Design, synthesis, and evaluation of a mechanism-based inhibitor for gelatinase A

[structure: see text] Matrix metalloproteinases (MMPs), of which 26 are known, have been implicated in a number of pathological conditions, including tumor metastasis. We have previously described the first mechanism-based inhibitor for MMPs (J. Am. Chem. Soc. 2000, 122, 6799-6800), which in chemistry mediated by the active site zinc ion selectively and covalently inhibits MMP-2, -3, and -9. Computational analyses indicated that this selectivity in inhibition of MMPs could be improved by design of new variants of the inhibitor class. We report herein the syntheses of methyl 2-(4-{4-[(2-thiiranylpropyl)sulfonyl]phenoxy}phenyl)acetate (3) and 2-(4-{4-[(2-thiiranylpropyl)sulfonyl]phenoxy}phenyl)acetic acid (4), and show that compound 3 serves as a mechanism-based inhibitor exclusively for MMP-2. This molecule should prove useful in delineating the functions of MMP-2 in biological systems.     

A system of metrological assurance of measurement quality for the determination of chemical composition of light alloys and superalloys

 The paper covers the main principles of setting up and the function of the Russian system of metrological assurance of analytical measurements for the production of light alloys and superalloys. Received: 20 October 1998 / Accepted: 9 November 1998     

Floating Electrode Dielectric Barrier Discharge Plasma in Air Promoting Apoptotic Behavior in Melanoma Skin Cancer Cell Lines

Initiation of apoptosis, or programmed cell death, is an important issue in cancer treatment as cancer cells frequently have acquired the ability to block apoptosis and thus are more resistant to chemotherapeutic drugs. Targeted and perhaps selective destruction of cancerous tissue is desirable for many reasons, ranging from the enhancement of or aid to current medical methods to problems currently lacking a solution, i.e., lung cancer. Demonstrated in this publication is the inactivation (killing) of human Melanoma skin cancer cell lines, in vitro, by Floating Electrode Dielectric Barrier Discharge (FE-DBD) plasma. Not only are these cells shown to be killed immediately by high doses of plasma treatment, but low doses are shown to promote apoptotic behavior as detected by TUNEL staining and subsequent flow cytometry. It is shown that plasma acts on the cells directly and not by “poisoning” the solution surrounding the cells, even through a layer of such solution. Potential mechanisms of interaction of plasma with cells are discussed and further steps are proposed to develop an understanding of such systems.     

Upper semicontinuity of automorphism groups

The second author was partially supported by NSF#DMS-9101826     

The region of nonlinear effects for intensive sound pulses in the ocean

The formation of a stationary shock wave is studied in media with an arbitrary power dependence of the damping coefficient on the frequency. The conditions for existence of a stationary shock wave are defined and it is shown that when acoustic signals propagate in the ocean the region of nonlinear effects is limited. For acoustic waves generated by explosive sources a calculation is given of the location of the transition point of the nonlinear wave into a linear one, and the dependence of this point on the charge weight is defined.     

Synthesis and proton conductivity of adsorption-saturated and solvated porous hydroxyethylated cyclam layers on the surface of PVC-coated cellulose fabric

Porous layers of associates of adsorption-saturated and benzene- and hexane-solvated chloride and sulfate of hydroxyethylated cyclams with acid aqua complexes were synthesized on the surface of PVC-coated cellulose fabric. The porous structure of the layers includes a system of internal pores connected with the external pores via the diamine rings of the common walls of the hydroxyethylated cyclam nets; the internal pores are filled with the associates; the solvent molecules are adsorbed on the developed surface of the layers or solvate it. The H⁺ motion rate in a layer placed in solvent vapors or liquid solvents was measured; the layers were found to be nonlinear H⁺ conductors. The potential of H⁺ transition from the acid solution into the layer, the H⁺ mobility constant, and the field variation constant of the H⁺ mobility of the layer depend on the layer composition. The adsorption and solvation are accompanied by the formation of host-guest molecular complexes between the diamine rings of the cyclam nets and the benzene or hexane molecules, affecting the resistance of the associates to the incorporation of H⁺ ions and the H⁺ mobility in the associates.