DNA joining enzymes play an essential role in the maintenance of genomic integrity and stability. Three mammalian genes encoding DNA ligases, LIG1, LIG3 and LIG4, have been identified. Since DNA ligase II appears to be derived from DNA ligase III by a proteolytic mechanism, the three LIG genes can account for the four biochemically distinct DNA ligase activities, DNA ligases I, II, III and IV, that have been purified from mammalian cell extracts. It is probable that the specific cellular roles (...) of these enzymes are determined by the proteins with which they interact. The specific involvement of DNA ligase I in DNA replication is mediated by the non‐catalytic amino‐terminal domain of this enzyme. Furthermore, DNA ligase I participates in DNA base excision repair as a component of a multiprotein complex. Two forms of DNA ligase III are produced by an alternative splicing mechanism. The ubiqitously expressed DNA ligase III‐α forms a complex with the DNA single‐strand break repair protein XRCC1. In contrast, DNA ligase III‐β, which does not interact with XRCC1, is only expressed in male meiotic germ cells, suggesting a role for this isoform in meiotic recombination. At present, there is very little information about the cellular functions of DNA ligase IV. (shrink)

Various theories of moral cognition posit that moral intuitions can be understood as the output of a computational process performed over structured mental representations of human action. We propose that action plan diagrams—“act trees”—can be a useful tool for theorists to succinctly and clearly present their hypotheses about the information contained in these representations. We then develop a methodology for using a series of linguistic probes to test the theories embodied in the act trees. In Study 1, we validate the (...) method by testing a specific hypothesis (diagrammed by act trees) about how subjects are representing two classic moral dilemmas and finding that the data support the hypothesis. In Studies 2–4, we explore possible explanations for discrete and surprising findings that our hypothesis did not predict. In Study 5, we apply the method to a less well‐studied case and show how new experiments generated by our method can be used to settle debates about how actions are mentally represented. In Study 6, we argue that our method captures the mental representation of human action better than an alternative approach. A brief conclusion suggests that act trees can be profitably used in various fields interested in complex representations of human action, including law, philosophy, psychology, linguistics, neuroscience, computer science, robotics, and artificial intelligence. (shrink)

Almost since their publication, the writings of Michel de Montaigne have provided rich fodder for the work of scholars in myriad disciplines. Philosophers have considered Montaigne's views on skepticism; historians have examined his views on the Indians; deconstructionists and literary scholars have examined Montaigne's view of the self; and, political scientists have touched on his arguments for toleration. However, because each of these projects has been done largely in isolation, most scholars have failed to see the relationships between the various (...) aspects of Montaigne's thought. Alan Levine, in Sensual Philosophy, unites Montaigne's thought for the first time, ably and convincingly demonstrating the significant role Montaigne played in establishing the liberal ethos in the West. In exploring Montaigne's grounding for liberalism, Levine considers Montaigne's conceptualization of skepticism and its relationship to toleration. He argues that Montaigne's theories of self ground his idea of toleration without leaving it open to the corrosive charges of relativism and nihilism. Levine also articulates the importance of Montaigne's thought for contemporary conceptions of personal freedom, individuality, subjectivity, and self-creation by bringing him into dialogue with modern and postmodern political theorists such as Heidegger, Nietzsche, and Richard Rorty. This lively book persuades those who might be tempted by postmodernism that they should turn to Montaigne instead. (shrink)

Biomedical and behavioral research may affect strongly held social values and thereby create significant controversy over whether such research should be permitted in the first place. Institutional review boards responsible for protecting the rights and welfare of participants in research are sometimes faced with review of protocols that have significant implications for social policy and the potential for negative social consequences. Although IRB members often raise concerns about potential long-term social implications in protocol review, federal regulations strongly discourage IRBs from (...) considering them in their decisions. Yet IRBs often do consider the social implications of research protocols and sometimes create significant delays in initiating or even prevent such research. The social implications of research are important topics for public scrutiny and professional discussion. This article examines the reasons that the federal regulations preclude IRBs from assessing the social risks of research, and examines alternative approaches that have been used with varying success by national advisory groups to provide such guidance. The article concludes with recommendations for characteristics of a national advisory group that could successfully fulfill this need, including sustainability, independence, diverse and relevant expertise, and public transparency. (shrink)

