Invariance of the dissipative action at ultrahigh strain rates above the strong shock threshold

We have directly resolved shock structures in pure aluminum in the first few hundred picoseconds subsequent to a dynamic load at peak stresses up to 43 GPa and strain rates in excess of 10(10) s(-1). For strong shocks we obtain peak stresses, strain rates, and rise times. From these data, we directly validate the invariance of the dissipative action in the strong shock regime, and by comparing with data obtained at much lower strain rates show that this invariance is observed over at least 5 orders of magnitude in the strain rate. Over the same range, we similarly validate the fourth-power scaling of the strain rate with the peak stress (the Swegle-Grady relation).     

Novel synthesis of sulfones from α,α-dibromomethyl aromatics

A novel, high yielding preparation of sulfones from α,α-dibromomethyl aromatics through reaction with a sulfinate salt is reported.     

NKT cell-dependent glycolipid–peptide vaccines with potent anti-tumour activity

It is known that T cells can eliminate tumour cells through recognition of unique or aberrantly expressed antigens presented as peptide epitopes by major histocompatibility complex (MHC) molecules on the tumour cell surface. With recent advances in defining tumour-associated antigens, it should now be possible to devise therapeutic vaccines that expand specific populations of anti-tumour T cells. However there remains a need to develop simpler efficacious synthetic vaccines that possess clinical utility. We present here the synthesis and analysis of vaccines based on conjugation of MHC-binding peptide epitopes to α-galactosylceramide, a glycolipid presented by the nonpolymorphic antigen-presenting molecule CD1d to provoke the stimulatory activity of type I natural killer T (NKT) cells. The chemical design incorporates an enzymatically cleavable linker that effects controlled release of the active components in vivo. Chemical and biological analysis of different linkages with different enzymatic targets enabled selection of a synthetic vaccine construct with potent therapeutic anti-tumour activity in mice, and marked in vitro activity in human blood.     

The intramolecular Morita-Baylis-Hillman-type alkylation reaction

From the initial development of a homologous Morita-Baylis-Hillman reaction utilizing epoxides as electrophiles, the method was expanded to enable the exclusively organocatalyzed intramolecular allylation of enones and to develop the intramolecular MBH-type alkylation of activated alkenes. We successfully utilized both enones and unsaturated thioesters as the activated alkene component. This work, carried out using stoichiometric amounts of the trialkylphosphine, gave an array of functionalized five- and six-membered carbocycles in high yields. With the cycloalkylation of enones and thioesters, conditions that allowed the use of substoichometric amounts of the phosphine catalyst were developed. As a result both five- and six-membered rings can be formed efficiently with little to no loss in yield upon comparison to yields obtained when stoichiometric amounts of trialkylphosphines were employed. We isolated, for the first time, an MBH-type intermediate exhibiting unprecedented trans geometry of the phosphonium salt and acyl group.     

Blue fluorescent dye-protein complexes based on fluorogenic cyanine dyes and single chain antibody fragments

Fluoromodules are complexes formed upon the noncovalent binding of a fluorogenic dye to its cognate biomolecular partner, which significantly enhances the fluorescence quantum yield of the dye. Previously, several single-chain, variable fragment (scFv) antibodies were selected from a yeast cell surface-displayed library that activated fluorescence from a family of unsymmetrical cyanine dyes covering much of the visible and near-IR spectrum. The current work expands our repertoire of genetically encodable scFv-dye pairs by selecting and characterizing a group of scFvs that activate fluorogenic violet-absorbing, blue-fluorescing cyanine dyes, based on oxazole and thiazole heterocycles. The dye binds to both yeast cell surface-displayed and soluble scFvs with low nanomolar K(d) values. These dye-protein fluoromodules exhibit high quantum yields, approaching unity for the brightest system. The promiscuity of these scFvs with other fluorogenic cyanine dyes was also examined. Fluorescence microscopy demonstrates that the yeast cell surface-displayed scFvs can be used for multicolor imaging. The prevalence of 405 nm lasers on confocal imaging and flow cytometry systems make these new reagents potentially valuable for cell biological studies.