The metabolic organization of both normal and malignant prostate cellular phenotypes involves some unusual and surprising features. In particular, both conditions exhibit ratios of NADH/NAD+ and NADPH/NADP+ charactersitic of high oxidative states despite a chronic shortage of O2 in both conditions. In this paper, we observe that, in prostate cancer cells, the oxidizing power of the fatty acid synthesis (FAS) pathway is so large that redox is stabilized more favorably (more oxidized) than in normal prostate cells. This FAS‐facilitated redox improvement (...) occurs despite the fact that malignant cells are more O2 limited and therefore express more hypoxia inducible factor 1 (HIF1) and express hypoxia‐regulated genes more robustly. This unusual metabolic situation clearly separates direct regulatory effects of redox balance from secondary effects of hypoxia per se. The physiological significance of the FAS pathway is thus the harnessing of its oxidizing power for improving redox balance despite conditions of more extreme hypoxia. Similar hypoxia defense strategies are found in animal species that are unusually tolerant to oxygen lack. Our hypothesis is that the metabolic organization in the “low zinc, low citrate” phenotype reflects an hypoxia‐defense adaptation geared toward redox balance, with prostate cancer cells being relatively more oxidized, even if more hypoxic, than normal prostate cells. Recognition and understanding of these redox balancing and hypoxia defense functions may lead to new intervention strategies by developing new intracellular targets for prostate cancer therapy. BioEssays 24:749–757, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

In 5, Tait identifies a set of reflection principles called equation image-reflection principles which Peter Koellner has shown to be consistent relative to the existence of κ, the first ω-Erdős cardinal 1. Tait also defines a set of reflection principles called equation image-reflection principles; however, Koellner has shown that these are inconsistent when m > 2, but identifies restricted versions of them which he proves consistent relative to κ 2. In this paper, we introduce a new large-cardinal property, the α-reflective (...) cardinals. Their definition is motivated by Tait's remarks on parameters of third or higher order in reflection principles. We prove that if κ is ℶκ + α + 1-supercompact and 0 < α < κ then κ is α-reflective. Furthermore we show that α-reflective cardinals relativize to L, and that if κ exists then the set of cardinals λ < κ, such that λ is α-reflective for all α such that 0 < α < λ, is a stationary subset of κ. We show that an ω-reflective cardinal satisfies some restricted versions of equation image-reflection, as well as all the reflection properties proved consistent in 2. (shrink)

forthcoming in P. Robbins and M. Aydede (eds.), The Cambridge Handbook of Situated Cognition (Cambridge UP).

Naturalistically minded philosophers hope to identify a privileged nonsemantic relation that holds between a mental representation m and that which m represents, a relation whose privileged status underwrites the assignment of reference to m. The naturalist can accomplish this task only if she has in hand a nonsemantic criterion for individuating mental representations: it would be question-begging for the naturalist to characterize m, for the purpose of assigning content, as 'the representation with such and such content'. If we individuate mental (...) representations using the tools of dynamical systems theory, we find that a given mental representation, characterized nonsemantically, emerges in the cognitive system as the result of causal interactions between the subject and her environment. At least for the most basic of our mental representations, I argue that the dynamical systems-based approach to individuation increases the plausibility of a theory that assigns reference as a function of the subject's causal history. (shrink)

Much has been written on the relative merits of different readings of Wittgenstein's Tractatus Logico-Philosophicus. The recent renewal of the debate has almost exclusively been concerned with variants of the ineffabilist (metaphysical) reading of TL-P - notable such readings have been advanced by Elizabeth Anscombe, P. M. S. Hacker and H. O. Mounce - and the recently advanced variants of therapeutic (resolute) readings - notable advocates of which are James Conant, Cora Diamond, Juliet Floyd and Michael Kremer. During this debate, (...) there have been a number of writers who have tried to develop a third way, incorporating what they see as insights and avoiding what they see as flaws in both the ineffabilist and resolute readings. The most prominent advocates of these elucidatory readings of TL-P are Dan Hutto (2003) and Marie McGinn (1999). In this paper we subject Hutto's and McGinn's readings of TL-P to critical scrutiny. We find that in seeking to occupy the middle ground they ultimately find themselves committed to (and in the process commit Wittgenstein to) the very ineffabilism they (and Wittgenstein) are seeking to overcome. (shrink)

Wittgenstein once remarked: ?nobody can truthfully say of himself that he is filth. Because if I do say it, though it can be true in a sense, this is not a truth by which I myself can be penetrated: otherwise I should either have to go mad or change myself.? This has an immediate corollary, previously unnoted: that it may be true that someone is simply filth?a rotten person through and through?and also true that they don?t believe that they are (...) filth (or, in a certain sense, that they do), but that it is absurd or means nothing to say ?I?m filth.? Even considering the possibility seriously already prevents it from being true of one that one is (simply) filth. You just can't say ?I'm filth? and mean it. In the act of saying it, it is already untrue. Nor can you even say and mean it: ?it may be true that I?m filth,? and it still be true that you are filth. This paper considers cases of delusional belief and of depressive self-loathing in which people may find themselves believing things along the lines of ?I?m filth.? (shrink)

Wittgenstein's Method: Neglected Aspects By Gordon Baker. Oxford: Blackwell, 2004 pp. 328. £40.00 HB.. Wittgenstein's Copernican Revolution: The Question of Linguistic Idealism By Ilham Dilman. Basingstoke: Palgrave, 2002. pp. 240. £52.50 HB. Wittgenstein: Connections and Controversies By P. M. S. Hacker. Oxford: Oxford University Press,. pp. 400. £45.00 HB; £19.99 PB. Wittgenstein's Philosophical Investigations: An Introduction By David G. Stern. Cambridge: Cambridge University Press, 2004. pp. 224. £40.00 HB; £10.99 PB.

It is time for a reconsideration of the dating and interpretation of the Middle English narrative work in rhyming couplets known as The Prophecy of the Six Kings to Follow John . It has hitherto been confidently given a rough date of composition and a particular political role. Its only editor, Joseph Hall, says that “it was most probably written with a view to discredit Henry the Fourth.” He continues: “the poem says he is the Mole cursed from God's mouth, (...) in whose days terrible evils must come on England. It is a good example of the political use made of the popular belief in the ‘prophecies of Merlin.’” The notes to his text identify figures in the prophecy as representing, for example, Thomas of Woodstock, Henry Percy , Owen Glendower, and “perhaps Macmurrugh.” The only historian of the whole genre of political prophecy in medieval England, Rupert Taylor, says that the work “is very important because of its historical connections, for it is the prophecy that was used against Henry the Fourth by the Percy-Glendower faction, the ‘skimble-skamble stuff’ of Shakspere.”. (shrink)