Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid sites shared (...) by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis. (shrink)

Modern logicians have sought to unlock the modal secrets of Aristotle's Syllogistic by assuming a version of essentialism and treating it as a primitive within the semantics. These attempts ultimately distort Aristotle's ontology. None of these approaches make full use of tests found throughout Aristotle's corpus and ancient Greek philosophy. I base a system on Aristotle's tests for things that can never combine (polarity) and things that can never separate (inseparability). The resulting system not only reproduces Aristotle's recorded results for (...) the apodictic syllogistic in the Prior Analytics but it also generates rather than assumes Aristotle's distinctions among 'necessary', 'essential' and 'accidental'. By developing a system around tests that are in Aristotle and basic to ancient Greek philosophy, the system is linked to a history of practices, providing a platform for future work on the origins of logic. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Journal of the History of Philosophy 41.4 (2003) 568-569 [Access article in PDF] James P. Scanlan. Dostoevsky the Thinker. Ithaca, NY: Cornell University Press, 2002. Pp. xiii + 251. Cloth, $29.95. Important works on Dostoevsky's life and thought abound, but James Scanlan offers the first comprehensive treatment and evaluation of Dostoevsky as a philosophical thinker. Scanlan uses Dostoevsky's thousands of letters, essays, and "capacious notebooks" (3), as well as (...) his literary work, to analyze systematically Dostoevsky's philosophical worldview and to argue for its coherence. Scanlan's commitment to careful scholarship is apparent throughout, including his translations of the texts. A philosopher himself, Scanlan contextualizes Dostoevsky's work in relation to traditional philosophers, including Descartes, Kant, and Kierkegaard. The result is a balanced, rich, and provocative treatment that also suggests new interpretations of some of Dostoevsky's literary works.If Bakhtin is right to describe Dostoevsky's novels as "polyphonic," how does one ascertain their author's position? Scanlan grants the challenges of approaching Dostoevsky as a philosopher. Nineteenth-century Russian thinkers rarely identified with particular philosophical schools, and Dostoevsky never thought of himself as a philosopher. Yet Dostoevsky was intensely interested in philosophy, and Scanlan argues that Dostoevsky's characters serve as surrogates for competing philosophical positions. Scanlan also reminds readers of Dostoevsky's often-neglected nonfiction works and weaves masterfully the nonfiction and the literature to support his argument.Echoing Bakhtin, Scanlan labels Dostoevsky's methodology "dialogical in style, monological in substance" (4). Doing so effectively rejects critical perspectives that suggest the author held contradictory positions. For Scanlan, Dostoevsky's dialectical method resulted from his preoccupation with combating others' ideas, implied by his frequent use of reductio ad absurdum arguments. Dostoevsky "sought to establish his own positions by demonstrating the failure of their antitheses" (231). Not only does Scanlan persuasively demonstrate the consistency of Dostoevsky's philosophical commitments, he also challenges the appropriation of Dostoevsky by existentialists as an "irrationalist," despite Dostoevsky's "convincing portrayals of human irrationality" and skepticism concerning rationality's powers (5).Scanlan examines Dostoevsky's vision of Christianity that included a strict binary of matter and spirit, and a rejection of rational egoism and mechanism (termed "nihilism"). Dostoevsky's positive deontologism, his "law of love" (with Christ as exemplar) was, for Dostoevsky, necessary to overcome the "law of personality," and conscience grounded in Christian love was the basis for salvation. Scanlan persuasively argues that Dostoevsky, if irrationalist, belongs more with Kant than Kierkegaard in viewing rationality as limited but not to be rejected wholesale. Scanlan uses this analysis to ground a provocative new reading of Notes from Underground.Scanlan also explores the connectedness of Dostoevsky's ethics and aesthetics in Dostoevsky's insistence that artists should create moral beauty beyond the purely aesthetic or cognitive. Much has been written about Dostoevsky's aesthetics, but Scanlan exposes its logical grounding in Dostoevsky's rejection of the subjective utilitarian aesthetics of Chernyshevsky and the radical materialism of Dobrolyubov. For Dostoevsky, the need for [End Page 568] beauty and creativity is intrinsic to human nature, and art serves an epistemological function that gestures toward reality, not as a "mindless photographer" (140) but as a cognitive vision penetrating "the core of his subject" (141). Dostoevsky also justified his use of the anomalous, noting that the exceptional might be "an avenue of access to the universal" (143).Dostoevsky's "dream of a community of perfect Christian brotherhood and love" (160) grounds Scanlan's examination of Dostoevsky's sociopolitical philosophy and his rejection of the critical view that Dostoevsky's politics radically changed over time. Though Scanlan agrees with biographers that Dostoevsky despised the "moral blight" (169) of serfdom, he argues that Dostoevsky's vision of Christian society permitted social stratification so long as service to masters was voluntary, cooperative, and rational. This analysis makes clear the distance between Dostoevsky and Western liberal political theorists.For Dostoevsky, society based on universal Christian love is the only acceptable "socialism," and the last part of Scanlan's work analyzes Dostoevsky's nationalism and its relation to his attacks on socialism. In addition to... (shrink)

