How transcription factors achieve their in vivo specificities is a fundamental question in biology. For the Homeotic Complex (HOM/Hox) family of homeoproteins, specificity in vivo is likely to be in part determined by subtle differences in the DNA binding properties inherent in these proteins. Some of these differences in DNA binding are due to sequence differences in the N‐terminal arms of HOM/Hox homeodomains. Evidence also exists to suggest that cofactors can modify HOM/Hox function by cooperative DNA binding interactions. The Drosophila (...) homeoprotein extradenticle (exd) is likely to be one such cofactor. In HOM/Hox proteins, both the conserved ‘YPWM’ peptide motif and the homeodomain are important for interacting with exd. Although exd provides part of the answer as to how specificity is achieved, there may be additional cofactors and mechanisms that have yet to be identified. (shrink)

The evolutionarily conserved genomic organization of the Hox genes has been a puzzle ever since it was discovered that their order along the chromosome is similar to the order of their functional domains along the antero‐posterior axis. Why has this colinearity been maintained throughout evolution? A close look at regulatory sequences from the mouse Hox clusters(1,2) suggests that enhancer sharing between adjacent Hox genes may be one reason. Moreover, characterizing the activity of one of these mouse enhancers in Drosophila(2) illustrates (...) that despite many similarities, not all Hox clusters are built in the same way. (shrink)

How size is controlled during animal development remains a fascinating problem despite decades of research. Here we review key concepts in size biology and develop our thesis that much can be learned by studying how different organ sizes are differentially scaled by homeotic selector genes. A common theme from initial studies using this approach is that morphogen pathways are modified in numerous ways by selector genes to effect size control. We integrate these results with other pathways known to regulate organ (...) size in developing a comprehensive model for organ size control. ©2007 Wiley Periodicals, Inc BioEssays 30:843–853, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

This book offers a unique interpretation of tragic literature in the Western tradition, deploying the method and style of Analytic philosophy. Richard Gaskin argues that tragic literature seeks to offer moral and linguistic redress for suffering. Moral redress involves the balancing of a protagonist's suffering with guilt : Gaskin contends that, to a much greater extent than has been recognized by recent critics, traditional tragedy represents suffering as incurred by avoidable and culpable mistakes of a cognitive nature. Moral redress (...) operates in the first instance at the level of the individual agent. Linguistic redress, by contrast, operates at a higher level of generality, namely at the level of the community: its fundamental motor is the sheer expressibility of suffering in words. Against many writers on tragedy, Gaskin argues that language is competent to express pain and suffering, and that tragic literature has that expression as one its principal purposes. The definition of tragic literature in this book is expanded to include more than stage drama: the treatment stretches from the Classical and Medieval periods through to the early twentieth century. There is a special focus on Sophocles, but Gaskin takes account of most other major tragic authors in the European tradition, including Homer, Aeschylus, Euripides, Virgil, Seneca, Chaucer, Marlowe, Shakespeare, Corneille, Racine, Lessing, Goethe, Schiller, Kleist, Büchner, Ibsen, Hardy, Kafka, and Mann; lesser-known areas, such as Renaissance neo-Latin tragedy, are also covered. Among theorists of tragedy, Gaskin concentrates on Aristotle and Bradley; but the contributions of numerous contemporary commentators are also assessed. Tragedy and Redress in Western Literature: A Philosophical Perspective offers a new and genuinely interdisciplinary perspective on tragedy that will be of considerable interest both to philosophers of literature and to literary critics. (shrink)

Louis Dumont is a distinguished and versatile French social anthropologist. His Homo Hierarchicus examined the Indian caste system; in a series of writings under the general title Homo Aequalis, he has investigated modern European ideology, moving deftly through intellectual history from Aquinas to Schiller, from Adam Smith to Thomas Mann. German Ideology forms part of this general project; it comprises a number of essays, some previously published, centering on the distinctive German understanding of the individual's relation to society.

Ours is a time of dramatic and confusing transformations in everyday life, many of them originating in the social enfranchisement of women that has occurred over the past twenty-five years. Sociologist Arlie Hochschild demonstrates a widespread phenomenon of work-family imbalance in our society, experienced by people in terms of a time bind, and a devaluation of familial relationships. As large numbers of women have moved into the workplace, familial relations of all sorts have been colonized by what Virginia Held critically (...) refers to as the contractual paradigm. Even the mother/child relationship, representing for Held an alternative feminist paradigm of selfhood and agency, has been in large part "outsourced." I believe that an Arendtian conception of speech and action might enable us to assert anew the grounds for familial relations. If we require a new site upon which to address our human plurality and natality, the postpatriarchal family may provide that new site upon which individuals can freely act to recreate the fabric of human relationships. It would seem to be our moral and political responsibility as social philosophers today to speculatively contribute to the difficult yet imperative task of reconfiguring the family. In this paper, I attempt to articulate the basic assumptions from which such a reconfiguration must begin. (shrink)

Athletics, body imagery and spectacle : Greco-Roman practices, discourses and ideologies -- The politics of representation : English sport as an object and project of modernity -- "Staging" (capitalist/colonial) modernity : international exhibitions and Olympics -- German modernism, anti-modernism and the critical theory of sport -- A savage sorting of "winners" and "losers" : modernization, development, sport, and the challenge of slums.

