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 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)

One of the standard principles of rationality guiding traditional accounts of belief change is the principle of minimal change: a reasoner's belief corpus should be modified in a minimal fashion when assimilating new information. This rationality principle has stood belief change in good stead. However, it does not deal properly with all belief change scenarios. We introduce a novel account of belief change motivated by one of Grice's maxims of conversational implicature: the reasoner's belief corpus is modified in a minimal (...) fashion to assimilate exactly the new information. In this form of belief change, when the reasoner revises by new information p ∨ q their belief corpus is modified so that p∨q is believed but stronger propositions like p∧q are not, no matter what beliefs are in the reasoner's initial corpus. We term this conservative belief change since the revised belief corpus is a conservative extension of the original belief corpus given the new information. (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)

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)

: The principle of alternative possibilities (PAP) says that doing something freely implies being able to do otherwise. I show that Descartes consistently believed not only in PAP, but also in clear and distinct determinism (CDD), which claims that we sometimes cannot but judge true what we clearly perceive. Because Descartes thinks judgment is always a free act, PAP and CDD seem contradictory, but Descartes consistently resolved this apparent contradiction by distinguishing between two senses of 'could have done otherwise.' In (...) one sense alternative possibilities are necessary for freedom and in another they are not. I discuss three possible interpretations of the two senses. (shrink)

C P Ormell; Ideology and the Reform of School Mathematics, Journal of Philosophy of Education, Volume 3, Issue 1, 30 May 2006, Pages 37–54, https://doi.org/10.1.

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.

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.

Becoming autonomous is a process of coming to realise oneself in shared, socio-historical practices. There can be no self before these practices, but their existence is no guarantee for selfhood either: one can be heteronomous through one's successful participation in various practices if that participation is not a genuine expression of one's own personhood. This means that the sheer capability to participate in the practices in which one finds oneself is not sufficient for personal autonomy. Something else is required before (...) the self is realised in shared, socio-historical practices. How can this be, if as we said, there can be no self before these practices? By what principle do we decide whether a particular expression of selfhood in a socio-historical practice is genuine? If there can only be a self within socio-historical practices, it stands to reason that we can find it only there. If, however, one's participation cannot be considered in advance as a genuine expression of oneself, what we may expect to find is perhaps only a fragment, a hint of autonomy always already entangled in heteronomous elements, or things that would be different if one could have so chosen. To come to an understanding of oneself, then, will require more than just a handle on one's existence in various practices. It will require the capacity to see one's participation in this socio-historically determined practice as a fragment of a whole, a particular instance of something more general which points beyond our present participation in these particular, socio-historically determined practices towards a horizon of possibility that recedes beyond our grasp whenever we try to make definitive sense out of a possibility for agency. (shrink)

In an influential article, Anthony Kenny charged that (a) the view of freedom in Descartes’ “1645 letter to Mesland” is incoherent, and (b) that this incoherence was present in Descartes’ thought from the beginning. Against (b), I argue that such incoherence would rather support Gilson’s suspicions that the 1645 letter is dishonest. Against (a), I offer a close reading of the letter, showing that Kenny’s objection seems plausible only if we misconstrue a key ambiguity in the text. I close by (...) defending Descartes against some related worries of my own about the degrees of Cartesian freedom. I conclude that there is really no good reason to deny that Descartes’ view in the 1645 letter is both internally coherent and a genuine explication of the Meditations’ account of freedom. (shrink)

God’s providence appears to threaten the existence of human freedom. This paper examines why Descartes considered this threat merelyapparent. Section one argues that Descartes did not reconcile providence and freedom by adopting a compatibilist conception of freedom. Sections two and three argue that for Descartes, God’s superior knowledge allows God to providentially arrange free choices without causally determining them. Descartes’ position thus strongly resembles the “middle knowledge” solution of the Jesuits. Section four examines the problematic relationship between this solution and (...) the creation of the eternal truths, arguing that Descartes’ position depends on his unique understanding of divine simplicity. (shrink)