Design and optimization of cyclized NK1 antagonists with controlled atropisomeric properties

We have previously described a series of antagonists that showed high potency and selectivity for the NK₁ receptor. However, these compounds also had the undesirable property of existing as a mixture of four interconverting rotational isomers. Through biological and structural analysis of the atropisomers, a binding model was developed and used to guide the design of compounds, which were rigidified by installation of a cyclizing linkage. These compounds existed as a mixture of two atropisomers. Further elaboration of the ring system reinforced the desired conformation and eliminated atropisomeric properties. We found that the region distal to the 8-membered ring system could be modified while retaining NK₁ potency, and optimization led to further improvements in the in vivo activity.     

Polyhedral study of the capacitated vehicle routing problem

The capacitated vehicle routing problem (CVRP) considered in this paper occurs when goods must be delivered from a central depot to clients with known demands, usingk vehicles of fixed capacity. Each client must be assigned to exactly one of the vehicles. The set of clients assigned to each vehicle must satisfy the capacity constraint. The goal is to minimize the total distance traveled. When the capacity of the vehicles is large enough, this problem reduces to the famous traveling salesman problem (TSP). A variant of the problem in which each client is visited by at least one vehicle, called the graphical vehicle routing problem (GVRP), is also considered in this paper and used as a relaxation of CVRP. Our approach for CVRP and GVRP is to extend the polyhedral results known for TSP. For example, the subtour elimination constraints can be generalized to facets of both CVRP and GVRP. Interesting classes of facets arise as a generalization of the comb inequalities, depending on whether the depot is in a handle, a tooth, both or neither. We report on the optimal solution of two problem instances by a cutting plane algorithm that only uses inequalities from the above classes.This work was supported in part by NSF grant DDM-8901495.     

Residual finiteness of a class of semigroups presented by a single relation

Communicated by Dominique Perrin     

Heats of mixing of 2,2-dimethoxypropane and diethoxymethane with some 1-alkenes

The excess enthalpies of 2,2-dimethoxypropane + 1-hexene, + 1-heptene and + 1-octene, and of diethoxymethane + 1-hexene + 1-octene have been measured at 298.15 K. The values of H^E for all the systems are positive and increase with increasing chain length of the alkene. The results are analysed in term of the quasi-lattice theory of mixtures using the zeroth approximation.     

Microdetermination of monosaccharides in glycoproteins: I. Electrophoretic methods

A sensitive method that has been developed for determination of monosaccharides in glycoproteins is based on high-voltage electrophoretic separation of tritium-labeled monosaccharides. Precise quantitation is mediated by using internal standards, specific for each monosaccharide in the sample. The application of this method and its reproducibility has been demonstrated by analysis of the carbohydrate moiety of immunoglobulins.     

A canonical structure for iterative procedures

In this paper a canonical structure for multistep finite memory algorithms is presented. The concept of characteristic set is introduced and some of the finite and limit properties of the structure are proved. Then it is shown that the use of the theory developed in the paper's first part greatly simplifies the analysis of complicated iterative procedures.     

Generation and amplification of sub-picosecond pulses using a frequency-doubled neodymium YAG pumping source

Stable, tunable, sub-picosecond pulses have been obtained by synchronously pumping a Rhodamine 6G dye laser with a frequency-doubled CW modelocked neodymium YAG laser. Careful attention has been paid to minimize amplitude and timing instabilities, resulting in dye laser pulses shorter than 500 fs. The main advantage of this new pumping source over current synchronously pumped dye lasers is that it is particularly well suited to short pulse amplification. Using this technique amplification of 2 × 10⁶ has been achieved.