Understanding how transcription factor (TF) binding is related to gene regulation is a moving target. We recently uncovered genome‐wide evidence for a “Hit‐and‐Run” model of transcription. In this model, a master TF “hits” a target promoter to initiate a rapid response to a signal. As the “hit” is transient, the model invokes recruitment of partner TFs to sustain transcription over time. Following the “run”, the master TF “hits” other targets to propagate the response genome‐wide. As such, a TF may act (...) as a “catalyst” to mount a broad and acute response in cells that first sense the signal, while the recruited TF partners promote long‐term adaptive behavior in the whole organism. This “Hit‐and‐Run” model likely has broad relevance, as TF perturbation studies across eukaryotes show small overlaps between TF‐regulated and TF‐bound genes, implicating transient TF‐target binding. Here, we explore this “Hit‐and‐Run” model to suggest molecular mechanisms and its biological relevance. (shrink)

This paper is about an avian influenza outbreak in South Africa’s commercial ostrich industry. The outbreak was managed according to international best practice and led to the destruction of 30,000 ostriches in two of South Africa’s provinces. However, the industry has a long history of managing low pathogenic avian influenza outbreaks in a different way. We use the 2004 outbreak and earlier approaches to managing disease to shed light on recent debates on how we might live differently with livestock diseases. (...) The paper is based on in-depth interviews with farmers, veterinarians, scientists and agriculture officials. (shrink)

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human‐nonhuman chimeric research. Led by bioethics researchers working closely with an (...) interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human‐nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics’ previous focus on human‐centered questions about the ethics of “humanization” and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less‐siloed governance and oversight and more‐comprehensive public communication. (shrink)

In June 1993, conjoined twins Amy and Angela Lakeberg became the focus of national attention. They shared a complex six‐chambered heart and one liver; only one could survive separation surgery, and even her chances were slim. The medical challenge was great and the ethical challenges were even greater.

We often talk of people as being more or less imaginative than one another – as being better or worse at imagining – and we also compare various feats of imagination to one another in terms of how easy or hard they are. Facts such as these might be taken to suggest that imagination is often implicitly understood as a skill. This implicit understanding, however, has rarely (if ever) been made explicit in the philosophical literature. Such is the task of (...) this chapter. I first attempt to flesh out several conditions for an activity to count as a skill. I then attempt to show how imagination can meet such conditions. The chapter concludes with an attempt to answer various worries that might be raised to the claim that imagination should be thought of as a skill. (shrink)

Physicians generally recommend that patients resuscitated with naloxone after opioid overdose stay in the emergency department for a period of observation in order to prevent harm from delayed sequelae of opioid toxicity. Patients frequently refuse this period of observation despiteenefit to risk. Healthcare providers are thus confronted with the challenge of how best to protect the patient’s interests while also respecting autonomy, including assessing whether the patient is making an autonomous choice to refuse care. Previous studies have shown that physicians (...) have widely divergent approaches to navigating these conflicts. This paper reviews what is known about the effects of opioid use disorder on decision-making, and argues that some subset of these refusals are non-autonomous choices, even when patients appear to have decision making capacity. This conclusion has several implications for how physicians assess and respond to patients refusing medical recommendations after naloxone resuscitation. (shrink)

In the past two decades, much work on Kant has aimed to delimit and evaluate the bedrock assumptions of Kant's mature Critical philosophy. This volume brings together leading Kant scholars to address this issue in conversation with each other, articulating and interrogating Kant's critical assumptions.

The authors offer ways to encourage and educate Americans to participate in the public deliberations that make democracy work and lay out the principles of..

