scholarly journals Analysis of the combined effect of two linear inhibitors on a single enzyme

1998 ◽  
Vol 329 (3) ◽  
pp. 689-698 ◽  
Author(s):  
Juan J. MARTINEZ-IRUJO ◽  
María L. VILLAHERMOSA ◽  
Javier MERCAPIDE ◽  
Jesús F. CABODEVILLA ◽  
Esteban SANTIAGO

Different methods for studying the concurrent effects of two linear inhibitors on a single enzyme have been published, including the fractional product of Webb, the Yonetani-Theorell plot or the method of Chou and Talalay. Recently the use of combination plots has also been advocated for this purpose. We have evaluated the applicability of these methods and found that most of them depend on assumptions about the mechanism of action of the inhibitors. If the mechanism of action is not completely understood, or if some assumptions about the mechanism are unfounded, the parameters obtained may be meaningless. Even if these assumptions are correct, the interaction can be advantageously measured using an alternative representation that does not require a knowledge of the inhibition constants and allows experimental data to be retrieved from the plot. In other cases it is the interpretation of the results rather than the validity of the method that is misleading. A common mistake is to take the exclusivity of the effects of two inhibitors as exclusivity of their binding. We show that this assumption is seldom justified. In any case, it is possible to decide whether the combination of two or more inhibitors is more effective than their individual use by means of isobolographic analysis, even when no information about their mechanism of action is available.

1938 ◽  
Vol 34 (1) ◽  
pp. 104-105
Author(s):  
L. A. Yurieva

At the meeting of the Council of the Kazan Medical Institute on 30 / XII 1937, LS Persianinov defended his dissertation for the degree of candidate of medical sciences. sciences. Dissertation topic: "Streptocide action in clinic and experiment". The dissertation was completed at the departments of microbiology and obstetric-gynecological Kazan. state Institute for Advanced Training of Physicians. V.I. Lenin. The dissertation candidate reviewed the literature of Russian and foreign sources, presented the clinical and experimental data obtained by various authors (Ulesko-Stroganova, Lebedeva, etc.), gave different views on the mechanism of action of streptocide: through the reticulo-endoelial system or due to the direct bactericidal property of the streptocide itself. The author's own research consists of an experimental and a clinical part.


Development ◽  
1961 ◽  
Vol 9 (3) ◽  
pp. 514-533
Author(s):  
Lauri Saxén ◽  
Sulo Toivonen

On the basis of certain earlier suggestions made by Lehmann (1950) and Yamada (1950), together with our own experimental data, a modification of the two-gradient hypothesis of primary induction was presented by us some years ago (Toivonen & Saxén, 1955). Subsequently, this theory has often been referred to, accepted or criticized, and even misunderstood. There may thus be reasons for discussing it in the light of some recent experimental data. At present there are limits to our opportunities of studying what is obviously the most important point in embryonic induction, the induction process itself. Simultaneously with such experiments on the induction process it is therefore necessary to continue research work on classical lines, and to obtain a further clarification of the causal relationships between the inductor and its morphogenetic action. A variety of qualitative investigations in this category have been made, but conceptions of the different quantities and the ratios of the active agents which participate in the primary induction are still based on indirect data.


2021 ◽  
Vol 66 (1) ◽  
pp. 26-31
Author(s):  
Balázs András-Tövissi ◽  
László Kajtár

If the draught and the radiant thermal asymmetry caused by the warm ceiling appear simultaneously, will women and men be affected in the same way? This research aims to answer this question, by clarifying the understanding of the joint mechanism of action of the two local discomfort factors with the help of instrumental and human subject measurements. The most important result of the present research is identifying that if PPD < 6%, radiant thermal asymmetry varies in the range of 5–15 °C and the draught rate DR = 15% or DR = 25%, then at a given range of the interval men are significantly more dissatisfied with warm ceilings than women; women’s AMV votes are significantly lower than men's; In the case of DR = 15%, the work accuracy of women is significantly higher, while in the case of men, the work accuracy is higher at DR = 25%.


1982 ◽  
Vol 60 (14) ◽  
pp. 1863-1871 ◽  
Author(s):  
Otto Hoffmann-Ostenhof ◽  
F. Pittner

The present state of our knowledge about the biosynthetic processes leading to the inositols is reviewed. On the basis of experimental data obtained in the laboratory of the authors and by other groups working on the problem, anew mechanism of action for the mammalian myo-inositol- 1-phosphate synthase is suggested. The central position of myo-inositol in the synthesis of the other inositols is described.


