Based on the full BABAR data sample, we report improved measurements of the ratios R(D(*))=B(B[over ¯]→D(*)τ(-)ν[over ¯](τ))/B(B[over ¯]→D(*)ℓ(ℓ)(-)ν[over ¯](ℓ)), where ℓ is either e or μ. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D)=0.440±0.058±0.042 and R(D(*))=0.332±0.024±0.018, which exceed the standard model expectations by 2.0σ and 2.7σ, respectively. Taken together, our results disagree with these expectations at the 3.4σ level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model.

Nitric oxide (NO) is a widespread, potent, biological mediator that has many physiological and pathophysiological roles. Research in the field of NO appears to have followed a straightforward path, and the findings have been progressive: NO and cyclic GMP are involved in vasodilatation; glycerol trinitrate relaxes vascular smooth muscles by bioconversion to NO; mammalian cells synthesize NO; and last, NO mediates vasodilatation by stimulating the soluble guanylate cyclase (sGC), a heterodimeric (alpha/beta) haem protein that converts GTP to cGMP2-4. Here we report the discovery of a regulatory site on sGC. Using photoaffinity labelling, we have identified the cysteine 238 and cysteine 243 region in the alpha1-subunit of sGC as the target for a new type of sGC stimulator. Moreover, we present a pyrazolopyridine, BAY 41-2272, that potently stimulates sGC through this site by a mechanism that is independent of NO. This results in antiplatelet activity, a strong decrease in blood pressure and an increase in survival in a low-NO rat model of hypertension, and as such may offer an approach for treating cardiovascular diseases.

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