosophers have accused intellectual historians of writing bad - antiquarian - history of philosophy. The essays here address this controversy and ask what purpose the history of philosophy should serve. Part I contains more purely theoretical and methodological discussion, of such (...) questions as whether there are 'timeless' philosophical problems, whether the issues of one epoch are commensurable with those of another, and what style is appropriate to the historiography of the subject. The essays in Part II consider a number of case-histories. They present important revisionist scholarship and original contributions on topics drawn from ancient, early modern and more recent philosophy. All the essays have been specially commissioned, and the contributors include many of the leading figures in the field. The volume as a whole will be of vital interest to everyone concerned with the study of philosophy and of its history. (shrink)

Mark Platts; VIII*—Natural Kind Words and “Rigid Designators”, Proceedings of the Aristotelian Society, Volume 82, Issue 1, 1 June 1982, Pages 103–114, https://.

Thinking through the body: educating for the humanities -- The body as background -- Self-knowledge and its discontents: from Socrates to somaesthetics -- Muscle memory and the somaesthetic pathologies of everyday life -- Somaesthetics in the philosophy classroom: a practical approach -- Somaesthetics and the limits of aesthetics -- Somaesthetics and Burke's sublime -- Pragmatism and cultural politics: from textualism to somaesthetics -- Body consciousness and performance -- Somaesthetics and architecture: a critical option -- Photography as performative process -- Asian (...) ars erotica and the question of sexual aesthetics -- Philosophy as awakened life : everyday aesthetics of embodiment in American transcendentalism and Japanese Zen practice -- Somatic style. (shrink)

This Element, written for researchers and students in philosophy and the behavioral sciences, reviews and critically assesses extant work on number concepts in developmental psychology and cognitive science. It has four main aims. First, it characterizes the core commitments of mainstream number cognition research, including the commitment to representationalism, the hypothesis that there exist certain number-specific cognitive systems, and the key milestones in the development of number cognition. Second, it provides a taxonomy of influential views within mainstream number cognition research, (...) along with the central challenges these views face. Third, it identifies and critically assesses a series of core philosophical assumptions often adopted by number cognition researchers. Finally, the Element articulates and defends a novel version of pluralism about number concepts. (shrink)

A large campaign has sought to destigmatize psychiatric disorders by disseminating the view that they are in fact brain disorders. But when psychiatric disorders are associated with neurobiological correlates, laypeople's attitudes toward patients are harsher, and the prognoses seem poorer. Here, we ask whether these misconceptions could result from the essentialist presumption that brain disorders are innate. To this end, we invited laypeople to reason about psychiatric disorders that are diagnosed by either a brain or a behavioral test that were (...) strictly matched for their informative value. Participants viewed disorders as more likely to be innate and immutable when the diagnosis was supported by a brain test as compared to a behavioral test. These results show for the first time that people spontaneously essentialize psychiatric conditions that are linked to the brain, even when the brain probe offers no additional diagnostic or genetic information. This bias suggests that people consider the biological essence of living things as materially embodied. (shrink)

Disagreement is common: even informed, intelligent, and generally reasonable people often come to different conclusions when confronted with what seems to be the same evidence. Can the competing conclusions be reasonable? If not, what can we reasonably think about the situation? This volume examines the epistemology of disagreement. Philosophical questions about disagreement arise in various areas, notably politics, ethics, aesthetics, and the philosophy of religion: but this will be the first book focusing on the general epistemic issues arising from informed (...) disagreement. Ten leading philosophers offer specially written essays which together will offer a starting-point for future work on this topic. (shrink)