Author(s):  
Rakesh Yadav ◽  
Abhijit Kushari ◽  
Vinayak Eswaran ◽  
Atul K. Verma

PDF transport modeling has been known to be the most accurate for modeling turbulence chemistry interactions with finite rate chemistry effects. But, this is computationally very expensive. The Direct quadrature method of moments with Interaction by exchange with mean closure (DQMOM-IEM) can be a potential alternative to solve the PDF transport equation in an efficient manner. The current work involves the validation of presumed shape multi-environment Eulerian PDF Transport method (MEPDF) using DQMOM-IEM approach for modeling turbulence chemistry interactions in non-premixed combustion problems. The joint composition PDF is represented as a collection of finite number of Delta functions. The PDF shape is resolved by solving the governing transport equations for probability of occurrence of each environment and probability weighted mass fraction of species and enthalpy in Eulerian frame for each environment. A generic implementation of the MEPDF approach is carried out for an arbitrary number of environments. In the current work, the MEPDF approach is used for a series of problems to validate each component of MEPDF approach in an isolated manner as well as their combined effect. First of all, a non reactive turbulent mixing problem with two different Reynolds number (Re = 7000, 11900) is used for validation of the mixing and correction terms appear in the MEPDF approach. The second problem studied is a diffusion flame with infinitely fast chemistry having an analytical solution. The reaction component is validated by considering a 1D premixed laminar flame. In order to validate the combined effect of mixing and turbulence chemistry interactions, two different turbulent non premixed problems using global one step chemistry are used. The first reactive problem used is H2 combustion (DLR Flame H3) while the second reactive validation case is a pilot stabilized CH4 flame. The current predictions for all validation problems are compared with experimental data or published results. The study is further extended by modeling a turbulent non premixed H2 combustion using finite rate chemistry effects and radiative heat transfer. The current model predictions for different flame lengths as well as minor species are compared with experimental data. The current model gave excellent predictions of minor species like OH. The differences in the current predictions with experimental data are discussed.


1987 ◽  
Vol 42 (4) ◽  
pp. 349-352 ◽  
Author(s):  
Erich Gerlinger ◽  
János Rétey

Incubation of urocanase with 2-methylurocanate leads, after an initial normal reaction, to a time dependent inactivation of the enzyme. It is suggested that a tautomeric form (1) of the product, 2-methyl-imidazolone propionate, is the actual inhibitor. On the basis of these and of published experimental data a novel mechanism is proposed for the urocanase reaction. The crucial and initial step is the electrophilic addition of enzyme-bound NAD to the 2-position of the imidazole nucleus of urocanate.


1980 ◽  
Vol 58 (6) ◽  
pp. 768-771 ◽  
Author(s):  
Edward T. Dressler ◽  
Edward L. Tomusiak

The effects of contributions from pion momentum, Fermi momentum, and Δ-resonance terms on the 3He(γ,π+)3H cross section near threshold are investigated in this paper. The pion momentum terms are shown to give important corrections individually, but their combined effect gives results which are almost equivalent to previous simpler calculations. Using a simple nuclear model, the results agree well with recent experimental data.


2001 ◽  
Vol 64 (10) ◽  
pp. 1631-1635 ◽  
Author(s):  
W. TEJEDOR ◽  
M. RODRIGO ◽  
A. MARTÍNEZ

The combined effect of pH and temperature on the heat resistance of Bacillus stearothermophilus spores heated in an extract of complex food was studied. The results showed that, in general, reducing the pH reduced the heat resistance of the spores. Similarly, the value for the D parameter in the nonacidified extract was between 30 and 70% lower than the one obtained with double-distilled water. This result once again shows the importance of the substrate in inactivation studies of microorganisms. The experimental data were used to carry out a comparison of two predictive mathematical models of inactivation, one based on a multiparametric regression obtained in this study and the other obtained from the bibliography and based on a linear-Bigelow equation. Both models predict reasonably well, although the multiparametric model presented a slightly better accuracy factor (1.11) than the one obtained with the linear-Bigelow equation (1.13).


Author(s):  
Rakesh Yadav ◽  
Abhijit Kushari ◽  
Vinayak Eswaran ◽  
Atul K. Verma

The current work involves the validation of presumed shape multi-environment Eulerian probability density function (PDF) transport method (MEPDF) using direct quadrature method of moments (DQMOM)-interaction by exchange with mean (IEM) approach for modeling turbulence chemistry interactions in nonpremixed combustion problems. The joint composition PDF is represented as a collection of finite number of Delta functions. The PDF shape is resolved by solving the governing transport equations for probability of occurrence of each environment and probability-weighted mass fraction of species and enthalpy in Eulerian frame for each environment. A generic implementation of the MEPDF approach is carried out for an arbitrary number of environments. In the current work, the MEPDF approach is used for a series of problems to validate each component of MEPDF approach in an isolated manner as well as their combined effect. First of all, a nonreactive turbulent mixing problem with two different Reynolds numbers (Re = 7000 and 11,900) is used for validation of the mixing and correction terms appear in the MEPDF approach. The second problem studied is a diffusion flame with infinitely fast chemistry having an analytical solution. The reaction component is validated by considering a 1D premixed laminar flame. In order to validate the combined effect of mixing and turbulence chemistry interactions, two different turbulent nonpremixed problems using global one-step chemistry are used. The first reactive problem used is H2 combustion (DLR Flame H3), while the second reactive validation case is a pilot-stabilized CH4 flame. The current predictions for all validation problems are compared with experimental data or published results. The study is further extended by modeling a turbulent nonpremixed H2 combustion using finite-rate chemistry effects and radiative heat transfer. The current model predictions for different flame lengths as well as minor species are compared with experimental data. The current model gave excellent predictions of minor species like OH. The differences in the current predictions with experimental data are discussed.


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