In contrast with Aristotle's assertoric logic, which became the logic of the west, suffering only minor modifications at the edges, Aristotle's modal logic appears to be rife with errors. It...

In this essay, I examine the arguments against physician-assisted suicide Susan Wolf offers in her essay, "Gender, Feminism, and Death: Physician-Assisted Suicide and Euthanasia." I argue that Wolf's analysis of PAS, while timely and instructive in many ways, does not require that feminists reject policy approaches that might permit PAS. The essay concludes with reflections on the relationship between feminism and questions of agency, especially women's agency.

: In this essay, I examine the arguments against physician - assisted suicide Susan Wolf offers in her essay, "Gender, Feminism, and Death : Physician - Assisted Suicide and Euthanasia." I argue that Wolf's analysis of PAS, while timely and instructive in many ways, does not require that feminists reject policy approaches that might permit PAS. The essay concludes with reflections on the relationship between feminism and questions of agency, especially women's agency.

Matter and Form explores the relationship between natural science and political philosophy from the classical to contemporary eras, taking an interdisciplinary approach to the philosophic understanding of the structure and process of the natural world and its impact on the history of political philosophy. It illuminates the importance of philosophic reflection on material nature to moral and political theorizing, mediating between the sciences and humanities and making a contribution to ending the isolation between them.

This review discussion outlines Justin Barrett’s Preparedness Model. This evolutionary model for belief in God is shown to posit a maladaptive mind for infants. Questions about its implications and the supporting data are considered.

In this essay, I examine the arguments against physician-assisted suicide Susan Wolf offers in her essay, “Gender, Feminism, and Death: Physician-Assisted Suicide and Euthanasia.” I argue that Wolf's analysis of PAS, while timely and instructive in many ways, does not require that feminists reject policy approaches that might permit PAS. The essay concludes with reflections on the relationship between feminism and questions of agency, especially women's agency.

In this essay, I examine the arguments against physician-assisted suicide Susan Wolf offers in her essay, “Gender, Feminism, and Death: Physician-Assisted Suicide and Euthanasia.” I argue that Wolf's analysis of PAS, while timely and instructive in many ways, does not require that feminists reject policy approaches that might permit PAS. The essay concludes with reflections on the relationship between feminism and questions of agency, especially women's agency.

