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  • 1
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Deacetoxy/deacetylcephalosporin C synthase (acDAOC/DACS) from Acremonium chrysogenum is a bifunctional enzyme that catalyzes both the ring-expansion of penicillin N to deacetoxycephalosporin C (DAOC) and the hydroxylation of the latter to deacetylcephalosporin C (DAC). Three residues N305, R307 and R308 located in close proximity to the C-terminus of acDAOC/DACS were each mutated to leucine. The N305L and R308L mutant acDAOC/DACSs showed significant improvement in their ability to convert penicillin analogs. R308 was identified for the first time as a critical residue for DAOC/DACS activity. Kinetic analyses of purified R308L enzyme indicated its improved catalytic efficiency is due to combined improvements of Km and kcat. Comparative modeling of acDAOC/DACS supports the involvement of R308 in the formation of substrate-binding pocket.
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  • 2
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Notes: G protein-coupled receptors (GPCRs) modulate diverse physiological and behavioral signaling pathways by virtue of changes in receptor activation and inactivation states. Functional changes in receptor properties include dynamic interactions with regulatory molecules and trafficking to various cellular compartments at various stages of the life cycle of a GPCR. This review focuses on trafficking of GPCRs to the cell surface, stabilization there, and agonist-regulated turnover. GPCR interactions with a variety of newly revealed partners also are reviewed with the intention of provoking further analysis of the relevance of these interactions in GPCR trafficking, signaling, or both. The disease consequences of mislocalization of GPCRs also are described.
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  • 3
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 73 (1998), S. 91-92 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Admittance spectroscopy and deep-level transient spectroscopy measurements have been performed on n+-on-p Hg1−xCdxTe (x=0.595) planar photodiodes grown by improved zone melt method. After 1.0 Mrads gamma irradiation, a new trap center is observed at 0.19 eV above the valence band, while the well-known 0.15 eV trap level disappears. The trap densities for these two levels are almost the same. We attribute this phenomenon to the gamma irradiation, which produces a compound defect correlated with Hg vacancy. © 1998 American Institute of Physics.
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  • 4
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We have measured at low temperatures the conductance of electron waveguides fabricated from modulation-doped quantum wells by wet etching and regrowth. We have found that, for a waveguide with abruptly changed geometry at the entrance and exit, the conductance shows oscillations, which are superimposed on a conventional conductance plateau structure. The periods and amplitudes of conductance oscillations depend on the length to width aspect ratio of the waveguide. In addition, the amplitudes of conductance oscillations decrease with increasing temperature. We propose that the observed oscillations are caused by the formation of longitudinal resonant electron states in the waveguide, in analogy with optical Fabry–Perot effects. © 2000 American Institute of Physics.
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  • 5
    Electronic Resource
    Electronic Resource
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 76 (2000), S. 1704-1706 
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The influence of a layer of InAs quantum dots on the transport properties of a nearby two-dimensional electron gas (2DEG) in an InGaAs/InP quantum well is investigated. The probability of the scattering between edge states is found to increase as the distance between the layer of the dots and the 2DEG decreases. It is shown that Coulomb scattering by electrons in the charged quantum dots play an important role in the scattering between edge states. An effect of the electrons in the dots is to mediate scattering between spin-split edge states. This is demonstrated by showing that the overshoot effect in the quantum Hall regime is only present when the dots are charged with electrons. © 2000 American Institute of Physics.
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  • 6
    ISSN: 1573-904X
    Keywords: intravenous microdialysis ; blood sampling ; fluconazole ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of this study was to design and validate a concentric, flexible intravenous microdialysis probe to determine drug concentrations in blood from the inferior vena cava of a freely-moving animal model. Methods. An intravenous microdialysis probe was constructed using fused-silica tubing and an acrylonitrile/sodium methallyl sulfonate copolymer hollow fiber. The probe was tested in vitro for the recovery of fluconazole and UK-54,373, a fluconazole analog used for probe calibration by retrodialysis. Subsequent in vivo validation was done in rats (n = 7) that had a microdialysis probe inserted into the inferior vena cava via the femoral vein, and the femoral artery was cannulated for simultaneous blood sampling. Comparisons of fluconazole pharmacokinetic parameters resulting from the two sampling methods were performed at 2 and 10 days after probe implantation. Results. There were no statistical differences between the microdialysis sampling and conventional blood sampling methods for the T1/2, Cl, Vdss, and dose-normalized AUC by paired t-test (p 〉 0.05) for repeated dosing at day 2 and day 10 after probe placement. The probe recovery, as determined by retrodialysis, significantly decreased over the ten day period. This finding indicates the necessity for frequent recovery determinations during a long-term blood microdialysis experiment. Conclusions. These results show that microdialysis sampling in the inferior vena cava using this unique and robust probe design provides an accurate method of determining blood pharmacokinetics in the freely-moving rat for extended experimental periods. The probe design allows for a simple surgical placement into the inferior vena cava which results in a more stable animal preparation for long-term sampling and repeated-measures experimental designs.
