The carbocyclic analog of 2′-deoxyguanosine (CdG) has broad-spectrum antiviral activity. Because ... more The carbocyclic analog of 2′-deoxyguanosine (CdG) has broad-spectrum antiviral activity. Because of recent observations with other nucleoside analogs that biological activity may be associated thel enantiomer rather than, as expected, with thed enantiomer, we have studied the metabolism of both enantiomers of CdG to identify the enzymes responsible for the phosphorylation of CdG in noninfected and virally infected human and duck cells. We have examined the enantiomers as substrates for each of the cellular enzymes known to catalyze phosphorylation of deoxyguanosine. Both enantiomers of CdG were substrates for deoxycytidine kinase (EC 2.7.1.74) from MOLT-4 cells, 5′-nucleotidase (EC 3.1.3.5) from HEp-2 cells, and mitochondrial deoxyguanosine kinase (EC 2.7.1.113) from human platelets and CEM cells. For both deoxycytidine kinase and mitochondrial deoxyguanosine kinase, thel enantiomer was the better substrate. Even though thed enantiomer was the preferred substrate with 5′-nucleotidas...
Alternative silvicultural systems to clearfelling are being adopted in Great Britain as a means o... more Alternative silvicultural systems to clearfelling are being adopted in Great Britain as a means of increasing the species and structural diversity of conifer plantation forests. One area where knowledge is lacking is the critical level of below-canopy light for survival and growth of young seedlings. This was investigated by planting seedlings of European larch Larix decidua (Mill.), Scots pine Pinus sylvestris L., Sitka spruce Picea sitchensis (Bong.(Carr.)), Douglas fir Pseudotsuga menziesii (Mirb.(Franco.)), and western hemlock Tsuga heterophylla (Raf. (Sarg.)) in a Sitka spruce plantation thinned to 3 different spacings. The incident light intensity beneath the canopy ranged from about 2 to over 60 per cent of full light. Planting in an adjoining open area provided an indication of growth under full light. Growth and survival of these seedlings were followed for 4 growing seasons. The highest seedling survival was found under the widest spacing and declined with closer spacing a...
With optimization increasingly used in engineering applications, a series of optimization runs ma... more With optimization increasingly used in engineering applications, a series of optimization runs may be required, and it may be too expensive to converge them to very high accuracy. A procedure for estimating average optimization convergence errors from a set of poorly converged optimization runs is developed. A probabilistic model is fitted to the errors in optimal objective function values of
The patch-clamp technique has been used to measure changes in membrane capacitance (Cm) of bovine... more The patch-clamp technique has been used to measure changes in membrane capacitance (Cm) of bovine lactotrophs in order to monitor fluctuations in cell surface area associated with exo- and endocytosis. Cells were prepared by an enrichment procedure and cultured for up to 14 d before use. Under whole-cell recording, cell cytoplasm was dialyzed with various Ca2(+)-containing solutions. The resting Cm of 6.05 +/- 1.68 pF was found to correlate well with squared cell radius, suggesting a specific Cm of 0.8 microF/cm2. Discrete Cm steps of 2-10 fF were recorded, which most likely reflect single fusion and retrieval events of prolactin-containing granules (0.2-0.6 microns in diameter). High Ca2+ resulted in a Cm increase of 20-50% from the resting value, demonstrating a role for [Ca2+]i in stimulus-secretion coupling. Spontaneous Cm changes have also been recorded, which presumably reflect prolactin secretion supported by a tonic influx of Ca2+ through the membrane. This is supported by t...
The carbocyclic analog of 2′-deoxyguanosine (CdG) has broad-spectrum antiviral activity. Because ... more The carbocyclic analog of 2′-deoxyguanosine (CdG) has broad-spectrum antiviral activity. Because of recent observations with other nucleoside analogs that biological activity may be associated thel enantiomer rather than, as expected, with thed enantiomer, we have studied the metabolism of both enantiomers of CdG to identify the enzymes responsible for the phosphorylation of CdG in noninfected and virally infected human and duck cells. We have examined the enantiomers as substrates for each of the cellular enzymes known to catalyze phosphorylation of deoxyguanosine. Both enantiomers of CdG were substrates for deoxycytidine kinase (EC 2.7.1.74) from MOLT-4 cells, 5′-nucleotidase (EC 3.1.3.5) from HEp-2 cells, and mitochondrial deoxyguanosine kinase (EC 2.7.1.113) from human platelets and CEM cells. For both deoxycytidine kinase and mitochondrial deoxyguanosine kinase, thel enantiomer was the better substrate. Even though thed enantiomer was the preferred substrate with 5′-nucleotidas...
Alternative silvicultural systems to clearfelling are being adopted in Great Britain as a means o... more Alternative silvicultural systems to clearfelling are being adopted in Great Britain as a means of increasing the species and structural diversity of conifer plantation forests. One area where knowledge is lacking is the critical level of below-canopy light for survival and growth of young seedlings. This was investigated by planting seedlings of European larch Larix decidua (Mill.), Scots pine Pinus sylvestris L., Sitka spruce Picea sitchensis (Bong.(Carr.)), Douglas fir Pseudotsuga menziesii (Mirb.(Franco.)), and western hemlock Tsuga heterophylla (Raf. (Sarg.)) in a Sitka spruce plantation thinned to 3 different spacings. The incident light intensity beneath the canopy ranged from about 2 to over 60 per cent of full light. Planting in an adjoining open area provided an indication of growth under full light. Growth and survival of these seedlings were followed for 4 growing seasons. The highest seedling survival was found under the widest spacing and declined with closer spacing a...
With optimization increasingly used in engineering applications, a series of optimization runs ma... more With optimization increasingly used in engineering applications, a series of optimization runs may be required, and it may be too expensive to converge them to very high accuracy. A procedure for estimating average optimization convergence errors from a set of poorly converged optimization runs is developed. A probabilistic model is fitted to the errors in optimal objective function values of
The patch-clamp technique has been used to measure changes in membrane capacitance (Cm) of bovine... more The patch-clamp technique has been used to measure changes in membrane capacitance (Cm) of bovine lactotrophs in order to monitor fluctuations in cell surface area associated with exo- and endocytosis. Cells were prepared by an enrichment procedure and cultured for up to 14 d before use. Under whole-cell recording, cell cytoplasm was dialyzed with various Ca2(+)-containing solutions. The resting Cm of 6.05 +/- 1.68 pF was found to correlate well with squared cell radius, suggesting a specific Cm of 0.8 microF/cm2. Discrete Cm steps of 2-10 fF were recorded, which most likely reflect single fusion and retrieval events of prolactin-containing granules (0.2-0.6 microns in diameter). High Ca2+ resulted in a Cm increase of 20-50% from the resting value, demonstrating a role for [Ca2+]i in stimulus-secretion coupling. Spontaneous Cm changes have also been recorded, which presumably reflect prolactin secretion supported by a tonic influx of Ca2+ through the membrane. This is supported by t...
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