The transcription factor Pax5 is essential for the initial commitment of hematopoietic progenitors to the B cell lineage. Recently, our understanding of the lineage commitment process has been extended with the finding that Pax5 is also continuously required throughout B cell development to reinforce commitment, as inactivation of Pax5 in mature B cells results in their de‐differentiation to a progenitor stage that is capable of multi‐lineage potential.1 The reliance of B cell identity on a single gene is not without its (...) problems as the loss of Pax5 results in B cell malignancies in mouse models and mutation in human PAX5 is the most‐common genetic lesion in acute lymphoblastic leukemia. BioEssays 30:203–207, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The result is nothing less than a fundamental reorientation of moral theory that enables it at last to account for morality's supreme authority--an account that ...

My aim in what follows is to sketch with a broad brush fundamental changes involving the concept of obligation in British ethics of the early modern period, as it developed in the direction of the view that obligatory force is a species of motivational force – an idea that deeply informs present thought. I shall also suggest, although I can hardly demonstrate it conclusively here, that one important source for this view was a doctrine which we associate with Kant, and (...) which it may seem surprising to find in British ethics, especially of the early modern period, viz., that rational agents are obligated by motives available through a form of practical thinking necessary for rational autonomy. (shrink)

What are ethical judgments about? And what is their relation to practice? How can ethical judgment aspire to objectivity? The past two decades have witnessed a resurgence of interest in metaethics, placing questions such as these about the nature and status of ethical judgment at the very center of contemporary moral philosophy. Moral Discourse and Practice: Some Philosophical Approaches is a unique anthology which collects important recent work, much of which is not easily available elsewhere, on core metaethical issues. Reinvigorated (...) naturalist moral realism and the various versions of moral realism, as well as irrealist, expressivist, and neo-Kantian constructivist theories are all represented in this fine collection, constituting a rich array of approaches to contemporary moral philosophy's most fundamental debates. An extensive introduction by Darwall, Gibbard, and Railton is also included, making this volume the most comprehensive and up-to-date work of its kind. Moral Discourse is ideally suited for use in courses in contemporary ethics, ethical theory, and metaethics. (shrink)

In these essays Stephen White examines the forms of psychological integration that give rise to self-knowable and self-conscious individuals who are responsible, concerned for the future, and capable of moral commitment. The essays cover a wide range of basic issues in philosophy of mind, metaphysics, moral psychology, and political philosophy, providing a coherent, sophisticated, and forcefully argued view of the nature of the self. Beginning with mental content and ending with Rawls and utilitarianism, each essay argues a distinctive line. (...) Together they are a unified and powerful philosophical position of considerable scope, one that provides a unique vision of the mind, consciousness, personhood, and morality. White argues that the unity of the self revealed in personal identity and moral responsibility is best understood in normative terms. Basic to such features of the self are the patterns of self-concern in which they are characteristically displayed and the internal justification that supports such concern. The treatment of intentionality and consciousness that grounds this account emphasizes privileged selfknowledge and practical rationality and their corresponding contributions to the unity of the self. A final source of unity emerges from the analysis of our fundamental commitments, an analysis that ensures a central place in moral theory for the notion of the self. (shrink)

This book is a major work in the history of ethics, and provides the first study of early modern British philosophy in several decades. Professor Darwall discerns two distinct traditions feeding into the moral philosophy of the seventeenth and eighteenth centuries. On the one hand, there is the empirical, naturalist tradition, comprising Hobbes, Locke, Cumberland, Hutcheson, and Hume, which argues that obligation is the practical force that empirical discoveries acquire in the process of deliberation. On the other hand, there is (...) a group including Cudworth, Shaftesbury, Butler, and in some moments Locke, which views obligation as inconceivable without autonomy and which seeks to develop a theory of the will as self-determining. (shrink)

