The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform

Michael Gunther - One of the best experts on this subject based on the ideXlab platform.

  • Hill Equation and hatze s muscle activation dynamics complement each other enhanced pharmacological and physiological interpretability of modelled activity pca curves
    Journal of Theoretical Biology, 2017
    Co-Authors: Robert Rockenfeller, Michael Gunther
    Abstract:

    Abstract In pharmacology, particularly receptor theory, the drug dose-effect relation of bio-active substances is frequently described by a sigmoidal function formulated by A.V. Hill. In biomechanics and muscle physiology then again, H. Hatze had elaborated a mathematical model for the stimulation- and length-dependent dynamics of the calcium-induced activation of mammalian skeletal muscle. Here, we prove that muscular activity-pCa curves described by the Hill Equation and the equilibrium state predicted by Hatze’s activation dynamics are equivalent. Thus, the exponent introduced by Hatze can be directly identified with its counterpart in the Hill Equation, by which the former model gains further physiological interpretability. Conversely, the Hill constant can now be interpreted as a function of the fibre length, generally allowing for advanced Hill plots based on model ideas. We derive and examine the complementary relation of both model approaches, highlight the benefits of mutually viewing one approach from the perspective of the other, and address the physiology behind sigmoidal curves.

James R Halpert - One of the best experts on this subject based on the ideXlab platform.

  • concurrent cooperativity and substrate inhibition in the epoxidation of carbamazepine by cytochrome p450 3a4 active site mutants inspired by molecular dynamics simulations
    Biochemistry, 2015
    Co-Authors: Christian Muller, Tim Knehans, Dmitri R Davydov, Patricia L Bounds, Ursula Von Mandach, James R Halpert, Amedeo Caflisch, Willem H Koppenol
    Abstract:

    Cytochrome P450 3A4 (CYP3A4) is the major human P450 responsible for the metabolism of carbamazepine (CBZ). To explore the mechanisms of interactions of CYP3A4 with this anticonvulsive drug, we carried out multiple molecular dynamics (MD) simulations, starting with the complex of CYP3A4 manually docked with CBZ. On the basis of these simulations, we engineered CYP3A4 mutants I369F, I369L, A370V, and A370L, in which the productive binding orientation was expected to be stabilized, thus leading to increased turnover of CBZ to the 10,11-epoxide product. In addition, we generated CYP3A4 mutant S119A as a control construct with putative destabilization of the productive binding pose. Evaluation of the kinetics profiles of CBZ epoxidation demonstrate that CYP3A4-containing bacterial membranes (bactosomes) as well as purified CYP3A4 (wild-type and mutants I369L/F) exhibit substrate inhibition in reconstituted systems. In contrast, mutants S119A and A370V/L exhibit S-shaped profiles that are indicative of homotropic cooperativity. MD simulations with two to four CBZ molecules provide evidence that the substrate-binding pocket of CYP3A4 can accommodate more than one molecule of CBZ. Analysis of the kinetics profiles of CBZ metabolism with a model that combines the formalism of the Hill Equation with an allowance for substrate inhibition demonstrates that the mechanism of interactions of CBZ with CYP3A4 involves multiple substrate-binding events (most likely three). Despite the retention of the multisite binding mechanism in the mutants, functional manifestations reveal an exquisite sensitivity to even minor structural changes in the binding pocket that are introduced by conservative substitutions such as I369F, I369L, and A370V.

  • analysis of four residues within substrate recognition site 4 of human cytochrome p450 3a4 role in steroid hydroxylase activity and α naphthoflavone stimulation
    Archives of Biochemistry and Biophysics, 1998
    Co-Authors: Tammy L Domanski, Greg R Harlow, James R Halpert
    Abstract:

    Abstract Sequence alignment of human cytochrome P450 3A4 with bacterial enzymes of known structure has provided a basis from which to predict residues involved in substrate oxidation. Substitutions were made at four residues (I301, F304, A305, and T309) predicted to be located within the highly conserved substrate recognition site 4. Site-directed mutants engineered to contain carboxy-terminal histidine tags were expressed in Escherichia coli and purified on a metal affinity column. The integrity of each protein was assessed by SDS–polyacrylamide gel electrophoresis and immunoblotting. Functional analysis was performed using progesterone and testosterone as substrates and α-naphthoflavone as an activator. In testosterone hydroxylase assays, all of the mutants displayed rates of total product formation similar to wild-type 3A4, with several mutants showing small differences in specific products formed. However, with progesterone as the substrate, mutants F304A, A305V, and T309A exhibited altered product ratios and/or changes in the rates of product formation. F304A and A305V also displayed altered flavonoid stimulation that resulted in product ratios dramatically different from wild-type 3A4. Therefore, the kinetics of progesterone hydroxylation of these mutants and the wild-type enzyme were further assessed, and the data were analyzed with the Hill Equation. Results with wild-type 3A4 and F304A indicated that at high progesterone concentrations, hydroxylation rates and product ratios are independent of the presence of α-NF. This suggests that progesterone may be equivalent to α-NF as an activator. In contrast, A305V exhibited autoactivation by progesterone but inhibition by α-NF.

Jürg Solms - One of the best experts on this subject based on the ideXlab platform.

