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)

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)

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)

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 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.

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)

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)

Through a glass darkly / Joshua Mitchell -- Skepticism, self, and toleration in Montaigne's political thought / Alan Levine -- French free-thinkers in the first decades of the Edict of Nantes / Maryanne Cline Horowitz -- Descartes and the question of toleration / Michael Gillepsie -- Toleration and the skepticism of religion in Spinoza's Tractatus Theologico-Politicus / Steven B. Smith -- Monopolizing faith / Alan Houston -- Skepticism and toleration in Hobbes' political thought / Shirley Letwin -- John (...) Locke and the foundations of toleration / Nathan Tarcov -- Pierre Bayle's atheist politics / Kenneth R. Weinstein -- Of believers and barbarians / Diana Schaub -- Tolerant skepticism of Voltaire and Diderot / Patrick Riley. (shrink)

When do two sentences say the same thing, that is, express the same content? We defend two-component (2C) semantics: the view that propositional contents comprise (at least) two irreducibly distinct constituents, (1) truth-conditions, and (2) subject-matter. We contrast 2C with one-component (1C) semantics, focusing on the view that subject-matter is reducible to truth- conditions. We identify exponents of this view and argue in favor of 2C. An appendix proposes a general formal template for propositional 2C semantics.

Alan Gross applies the principles of rhetoric to the interpretation of classical and contemporary scientific texts to show how they persuade both author and audience. This invigorating consideration of the ways in which scientists--from Copernicus to Darwin to Newton to James Watson--establish authority and convince one another and us of the truth they describe may very well lead to a remodeling of our understanding of science and its place in society.

I argue that metaphysical views of material objects should be understood as 'packages', rather than individual claims, where the other parts of the package include how the theory addresses 'recalcitant data', and that when the packages meet certain general desiderata - which all of the currently competing views *can* meet - there is nothing in the world that could make one of the theories true as opposed to any of the others.

The first book length study of property-owning democracy, Republic of Equals argues that a society in which capital is universally accessible to all citizens is uniquely placed to meet the demands of justice. Arguing from a basis in liberal-republican principles, this expanded conception of the economic structure of society contextualizes the market to make its transactions fair. The author shows that a property-owning democracy structures economic incentives such that the domination of one agent by another in the market is structurally (...) impossible. The result is a renovated form of capitalism in which the free market is no longer a threat to social democratic values, but is potentially convergent with them. It is argued that a property-owning democracy has advantages that give it priority over rival forms of social organization such as welfare state capitalism and market socialist institutions. The book also addresses the currently high levels of inequality in the societies of the developed West to suggest a range of policies that target the "New Inequality" of our times. For this reason, the work engages not only with political philosophers such as John Rawls, Philip Pettit and John Tomasi, but also with the work of economists and historians such as Anthony B. Atkinson, François Bourguignon, Jacob S. Hacker, Lane Kenworthy, and Thomas Piketty. (shrink)

These paperback editions preserve the original texts of these important books while presenting them in durable paperback editions.

One obvious solution to the puzzles of apparently coincident objects is a sort of reductionism - the tree really just is the wood, the statue is just the clay, and nothing really ceases to exist in the purported non-identity showing cases. This paper starts with that approach and its underlying motivation, and argues that if one follows those motivations - specifically, the rejection of coincidence, and the belief that 'genuine' object-destroying changes must differ non-arbitrarily from accidental changes, that one can (...) plausibly be pushed to an extreme nihilism, that denies the existence of any objects at all. (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)

The debate over moral bioenhancement has incrementally intensified since 2008, when Persson and Savulescu, and Douglas wrote two separate articles on the reasons why enhancing human moral capabilities and sensitivity through technological means was ethically desirable. In this article, we offer a critique of how Persson and Savulescu theorize about the possibility of moral bioenhancement, including the problem of weakness of will, which they see as a motivational challenge. First, we offer a working definition of moral bioenhancement and underscore some (...) of the challenges in determining whether moral bioenhancement, as conceptualized by Persson and Savulescu, falls into the category of enhancement or constitutes a type of therapeutic intervention. Second, we provide a critical analysis of the way Persson and Savulescu pathologize human behavior in relation to what they see as the main threat to the survival of the human species: weak moral motivation. Next, we critique the claim that the use of genetic manipulation and drug treatment will increase moral motivation. We argue that Persson and Savulescu mischaracterize the nature of human moral psychology because moral motivation includes affective and cognitive dimensions. The type of interventions they envision focus almost exclusively on the former. In the final two sections, we outline three main criticisms of moral bioenhancement and offer a more robust account of moral psychology and moral development than what Persson and Savulescu recommend, through the lens of Aristotle’s work on virtue ethics. Ultimately, we argue that what Persson and Savulescu, and Douglas consider as moral bioenhancement is a misnomer because they do not fully account for the complexity of moral agency. (shrink)

In this essay I will argue, as does Bernard Williams, that lying and misleading are both commonly wrong because they involve an aim to breach a trust. I will also argue, contrary to Williams, that lying and misleading threaten trust differently, and that when they are wrong, they are wrong differently. Indeed, lying may be wrong when misleading is not.

