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131.
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   
132.
The partial oxidation of methanol to formaldehyde was studied over YBa2Cu3O7-x catalyst in a flow reactor. The structural change of YBa2Cu3O7-x before and after the reaction was measured by means of XRD and iodometric titration method. The catalytic characteristics of YBa2Cu3O7-x for the partial oxidation of methanol to formaldehyde was due to copper ions. It was found that Cu+2 was responsible for the higher selectivity for formaldehyde.  相似文献   
133.
Consistent calculation of fugacities of fluid mixtures remains as one of the most important subjects in contemporary molecular thermodynamics. In practice, equations of state (EOSs) and gE-models have been used. However, most EOSs are erroneous for condensed phases at high densities and gE-models are inapplicable for pressuresensitive systems. Recently to remedy the shortcomings in both approaches, there has been a surge of new gE-EOS mixing rules. By equating any set of EOS and gE-models, the limitations in both approaches could be resolved significantly. However, the self-consistency in the underlying concept of those mixing rules remains controversial. During the last several years, the present authors proposed a new lattice-fluid EOS and its simplification relevant to phase equilibrium calculations. Without employing any gE-EOS mixing rule and with only two parameters for a pure component and one adjustable interaction energy parameter for a binary mixture, results obtained to date demonstrated that the EOSs are quantitatively applicable to a great variety of phase equilibrium properties of mixtures, especially, for complex and/or macromolecular systems. In the present article we summarize the EOSs and extended the applications to liquid-liquid Equilibria. In part I, we discussed briefly the molecular thermodynamic aspects of general derivation of the EOS and a brief discussion of applying the EOSs to pure fluids while the illustrative application to various real mixture systems is discussed in part II.  相似文献   
134.
The authors report significantly improved performances of a symmetric self-electrooptic-effect device (S-SEED), with high on-off contrast ratio (>30:l) and large optical bistability loop widths (ΔP=44%) at an applied bias of Va=0 V, i.e., with no power supply. The S-SEED is made of extremely shallow quantum wells (ESQWs) in an asymmetric Fabry-Perot (AFP) cavity structure. At Va =5 V ΔP increased by up to 95%, preserving the high contrast ratio. The reflectivity changes at Va=0 and 5 V were about 15% and 30%, respectively. These are believed to be the largest values ever reported for such structures  相似文献   
135.
The eigenstructures of common covariance matrices are identified for the general case of M closely spaced signals. It is shown that the largest signal-space eigenvalue is relatively insensitive to signal separation. By contrast, the ith largest eigenvalue is proportional to δω2(i-1) or δω4(i-1), where δω is a measure of signal separation. Therefore, matrix conditioning degrades rapidly as signal separation is reduced. It is also shown that the limiting eigenvectors have remarkably simple structures. The results are very general, and apply to planar far-field direction-finding problems involving almost arbitrary scenarios, and also to time-series analysis of sinusoids, exponentials, and other signals  相似文献   
136.
137.
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   
138.
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   
139.
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   
140.
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