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41.
The three-dimensional solution structure of des-[Phe(B25)] human insulin has been determined by nuclear magnetic resonance spectroscopy and restrained molecular dynamics calculations. Thirty-five structures were calculated by distance geometry from 581 nuclear Overhauser enhancement-derived distance constraints, ten phi torsional angle restraints, the restraints from 16 helical hydrogen bonds, and three disulfide bridges. The distance geometry structures were optimized using simulated annealing and restrained energy minimization. The average root-mean-square (r.m.s.) deviation for the best 20 refined structures is 1.07 angstroms for the backbone and 1.92 angstroms for all atoms if the less well-defined N and C-terminal residues are excluded. The helical regions are more well defined, with r.m.s. deviations of 0.64 angstroms for the backbone and 1.51 angstroms for all atoms. It is found that the des-[Phe(B25)] insulin is a monomer under the applied conditions (4.6 to 4.7 mM, pH 3.0, 310 K), that the overall secondary and tertiary structures of the monomers in the 2Zn crystal hexamer of native insulin are preserved, and that the conformation-averaged NMR solution structure is close to the structure of molecule 1 in the hexamer. The structure reveals that the lost ability of des-[Phe(B25)] insulin to self-associate is caused by a conformational change of the C-terminal region of the B-chain, which results in an intra-molecular hydrophobic interaction between Pro(B28) and the hydrophobic region Leu(B11)-Leu(B15) of the B-chain alpha-helix. This interaction interferes with the inter-molecular hydrophobic interactions responsible for the dimerization of native insulin, depriving the mutant of the ability to dimerize. Further, the structure displays a series of features that may explain the high potency of the mutant on the basis of the current model for the insulin-receptor interaction. These features are: a change in conformation of the C-terminal region of the B-chain, the absence of strong hydrogen bonds between this region and the rest of the molecule, and a relatively easy accessibility to the Val(A3) residue. 相似文献
42.
JE Myers T Mieczkowski J Perel D Abbondanza TB Cooper JJ Mann 《Canadian Metallurgical Quarterly》1994,35(2):112-120
Serotonergic responsivity was assessed in 20 psychiatric patients by the prolactin response to a fenfluramine challenge test. During the fenfluramine challenge 6 of 20 patients (30%) spontaneously reported psychopathologic reactions that included: increased anxiety/agitation, psychotic symptoms, illusions, mood elevation, and anergia. The time of peak behavioral symptoms (2.5 +/- 0.8 hrs) corresponded closely to the time of peak increase in prolactin levels (3.0 +/- 1.1 hr). Abnormal behavioral responders had statistically significant greater increases in prolactin 1 to 4 hr after fenfluramine when compared to normal responders. Patients who developed an abnormal psychopathologic response to fenfluramine were characterized by higher levels of anxiety and agitation at the time of admission to the hospital but otherwise were not distinguishable on the basis of severity of other psychiatric symptoms. This study suggests that increased serotonergic transmission may trigger anxiety, psychosis, and mood elevation in specific vulnerable individuals, whereas other patients with similar psychiatric illnesses are not affected. 相似文献
43.
Wen-Chau Liu Lih-Wen Laih Shiou-Ying Cheng Wen-Lung Chang Wei-Chou Wang Jing-Yuh Chen Po-Hung Lin 《Electron Devices, IEEE Transactions on》1998,45(2):373-379
In this paper, a new multiple negative-differential-resistance (MNDR) device based on a metal-insulator-semiconductor-insulator-metal (MISIM)-like structure with step-compositional InxGa1-x As quantum wells has been fabricated and demonstrated. The interesting MNDR phenomena are found in the current-voltage (I-V) characteristics of this device. At room temperature, the triple switching behaviours and quadruple stable operation states are obtained. In addition, the sixfold switching behaviors and a staircase-shaped I-V characteristic are observed at -105°C. A sequential carrier accumulation at InGaAs subwells and the potential lowering process are used to qualitatively explain the interesting MNDR phenomena. From the experimental results, it is shown that the studied device has good potential in multiple-valued logic applications 相似文献
44.
从冷却曲线上相变段倾角最小原则出发,研究了新型激冷剂的配比与热分析法检测铸铁成分精度的关系,实验结果表明,能使相变段倾角最小的成分配比,也能提高对铸铁成分的热分析和检测精度。 相似文献
45.
46.
GIS技术与微机制图 总被引:1,自引:0,他引:1
地理信息系统(GIS)随着信息社会的发展愈发显示出强大的生命力。本文简要叙述GIS的重要作用及其发展进程中涌出出来的四个设计模型,总结了运用GIS国产软件平台MAPGIS制作遥感地质构造解译图的工作步骤和技术方法。 相似文献
47.
48.
This is the second in a series of articles provided to the readers of PENNSYLVANIA MEDICINE as an update from researchers and clinicians in this cutting-edge medical field. The series is partially sponsored through a grant from the Pennsylvania Department of Health to the University of Pittsburgh Department of Human Genetics. 相似文献
49.
M Al-Sarraf TF Pajak RW Byhardt JJ Beitler MM Salter JS Cooper 《Canadian Metallurgical Quarterly》1997,37(4):777-782
PURPOSE: Despite aggressive surgery and postoperative radiation therapy, only 30% of patients who have advanced, potentially resectable carcinomas of the head and neck survive for 5 years. In the hope of improving this situation we studied the effect of postoperative radiotherapy delivered concurrently with cisplatin. METHODS AND MATERIALS: Patients who had Stage IV tumors and/or involved surgical margins received 60 Gy in 30 fractions over 6 weeks plus 100 mg/m2 of cisplatin on radiotherapy days 1, 23 and 43. Fifty-two patients participated in this trial and 51 were evaluated. Forty-three (84%) patients had pathologic T3 or T4 disease, 43 (84%) had Stage IV disease, and 27 (53%) had histologically involved surgical margins. RESULTS: Severe and life-threatening toxicities occurred in 20% and 12% of patients, respectively; the most common drug-related toxicities were leukopenia, anemia, nausea, and vomiting. Seventeen patients (43%) remain alive with no evidence of disease. Four patients (8%) died with no evidence of neoplastic disease, and one patient has died of a second independent malignancy. By actuarial analysis at 3 years, 48% of patients are alive, 81% have locoregional control of disease, and 57% are free of distant metastases. CONCLUSIONS: Based on comparison with similar patients treated in a prior Radiation Therapy Oncology Group/Intergroup trial (RTOG), we conclude that postoperative radiotherapy with concurrent cisplatin may improve locoregional control rates and should be prospectively tested. 相似文献
50.
We examined the molecular mechanism of metronidazole resistance by constructing a lambda-Zap II phagemid expression library with genomic DNA from a metronidazole-resistance strain of Helicobacter pylori. Twenty-two clones were found to have elevated MTZ resistances in XLOLR strain of E. coli. Phagemids belonging to the twenty two clones were extracted and then retransformed into the XLOLR strain of E. coli. After MTZ selection, five clones could confer metronidazole resistance consistently. According to Southern hybridization and DNA sequencing, the five clones contained a same locus, recA. In addition, transforming the five clones into BL21 strain of E. coli produced a higher resistance to MTZ. Interestingly, electroporation of one of the five phagemid clones into two MTZ sensitive H. pylori yielded MTZ resistant strains. Comparing amino acid sequence in MTZ resistant with sensitive isolates revealed two point mutations at this locus. Above results suggest that mutation in recA may be associated with metronidazole resistance of H. pylori. 相似文献