Synthesis of 1-arylmethyl-2-(cyanomethyl)aziridines and their ring transformation into methyl N-(2-cyanocyclopropyl)benzimidates

1-Arylmethyl-2-(cyanomethyl)aziridines were prepared in high yields from the corresponding 2-(bromomethyl)aziridines upon treatment with potassium cyanide in DMSO. Ring opening of the aziridine moiety with N-chlorosuccinimide in CCl4 and subsequent treatment of the thus formed 4-chloro-3-(N-chloro-N-(alpha,alpha-dichlorobenzyl)amino)butanenitriles with sodium methoxide in methanol resulted in novel methyl N-(2-chloro-1-(cyanomethyl)ethyl)benzimidates, although in low yields. The latter gamma-chloro nitriles were smoothly converted into methyl N-(2-cyanocyclopropyl)benzimidates as precursors of biologically relevant beta-ACC derivatives through a 1,3-cyclization protocol by reaction with potassium tert-butoxide in THF.     

Objective Vocal Quality in Children Using Cochlear Implants: A Multiparameter Approach

Objectives

The purpose of this study was to determine the objective vocal quality in 36 prelingually deaf children using cochlear implant (CI) with a mean age of 9 years. An additional purpose was to compare the objective vocal quality of these 36 CI users with 25 age-matched children with prelingual severe hearing loss using conventional hearing aids (HAs) and 25 normal hearing (NH) children.

Study Design

The design for this cross-sectional study was a multigroup posttest-only design.

Methods

The objective vocal quality was measured by means of the dysphonia severity index (DSI). Moreover, perceptual voice assessment using the GRBASI scale was performed.

Results

CI children have a vocal quality by means of the DSI of +1.8, corresponding with a DSI% of 68%, indicating a borderline vocal quality situated 2% above the limit of normality. The voice was perceptually characterized by the presence of a very slight grade of hoarseness, roughness, strained phonation, and higher pitch and intensity levels. No significant objective vocal quality differences were measured between the voices of the CI children, HA users, and NH children.

Conclusions

According to the results, one aspect of the vocal approach in children with CI and using HAs must be focused on the improvement of the strained vocal characteristic and the use of a lower pitch and intensity level.     

The emergence of groups in the evolution of friendship networks

Friendship networks usually show a certain degree of segmentation: subgroups of friends. The explanation of the emergence of such groups from initially dyadic pair friendships is a difficult but important problem. In this paper we attempt to provide a first contribution to the explanation of subgroup formation in friendship networks by using the LS set as a definition for a friendship group. We construct a dynamic individual oriented model of friendship formation and provide preliminary simulation results that give an idea of how to continue the process of explaining group formation.     

Evolution of sociology freshmen into a friendship network

In this paper we both describe and analyze the meeting process and the evolution of a friendship network among sociology freshmen in the Netherlands. We develop a theory that explains how changes in the network structure depend on one or more of four main effects: proximity, visible similarity, invisible similarity, and network opportunity. We formulate expectations with regard to what factors are important at what stages of the friendship development, making a distinction between 'meeting' and 'mating.' To some extent, the results confirm our expectations. The proximity and visible similarity variables determine change in network structure in the early stages, whereas network opportunity is important during all stages. Unfortunately, no significant effects of invisible similarity are found.     

Development of an on-line high performance liquid chromatography detection system for human cytochrome P450 1A2 inhibitors in extracts of natural products

An on-line HPLC screening method for detection of inhibitors of human cytochrome P450 1A2 in extracts was developed. HPLC separation of extracts is connected to a continuous methoxyresorufin-O-demethylation (MROD) assay in which recombinant human P450 1A2 converts methoxyresorufin to its fluorescent metabolite resorufin. The system was tested with three P450 1A2 inhibitors, for which minimum detectable amounts (MDA) ranging from 0.7 to 9.5 ng were obtained. Analysis of a kava kava and a basil extract showed that the on-line system is applicable to complex mixtures, since in both extracts, peaks with P450 1A2 inhibiting activity were observed.