Synthesis of a New β-Galactosidase Inhibitor Displaying Pharmacological Chaperone Properties for GM1 Gangliosidosis

GM1 gangliosidosis is a rare lysosomal disease caused by the deficiency of the enzyme β-galactosidase (β-Gal; GLB1; E.C. 3.2.1.23), responsible for the hydrolysis of terminal β-galactosyl residues from GM1 ganglioside, glycoproteins, and glycosaminoglycans, such as keratan-sulfate. With the aim of identifying new pharmacological chaperones for GM1 gangliosidosis, the synthesis of five new trihydroxypiperidine iminosugars is reported in this work. The target compounds feature a pentyl alkyl chain in different positions of the piperidine ring and different absolute configurations of the alkyl chain at C-2 and the hydroxy group at C-3. The organometallic addition of a Grignard reagent onto a carbohydrate-derived nitrone in the presence or absence of a suitable Lewis Acid was exploited, providing structural diversity at C-2, followed by the ring-closure reductive amination step. An oxidation-reduction process allowed access to a different configuration at C-3. The N-pentyl trihydroxypiperidine iminosugar was also synthesized for the purpose of comparison. The biological evaluation of the newly synthesized compounds was performed on leucocyte extracts from healthy donors and identified two suitable β-Gal inhibitors, namely compounds 10 and 12. Among these, compound 12 showed chaperoning properties since it enhanced β-Gal activity by 40% when tested on GM1 patients bearing the p.Ile51Asn/p.Arg201His mutations.     

Determination of organophosphorus pesticides in fruits by on-line size-exclusion chromatography-liquid chromatography-gas chromatography-flame photometric detection.

The determination of organophosphorus pesticides in fruits by size-exclusion chromatography (SEC) on a polystyrene column coupled on-line to a gas chromatography (GC) system was unsatisfactory as a result of interfering peaks in GC. A liquid chromatography step on silica gel was therefore inserted between the SEC and GC steps to filter out polar by-products. Samples of fruit (apples, grapes and kiwi fruits) were extracted, then the extract filtered or centrifuged and injected into an automated on-line SEC-liquid chromatography-GC-flame photometric detection. Recoveries were about 95% and the detection limits about 1 ng/g.     

Asymptotics for some vibro-impact problems with a linear dissipation term

We consider a mechanical system with a finite number of degrees of freedom submitted to a non smooth potential Φ and a viscous dissipation force. We study the asymptotic behavior of dissipative solutions when the time variable tends to +∞. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Temperature dependent effects and statistical gamma-ray multiplicities in the147Sm(3He, α)146Sm reaction

Gamma-ray multiplicities associated with the statistical decay from highly excited states in¹⁴⁶Sm are calculated. The formalism, which accounts for the temperature dependence of the level density parameter, is applied to the analysis of the statistical gamma decay from states populated by the (³He, α) reaction. The results are found to be in a reasonable agreement with the experimental data.     

Gas chromatographic system for the identification of halogenated pesticides by retention indices using n-alkanes as standards

A gas chromatographic system for the evaluation of linear temperature-programmed retention indices allowing n-alkanes to be adopted as the reference retention markers for any type of analyte, irrespective of the atoms present in their molecules, is described. It is based on the simultaneous use of two different detectors (a flame ionization detector and a specific detector suitable for the sample components), both connected (in parallel) to the same column outlet. The performance of this system has been tested by measuring the retention indices of fifteen chlorinated pesticides under conditions of linear programming temperature, by adopting an electron-capture detector as the specific detector. The reliability of the retention indices thus determined has been proven by verifying that they can be reproduced under different chromatographic conditions.     

Thermo-mechanical degradation of polypropylene, low-density polyethylene and their 1:1 blend

Thermo-mechanical degradation of isotactic polypropylene (iPP) and low-density polyethylene (LDPE), and the effect of the specific degradation processes of each polymer on the degradation of a 1:1 blend of these polymers, have been studied by using a conrotatory double-screw mixer coupled to a torque rheometer. The products were characterized by Fourier transform infra-red spectroscopy and thermogravimetry under inert and oxidative atmospheres. Data for the blend were compared with curves simulated from a combination of the results for the single polymers. LDPE is shown to form three to four times more carbonyl-containing products than iPP in the processing conditions used to prepare the blend. The main reason for this difference are the stabilizers added to iPP by the producer before its pelletization. Blending with LDPE stabilizes iPP, even at temperatures well above its melting point.     

Large regular graphs with no induced 2K 2

Letr be a positive integer. Considerr-regular graphs in which no induced subgraph on four vertices is an independent pair of edges. The numberv of vertices in such a graph does not exceed 5r/2; this proves a conjecture of Bermond. More generally, it is conjectured that ifv>2r, then the ratiov/r must be a rational number of the form 2+1/(2k). This is proved forv/r≥21/10. The extremal graphs and many other classes of these graphs are described and characterized. Research supported in part by the National Science Foundation under ISP 80110451. Research supported in part by the National Science Foundation under DMS-8401281. Research supported in part by the National Science Foundation under DMS-8504322, and by the Office of Naval Research under N00014-85K0570.