While post- and decolonial theorists have thoroughly debunked the idea of historical progress as a Eurocentric, imperialist, and neocolonialist fallacy, many of the most prominent contemporary thinkers associated with the Frankfurt School--Jürgen Habermas, Axel Honneth, and Rainer Forst--have persistently defended ideas of progress, development, and modernity and have even made such ideas central to their normative claims. Can the Frankfurt School's goal of radical social change survive this critique? And what would a decolonized critical theory look like? Amy Allen fractures (...) critical theory from within by dispensing with its progressive reading of history while retaining its notion of progress as a political imperative, so eloquently defended by Adorno. Critical theory, according to Allen, is the best resouce we have for achieving emancipatory social goals. In reimagining a decolonized critical theory after the end of progress, she rescues it from oblivion and gives it a future. (shrink)

In this acclaimed exploration of the search for "authentic" individual identity, Marshall Berman explores the historical experiences and needs out of which this new radicalism arose. Focussing on eighteenth-century Paris, a time and place in which a distinctively modern form of society was just coming into its own, Berman shows how the ideal of authenticity—of a self that could organize the individual's energy and direct it toward his own happiness—articulated eighteenth-century man's deepest responses to this brave new world, and (...) his most ardent hope for a new life in it. Exploring in particular the ideas of Montesquieu and Rousseau, Berman shows how the ideal of authenticity was radically opposed to the bourgeois, capitalistic idea of "self-interest.". (shrink)

Considered the most original thinker in the Italian philosophical tradition, Giambattista Vico has been the object of much scholarly attention but little consensus. In this new interpretation, David L. Marshall examines the entirety of Vico's oeuvre and situates him in the political context of early modern Naples. He demonstrates Vico's significance as a theorist who adapted the discipline of rhetoric to modern conditions. Marshall presents Vico's work as an effort to resolve a contradiction. As a professor of rhetoric (...) at the University of Naples, Vico had a deep investment in the explanatory power of classical rhetorical thought, especially that of Aristotle, Cicero, and Quintilian. Yet as a historian of the failure of Naples as a self-determining political community, he had no illusions about the possibility or worth of democratic and republican systems of government in the post-classical world. As Marshall demonstrates, by jettisoning the assumption that rhetoric only illuminates direct, face-to-face interactions between orator and auditor, Vico reinvented rhetoric for a modern world in which the Greek polis and the Roman res publica are no longer paradigmatic for political thought. (shrink)

While Roman Ingarden is well known for his work in aesthetics and studies in ontology, one of his most important and lasting contributions has been largely overlooked: his approach to a general ontology of social and cultural objects. Ingarden himself discusses cultural objects other than works of art directly in the first section of “The Architectural Work”1, where he develops a particularly penetrating view of the ontology of buildings, flags, and churches. This text provides the core insight into how his (...) more lengthy studies of the ontology of works of art in The Literary Work of Art and the rest of The Ontology of the Work of Art, combined with the ontological distinctions of Der Streit um die Existenz der Welt, may be used to understand social and cultural objects. The view that results, I will argue, is based in foreseeing problems with the reductivist and projectivist views that remain popular, and is capable of resolving central problems still thought to plague those who would offer a theory of cultural objects. (shrink)

Empathy has for a long time, at least since the eighteenth century, been seen as centrally important in relation to our capacity to gain a grasp of the content of other people's minds, and predict and explain what they will think, feel, and do; and in relation to our capacity to respond to others ethically. In addition, empathy is seen as having a central role in aesthetics, in the understanding of our engagement with works of art and with fictional characters. (...) A fuller understanding of empathy is now offered by the interaction of research in science and the humanities. This volume draws together nineteen original chapters by leading researchers across several disciplines, together with an extensive Introduction by the editors. The individual chapters reveal how important it is, in a wide range of fields of enquiry, to bring to bear an understanding of the role of empathy in its various guises. It offers the ideal starting-point for the exploration of this intriguing aspect of human life. (shrink)

Imagination is celebrated as our vehicle for escape from the mundane here and now. It transports us to distant lands of magic and make-believe, and provides us with diversions during boring meetings or long bus rides. Yet the focus on imagination as a means of escape from the real world minimizes the fact that imagination seems also to furnish us with knowledge about it. Imagination seems an essential component in our endeavor to learn about the world in which we live--whether (...) we're planning for the future, aiming to understand other people, or figuring out whether two puzzle pieces fit together. But how can the same mental power that allows us to escape the world as it currently is also inform us about the world as it currently is? Ten original essays grapple with this neglected question; in doing so, they present a diverse array of positions ranging from cautious optimism to deep-seated pessimism. Blending perspectives from philosophy of mind, cognitive science, epistemology, aesthetics, and ethics, Knowledge Through Imagination sheds new light on the epistemic role of imagination. (shrink)