The human science or qualitative approaches to research have always argued that methodology must be determined by the subject matter under study. Yet the same approaches to data collection (i.e., the qualitative interview) and data analysis have been utilized by these approaches since their inception. The most essential lesson of van den Berg's metabletics is that no phenomenon is static or absolute. If human phenomena are ever-changing then the methodologies we use to study them must also change and adapt, so (...) that we can more fully and authentically capture their meaning structures. This paper will develop this argument, and demonstrate the limitation of interviews for the study of the changing nature of human phenomena, utilizing psychotherapy research as an example. (shrink)

Taking Isaac Newton at his own word, historians have long agreed that the decade of the 1660s, when Newton was a young man in his twenties, was the critical period in his scientific career. In the years 1665 and 1666, he has told us, he hit on the ideas of cosmic gravitation, the composition of white light, and the fluxional calculus. The elaboration of these basic ideas constituted his scientific achievement. Nevertheless, the decade of the 1660s has remained a virtual (...) blank in our knowledge of Newton. It need not remain so always. His papers contain a wealth of manuscripts from his undergraduate years and the period immediately following. The first volume of his mathematical papers, which will soon be published, will demonstrate how extensive the information on his early mathematical development is. The development of his non-mathematical studies, especially of what I shall call his scientific studies to distinguish them from the mathematical, can be followed as well—in his reading notes, in his notebooks, above all in the passage in his philosophical notebook labelled Quaestiones quaedam Philosophicae. In this passage we see emerging into consciousness for the first time the questions on which Newton's philosophy of nature was built. (shrink)

Conflicts of interest have been reduced to financial conflicts. The National Institutes of Health’s new rules for managing conflicts of interest in medical research, the first major change to the regulations in over 15 years, address only financial ties. Although several commentators urged that the regulations also cover non-financial interests, the Department of Health and Human Services declined to do so. Similarly, the Institute of Medicine’s influential 2009 Conflict of Interest Report focuses almost exclusively on financial conflicts. Institutional policies at (...) academic medical centers and guidance from professional bodies and medical journals also primarily emphasize financial ties. Even broadly worded rules are applied more readily to financial ties than non-financial interests, such as the regulations that restrict institutional review board members with conflicting interests from participating in protocol reviews. (shrink)

Isaac Newton was indisputably one of the greatest scientists in history. His achievements in mathematics and physics marked the culmination of the movement that brought modern science into being. Richard Westfall's biography captures in engaging detail both his private life and scientific career, presenting a complex picture of Newton the man, and as scientist, philosopher, theologian, alchemist, public figure, President of the Royal Society, and Warden of the Royal Mint. An abridged version of his magisterial study Never at Rest, (...) this concise biography makes Westfall's highly acclaimed portrait of Newton newly accessible to general readers. (shrink)

From the very day in 1686 when Edmond Halley placed Book I of the Principia before the Royal Society, Robert Hooke's claim to prior discovery has been associated with the law of universal gravitation. If the seventeenth century rejected Hooke's claim summarily, historians of science have not forgotten it, and a steady stream of articles continues the discussion. In our own day particularly, when some of the glitter has worn off, not from the scientific achievement, but from the character of (...) Newton, there has been a tendency vicariously to atone for the treatment Hooke received. The judgement Lohne cites with approval from Vavilov appears to summarize the current estimate of the issue—in the seventeenth century only Newton could have written the Principia; nevertheless Hooke first sketched out its programme. What with all the knocks he has received both alive and dead, one feels guilty in assuming the role of “debunker” at this late date. Apologetically draped in sackcloth then, head covered with ashes I venture softly to suggest that Hooke has received more than his due. There is no question here of justifying Newton's behaviour toward Hooke. Wholly lacking in generosity as it appears to me, Newton's behaviour neither deserves nor can receive justification. The question turns rather on Hooke's scientific theories. Granting always his lack of demonstrations, historians have been prone to interpret his words in the light of Newton's demonstrations. A close examination of Hooke's writings does not sustain the interpretation. Contrary to what is generally asserted, he did not hold a conception of universal gravitation. And if he announced the inverse square relation, he derived it from such a medley of confusion as will not allow his claim to priority. (shrink)

While it seems to be evident that the vision of the eternal return of the same is the solution to the riddle mentioned in "On the vision and the riddle," exactly what constitutes the riddle is anything but clear. Li ke all good riddles the solution demands a paradigm shift. Nietzsche's riddle is solved by a radical rethinking of the concept of time, from a straight line to a circle. I give a detailed account of how Nietzsche's riddle is formulated (...) in such a way tha t the eternal return of the same is the only possible solution. (shrink)