In lieu of an abstract, here is a brief excerpt of the content:Journal of the History of Philosophy 41.4 (2003) 568-569 [Access article in PDF] James P. Scanlan. Dostoevsky the Thinker. Ithaca, NY: Cornell University Press, 2002. Pp. xiii + 251. Cloth, $29.95. Important works on Dostoevsky's life and thought abound, but James Scanlan offers the first comprehensive treatment and evaluation of Dostoevsky as a philosophical thinker. Scanlan uses Dostoevsky's thousands of letters, essays, and "capacious notebooks" (3), as well as (...) his literary work, to analyze systematically Dostoevsky's philosophical worldview and to argue for its coherence. Scanlan's commitment to careful scholarship is apparent throughout, including his translations of the texts. A philosopher himself, Scanlan contextualizes Dostoevsky's work in relation to traditional philosophers, including Descartes, Kant, and Kierkegaard. The result is a balanced, rich, and provocative treatment that also suggests new interpretations of some of Dostoevsky's literary works.If Bakhtin is right to describe Dostoevsky's novels as "polyphonic," how does one ascertain their author's position? Scanlan grants the challenges of approaching Dostoevsky as a philosopher. Nineteenth-century Russian thinkers rarely identified with particular philosophical schools, and Dostoevsky never thought of himself as a philosopher. Yet Dostoevsky was intensely interested in philosophy, and Scanlan argues that Dostoevsky's characters serve as surrogates for competing philosophical positions. Scanlan also reminds readers of Dostoevsky's often-neglected nonfiction works and weaves masterfully the nonfiction and the literature to support his argument.Echoing Bakhtin, Scanlan labels Dostoevsky's methodology "dialogical in style, monological in substance" (4). Doing so effectively rejects critical perspectives that suggest the author held contradictory positions. For Scanlan, Dostoevsky's dialectical method resulted from his preoccupation with combating others' ideas, implied by his frequent use of reductio ad absurdum arguments. Dostoevsky "sought to establish his own positions by demonstrating the failure of their antitheses" (231). Not only does Scanlan persuasively demonstrate the consistency of Dostoevsky's philosophical commitments, he also challenges the appropriation of Dostoevsky by existentialists as an "irrationalist," despite Dostoevsky's "convincing portrayals of human irrationality" and skepticism concerning rationality's powers (5).Scanlan examines Dostoevsky's vision of Christianity that included a strict binary of matter and spirit, and a rejection of rational egoism and mechanism (termed "nihilism"). Dostoevsky's positive deontologism, his "law of love" (with Christ as exemplar) was, for Dostoevsky, necessary to overcome the "law of personality," and conscience grounded in Christian love was the basis for salvation. Scanlan persuasively argues that Dostoevsky, if irrationalist, belongs more with Kant than Kierkegaard in viewing rationality as limited but not to be rejected wholesale. Scanlan uses this analysis to ground a provocative new reading of Notes from Underground.Scanlan also explores the connectedness of Dostoevsky's ethics and aesthetics in Dostoevsky's insistence that artists should create moral beauty beyond the purely aesthetic or cognitive. Much has been written about Dostoevsky's aesthetics, but Scanlan exposes its logical grounding in Dostoevsky's rejection of the subjective utilitarian aesthetics of Chernyshevsky and the radical materialism of Dobrolyubov. For Dostoevsky, the need for [End Page 568] beauty and creativity is intrinsic to human nature, and art serves an epistemological function that gestures toward reality, not as a "mindless photographer" (140) but as a cognitive vision penetrating "the core of his subject" (141). Dostoevsky also justified his use of the anomalous, noting that the exceptional might be "an avenue of access to the universal" (143).Dostoevsky's "dream of a community of perfect Christian brotherhood and love" (160) grounds Scanlan's examination of Dostoevsky's sociopolitical philosophy and his rejection of the critical view that Dostoevsky's politics radically changed over time. Though Scanlan agrees with biographers that Dostoevsky despised the "moral blight" (169) of serfdom, he argues that Dostoevsky's vision of Christian society permitted social stratification so long as service to masters was voluntary, cooperative, and rational. This analysis makes clear the distance between Dostoevsky and Western liberal political theorists.For Dostoevsky, society based on universal Christian love is the only acceptable "socialism," and the last part of Scanlan's work analyzes Dostoevsky's nationalism and its relation to his attacks on socialism. In addition to... (shrink)

Nietzsche a été continuellement malade. Or, si la maladie n'est pas l'inspiratrice de l'œuvre de Nietzsche, elle est source continuelle de réflexions et enrichit les perspectives de Nietzsche sur la santé. Les oppositions affirmatif -réactif, grégaire - solitaire, noble-vulgaire se ramènent à cette opposition santé-maladie (c'est le vécu de la maladie qui a appris à Nietzsche à se faire un point de vue sur sa santé et vice-versa). La maladie est même devenue source du renversement des valeurs et d'affirmation de (...) sa grande santé. C'est pourquoi ces expériences de la maladie qui ponctuent toute la vie de Nietzsche ont une telle importance dans la genèse et l'approfondissement de sa pensée. (shrink)