What a person is doing often depends on that person’s thought about what they are doing, or about the wider circumstances of their action. For example, whether my killing is murder or manslaughter depends, in part, on whether I understand that what I am doing is killing you, and on whether I understand that my killing is unjustified. Similarly, if I know that the backpack I am taking is yours, then my taking it may be an act of theft; but (...) it is not theft if I simply mistook your backpack for my own. And if I don’t know that in signing a document I’m promising to do some thing, then in signing it I’m not promising to do this at all. -/- According to Elizabeth Anscombe, a central task of philosophical psychology is to articulate this dependency of action on thought. And in a range of papers published during the 1960s, Anscombe sought to elucidate various aspects of this dependency. In this paper we give a systematic overview of how Anscombe understands this dependency, and in the process reveal the conceptual framework underlying Anscombe’s thinking about perception, desire, intention, voluntariness, responsibility, guilt, and sin. (shrink)

Dan Marshall and Josh Parsons note, correctly. that the property of being either a cube or accompanied by a cube is incorrectly classified as intrinsic under the definition we have given unless it turns out to be disjunctive. Whether it is disjunctive, under the definition we gave, turns on certain judgements of the relative naturalness of properties. They doubt the judgements of relative naturalness that would classify their property as disjunctive. We disagree. They also suggest that the whole idea (...) of judging relative naturalness is a dubious business. We reply that, like them or not, such judgements cannot easily be avoided. (shrink)

Opponents of abortion sometimes hold that it is impermissible because fetuses are persons from the moment of conception. But miscarriage, which ends up to 89 % of pregnancies, is much deadlier than abortion. That means that if opponents of abortion are right, then miscarriage is the biggest public-health crisis of our time. Yet they pay hardly any attention to miscarriage, especially very early miscarriage. Attempts to resolve this inconsistency by adverting to the distinction between killing and letting die or to (...) the difficulty of preventing miscarriage fail, leaving a dilemma. Opponents of abortion should either advocate a substantial shift in our political and medical priorities or else give up the view that fetuses are persons from the moment of conception. (shrink)

Providing an overview of the intellectual roots of the worldwide environmental movement - from ancient religions and philosophies to modern science and ethics - this book synthesises them into a new philosophy of nature in which to ground ...

To what extent are countability distinctions subject to systematic semantic variation? Could there be a language with no countability distinctions—in particular, one where all nouns are count? I argue that the answer is no: even in a language where all NPs have the core morphosyntactic properties of English count NPs, such as combining with numerals directly and showing singular/plural contrasts, countability distinctions still emerge on close inspection. I divide these distinctions into those related to sums and those related to parts. (...) In the Sahaptian language Nez Perce, evidence can be found for both types of distinction, in spite of the absence of anything like a traditional mass–count division in noun morphosyntax. I propose an extension of the Nez Perce analysis to Yudja, analyzed by Lima as lacking any countability distinctions. More generally, I suggest that at least one countability distinction may be universal and that languages without any countability distinctions may be unlearnable. (shrink)

PREFACE -/- WHEN first I undertook the study of the theory of Art, many years ago, I was impressed by the emphasis of pleasure attainment in all descriptions of art works, and by the emphatic pleasurableness of my own mental state during the contemplation of artistic productions. -/- My thought being thus turned to the consideration of the relation of æsthetics to hedonics, I was led to make a careful study of the psychology of pleasure and of its correlate pain: (...) the results of this study I here lay before those who may be interested. (shrink)

Organisms' environments are thought to play a fundamental role in determining their fitness and hence in natural selection. Existing intuitive conceptions of environment are sufficient for biological practice. I argue, however, that attempts to produce a general characterization of fitness and natural selection are incomplete without the help of general conceptions of what conditions are included in the environment. Thus there is a "problem of the reference environment"—more particularly, problems of specifying principles which pick out those environmental conditions which determine (...) fitness. I distinguish various reference environment problems and propose solutions to some of them. While there has been a limited amount of work on problems concerning what I call "subenvironments", there appears to be no earlier work on problems of what I call the "whole environment". The first solution I propose for a whole environment problem specifies the overall environment for natural selection on a set of biological types present in a population over a specified period of time. The second specifies an environment relevant to extinction of types in a population; this kind of environment is especially relevant to certain kinds of long-term evolution. (shrink)