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  • 7
    ISSN: 1573-904X
    Keywords: microdialysis ; fluconazole ; pharmacokinetics ; brain distribution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The purpose of this study was to determine if the microdialysis sampling technique is feasible to study the central nervous system distributional kinetics of a novel triazole antifungal agent, fluconazole, in an awake, freely-moving rat model, and to determine fluconazole distribution to the extracellular fluid (ECF) of the brain. Methods. The relative recovery of the microdialysis probes (CMA-12) was determined in vitro and in vivo by retrodialysis using UK-54,373, a fluorinated analog of fluconazole. Sprague-Dawley rats received 10 mg/kg and 20 mg/kg fluconazole IV bolus doses in a crossover design, and brain extracellular fluid fluconazole concentrations were monitored using microdialysis and on-line HPLC analysis. The plasma fluconazole concentration vs. time data were determined using sequential blood sampling and HPLC analysis. Results. There was no statistical difference between relative probe recoveries for both fluconazole and UK-54,373, either in vitro or in vivo, and probe recoveries did not change during the course of the in vivo crossover experiment. Fluconazole rapidly distributes into in the brain ECF and the average brain distribution coefficient (brain/plasma AUC ratio) was 0.60 ± 0.18 and was independent of dose. Plasma pharmacokinetic parameters were linear in the dose range studied. Conclusions. Fluconazole rapidly reaches a distributional equilibrium between brain extracellular fluid and plasma, and the distribution to the brain is substantial and not dependent on dose over a two-fold range. Furthermore, the results indicate that microdialysis utilizing UK-54,373 as the in vivo retrodialysis probe calibrator is a feasible method to study the transport of fluconazole into the central nervous system.
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  • 8
    ISSN: 1437-160X
    Keywords: Key words Systemic lupus erythematosus ; Pulmonary hypertension ; Echocardiography ; Cardiac catheterization ; Endothelin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A prospective echocardiographic and clinical study was performed on 84 Chinese patients with systemic lupus erythematosus (SLE) and 99 controls to investigate the prevalence and the mechanism of pulmonary hypertension (PH) in SLE. Comparison between Doppler estimation and catheterization measurement was made in 12 cases to validate the predictive method. Compared to normal subjects, lupus patients had significantly increased sys-tolic pulmonary artery pressure (SPAP) (29.59±12.52 vs 19.64±5.82, P〈0.001), mean pulmonary artery pressure (MPAP) (15.11±7.36 vs 10.21±4.72, P〈0.001) and total pulmonary resistance (TPR) (315.85±190.65 vs 220.37± 55.92, P〈0.001). Nine of the 84 patients presented PH, defined as SPAP 〉30 mmHg and MPAP 〉20 mmHg. Pulmonary hypertensive patients had higher serum endothelin (ET) than non-pulmonary hypertensive patients, were more commonly in active stages, and presented Raynaud's phenomenon and rheumatoid factors. ET level was correlated with echocardiographic pulmonary pressure. Pulmonary hypertension commonly occurs in Chinese patients with SLE (11%), and it correlates with the lupus activity and the elevation of serum endothelin.
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  • 9
    ISSN: 1572-879X
    Keywords: Fischer-Tropsch synthesis ; reaction activation barrier ; carbon chain growth and termination ; kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A method is established, by which the difference of the reaction activation barriers of carbon chain growth and termination in Fischer-Tropsch (FT) synthesis can be determined from experiments. A FT synthesis is carried out on Fe/Zn catalyst. We apply the method to analyze the experimental result and obtain the difference of reaction activation barriers of carbon chain growth and termination of α-olefins on the catalyst.
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  • 10
    ISSN: 1572-879X
    Keywords: Fe-Mn catalyst ; ultrafine particle ; FT synthesis ; active phase ; role of Mn
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The Fischer-Tropsch (FT) synthesis on Fe-Mn ultrafine catalysts prepared by a special degradation method of Fe-Mn complexes is presented. The effects of preparation method and Mn content on the FT performance are examined and the active phases and the role of Mn are elucidated.
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