Mannose-pepstatin conjugates as targeted inhibitors of antigen processing

The molecular details of antigen processing, including the identity of the enzymes involved, their intracellular location and their substrate specificity, are still incompletely understood. Selective inhibition of proteolytic antigen processing enzymes such as cathepsins D and E, using small molecular inhibitors such as pepstatin, has proven to be a valuable tool in investigating these pathways. However, pepstatin is poorly soluble in water and has limited access to the antigen processing compartment in antigen presenting cells. We have synthesised mannose-pepstatin conjugates, and neomannosylated BSA-pepstatin conjugates, as tools for the in vivo study of the antigen processing pathway. Conjugation to mannose and to neomannosylated BSA substantially improved the solubility of the conjugates relative to pepstatin. The mannose-pepstatin conjugates showed no reduction in inhibition of cathepsin E, whereas the neomannosylated BSA-pepstatin conjugates showed some loss of inhibition, probably due to steric factors. However, a neomannosylated BSA-pepstatin conjugate incorporating a cleavable disulfide linkage between the pepstatin and the BSA showed the best uptake to dendritic cells and the best inhibition of antigen processing.     

Differential non-destructive image current detection in a fourier transform quadrupole ion trap

Dual-detector differential non-destructive Fourier transform detection in a quadrupole ion trap is shown to improve signal intensity and reduce noise compared with spectra recorded using a single detector. A larger area detector in each end-cap electrode is machined to fit its hyperbolic shape and so minimize field imperfections on the z-axis. Argon, acetophenone and bromobenzene spectra were recorded to allow a comparison between single- and dual-detector (differential) modes of detection and to demonstrate the improvement achieved with differential detection. Copyright 1999 John Wiley & Sons, Ltd.     

Detection of ultrafast phenomena by use of a modified Sagnac interferometer

We describe a time-division interferometer based on the Sagnac geometry for monitoring ultrafast changes in the real and the imaginary components of the refractive index as well as phase changes that are due to surface displacement. Particular advantages of this interferometer are its simple common-path design and operation at normal incidence with a microscope objective for both pumping and probing. Operation is demonstrated by detection of temperature changes and coherent phonon generation in a gold film.     

Pseudo-steady-state solutions for solidification in a wedge

Polubarinova-Kochina's analytical differential equation methodis used to determine the pseudo-steady-state solution to problemsinvolving the freezing (solidification) of wedges of liquidwhich are initially at their fusion temperature. In particular,we consider four distinct problems for wedges which are: freezingwith the same constant boundary temperature, freezing with thesame constant boundary heat fluxes, freezing with distinct constantboundary temperatures and freezing with distinct constant fluxesat the boundaries. For the last two problems, a Heun's differentialequation with an unknown singularity is derived, which in bothcases admits a particularly elegant simple solution for thespecial case when the wedge angle is . The moving boundariesobtained are shown pictorially.     

Explicit Galois resolvents for sextic equations

Several techniques for calculating the Galois resolvents of polynomial equations are discussed and implemented. In particular, the method of power sums, in conjunction with the symbolic algebra program muMATH, is used to derive a complete set of explicit algebraic resolvents for the general sextic equation. A simple example, drawn from the theory of crystal elasticity, illustrates the utility of these results in answering the question “When is a polynomial equation (with multinomial coefficients) solvable?”.