The effective altruism movement (EA) is one of the most influential philosophically savvy movements to emerge in recent years. Effective Altruism has historically been dedicated to finding out what charitable giving is the most overall-effective, that is, the most effective at promoting or maximizing the impartial good. But some members of EA want the movement to be more inclusive, allowing its members to give in the way that most effectively promotes their values, even when doing so isn’t overall-effective. When we (...) examine what it means to give according to one’s values, I argue, we will see that this is both inconsistent with what EA is like now and inconsistent with its central philosophical commitment to an objective standard that can be used to critically analyze one’s giving. While EA is not merely synonymous with act utilitarianism, it cannot be much more inclusive than it is right now. (shrink)

In recent analytic metaphysics, the view that ‘ordinary inanimate objects such as sticks and stones, tables and chairs, simply do not exist’ has been defended by some noteworthy writers. Thomasson opposes such revisionary ontology in favour of an ontology that is conservative with respect to common sense. The book is written in a straightforward, methodical and down-to-earth style. It is also relatively non-specialized, enabling the author and her readers to approach problems that are often dealt with in isolation in a (...) more unified way.Thomasson's arguments are mainly counter-attacks on six ‘eliminativist’ arguments against ordinary objects. A causal redundancy argument espoused by Trenton Merricks holds that to suppose that there are ordinary objects is to suppose that these objects have distinctive causal powers. However, the casual efficacy of a baseball, for example, is exhausted by that of some suitably arranged …. (shrink)

I describe a realist, ontologically objective interpretation of probability, "far-flung frequency (FFF) mechanistic probability". FFF mechanistic probability is defined in terms of facts about the causal structure of devices and certain sets of frequencies in the actual world. Though defined partly in terms of frequencies, FFF mechanistic probability avoids many drawbacks of well-known frequency theories and helps causally explain stable frequencies, which will usually be close to the values of mechanistic probabilities. I also argue that it's a virtue rather than (...) a failing of FFF mechanistic probability that it does not define single-case chances, and compare some aspects of my interpretation to a recent interpretation proposed by Strevens. (shrink)

Creations of the Mind: Essays on Artifacts and their Representation, ed. Stephen Laurence and Eric Margolis, Oxford: Oxford University Press, 2007.

This book showcases the best in modern medieval and religious scholarship, deploying spirited and progressive approaches to the study of Christian mysticism and the philosophy of religion. The volume explores excessive forms of desire and eroticism at play within Christian mystical texts and the historiographical, theological, and philosophical problems bound up in the interrogation of extraordinary experiences of the divine. Amy Hollywood examines how feminist and queer studies have changed the history of mysticism and how the study of religion in (...) general has altered our understanding of what is true, what is real, and what it means to research a historical subject. Ideal for novices and experienced scholars alike, this volume models cutting-edge methods for the ethical study of divine embodiment and religious experience in the Middle Ages. It makes a forceful case for thinking about religion as both belief and practice, in which traditions marked by change are passed down through generations, laying the groundwork for their own critique. Through a provocative integration of medieval sources and texts by Derrida, Butler, Asad, and Chakrabarty this book redefines what it means to engage critically with history and those embedded within it. (shrink)

Introduction : the politics of our selves -- Foucault, subjectivity, and the enlightenment : a critical reappraisal -- The impurity of practical reason : power and autonomy in Foucault -- Dependency, subordination, and recognition : Butler on subjection -- Empowering the lifeworld? autonomy and power in Habermas -- Contextualizing critical theory -- Engendering critical theory.

Citing a lifelong engagement with Marxism, critic and writer Marshall Berman reveals the movement's positive points and suggests a new beginning for Marxism may be on the horizon with its recent 150th anniversary attention.