We develop a general method for applying functional models to natural systems and cite recent progress in protein modeling that demonstrates the power of this approach. Functional modeling constrains the range of acceptable structural models of a system, reduces the difficulty of finding them, and improves their fidelity. However, functional models are distinctly different from the structural models that are more commonly applied in science. In particular, structural and functional models ask different questions and provide different kinds of answers. As (...) we clarify these differences and articulate how to use these models jointly, we extend our ability to do science and gain insight into the proper use of the terms organization , order , and emergence when describing systems in nature. (shrink)

This book taps the best American thinkers to answer the essential American question: How do we sustain our experiment in government of, by, and for the people? Authored by an extraordinary and politically diverse roster of public officials, scholars, and educators, these chapters describe our nation's civic education problem, assess its causes, offer an agenda for reform, and explain the high stakes at risk if we fail.

The contributors to The Moral of the Story, all preeminent political theorists, are unified by their concern with the instructive power of great literature. This thought-provoking combination of essays explores the polyvalent moral and political impact of classic world literatures on public ethics through the study of some of its major figures-including Shakespeare, Dante, Cervantes, Jane Austen, Henry James, Joseph Conrad, Robert Penn Warren, and Dostoevsky. Positing the uniqueness of literature's ability to promote dialogue on salient moral and intellectual virtues, (...) editor Henry T. Edmonson III has culled together a wide-ranging exploration of such fundamental concerns as the abuse of authority, the nature of good leadership, the significance of "middle class virtues" and the needs of adolescents. This collection reinvigorates the study of classic literature as an endeavor that is not only personally intellectually satisfying, but also an inimitable and unique way to enrich public discourse. (shrink)

The arts of rule cover the exercise of power by princes and popular sovereigns, but they range beyond the domain of government itself, extending to civil associations, political parties, and religious institutions. Making full use of political philosophy from a range of backgrounds, this festschrift for Harvey Mansfield recognizes that although the arts of rule are comprehensive, the best government is a limited one.

lthough it was in the early eighties when I began to feel a growing disaff'ection with the radicalized academic left, a decisive nausea-inducing body blow was administered by the PMLA of January 1989. In that infamous issue appeared a letter signed by twenty-four feminist academics attacking the eminent Shakespeare scholar Richard Levin, for "Feminist Thematics and Shakespearean Tragedy," which had appeared in PMLA the year before. Levin's essay, the work of a well-tempered, open-minded, and liberal supporter of many radical reforms (...) in the academy, was a penetrating critique of the feminist identity politics that were trying to wrest Shakespeare into the persona of a feminist scourge of sexism and patriarchy. Levin's temerity in taking on the distortions of identity politics was threatening enough, but his Enlightenment style and Swiftian wit, which he brilliantly deployed to dismantle the tendentious and self-serving hermeneutics of the "dictatorship of virtue" (a phrase I borrow here from Richard Bernstein) that constitutes avant-garde millenarianism in the U.S. academy, served further to inflame the hypersensitive skins of his holier-than-thou critics, who brook no criticism.. (shrink)

Studies of change blindness indicate that more intentional monitoring of changes is necessary to successfully detect changes as scene complexity increases. However, there have been conflicting reports as to whether people are aware of this relation between intention and successful change detection as scene complexity increases. Here we continue our dialogue with [Beck, M. R., Levin, D. T., & Angelone, B. . Change blindness blindness: Beliefs about the roles of intention and scene complexity in change detection. Consciousness and Cognition, 16, (...) 31–51; Beck, M. R., Levin, D. T., & Angelone, B. . Metacognitive errors in change detection: Lab and life converge. Consciousness and Cognition, 16, 58–62] by reporting two experiments that show participants do in fact intuit that more intentional monitoring is needed to detect changes as scene complexity increases. We also discuss how this dialogue illustrates the need for psychological studies to be grounded in measurements taken from real world situations rather than laboratory experiments or questionnaires. (shrink)

Throughout, this book questions our accepted definitions and biases, showing the self-reflective nature of scientific activity within society.

