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991.
992.
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
993.
A B?lcskei G Bilkei O Biro E Clavadetscher T Goos P Orban C Waller P Stelzer 《Canadian Metallurgical Quarterly》1996,109(3):108-111
The most important postweaning factorial diseases are at least partly caused by E. coli. The term postweaning coli complex can be subcategorized into the following manifestations: postweaning diarrhoea, edema disease, postweaning wasting and hemorrhagic gastroenteritis. In the presented study the effect of prophylactic zootechnique alone and zoo- and biotechnique in combination was evaluated during the first weeks postweaning. The results showed that combined zoo- and biotechnique is superior to simple zootechnique regarding food conversion (1.41 kg versus 1.73 kg), average daily weight gain (390 g versus 325 g) and postweaning piglet mortality (3.1% versus 4.9%). It is the opinion of the authors that combined postweaning zoo- and biotechnique should be performed in such pig production units where ETEC and/or SLTEC are present. 相似文献
994.
The authors present a push-pull transformer-coupled amplifier for monolithic microwave applications, and discuss how its stability and layout have been improved with respect to conventional approaches by means of opposite-phase feedback and fully symmetrical layout. The circuit provides state-of-the-art performance (10-dB gain and 18-dBm saturated power in the 4-8-GHz band) with only 165-mW DC power consumption 相似文献
995.
One requirement in designing and operating and operating system is to minimize the moisture change in stored grain. Moisture transfer during the aeration process is generally believed to be caused by the partial pressure difference between water in grain and water in air (P3-P4). A mathematical model was developed for rough rice, which predicts the partial pressure difference under various grain and ambient conditions. Observations of moisture change over 10 aeration tests confirmed the good correlation between sorption phenomena and partial pressure differences. Studies indicated that air relative humidity, air temperature, grain temperature and grain moisture are significant factors influencing the partial pressure differences and, thus, affecting 相似文献
996.
Until now, attention has been focused solely in the drying of squid mantle from an experimental point of view, neglecting the transport phenomenon studies of water in squid muscle. This work studies the drying of squid mantle (Loligo brasiliensis), previously salted and smoked by liquid smoking (hickory extract), using a tubular dryer in closed cycle with a silicagel fixed bed in series. The mass transfer phenomenon during drying was studied, based on the Fick's second law, with the effective diffusivity supposed constant, which enabled an analytical solution to the problem. The drying curve calculated with the resulting equation was compared with experimental data. The model was applied to a hollow cylinder geometry (round squid mantle), with its internal surface isolated from the drying environment by a plastic film. The latter was given a tubular form and introduced inside the mantle cavity (impervious wall boundary condition). 相似文献
997.
Arafa M. Fay P. Ismail K. Chu J.O. Meyerson B.S. Adesida I. 《Electron Device Letters, IEEE》1996,17(3):124-126
We report on the fabrication and characterization of high-speed p-type modulation-doped field-effect transistors (MODFETs) with 0.7-μm and 1-μm gate-lengths having unity current-gain cut-off frequencies (fT) of 9.5 GHz and 5.3 GHz, respectively. The devices were fabricated on a high hole mobility SiGe heterostructure grown by ultra-high-vacuum chemical vapor deposition (UHV-CVD). The dc maximum extrinsic transconductance (gm) is 105 mS/mm (205 mS/mm) at room temperature (77 K) for the 0.7-μm gate length devices. The fabricated devices show good pinch-off characteristics and have a very low gate leakage current of a few μA/mm at room temperature and a few nA/mm at 77 K 相似文献
998.
999.
Surface-induced dissociation (SID) has been used to produce daughter ion spectra of small protonated peptides generated by fast atom bombardment (FAB). The relative abundances of daughter ions depends critically upon the energy of the ion/surface collision. A wide array of decomposition processes may be observed using ELAB collision energies in the range 10-20 eV. At approximately 13-eV collision energy, the variety of decomposition processes is maximized for the small peptides studied; hence, maximum structural information may be deduced. Collisionally-activated dissociations (CAD) using argon gas and the identical protonated peptides could not produce as large an array of daughter ions in a constant condition experiment. An apparent contradiction is thereby posed because SID is known to produce a narrow distribution of ion internal energies relative to CAD. This apparent contradiction is resolved by considering the rather large kinetic energy spread of ions leaving the FAB source. For the SID process, this large initial kinetic energy distribution is converted into a significantly wider spread in center-of-mass collision energy, leading to a broader variety of decomposition processes (high and low energy) compared to CAD. 相似文献
1000.