Home About us Contact
|
Home About us Contact | ||
|
|
||
Kinetic Modelling (kinetic + modelling)
Selected AbstractsHydrodynamic and Kinetic Modelling of Dust Free and Dusty Radio-Frequency DischargesCONTRIBUTIONS TO PLASMA PHYSICS, Issue 5-6 2004W. J. Goedheer Abstract In this paper hydrodynamic and kinetic approaches to model low pressure capacitively coupled radio-frequency discharges are discussed. In particular approaches and results for power modulated discharges in a mixture of silane and hydrogen and for discharges containing a considerable amount of dust particles will be presented. (© 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Kinetic evidences for facilitation of peptide channelling by the proteasome activator PA28FEBS JOURNAL, Issue 20 2000Ralf Stohwasser The activation kinetics of constitutive and IFN,-stimulated 20S proteasomes obtained with homomeric (recPA28,, recPA28,) and heteromeric (recPA28,,) forms of recombinant 11S regulator PA28 was analysed by means of kinetic modelling. The activation curves obtained with increasing concentrations of the individual PA28 subunits (RecP28,/RecP28,/RecP28,+ RecP28,) exhibit biphasic characteristics which can be attributed to a low-level activation by PA28 monomers and full proteasome activation by assembled activator complexes. The dissociation constants do not reveal significant differences between the constitutive and the immunoproteasome. Intriguingly, the affinity of the proteasome towards the recPA28,, complex is about two orders of magnitude higher than towards the homomeric PA28, and PA28, complexes. Striking similarities can been revealed in the way how PA28 mediates the kinetics of latent proteasomes with respect to three different fluorogenic peptides probing the chymotrypsin-like, trypsin-like and peptidylglutamyl-peptide hydrolyzing like activity: (a) positive cooperativity disappears as indicated by a lack of sigmoid initial parts of the kinetic curves, (b) substrate affinity is increased, whereby (c), the maximal activity remains virtually constant. As these kinetic features are independent of the peptide substrates, we conclude that PA28 exerts its activating influence on the proteasome by enhancing the uptake (and release) of shorter peptides. [source] Calorimetric investigations into the starvation response of Pseudomonas putida growing on phenol and glucoseJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2009Andreas Lißner Abstract Aims:, To investigate the stress response during nutrient deprivation, particularly with regard to the application of phenol as growth substrate of Pseudomonas putida with calorimetric measurements as a new method. Methods and Results:, The online and noninvasive measurement of the thermal power P0 permits the detection of microbial activity during the starvation period. While the results of the investigations with phenol reveal a significant loss of activity as a function of the temporal nutrient dosage, only a small loss of activity was detected by using glucose. Microbiological methods (colony forming units (CFU) and activity of catechol-2,3-dioxygenase) showed a loss of the enzyme activity at a constant CFU. The introduction of a simple decay parameter kD in the kinetic description of the growth process on phenol was sufficient for the successful kinetic modelling. Conclusions:, The combination of calorimetric measurements and the determination of the enzymatic activity proved the loss of activity of Ps. putida during the deprivation of the substrate phenol. Significance and Impact of the study:, The initial heat power (P0) proves to be a suitable parameter for the characterization of the physiological state of the culture and can be used for the regulation of nutrient supply in biotechnological process development. [source] Aromatic residues at position 55 of rat ,7 nicotinic acetylcholine receptors are critical for maintaining rapid desensitizationTHE JOURNAL OF PHYSIOLOGY, Issue 4 2008Elaine A. Gay The rat ,7 nicotinic acetylcholine receptor (nAChR) can undergo rapid onset of desensitization; however, the mechanisms of desensitization are largely unknown. The contribution of a tryptophan (W) residue at position 55 of the rat ,7 nAChR subunit, which lies within the ,2 strand, was studied by mutating it to other hydrophobic and/or aromatic amino acids, followed by voltage-clamp experiments in Xenopus oocytes. When mutated to alanine, the ,7-W55A nAChR desensitized more slowly, and recovered from desensitization more rapidly, than wildtype ,7 nAChRs. The contribution of desensitization was validated by kinetic modelling. Mutating W55 to other aromatic residues (phenylalanine or tyrosine) had no significant effect on the kinetics of desensitization, whereas mutation to various hydrophobic residues (alanine, cysteine or valine) significantly decreased the rate of onset and increased the rate of recovery from desensitization. To gain insight into possible structural rearrangements during desensitization, we probed the accessibility of W55 by mutating W55 to cysteine (,7-W55C) and testing the ability of various sulfhydryl reagents to react with this cysteine. Several positively charged sulfhydryl reagents blocked ACh-induced responses for ,7-W55C nAChRs, whereas a neutral sulfhydryl reagent potentiated responses; residue C55 was not accessible for modification in the desensitized state. These data suggest that W55 plays an important role in both the onset and recovery from desensitization in the rat ,7 nAChR, and that aromatic residues at position 55 are critical for maintaining rapid desensitization. Furthermore, these data suggest that W55 may be a potential target for modulatory agents operating via hydrophobic interactions. [source] In situ kinetic modelling of intestinal efflux in rats: functional characterization of segmental differences and correlation with in vitro resultsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2007Isabel González-Alvarez Abstract The objective was to devise and apply a novel modelling approach to combine segmental in situ rat perfusion data and in vitro cell culture data, in order to elucidate the contribution of efflux in drug absorption kinetics. The fluoroquinolone CNV97100 was used as a model P-gp substrate. In situ intestinal perfusion was performed in rat duodenum, jejunum, ileum and colon to measure the influence of P-gp expression on efflux. Inhibition studies of CNV97100 were performed in the presence of verapamil, quinidine, cyclosporin A and p -aminohippuric acid. Absorption/efflux parameters were modelled simultaneously, using data from both in situ studies as well as in vitro studies. The maximal efflux velocity was modelled as a baseline value, corrected for each segment based on the expression level. CNV97100 passive diffusional permeability (Pdiff) and its affinity for the efflux carrier (Km) were assumed to be the same in all segments. The results indicate the new approach to combine in situ data and in vitro data succeed in yielding a unified, quantitative model for absorption/efflux. The model incorporated a quantitative relationship between P-gp expression level and the efflux functionality, both across in situ and in vitro systems, as well across different intestinal segments in the in situ studies. Permeability values decreased from duodenum to ileum in accordance with the increasing P-gp expression levels in rat intestine. The developed model reflects a strong correlation between in vitro and in situ results, including intrinsic differences in surface area. The successful application of a model approach to combine absorption data from two different experimental systems holds promise for future efforts to predict absorption results from one system to a second system. Copyright © 2007 John Wiley & Sons, Ltd. [source] | ||||||||||