I propose to consider the question, "Can machines think?" This should begin with definitions of the meaning of the terms "machine" and "think." The definitions might be framed so as to reflect so far as possible the normal use of the words, but this attitude is dangerous, If the meaning of the words "machine" and "think" are to be found by examining how they are commonly used it is difficult to escape the conclusion that the meaning and the answer to (...) the question, "Can machines think?" is to be sought in a statistical survey such as a Gallup poll. But this is absurd. Instead of attempting such a definition I shall replace the question by another, which is closely related to it and is expressed in relatively unambiguous words. The new form of the problem can be described in terms of a game which we call the 'imitation game." It is played with three people, a man (A), a woman (B), and an interrogator (C) who may be of either sex. The interrogator stays in a room apart front the other two. The object of the game for the interrogator is to determine which of the other two is the man and which is the woman. He knows them by labels X and Y, and at the end of the game he says either "X is A and Y is B" or "X is B and Y is A." The interrogator is allowed to put questions to A and B. We now ask the question, "What will happen when a machine takes the part of A in this game?" Will the interrogator decide wrongly as often when the game is played like this as he does when the game is played between a man and a woman? These questions replace our original, "Can machines think?". (shrink)

In this book, Dr. Robert J. Levine reviews federal regulations, ethical analysis, and case studies in an attempt to answer these questions.

In many spheres, the law takes the legal concept of causation to correspond to the folk concept (the correspondence assumption). Courts, including the US Supreme Court, tend to insist on the "common understanding" and that which is "natural to say" (Burrage v. United States) when it comes to expressions relating to causation, and frequently refuse to clarify the expression to juries. As recent work in psychology and experimental philosophy has uncovered, lay attributions of causation are susceptible to a great number (...) of unexpected factors, some of which seem rather peripheral to causation. One of those is the norm effect (Knobe & Fraser, 2008): Agents who, in acting as they do, break a salient norm, are more likely to be considered as having caused a certain consequence than when they do not violate a norm. According to some (e.g., Alicke, 1992) this constitutes a bias. According to others (e.g., Sytsma, 2020), the folk concept of causation is sensitive to normative factors, and there’s nothing wrong with that. In this paper, we explore the question whether the norm effect should be considered a bias from the legal perspective on the one hand, and from the psychological perspective on the other. To do this, we test whether norms which are nonpertinent to the consequences or outright silly also impact causation judgements. The data from two preregistered experiments (total N=593) clearly show they do. This, we argue, makes the bias interpretation plausible from the psychological perspective, and both plausible and problematic from the legal perspective. It also shows that the law should abstain from unreflectively assuming conceptual correspondence between legal and ordinary language concepts. (shrink)

Darwin the writer -- Learning to see : Darwin's prophetic apprenticeship on the Beagle voyage -- The prose of On the origin of species -- Surprise and paradox : Darwin's artful legacy -- Darwinian mind and Wildean paradox -- Hardy's Woodlanders and the Darwinian grotesque -- Coda : the comic Darwin.

I offer a new interpretation of Heidegger’s analysis of anxiety in Being and Time as an account of the relationship between individual agents and the public normative practices of their communities. According to a prominent recent interpretation, Heidegger’s discussions of anxiety, death and the “call of conscience” together explain how we can respond to the norms of our practices as reasons and subject them to critical reflection. I argue that this is only part of the story. Anxiety is an occasion (...) for Dasein to take responsibility for its ongoing activity of interpreting the possibilities for living and acting made available by the normative practices of its community, which is presupposed and overlooked from the perspective of everyday Dasein. Public normativity underdetermines Dasein’s conception of what it would mean to take up any of the possibilities available in its world as a way of living its own life. (shrink)

The paper proposes a solution to the problem with Odysseus’ kingship in the Odyssey by maintaining that Odysseus is not officially considered dead. Consequently, Telemachus cannot inherit the position of king and Penelope must leave Odysseus’ household before remarrying. After discussing the modern concept of legal death and previous interpretations of the Ithacan situation, the paper focusses on Athena's speech at 1.275–92. A close reading demonstrates that erecting a cenotaph to Odysseus would be tantamount to a modern declaration of death (...) in absentia, since it will render Penelope a widow and Telemachus the head of the household. This legal convention chimes with the Homeric depiction of Hades. (shrink)