Some philosophical accounts imply that masturbation is inferior sexual activity. Against this, Soble argues that masturbation is central. Relying on the physical-anatomical indistinguishability of sexual act-types, he derives a Zeno-style paradox about sexual activity: either all sexual activity (even ordinary coitus) is masturbatory or none of it is (not even solitary masturbation). Soble argues for the first horn of the dilemma, thus ensuring that solitary masturbation is a member of the continuum of sexual activities. Going beyond anatomy, Soble also argues (...) that the central psychological features of paired sexual activity are normally exhibited also by solitary masturbation, which further establishes that solitary masturbation is on the continuum of sexual activity. Altogether, Soble's arguments support a "unary" model of sexuality, compelling us to take seriously the genuine sexual nature of solitary masturbation, a result that is important for the philosophy of sex, the scientific study of sexuality, and the politics of human sexuality. (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)

Sentences \(\varphi\) and \(\psi\) are _cognitive synonyms_ for one when they play the same role in one’s cognitive life. The notion is pervasive (Sect. 1 ), but elusive: it is bound to be hyperintensional (Sect. 2 ), but excessive fine-graining would trivialize it and there are reasons for some coarse-graining (Sect. 2.1 ). Conceptual limitations stand in the way of a natural algebra (Sect. 2.2 ), and it should be sensitive to subject matters (Sect. 2.3 ). A cognitively adequate individuation (...) of content may be intransitive (Sect. 3 ) due to ‘dead parrot’ series: sequences of sentences \(\varphi _1, \ldots, \varphi _n\) where adjacent \(\varphi _i\) and \(\varphi _{i+1}\) are cognitive synonyms while \(\varphi _1\) and \(\varphi _n\) are not (Sect. 3.1 ). Finding an intransitive account is hard: Fregean equipollence won’t do (Sect. 3.2 ) and a result by Leitgeb shows that it wouldn’t satisfy a minimal compositionality principle (Sect. 3.3 )._Sed contra_, there are reasons for transitivity, too (Sect. 3.4 ). In Sect. 4, we come up with a formal semantics capturing this jumble of desiderata, thereby showing that the notion is coherent. In Sect. 5, we re-assess the desiderata in its light. (shrink)

This essay offers a philosophical defense of deception about reservation prices in business negotiation. Its discussion is prompted by arguments that Charles N.C. Sherwood makes in a recent issue of Business Ethics Quarterly and develops ideas I put forward in an earlier issue of Business Ethics Quarterly. The essay argues that although reservation price deception cannot be justified by appeal to the consent of negotiating parties, it can be justified by appeal to a separate but related notion, assumption of risk, (...) as long as the assumption of risk occurs in a suitably fair context. (shrink)

This introductory textbook is an overview of the nature and the ethics of the many aspects of sex and love"--Provided by publisher.

Free Speech is a philosophical treatment of a topic which is of immense importance to all of us. Writing with great clarity, wit, and genuine concern, Alan Haworth situates the main arguments for free speech by tracing their relationship to contemporary debates in politics and political philosophy, and their historical roots to earlier controversies over religious toleration. Free Speech will appeal to anyone with an interest in philosophy, politics and current affairs.

Neo-Fregeans argue that substantial mathematics can be derived from a priori abstraction principles, Hume's Principle connecting numerical identities with one:one correspondences being a prominent example. The embarrassment of riches objection is that there is a plurality of consistent but pairwise inconsistent abstraction principles, thus not all consistent abstractions can be true. This paper considers and criticizes various further criteria on acceptable abstractions proposed by Wright settling on another one—stability—as the best bet for neo-Fregeans. However, an analogue of the embarrassment of (...) riches objection resurfaces in the metatheory and I conclude by arguing that the neo-Fregean program, at least insofar as it includes a platonistic ontology, is fatally wounded by it. (shrink)

The text- and argument-focused histories of philosophy that we have are mainly interested in teasing out the details of the positions taken on philosophical issues by individual philosophers. But this is a long way from having a historical explanation of the larger-scale trajectory of philosophical development. An empirical history of philosophy, however, examines the institutionalized places and venues for philosophical work that provide a rich, shared structure for the promotion of particular sorts of work. Mid-twentieth-century philosophers of science such as (...) Herbert Feigl and Philipp Frank knew what they were doing—they were creating the space to promote certain sorts of work in venues such as the Institute for the Unity of Science and the Minnesota Center for Philosophy of Science and, ultimately, in publication venues such as Daedalus and the Minnesota Studies in Philosophy of Science. Here the engine of progress is the institution-building activity of committed philosophers making a space within the institutional structures of philosophy for their own projects and other projects aligned with them and transmitting these as live philosophical projects to the next generation. (shrink)