Isonitrile-responsive and bioorthogonally removable tetrazine protecting groups.

In vivo compatible reactions have a broad range of possible applications in chemical biology and the pharmaceutical sciences. Here we report tetrazines that can be removed by exposure to isonitriles under very mild conditions. Tetrazylmethyl derivatives are easily accessible protecting groups for amines and phenols. The isonitrile-induced removal is rapid and near-quantitative. Intriguingly, the deprotection is especially effective with (trimethylsilyl)methyl isocyanide, and serum albumin can catalyze the elimination under physiological conditions. NMR and computational studies revealed that an imine-tautomerization step is often rate limiting, and the unexpected cleavage of the Si-C bond accelerates this step in the case with (trimethylsilyl)methyl isocyanide. Tetrazylmethyl-removal is compatible with use on biomacromolecules, in cellular environments, and in living organisms as demonstrated by cytotoxicity experiments and fluorophore-release studies on proteins and in zebrafish embryos. By combining tetrazylmethyl derivatives with previously reported tetrazine-responsive 3-isocyanopropyl groups, it was possible to liberate two fluorophores in vertebrates from a single bioorthogonal reaction. This chemistry will open new opportunities towards applications involving multiplexed release schemes and is a valuable asset to the growing toolbox of bioorthogonal dissociative reactions

Cosmic No Hair for Braneworlds with a Bulk Dilaton Field

Braneworld cosmology supported by a bulk scalar field with an exponential potential is developed. A general class of separable backgrounds for both single and two-brane systems is derived, where the bulk metric components are given by products of world-volume and bulk coordinates and the world-volumes represent any anisotropic and inhomogeneous solution to an effective four-dimensional Brans-Dicke theory of gravity. We deduce a cosmic no hair theorem for all ever expanding, spatially homogeneous Bianchi world-volumes and find that the spatially flat and isotropic inflationary scaling solution represents a late-time attractor when the bulk potential is sufficiently flat. The dependence of this result on the separable nature of the bulk metric is investigated by applying the techniques of Hamilton-Jacobi theory to five-dimensional Einstein gravity. We employ the spatial gradient expansion method to determine the asymptotic form of the bulk metric up to third-order in spatial gradients. It is found that the condition for the separable form of the metric to represent the attractor of the system is precisely the same as that for the four-dimensional world-volume to isotropize. We also derive the fourth-order contribution to the Hamilton-Jacobi generating functional. Finally, we conclude by placing our results within the context of the holographic approach to braneworld cosmology.Comment: 13 pages, uses RevTeX

The Minimal Persuasive Effects of Campaign Contact in General Elections: Evidence from 49 Field Experiments

Significant theories of democratic accountability hinge on how political campaigns affect Americans' candidate choices. We argue that the best estimate of the effects of campaign contact and advertising on Americans' candidates choices in general elections is zero. First, a systematic meta-analysis of 40 field experiments estimates an average effect of zero in general elections. Second, we present nine original field experiments that increase the statistical evidence in the literature about the persuasive effects of personal contact tenfold. These experiments' average effect is also zero. In both existing and our original experiments, persuasive effects only appear to emerge in two rare circumstances. First, when candidates take unusually unpopular positions and campaigns invest unusually heavily in identifying persuadable voters. Second, when campaigns contact voters long before election day and measure effects immediately-although this early persuasion decays. These findings contribute to ongoing debates about how political elites influence citizens' judgments

Hot dense capsule implosion cores produced by z-pinch dynamic hohlraum radiation

Hot dense capsule implosions driven by z-pinch x-rays have been measured for the first time. A ~220 eV dynamic hohlraum imploded 1.7-2.1 mm diameter gas-filled CH capsules which absorbed up to ~20 kJ of x-rays. Argon tracer atom spectra were used to measure the Te~ 1keV electron temperature and the ne ~ 1-4 x10^23 cm-3 electron density. Spectra from multiple directions provide core symmetry estimates. Computer simulations agree well with the peak compression values of Te, ne, and symmetry, indicating reasonable understanding of the hohlraum and implosion physics.Comment: submitted to Phys. Rev. Let