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51.
52.
Synthesis of poly(gamma-glutamate) metabolites of natural folates and antifolates is a critical process. Folypolyglutamates are essential for cell proliferation. Polyglutamates of glutamate (Glu)-containing antifolates are often critical for their cytotoxic action and are relevant to antifolate resistance. However, the role of polyglutamate synthesis in selectivity is less clear. We have undertaken a research program to further define the significance of polyglutamate metabolism and to devise ways to exploit this metabolism to achieve greater therapeutic selectivity in cancer chemotherapy. This article briefly reviews several approaches tested thus far. Inhibition of folypolyglutamate synthesis should lead to cell death. Current ornithine (Orn)-containing folate-based inhibitors of the enzyme responsible for their synthesis, folypolyglutamate synthetase (FPGS), are poorly transported, apparently because of interference by the protonated delta-amine. Replacement of Orn with 4, 4-difluoroOrn, the delta-amine of which has a much lower pKa and is thus less protonated at physiological pH, was explored. Since it is unclear how polyglutamylation contributes to selectivity, we explored generic means either to eliminate or to enhance polyglutamylation. The data indicate that substitution for Glu in an antifolate by some Glu analogs in which the gamma-COOH is either altered or replaced (e.g., gamma-tetrazole-Glu) leads to loss of both FPGS substrate activity and binding; antifolate target specificity is unchanged, while uptake is actually enhanced. Substitution of 3,3-difluoroGlu for Glu leads to enhanced polyglutamylation (although probably only to the diglutamate), retention of target specificity, and at least equal uptake. Comparative studies of the same antifolate containing different replacements for Glu, such as gamma-tetrazole-Glu (no polyglutamylation) or 3,3-difluoroGlu (enhanced polyglutamylation), will be useful in exploring the role and significance of polyglutamylation. 相似文献
53.
Cheol-Min Park Byung-Hyuk Min Jae-Hong Jun Juhn-Suk Yoo Min-Koo Han 《Electron Device Letters, IEEE》1997,18(1):16-18
We have fabricated a self-aligned offset-gated poly-Si thin film transistor (TFT) by employing a novel photoresist reflow process. The gate structure of the new device is consisted of two unique patterns: A main-gate and a sub-gate. The new fabrication method extends the gate-oxide over the offset region. With the assistance of the sub-gate and reflowed photoresist a self-aligned offset region is successfully obtained due to the offset oxide acting as an implantation mask. The poly-Si TFT with symmetrical offsets is easily fabricated and the new method does not require any additional offset mask step. Compared with the misaligned offset gated poly-Si TFTs, excellent symmetric electrical characteristics are obtained 相似文献
54.
55.
Motoharu Fujigaki In Hong Yang Yoshiharu Morimoto Eung Kyo Han 《NDT & E International》1996,29(4):197-203
There is no good method to measure the shape and the strain distributions of a structure changing with time. We have previously proposed the Fourier transform grid method (FTGM) to measure the three-dimensional shape and surface strain distributions of stationary objects by analysing the two-dimensional grating images recorded with two cameras. In the stereoscopic method, it is very important to determine the accurate geometric parameters of the camera system. In this paper, the positions and the directions of cameras are accurately determined using the FTGM applied to images of a reference object on which a two-dimensional grating is drawn. Applications for analysing shape and strain distributions of vibrating rubber plates and a moving human skin are shown. 相似文献
56.
Kwang Soo Lee In Soo Park & Dong Sun Lee 《International Journal of Food Science & Technology》1996,31(1):7-13
The aim of this study was to design a modified atmosphere package for a mixed vegetable salad consisting of 75 g of cut carrot, 55 g of cut cucumber, 20 g of sliced garlic and 50 g of whole green pepper. Respiration data of all the components were combined with film permeability data to predict package atmospheres and design optimal packages for experimental testing for improved shelf-life of the produce. The optimal package avoided minimum O2 and maximum CO2 tolerance limits, and chilling injury temperatures for any component. A pouch form package made of 27 mm low density polyethylene developed a modified atmosphere of 2.0–2.1% O2 and 5.5–5.7% CO2 , which was beneficial for all components and provided better quality retention than other test packages. 相似文献
57.
J. Lee R. T. Haftka O. H. Griffin Jr. L. T. Watson M. D. Sensmeier 《Structural and Multidisciplinary Optimization》1994,8(2-3):93-100
The present study proposes a detection technique for delaminations in a laminated beam. The proposed technique optimizes the spatial distribution of harmonic excitation so as to magnify the difference in response between the delaminated and intact beam. The technique is evaluated by numerical simulation of two-layered aluminum beams. Effects of measurement and geometric noise are included in the analysis. A finite element model for a delaminated composite, based on a layer-wise laminated plate theory is used in conjunction with a step function to simulate delaminations 相似文献
58.
A neural network-based power system stabilizer (neuro-PSS) is designed for a generator connected to a multi-machine power system utilizing the nonlinear power flow dynamics. The use of power flow dynamics provides a PSS for a wide range of operation with reduced size neural networks. The neuro-PSS consists of two neural networks: neuro-identifier and neuro-controller. The low-frequency oscillation is modeled by the neuro-identifier using the power flow dynamics, then a generalized backpropagation-through-time (GBTT) algorithm is developed to train the neuro-controller. The simulation results show that the neuro-PSS designed in this paper performs well with good damping in a wide operation range compared with the conventional PSS 相似文献
59.
60.
It is essential to automate the scanning path generation process to effectively implement the micro-stereolithography. However, a scanning path that is generated based only on a 3D CAD model introduces dimensional inaccuracies. In micro-stereolithography, the photopolymer solidification is affected by fabrication conditions, such as the optical properties (laser power, laser scanning speed, laser scanning pitch focusing condition, etc.) and material properties of the photopolymer. Thus, the photopolymer solidification phenomena must be considered when generating a laser scanning path. In this paper, a scanning path generation algorithm that uses 3D CAD data and considers the photopolymer solidification phenomena is proposed to improve the dimensional accuracy in micro-stereolithography. Multi-line photopolymer solidification experiments were performed for various laser scanning conditions to examine the photopolymer solidification phenomena. From these experiments, linear relations between the solidification length (width) and scanning length (width) were acquired and stored in a database. Subsequently, these data were utilized to compensate the scanning path of the laser beam. In addition, experiments for determining the layer thickness in the z-direction were performed and these results were also used in the scanning path generation algorithm.This research was supported by the Highly Advanced National Project (http://www.most.go.kr), which performs some of the National R&D Program, and sponsored by the Korean Ministry of Science and Technology under the contract project code M10214000116-02B1500-02010. 相似文献