This thesis presents and criticizes Hilary Putnam's argument that mathematics is as empirical as science, in particular the argument that the switch from Euclidean geometry to Riemannian geometry as the approporiate geometry for physical space constituted an instance of revising mathematics as a result of observation. The thesis explains Putnam's views on mathematics as following from his theory of meaning and reference for natural kind terms. It is argued that Putnam's account of reference is unsuitable for mathematical terms and that (...) an "if-thenist" approach to mathematical knowledge is more fruitful. (shrink)

Darwin in Argentina -- Conflicting Systems -- Francisco Javier Muniz (1795-1871) -- Hermann Burmeister (1807-1891) -- Francisco P. Moreno (1852-1919) -- Domingo F. Sarmiento (1811-1888) -- Eduardo Holmberg (1852-1937) -- Florentino Ameghino (1854-1911) -- Jose Ingenieros (1877-1925) -- Carlos Octavio Bunge (1875-1918).

I consider the question of what moral obligations prospective parents owe to their future children. It is taken as an almost axiomatic premise of a wide range of philosophical arguments that prospective parents have a moral obligation to take such steps as ensuring their own financial stability or waiting until they are emotionally mature before conceiving. This is because it is assumed that parents have a moral obligation to lay the groundwork for their children's lives to go well. While at (...) first glance such a premise seems benign, I will argue that when it is applied to arguments in assisted reproductive technology, as it is in Julian Savulescu's procreative beneficence argument or as it is in Daniel Groll's recent argument for open gamete donation, we see problems with this premise. Problems in Groll's argument also become apparent when it is scrutinized in connection with this premise. (shrink)

A growing body of literature has revealed ordinary causal judgement to be sensitive to normative factors, such that a norm-violating agent is regarded more causal than their non-norm-violating counterpart. In this paper, we explore two competing explanations for this phenomenon: the Responsibility View and the Bias View. The Bias View, but not the Responsibility View, predicts features peripheral to the agent’s responsibility to impact causal attributions. In a series of three preregistered experiments (N = 1162), we present new evidence that (...) the Norm Effect arises from such peripheral features, namely from nonpertinent or entirely silly norm violations. Furthermore, we show that this effect cannot be explained by recourse to the agent’s foreknowledge or desire of the outcome, nor by its foreseeability: the Norm Effect arises even when participants judge the norm-violating agent’s doing as equally foreseeable. This, we argue, provides evidence in favour of the Bias View. (shrink)

This Element offers a new account of the philosophical significance of logical empiricism that relies on the past forty years of literature reassessing the project. It argues that while logical empiricism was committed to empiricism and did become tied to the trajectory of analytic philosophy, neither empiricism nor logical analysis per se was the deepest philosophical commitment of logical empiricism. That commitment was, rather, securing the scientific status of philosophy, bringing philosophy into a scientific conception of the world.

Why do scientists do experiments? What do their experiments reveal? Scientifically, can we decide what to believe? Is evolution a scientific theory? Such apparently simple questions are brilliantly investigated by celebrated philosopher and professor Alan Musgrave in order to interrogate the worldviews we inhabit - and their consequences. Musgrave brings to these questions an expansive historical knowledge, provoking readers to enter the now-discredited belief-systems of earlier ages in order to compare these with their own beliefs. Discursive, entertaining, and provocative, (...) Secular Sermons contains fourteen essays by Musgrave - New Zealand's leading contemporary philosopher - examining the basic assumptions of science, religion, and mathematics. The book is an insightful introduction to the philosophical thought of Aristotle, Bacon, Copernicus, Galileo, Newton, Herschel, Darwin, and Einstein, among others. It puts modern science in a broader historical perspective and offers an entertaining introduction to the philosophical paradigm of Critical Rationalism. (shrink)