In this paper I distinguish three alternatives to the functionalist account of qualitative states such as pain. The physicalist-functionalist holds that (1) there could be subjects functionally equivalent to us whose mental states differed in their qualitative character from ours, (2) there could be subjects functionally equivalent to us whose mental states lacked qualitative character altogether and (3) there could not be subjects like us in all objective respects whose qualitative states differed from ours. The physicalist-functionalist holds (1) and (3) (...) but denies (2). The transcendentalist holds (1) and (2) and denies (3). I argue that both versions of physicalist-functionalism inherit the problem of property dualism which originally helped to motivate functionalist theories of mind. I also argue that neither version of physicalist-functionalism can distinguish in a principled way between those neurophysiological properties of a subject which are relevant to the qualitative character of that subject's mental states and those which are not. I conclude that the only alternative to a functionalist account of qualitative states is a transcendentalist account and that this alternative is not likely to appeal to the critics of functionalism. (shrink)

have come in for increasing attention and controversy. A good example would be recent debates about moral realism where question of the relation between ethics (or ethical judgment) and the will has come to loom large.' Unfortunately, however, the range of positions labelled internalist in ethical writing is bewilderingly large, and only infrequently are important distinctions kept clear.2 Sometimes writers have in mind the view that sincere assent to a moral (or, more generally, an ethical) judgment concerning what one should (...) do is necessarily connected to motivation (actual or dispositional).s This necessity may be conceptual, or perhaps metaphysical, the thought being.. (shrink)

Elizabeth Anscombe famously argued that "modern moral philosophy" centrally involved unsupported notions of obligation and culpability. Modern Moral Philosophy: From Grotius to Kant exhibits, for the first time, resources that modern moral philosophers had to respond to Anscombe's challenge, also enhancing our own philosophical grasp of morality and its foundations.

"Both Thomistic scholars and analytic philosophers interested in theories of human action and accountability will find this book a welcome addition to their libraries. Truly a substantive addition to both Thomistic scholarship and the ongoing analytic investigation into human action and responsible agency."—American Catholic Philosophical Quarterly "A first-rate book...Brock's lucid and illuminating analysis offers much of value to both intellectual historians and theologians, as well as philosophers."—Theological Studies"Brock's treatment of Aquinas's account of action exhibits a rare combination of rigor and (...) learning. It is, no doubt, the best we have."—The Thomist. (shrink)

Two characterizations are given of those structural consequence operations on a propositional language which can be defined via proofs from a finite number of polynomial rules.

James Madison is the thinker most responsible for laying the groundwork of the American commercial republic. But he did not anticipate that the propertied class on which he relied would become extraordinarily politically powerful at the same time as its interests narrowed. This and other flaws, argues Stephen L. Elkin, have undermined the delicately balanced system he constructed. In Reconstructing the Commercial Republic , Elkin critiques the Madisonian system, revealing which of its aspects have withstood the test of time (...) and which have not. The deficiencies Elkin points out provide the starting point for his own constitutional theory of the republic—a theory that, unlike Madison’s, lays out a substantive conception of the public interest that emphasizes the power of institutions to shape our political, economic, and civic lives. Elkin argues that his theory should guide us toward building a commercial republic that is rooted in a politics of the public interest and the self-interest of the middle class. He then recommends specific reforms to create this kind of republic, asserting that Americans today can still have the lives a commercial republic is intended to promote: lives with real opportunities for economic prosperity, republican political self-government, and individual liberty. (shrink)

This chapter defends the property dualism argument. The term “semantic premise” mentioned is used to refers to an assumption identified by Brian Loar that antiphysicalist arguments, such as the property dualism argument, tacitly assume that a statement of property identity that links conceptually independent concepts is true only if at least one concept picks out the property it refers to by connoting a contingent property of that property. It is argued that, the property that does the work in explaining the (...) possibility of a posteriori identities need not be a first-order property of the referent in question. On his view, the property dualism argument requires only a weaker semantic premise, which allows that the property in question be a higher order property. A refined version of the property dualism argument is formulated, which uses the weaker premise, and defends the argument against various objections. (shrink)

Varying conceptions of and purposes for dialogue exist. Recent dialogic theorists and advocates urge exploration of forms of dialogue for learning and applying relational responsibilities within stakeholder networks. A related phenomenon has been the recent emergence of multi-stakeholder dialogues that involve parties significantly affected by major issues or concerns, such as environmental sustainability, that have complex and wide-spread implications. The extent to which these recent multi-stakeholder dialogues assume anything resembling the relationship or caring and the learning potentials of dialogic goals (...) and processes suggested by recent advocates, however, can certainly be questioned. This article explores potential directions for research on enhanced forms of multi-stakeholder dialogues that emphasize goals of dialogic learning, relationship building, and business social responsiveness within a more reflective practice of corporate citizenship. Many issues and questions concerning appropriate antecedents, processes, and outcomes for these enhanced multi-stakeholder dialogues are raised and discussed. (shrink)

