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)

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)

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)

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)

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)

What is the basis for arguing that a volunteer army exploits citizens who lack civilian career opportunities? How do we determine that a doctor who has sex with his patients is exploiting them? In this book, Alan Wertheimer seeks to identify when a transaction or relationship can be properly regarded as exploitative--and not oppressive, manipulative, or morally deficient in some other way--and explores the moral weight of taking unfair advantage. Among the first political philosophers to examine this important topic (...) from a non-Marxist perspective, Wertheimer writes about ordinary experience in an accessible yet philosophically penetrating way. He considers whether it is seriously wrong for a party to exploit another if the transaction is consensual and mutually advantageous, whether society can justifiably prohibit people from entering into such a transaction, and whether it is wrong to allow oneself to be exploited. Wertheimer first considers several contexts commonly characterized as exploitive, including surrogate motherhood, unconscionable contracts, the exploitation of student athletes, and sexual exploitation in psychotherapy. In a section outlining his theory of exploitation, he sets forth the criteria for a fair transaction and the point at which we can properly say that a party has consented. Whereas many discussions of exploitation have dealt primarily with cases in which one party harms or coerces another, Wertheimer's book focuses on what makes a mutually advantageous and consensual transaction exploitive and analyzes the moral and legal implications of such exploitation. (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.

David Levine and Mathew Bowker explore cultural and political trends organized around the conviction that the world we live in is a dangerous place to be, that it is dominated by hate and destruction, and that in it our primary task is to survive by carrying on a life-long struggle against hostile forces. Their method involves the analysis of public fantasies to reveal their hidden meanings. The central fantasy explored is the fantasy of a destroyed world, which appears most (...) commonly in the form of post-apocalyptic and dystopian narratives. Their special concern in the book is with defenses against the painful consequences of the dominance of this fantasy in the inner world, especially defenses involving the use of guilt to assure that something can be done to repair the destroyed world. Topics explored include: the formation of internal fortresses and their projection into the world outside, forms of guilt including bystander guilt and survivor guilt, the loss of and search for home, and manic forms of reparation. (shrink)

This paper explores how phenomenological notions of rhythm might accommodate a richer description of preverbal infant-caregiver dialogue. Developmental psychologists have theorized a crucial link between rhythm and intercorporeality in the emergence of intersubjectivity and self. Drawing on the descriptions of rhythm in the phenomenology of Maurice Merleau-Ponty, Erwin Straus, Henri Maldiney and Maxine Sheets-Johnstone, the paper emphasizes the role of art and aesthetic processes proposing that they not only be considered as metaphorical or representational aspects of rhythm but as primary (...) resources that can enrich and deepen our understanding of self-emergence and intercorporeality in preverbal infant-caregiver dialogue. (shrink)

Introduction: Natural necessity, being, and becoming -- Accentuate the negative -- Diffracting dialectic -- Opening totality -- Constellating ethics -- Metacritique I : philosophy's primordial failing -- Metacritique II : dialectic and difference -- Conclusion: Natural necessity and the grounds of justice : natural necessity as material meshwork.

Introduction: sustainable critique and the lost vocation of international relations -- "For we born after:" the challenge of sustainable critique -- Sustainable critique and critical IR theory: against emancipation -- The realist dilemma: politics and the limits of theory -- Communitarian IR theory -- Individualist IR theory: disharmonious cooperation -- Conclusion: toward sustainably critical international theory.

According to transhumanists who urge the radical enhancement of human beings, humanity’s top priority should be engineering “posthumans,” whose features would include agelessness. Increasingly, transhumanism is critiqued on foundational grounds rather than based largely on anticipated results of its implementation, such as rising social inequality. This expansion is crucial but insufficient because, despite its radical aim, transhumanism reflects beliefs and attitudes that are evident in the broader culture. With a focus on the yearning to eliminate aging, I consider four of (...) these: a disproportionate reliance on science and technology to address major human challenges; the conceptualization of human beings in terms of binaries like “young-old”; a repudiation of vulnerability; and intensifying perfectionism. Illuminating these interlocked commitments both deepens an existing critique of transhumanism and draws our attention to deleterious cultural views that must be vigorously contested if our commitment to human flourishing is to be deep and unwavering. (shrink)

Alan H. Goldman argues for the internalist or subjectivist view of practical reasons on the grounds that it is simpler, more unified, and more comprehensible ...