Misunderstanding Science? offers a challenging new perspective on the public understanding of science. In so doing, it also challenges existing ideas of the nature of science and its relationships with society. Its analysis and case presentation are highly relevant to current concerns over the uptake, authority, and effectiveness of science as expressed, for example, in areas such as education, medical/health practice, risk and the environment, technological innovation. Based on several in-depth case-studies, and informed theoretically by the sociology of scientific knowledge, (...) the book shows how the public understanding of science questions raises issues of the epistemic commitments and institutional structures which constitute modern science. It suggests that many of the inadequacies in the social integration and uptake of science might be overcome if modern scientific institutions were more reflexive and open about the implicit normative commitments embedded in scientific cultures. (shrink)

Marx's Rebellion Against Lenin is a representative of the contemporary revitalization of the thought of Marx. It fulfils this task in three ways. First, it overthrows the dialectical materialism of Engels and of Stalinist Bolshevism by exploring 18th century historical thought and illustrating how these Enlightenment historians and political theorists first explored method of historical explanation that were later adopted by Marx. It is shown that contrary to the theory of Stalinist Bolshevism, Hegel was a vital influence on Marx. Second, (...) Levine's book represents Marx as an exponent of Classical Humanism. Marx did not define communism as a form of materialism, as economic egalitarianism, but rather related communism to the Classical ethics of Aristotle, to the Aristotelian ideas of polis citizenship and the ethics of distributive justice. Third, it is argued that the 17th and 18th Century Enlightenment was not simply a liberal center extolling property, individual rights and capitalism. Instead it is shown that the 17th and 18th century Enlightenment was divided between an Enlightenment Center and an Enlightenment Left, with the Enlightenment Left challenging the domination of capitalism and private property. Marx's Rebellion Against Lenin traces the flow of the theories of the Enlightenment Left into Marx and in doing so liberates Marxist thought from its imprisonment in 19th century materialism and relocates it within the traditions of Classical Humanism. (shrink)

Katrina Forrester’s book poses a problem for any reviewer that, I suspect, will be reflected in the experience of its readers. Unusually, the author is equally.

If Savulescu and Kahane’s Principle of Procreative Beneficence were implemented regarding cognitive enhancement, the result would be highly impoverishing for future children. For, apart from being inadequate to rationality itself, advocates’ accounts of cognitive enhancement sever reason from the input to judgments and decision-making that other faculties provide. When handling desire, supporters of cognitive enhancement frame conflicts between reason and the nonrational in terms of self-governance or akratic failure, depending on which one triumphs. Further, so-called negative emotions are treated as (...) simply deleterious and hostile to the rational. Alliances of the nonrational with reason toward shared ends are hence unthinkable. Having critiqued advocates’ views directly, I amplify my assessment through engagement with Aristotle’s Nicomachean Ethics. Per Savulescu and Kahane, to know how to direct enhancement endeavors, “we need to form reasonable opinions on difficult questions about the nature of well-being and the good life.” Thus far, however, enhancement supporters have been largely silent on this crucial matter. Because the debate over enhancement is ultimately over what values our views of flourishing embody, it should be recast so that this crux is squarely at the fore. What is more, for our own and our children’s sakes, as we embark on this reframing, we would do well to bear in mind Aristotle’s insights about the nonrational in relation to reason and his unwavering focus on the human “that for the sake of which” (hou heneka) all that we do is, perforce, undertaken. (shrink)

How we assess current calls for vigorous, or “radical”, enhancement through befitting procreative choices depends in part on the plausibility of supporters’ rejecting all substantive ties between their views and earlier eugenics. When denying such connections, today’s advocates of vigorous enhancement routinely emphasize that enhancement decisions would stem from individuals and families, not the state. In a multipronged critique, I show the untenability of transhumanists’ denials.

A selection of speeches and essays from the author's second decade as president of Yale University.

We are all concerned by the environmental threats facing us today. Environmental issues are a major area of concern for policy makers, industrialists and public groups of many different kinds. While science seems central to our understanding of such threats, the statements of scientists are increasingly open to challenge in this area. Meanwhile, citizens may find themselves labelled as "ignorant" in environmental matters. In Citizen Science Alan Irwin provides a much needed route through the fraught relationship between science, the (...) public and the environmental threat. (shrink)