Various measures related to individual values, ethical attitudes and moral reasoning exist and are being increasingly applied for research in business and professional ethics. The England Personal Values Questionnaire, the Rokeach Value Survey, and Rest's Defining Issues Test have received stronger support and application for management and organizational behavior research than other instruments, such as Gordon's Survey of Personal Values and Hogan's Survey of Ethical Attitudes. Beyond research usage, many of these measures offer potential for instructional purposes. Knowledge of the (...) characteristics and limitations of values and ethics-related measures allows business educators to make better selections of possible supplements to traditional instructional methods. (shrink)

_ Virtue Ethics_ collects, for the first time, the main classical sources and the central contemporary expressions of virtue ethics approach to normative ethical theory. Edited and introduced by Stephen Darwall, these readings are essential for anyone interested in normative theory. Introduced by Stephen Darwall, this collection brings together classic and contemporary readings which define and advance the literature on virtue ethics. Includes six essays which respond to the classic sources. Includes a contemporary discussion on character and virtue (...) by Gary Watson. Includes classic essays by Aristotle, Francis Hutcheson and David Hume, and recent reactions to this work by philosophers including Philippa Foot, John McDowell, Alasdair MacIntyre, Annette Baier, Rosalind Hursthouse, and Michael Slote. (shrink)

Stephen Darwall presents a series of essays that explore the Second-Person Standpoint --an argument which advances an analysis of central moral concepts as irreducibly second personal in the sense of entailing mutual accountability and the authority to address demands. He illustrates the power of the second-personal framework to illuminate a wide variety of issues in moral, political, and legal philosophy. Section I concerns morality: for example, its distinctiveness among normative concepts, the relation between 'bipolar' obligations and moral obligation period, (...) and whether morality requires general principles. Section II focuses on autonomy, its relation to the will, and the sense in which we can give ourselves reasons for acting. And Section III concerns the nature of authority and the law. It argues that only a second-personal framework is able to explain these and the differences between criminal and civil law. (shrink)

A host of metabolic enzymes reversibly self‐assemble to form membrane‐less, intracellular filaments under normal physiological conditions and in response to stress. Often, these enzymes reside at metabolic control points, suggesting that filament formation affords an additional regulatory mechanism. Examples include cytidine‐5′‐triphosphate (CTP) synthase (CTPS), which catalyzes the rate‐limiting step for the de novo biosynthesis of CTP; inosine‐5′‐monophosphate dehydrogenase (IMPDH), which controls biosynthetic access to guanosine‐5′‐triphosphate (GTP); and ∆1‐pyrroline‐5‐carboxylate (P5C) synthase (P5CS) that catalyzes the formation of P5C, which links the Krebs (...) cycle, urea cycle, and proline metabolism. Intriguingly, CTPS can exist in co‐assemblies with IMPDH or P5CS. Since GTP is an allosteric activator of CTPS, the association of CTPS and IMPDH filaments accords with the need to coordinate pyrimidine and purine biosynthesis. Herein, a hypothesis is presented furnishing a biochemical connection underlying co‐assembly of CTPS and P5CS filaments – potent inhibition of CTPS by glutamate γ‐semialdehyde, the open‐chain form of P5C. (shrink)

Between the later views of Wittgenstein and those of connectionism 1 on the subject of the mastery of language there is an impressively large number of similarities. The task of establishing this claim is carried out in the second section of this paper.

The formulation is persuasive. Yet clearly it does assert a necessary connection between any occurrence and its antecedents. In order for a different result to occur, there has to be a corresponding difference in the antecedents. This means that from any determinate set of antecedents, a single determinate result must follow. It is a formula for determinism. Anscombe wants to caution us not to take what it says for granted.

