Stephen Watson

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Mice deficient in the adaptor Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) exhibit a bleeding disorder and lack T cells. Linker for activation of T cells (LAT)-deficient mice exhibit a similar T cell phenotype, but show no signs of hemorrhage. Both SLP-76 and LAT are important for optimal platelet activation downstream of the(More)
Bruton's tyrosine kinase (Btk) is essential for normal B-cell receptor signalling. The lack of expression of functional Btk in humans leads to the B-cell deficiency X-linked agammaglobulinaemia (XLA). We report here that Btk is also important for signalling via the collagen receptor glycoprotein VI (GPVI) in platelets. GPVI is coupled to the Fc receptor(More)
Episodic memory deficits are a core feature of neurodegenerative disorders. Muscarinic M(1) receptors play a critical role in modulating learning and memory and are highly expressed in the hippocampus. We examined the effect of GSK1034702, a potent M(1) receptor allosteric agonist, on cognitive function, and in particular episodic memory, in healthy smokers(More)
A utility representation of a linear order (X, ≺) is a linear order (U, ≺) and an injective order-preserving function f : X → U (i.e., for each x, y ∈ X, x ≺ y implies f (x) ≺ f (y)). In Utility Theory the codomain U has been traditionally chosen to be R. Recently, some authors (see [3]) have sharply argued about the possibility of choosing a different(More)
A linear ordering (X, ≺) is a Debreu chain (or has the Debreu property) if each sub-ordering (Y, ≺) of X can be embedded into X with an injective function that is both order-preserving and continuous with respect to the order topology on X and Y. The most typical example of a Debreu chain is the linearly ordered topological space (R, <, τ <) of real numbers(More)
The optimisation of an HTS hit series (1) leading to the identification of structurally novel, selective, orally bioavailable mGluR2 positive modulators GSK1331258 and GSK1331268 is described. Structure-activity relationships, attenuation of dopaminergic activity, and potentiation of mGluR2 responses in rat hippocampal MPP-DG synapses are also reported.