N-terminal protein modification using simple aminoacyl transferase substrates

Methods for synthetically manipulating protein structure enable greater flexibility in the study of protein function. Previous characterization of the Escherichia coli aminoacyl tRNA transferase (AaT) has shown that it can modify the N-terminus of a protein with an amino acid from a tRNA or a synthetic oligonucleotide donor. Here, we demonstrate that AaT can efficiently use a minimal adenosine substrate, which can be synthesized in one to two steps from readily available starting materials. We have characterized the enzymatic activity of AaT with aminoacyl adenosyl donors and found that reaction products do not inhibit AaT. The use of adenosyl donors removes the substrate limitations imposed by the use of synthetases for tRNA charging and avoids the complex synthesis of an oligonucleotide donor. Thus, our AaT donors increase the potential substrate scope and reaction scale for N-terminal protein modification under conditions that maintain folding.     

Noninvasive imaging of cell death using an Hsp90 ligand

Cell death plays a central role in normal physiology and in disease. Common to apoptotic and necrotic cell death is the eventual loss of plasma membrane integrity. We have produced a small organoarsenical compound, 4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid, that rapidly accumulates in the cytosol of dying cells coincident with loss of plasma membrane integrity. The compound is retained in the cytosol predominantly by covalent reaction with the 90 kDa heat shock protein (Hsp90), the most abundant molecular chaperone of the eukaryotic cytoplasm. The organoarsenical was tagged with either optical or radioisotope reporting groups to image cell death in cultured cells and in murine tumors ex vivo and in situ. Tumor cell death in mice was noninvasively imaged by SPECT/CT using an (111)In-tagged compound. This versatile compound should enable the imaging of cell death in most experimental settings.     

The supersymmetry index and the construction of modular invariants

Relationships between the modular properties of affineG characters and the modular properties of the affine characters of regular subgroups ofG are derived by considering the branching functions that appear in calculation of the index of the Dirac-Ramond operator on super-coset models. Various applications of these relationships are described, and in particular a simple algorithm is given for generating modular invariant combinations of characters of affineG at any level by using the shift vector method on suitably chosen Lorentzian, self-dual lattices.Work supported in part by funds provided by the NSF under grant No. 87-08447 and by the U.S. Department of Energy (D.O.E) under contract # DE-AC02-76ER0306, and also by a fellowship from the Alfred P. Sloan foundation     

Spectroscopic study of a representative polar cap of buckminsterfullerene: Cyclopentacorannulene

The spectroscopic properties of corannulene and cyclopentacorannulene are examined by use of absorption and steady-state fluorescence measurements. A red shift in the emission maxima of cyclopentacorannulene is noted with respect to the emission maxima in the corannulene spectrum. Similar differences in the absorption spectra of both molecules are also observed. Reasons for the dissimilarities in the absorption and emission spectra of these molecules are discussed. The fluorescence quantum yields and lifetimes of the molecules measured in organic solvents are reported. The fluorescence quantum yield and lifetime of cyclopentacorannulene are lower than those of corannulene. This difference is attributed to the highly strained and nonplanar structure of cyclopentacorannulene. The effectiveness of nitromethane as a quencher of corannulene and cyclopentacorannulene fluorescence is examined. In contrast to previously reported results, the fluorescence of these molecules is quenched by nitromethane. Fluorescence quenching of the molecules has been attributed to complex formation in the ground state, i.e., static quenching.     

Initial-state distortion and final-state interactions in the 2H(3He, 3He p)n and 2H(3He, 3H p)p reactions

The predictions of two fully antisymmetrized reaction theories (DWBA and PWBA-FSI) are compared with absolute coincidence cross sections for the ²H(³He, ³He p)n and ²H(³He, ³H p)p reactions exhibiting final-state interactions (FSI) and quasi-elastic scattering (QES) both with and without charge exchange. The DWBA theory takes into account both the initial ³He-d and the final N-N interactions, while the PWBA-FSI theory includes only the latter. New QES data at E_He = 35.9 MeV, as well as previously reported 26.8 and 35.9 MeV data, are fitted. The DWBA theory gives good fits, both in shape and magnitude, to spectra showing N-N final-state interactions but gives somewhat poorer fits to QES spectra whose predicted magnitudes are two to ten times too large. The PWBA-FSI theory always predicts cross sections that are too large; however the predicted shapes are about as good as those from the DWBA. The initial-state interaction is shown to affect both the width and position of QES peaks from these reactions.     

A shortest path algorithm in robotics and its implementation on the FPS T-20 hypercube

A broad class of problems involving the optimal control of robot arms can be formulated as dynamic programming problems whose structure is particularly attractive for parallel processing. For certain simple cost functions the dynamic programming formulation reduces to determining the shortest path through a network. This algorithm has been implemented on a Floating Point Systems' T-20 hypercube computer. An analysis of the performance of the algorithm provides several important insights into the interplay between problem size and the number of processors in a parallel computer. The results also underscore the potential for parallel computers in real-time control applications.This work was supported in part by the Office of Naval Research, Contract N 00014-86-K-0693.     

Quantum insights from null-strut geometrodynamics

We discuss quantum insights due to the null-strut formalism. These insights deal primarily with two topics: the formalism of a theory of canonical simplicial quantum gravity based on the geometrodynamic duality of null-strut calculus, and the natural implementation of spinors and spin networks in null-strut calculus.