The art of interpretation has traditionally been an integral part of medical practice, but little attention has been devoted to its theory. Hermeneutics or the study of interpretation has grown as a methodological interest primarily within the humanities. Borrowing from the medieval fourfold sense of scripture, which organizes interpretive activity both logically and comprehensively, I propose a hermeneutical model of clinical decision-making. According to the model, a patient is analogous to a literary text which may be interpreted on four levels: (...) (1) the literal facts of the patient's body and the literal story told by the patient, (2) the diagnostic meaning of the literal data, (3) the praxis (prognosis and therapeutic decisions) emanating from the diagnosis, and (4) the change effected by the clinical encounter in both the patient's and clinician's life-worlds. The model is illustrated through application to a medical case. (shrink)

There are two ways in which philosophical controversialists can approach a classical opponent of their views. They can attempt to refute him, or they can try to show that, while generally assumed to be an opponent, the philosopher really was not, at least when he was thinking clearly. Of these two strategies, the latter, if it can be pulled off, is dialectically..

This note concerns the ultraproduct construction. It is observed that in the class of SCI models ultraproducts may be constructed by a method apparently dierent from the standard one. Since the standard models of veryday model theory form a subclass of SCI models, one obtains a new view of ultraproducts. Aside from a few remarks, the paper is self-contained.

In _The New Constitutionalism_, seven distinguished scholars develop an innovative perspective on the power of institutions to shape politics and political life. Believing that constitutionalism needs to go beyond the classical goal of limiting the arbitrary exercise of political power, the contributors argue that it should—and can—be designed to achieve economic efficiency, informed democratic control, and other valued political ends. More broadly, they believe that political and social theory needs to turn away from the negativism of critical theory to consider (...) how a good society should be "constituted" and to direct the work of designing institutions that can constitute a "good polity," in both the economic and civic senses. Stephen L. Elkin and Karol Edward Soltan begin with an overview of constitutionalist theory and a discussion of the new constitutionalism within the broader intellectual and historical context of political and social thought. Charles Anderson, James Ceaser, and the editors then offer different interpretations of the central issues regarding institutional design in a constitutionalist social science, consider various ways of performing the task, and discuss the inadequacy of recent political science to the job it ought to be doing. The book concludes with essays by Ted Lowi, Cass Sunstein and Edwin Haefele which apply these themes to the American regime. (shrink)

To the Editor. A correction is necessary with respect to one of the articles in the Fall 1994 issue of the journal. In the article by Robert Fuentes et al., “Sentinel Effect of Drug Testing for Anabolic Steroid Abuse,” at page 228, the authors say, “…on May 2, 1994, the United States Supreme Court ruled that random drug tests violated the privacy rights of [various people] at the University of Colorado at Boulder…. The Court further stated….” No footnote is given, (...) and thus no citation to the case. The superscripted note at the end of the previous sentence is to an article in the NCAA News, “Court Rules Against Colorado Drug Policy.” The Supreme Court of the United States decided no such thing as what the authors state. If the reference is to a denial of review, the authors should have said something like, “The Supreme Court denied review to … leaving in place a ruling that….” A denial of review is not the Supreme Court ruling anything beyond the announcement that it will not hear a case; inferences can be drawn from the denial, but that is not what happened here: a flat statement—and an erroneous one—was made. Prof. Stephen L. Wasby Dept. of Political Science SUNY at Albany Ed. The authors cite the NCAA News accurately, and the reference refers to both courts; however, the NCAA News article in question fails to make the necessary distinction that Professor Wasby correctly points out. Our thanks to Professor Wasby for his remarks. (shrink)

There is a well-known line of thought, associated with Donald Davidson, that connects the notion of a perceptual given—of non-linguistic or non-conceptual experience of the world—with skepticism. Against this, I argue that the notion of what is given in perception leads to skepticism only on certain interpretations. I argue, in fact, that there must be perceptual experience such that there is “something it is like” to have it, or that would provide the subject of a phenomenological analysis, if we are (...) to block skepticism in its most radical forms. In particular, I claim that there is a distinctive phenomenology of the experience of agency. These phenomenological claims are conclusions of a transcendental argument according to which our having such experience is a condition of our having a meaningful language. Moreover, the same transcendental argument is sufficient to show the incoherence of radical skepticism about the external world. And I argue that the proper understanding of perceptual experience—as object involving—renders the standard objections to transcendental arguments ineffective. (shrink)