In a discussion of rule-following inspired by Wittgenstein, Kripke asks us to consider the relation which holds between meaning plus by ‘+’ and answering questions like, ‘What is the sum of 68 and 57?’. A dispositional theory has it that if you mean plus by ‘+’ then you will probably answer, ‘125’. That is because, according to such a theory, to mean plus by ‘+’is, roughly speaking, to be disposed, by and large, and among other things, to answer such questions (...) with the correct sum. Kripke wants to emphasize, by contrast, that if you mean plus by ‘+’ then, faced with the question, ‘What is 68 + 57?’ yououghtto answer, ‘125’. One could sum up the assumption about meaning which appears to underpin this criticism of dispositional theories in terms of the slogan that meaning is normative. Allan Gibbard gives us a way of reading that slogan which is suggested by Kripke's brief remarks:The crux of the slogan that meaning is normative … might be another slogan: thatmeansimpliesought. To use roughly Kripke's example, from statements saying what I mean by the plus sign and other arithmetic terms and constructions, it will follow that Ioughtto answer ‘7’ when asked ‘What's 5 + 2?’. (shrink)

Four important arguments for probabilism—the Dutch Book, representation theorem, calibration, and gradational accuracy arguments—have a strikingly similar structure. Each begins with a mathematical theorem, a conditional with an existentially quantified consequent, of the general form: if your credences are not probabilities, then there is a way in which your rationality is impugned. Each argument concludes that rationality requires your credences to be probabilities. I contend that each argument is invalid as formulated. In each case there is a mirror-image theorem and (...) a corresponding argument of exactly equal strength that concludes that rationality requires your credences not to be probabilities. Some further consideration is needed to break this symmetry in favour of probabilism. (shrink)

This article argues that we could improve the design of research protocols by developing an awareness of and a responsiveness to the social contexts of all the actors in the research enterprise, including subjects, investigators, sponsors, and members of the community in which the research will be conducted. ?Social context? refers to the settings in which the actors are situated, including, but not limited to, their social, economic, political, cultural, and technological features. The utility of thinking about social contexts is (...) introduced and exemplified by the presentation of a hypothetical case in which one central issue is limitation of the probability of injury to subjects by selection of individuals who are not expected to live long enough for the known risks of the study to become manifest as harms. Benefits of such considerations may include enhanced subject satisfaction and cooperation, community acceptance, and improved data quality, among other desirable consequences. (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).

Explores language and mysticism, Buddhism and Zen, Christianity, comparative religion, psychedelics, and psychology and psychotherapy. Gold Winner for Philosophy, 2017 Foreword INDIES Book of the Year Awards To commemorate the 2015 centenary of the birth of Alan Watts (1915–1973), Peter J. Columbus and Donadrian L. Rice have assembled a much-needed collection of Watts’s scholarly essays and lectures. Compiled from professional journals, monographs, scholarly books, conferences, and symposia proceedings, the volume sheds valuable light on the developmental arc of Watts’s thinking (...) about language and mysticism, Buddhism and Zen, Christianity, comparative religion, psychedelics, and psychology and psychotherapy. This definitive collection challenges Watts’s reputation as a “popularizer” or “philosophical entertainer,” revealing his concerns to be much more expansive and transdisciplinary than is suggested by the parochial “Zen Buddhist” label commonly affixed to his writings. The editors’ authoritative introduction elucidates contemporary perspectives on Watts’s life and work, and supports a bold rethinking of his contributions to psychology, philosophy, and religion. Peter J. Columbus is Administrator of the Shantigar Foundation in Rowe, Massachusetts. Donadrian L. Rice is Professor of Psychology at the University of West Georgia. Together they are the coeditors of Alan Watts—Here and Now: Contributions to Psychology, Philosophy, and Religion, also published by SUNY Press. (shrink)

This paper lays out the basic structure of any view involving coincident entities, in the light of the grounding problem. While the account is not novel, I highlight fundamental features, to which attention is not usually properly drawn. With this in place, I argue for a number of further claims: The basic differences between coincident objects are modal differences, and any other differences between them need to be explained in terms of these differences. More specifically, the basic difference is not (...) a difference in sort. A number of recent defenses of coincidence, which share the basic structure I outline, misidentify what, in their accounts, plays the basic role of addressing the grounding problem. More tentatively, I argue Coincident entities differ only in these modal properties, and properties they entail. In particular, they do not differ in properties like ‘being a tree,’ ‘being a statue,’ or aesthetic properties, and finally in light of how the account of coincidence offered addresses the grounding problem, the grounding problem provides no reason to prefer monism to pluralism. (shrink)

Pragmatism established a philosophical presence over a century ago through the work of Charles Peirce, William James and John Dewey, and has enjoyed an unprecedented revival in recent years owing to the pioneering efforts of Richard Rorty and Hilary Putnam. The essays in this volume explore the history and themes of classic pragmatism, discuss the revival of pragmatism and show how it engages with a range of areas of inquiry including politics, law, education, aesthetics, religion and feminism. Together they provide (...) readers with an overview of the richness and vitality of pragmatist thinking and the influence that it continues to exert both in philosophy and other disciplines. The volume will be of interest to students and scholars of pragmatism, American philosophy and political theory. (shrink)

This volume offers the first substantial study of Heidegger’s phenomenology of perception, focusing on perception as capacities that can be developed in learning processes, notably in ways befitting ontological mindfulness. The author proposes new interpretations of Heidegger’s five most important key words.

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)