PDZ (also called DHR or GLGF) domains are found in diverse membraneassociated proteins including members of the MAGUK family of guanylate kinase homologues, several protein phosphatases and kinases, neuronal nitric oxide synthase, and several dystrophin‐associated proteins, collectively known as syntrophins. Many PDZ domain‐containing proteins appear to be localised to highly specialised submembranous sites, suggesting their participation in cellular junction formation, receptor or channel clustering, and intracellular signalling events. PDZ domains of several MAGUKs interact with the C‐terminal polypeptides of a subset (...) of NMDA receptor subunits and/or with Shaker‐type K+ channels. Other PDZ domains have been shown to bind similar ligands of other transmembrane receptors. Recently, the crystal structures of PDZ domains, with and without ligand, have been determined. These demonstrate the mode of ligand‐binding and the structural bases for sequence conservation among diverse PDZ domains. (shrink)

The notion that our society, its education system and its intellectual life, is characterised by a split between two cultures – the arts or humanities on one hand and the sciences on the other – has a long history. But it was C. P. Snow's Rede lecture of 1959 that brought it to prominence and began a public debate that is still raging in the media today. This fiftieth anniversary printing of The Two Cultures and its successor piece, A Second (...) Look features an introduction by Stefan Collini, charting the history and context of the debate, its implications and its afterlife. The importance of science and technology in policy run largely by non-scientists, the future for education and research, and the problem of fragmentation threatening hopes for a common culture are just some of the subjects discussed. (shrink)

The notion that our society, its education system and its intellectual life, is characterised by a split between two cultures – the arts or humanities on one hand, and the sciences on the other – has a long history. But it was C. P. Snow's Rede lecture of 1959 that brought it to prominence and began a public debate that is still raging in the media today. This 50th anniversary printing of The Two Cultures and its successor piece, A Second (...) Look features an introduction by Stefan Collini, charting the history and context of the debate, its implications and its afterlife. The importance of science and technology in policy run largely by non-scientists, the future for education and research, and the problem of fragmentation threatening hopes for a common culture are just some of the subjects discussed. (shrink)

Offering an original perspective on the central project of Descartes' Meditations, this book argues that Descartes' free will theodicy is crucial to his refutation of skepticism. A common thread runs through Descartes' radical First Meditation doubts, his Fourth Meditation discussion of error, and his pious reconciliation of providence and freedom: each involves a clash of perspectives-thinking of God seems to force conclusions diametrically opposed to those we reach when thinking only of ourselves. Descartes fears that a skeptic could exploit this (...) clash of perspectives to argue that Reason is not trustworthy because self-contradictory. To refute the skeptic and vindicate the consistency of Reason, it is not enough for Descartes to demonstrate that our Creator is perfect; he must also show that our errors cannot prove God's imperfection. To do this, Descartes invokes the idea that we err freely. However, prospects initially seem dim for this free will theodicy, because Descartes appears to lack any consistent or coherent understanding of human freedom. In an extremely in-depth analysis spanning four chapters, Ragland argues that despite initial appearances, Descartes consistently offered a coherent understanding of human freedom: for Descartes, freedom is most fundamentally the ability to do the right thing. Since we often do wrong, actual humans must therefore be able to do otherwise-our actions cannot be causally determined by God or our psychology. But freedom is in principle compatible with determinism: while leaving us free, God could have determined us to always do the good. Though this conception of freedom is both consistent and suitable to Descartes' purposes, when he attempts to reconcile it with divine providence, Descartes's strategy fails, running afoul of his infamous doctrine that God created the eternal truths. (shrink)

In this interview, C. P. Goodman invites British Polanyi scholar Richard T. Allen to reflect on his interest in Polanyi’s philosophical ideas and share what he believes is valuable in his thought.

Hsiao has recently developed what he considers a ‘simple and straightforward’ argument for the moral permissibility of corporal punishment. In this article we argue that Hsiao's argument is seriously flawed for at least two reasons. Specifically, we argue that a key premise of Hsiao's argument is question-begging, and Hsiao's argument depends upon a pair of false underlying assumptions, namely, the assumption that children are moral agents, and the assumption that all forms of wrongdoing demand retribution.

In this stimulating book, six leading philosophers--Karl-Otto Apel, Robert Brandom, Karsten Harries, Martha Nussbaum, Barry Stroud, and Allen Wood--consider the nature of philosophy. Although each of them has a unique perspective, they all seem to agree that philosophy seeks to uncover hidden assumptions and concepts in order to expose them to critical scrutiny. It is thus entirely fitting that philosophers should examine their own assumptions about the nature of their discipline. As they delve into the nature of philosophy, the authors (...) address many fascinating subjects: what makes philosophy different from natural science, religion, and other branches of the humanities; whether philosophy can contribute to political transformation, and if so, how; whether there can ever be an "end of philosophy"; and more. The editors' introduction ties together the contributors' diverse perspectives by noting common themes, similarities, and differences. (shrink)

According to “hard” compatibilists, we can be responsible for our actions not only when they are determined by mindless natural causes, but also when some agent other than ourselves intentionally determines us to act as we do. “Soft” compatibilists consider freedom compatible with merely natural determinism, but not with intentional determinism (e.g., theological determinism). Because he believes there is no relevant difference (NRD) between a naturally determined agent and a relevantly similar intentionally determined agent, John Martin Fischer is a hard (...) compatibilist. However, he argues for “historical” compatibilism by appealing to the intuition that certain manipulated agents are not responsible. By considering a new type of manipulation case, I show that Fischer’s appeal to ordinary intuitions about manipulation conflicts with NRD, so that he must choose between the two. The closing section explains why I think going “soft” is Fischer’s better option. (shrink)

Dan Baras has recently argued for the claim that Theistic Mathematical Platonism fares no better than Mathematical Platonism with respect to explaining why our mathematical beliefs are correlated with mind-independent mathematical truths. In this paper I argue that, insofar as TMP provides a proximate or local explanation for this truth-tracking correlation whereas MP fails to offer any corresponding explanation, Baras’s claim that TMP fares no better than MP with respect to explaining this correlation is false.