Polyamine analogue regulation of NMDA MK-801 binding: a structure-activity study

A series of analogues and homologues of spermine were synthesized, and their impact on MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor was evaluated. These tetraamines encompass both linear and cyclic compounds. The linear molecules include norspermine, N1, N11-diethylnorspermine, N1,N12-bis(2,2,2-trifluoroethyl)spermine, homospermine, and N1,N14-diethylhomospermine. The cyclic tetraamines consist of the piperidine analogues N1,N3-bis(4-piperidinyl)-1,3-diaminopropane, N1,N4-bis(4-piperidinyl)-1,4-diaminobutane, N1,N4-bis(4-piperidinylmethyl)-1,4-diaminobutane, and N1,N4-bis[2-(4-piperidinyl)ethyl]-1,4-diaminobutane and the pyridine analogues N1,N3-bis(4-pyridyl)-1,3-diaminopropane, N1,N4-bis(4-pyridyl)-1,4-diaminobutane, N1,N4-bis(4-pyridylmethyl)-1,4-diaminobutane, and N1,N4-bis[2-(4-pyridyl)-ethyl]-1,4-diaminobutane. This structure-activity set makes it possible to establish the importance of charge, intercharge distance, and terminal nitrogen substitution on polyamine-regulated MK-801 binding in the NMDA channel. Four families of tetraamines are included in this set: norspermines, spermines, homospermines, and tetraazaoctadecanes. Calculations employing a SYBYL modeling program revealed that the distance between terminal nitrogens ranges between 12.62 and 19.61 A. The tetraamines are constructed such that within families cyclics and acyclics have similar lengths but different nitrogen pKa's and thus different protonation, or charge, states at physiological pH. The pKa values for all nitrogens of each molecule and its protonation state at physiological pH are described. The modifications at the terminal nitrogens include introduction of ethyl and beta,beta,beta-trifluoroethyl groups and incorporation into piperidinyl or pyridyl systems. The studies clearly indicate that polyamine length, charge, and terminal nitrogen substitution have a significant effect on how the tetraamine regulates MK-801 binding to the NMDA receptor. Thus a structure-activity basis set on which future design of MK-801 agonists and antagonists can be based is now available.     

Thermal Characterization of 1.3 μm InAsP/InGaAsP Ridge Waveguide MQW Lasers Based on Spectroscopy Method

An experimental way to analyze the thermal characterization of semiconductor lasers based on spectroscopy method under pulse driving conditions has been developed. By using this way the thermal characteristics of strain compensated 1.3 μm InAsP/InGaAsP ridge waveguide MQW laser diodes have been investigated. Results show that by measuring and analyzing the lasing spectra under appropriate driving parameters and temperature ranges, the thermal resistance of the laser diodes could be deduced easily. A higher thermal resistance of 640 K/W has been measured on a narrow ridge laser chip without soldering. Other thermal and spectral properties of the lasers have also been measured and discussed.     

Characterization of dibromopolychlorodibenzo-p-dioxins and dibromopolychlorodibenzofurans in municipal waste incinerator fly ash using gas chromatography/mass spectrometry.

Several fly ash samples from different countries were analyzed for dibromopolychlorodibenzo-p-dioxins and -dibenzofurans (DBPCDD/Fs) using capillary column gas chromatography/high-resolution mass spectrometry. Concentrations of these compounds ranged from low to high parts-per-trillion (pptr) depending on the location where the samples were collected. The mass spectrometer, operated at greater than 10,000 mass resolution in combination with the high resolving power of capillary column GC, permitted characterization of DBPCDD/Fs in municipal waste incinerator fly ash for the first time. The isomer patterns of tetra- through octa-congener groups of DBPCDD/Fs are remarkably similar regardless of where the fly ash originated, indicating common mechanisms of formation of these compounds in the incinerators.     

Randomized trial of breast self-examination in Shanghai: methodology and preliminary results

BACKGROUND: The efficacy of breast self-examination in helping to reduce mortality from breast cancer has not been rigorously demonstrated. PURPOSE: To assess efficacy, a large, randomized trial was initiated in Shanghai, China. METHODS: From October 1989 to October 1991, 267040 current and retired female employees associated with 520 factories in the Shanghai Textile Industry Bureau were randomly assigned on the basis of factory to either a self-examination instruction group (133375 women) or a control group (133665 women). The women were born within the period from 1925 through 1958. Women in the instruction group were given intensive training in breast self-examination, including the use of silicone breast models and personalized instruction, plus two subsequent reinforcement sessions and multiple reminders to practice the technique. Women in the control group were asked to attend training sessions on the prevention of low back pain. All women have been followed for the development of breast diseases and for death from breast cancer. RESULTS: A high level of participation during the first 4-5 years of the trial was documented among women in the instruction group. Randomly sampled women in this group demonstrated greater proficiency in detecting lumps in breast models than did randomly sampled women in the control group. Approximately equal numbers of breast cancers were detected in the two groups (331 in the instruction group and 322 in the control group) through 1994, which is the last year for which case-finding efforts have been completed. The breast cancers detected in the instruction group were not diagnosed at an appreciably earlier stage or smaller size than those in the control group. More benign breast lesions were detected in the instruction group than in the control group (1457 versus 623, respectively), suggesting a higher index of suspicion for women who received training. Cumulative breast cancer mortality rates through 5 years from entry into the study were nearly equivalent for the two groups. CONCLUSIONS: Breast self-examination has not led to a reduction in mortality from breast cancer in this study cohort in the first several years since the trial began. A shift toward the diagnosis of disease at a less advanced stage in women given instruction has also not been demonstrated. Longer follow-up of participants in this trial is required before final assessment can be made of the efficacy of breast self-examination. IMPLICATIONS: At this time, there is insufficient evidence to recommend for or against the teaching of breast self-examination.     

Performance characteristics of parallel resonant convertor

Using a set of characteristic curves derived from the stateplane analysis, a novel approach to the design of the parallel resonant convertor (PRC) is presented. It will be shown that the steady-state response of the convertor can also be obtained from these characteristic curves