  • Formation of inclusion complexes of starch in ternary model systems with decanal, menthone, and 1-naphthol.
    Lebensmittel-Wissenschaft & Technologie, 1990
    Co-Authors: Marcel Andre Rutschmann, Jürg Solms
    Abstract:

    The complex formation between starch and the inclusion compounds decanal, menthone, and 1-naphthol was studied under equilibrium conditions in ternary model systems. Binding of decanal/menthone and menthone/1-naphthol to starch was analysed at constant concentrations of one ligand by variable concentration of the other ligand. Binding isotherms, approximated by the Hill Equation, were analysed by the «affinity spectrum method» and binding parameters were estimated by means of regression methods. To identify the helical conformations of the amylose molecule in the ternary complexes with decanal, menthone and 1-naphthol, crystalline complexes with constant proportions of the ligands were analysed by X-ray diffraction

  • the formation of ternary inclusion complexes of starch with menthone and monostearate a possible food model system
    Lwt - Food Science and Technology, 1990
    Co-Authors: Marcel Andre Rutschmann, Jürg Solms
    Abstract:

    The formation of inclusion complexes of gelatinized potato starch with the food grade emulsifier monostearate and with the flavor compound menthone was studied under equilibrium conditions in ternary model systems. The reaction was followed by a combination of amperometric iodine titration with GC analysis of the complex partners. X-ray analysis of the ternary complexes was conducted in order to identify the helical conformations of amylose in these complexes. Binding isotherms, approximated by the Hill Equation, were analysed by the «affinity spectrum method» and binding parameters were estimated by means of regression methods

S. Hamed S. Hosseini - One of the best experts on this subject based on the ideXlab platform.

  • Nonlinear dynamics and vibration of reinforced piezoelectric scale-dependent plates as a class of nonlinear Mathieu–Hill systems: parametric excitation analysis
    Engineering with Computers, 2020
    Co-Authors: Ali Shariati, S. Hamed S. Hosseini, Farzad Ebrahimi, Ali Toghroli
    Abstract:

    This work is motivated by little research in the nonlinear dynamic instability of the reinforced piezoelectric nanoplates. This paper, using an analytical approach, presents bifurcations in the nonlinear dynamic instability of the reinforced piezoelectric nanoplates caused by the parametric excitation. An axial parametric load is applied to excite the system, while the reinforced piezoelectric nanoplate is under an applied electric voltage, simultaneously. The governing Equations of motion for the reinforced piezoelectric nanoplate embedded on a visco-Pasternak foundation are derived using the nonlocal elasticity theory, Hamilton’s principle, and nonlinear von Karman theory. A class of nonlinear the Mathieu–Hill Equation is established to determine the bifurcations and the regions of the nonlinear dynamic instability. The numerical results are performed, while the emphasis is placed on investigating the effect of the applied electric voltage, visco-Pasternak foundation coefficients, and the parametric excitation. It is found that the damping coefficient is responsible of the bifurcation point variation, while the amplitude response depends on the term of the natural frequency.

  • Effect of residual surface stress on parametrically excited nonlinear dynamics and instability of double-walled nanobeams: an analytical study
    Engineering with Computers, 2020
    Co-Authors: Farzad Ebrahimi, S. Hamed S. Hosseini
    Abstract:

    A class of nonlinear Mathieu–Hill Equation is established to determine the bifurcations and the regions of nonlinear dynamic instability of a short double-walled nanobeam, while the emphasis is placed on investigating the effect of residual surface stress on instability. To achieve this goal, first, a short double-walled nanobeam is modeled and embedded on a viscoelastic foundation and subjected to an axial parametric force. Second, based on the nonlocal elasticity and nonlinear von Karman beam theories, the nonlinear governing Equation of motion is derived. Finally, Galerkin technique and multiple time scales method are used to solve the Equation. Numerical examples are treated which show various discontinuous bifurcations. Also, infinitely stable and unstable solutions are addressed.

  • Nonlinear dynamics and stability of viscoelastic nanoplates considering residual surface stress and surface elasticity effects: a parametric excitation analysis
    Engineering with Computers, 2020
    Co-Authors: Farzad Ebrahimi, S. Hamed S. Hosseini
    Abstract:

    The present study mainly investigates surface effect on nonlinear dynamic instability of viscoelastic nanoplates under parametric excitation. In fact, great attention is given to the influence of residual surface stress on nonlinear dynamic behavior of the system. To achieve this goal, the governing Equation of motion is derived by modeling a nanoplate embedded on a visco-Pasternak foundation and then, applying surface effect relations, nonlocal elasticity and nonlinear von Karman theories and Hamilton’s principle, respectively. Galerkin technique and multiple time scales method are also used to solve the Equation. A class of nonlinear Mathieu–Hill Equation is established to determine the bifurcations and the regions of nonlinear dynamic instability. The numerical results are performed, while the emphasis is placed on investigating the effect of residual surface stress, visco-Pasternak foundation coefficients, and parametric excitation. It is shown how residual surface stress leads to high values of amplitude response. Finally, stable and unstable regions in dynamic instability of viscoelastic nanoplates are addressed.

  • Parametrically excited nonlinear dynamics and instability of double-walled nanobeams under thermo-magneto-mechanical loads
    Microsystem Technologies, 2019
    Co-Authors: Farzad Ebrahimi, S. Hamed S. Hosseini
    Abstract:

    This work is motivated by lack of research in the nonlinear dynamics and the instability of the double-walled nanobeams caused by the parametric excitation and also subjected to the thermo-magneto-mechanical loads. In this paper, firstly, a short double-walled nanobeam is modeled and embedded on a viscoelastic foundation. The double-walled nanobeam is subjected to an axial parametric force and the thermo-magneto-mechanical loads simultaneously. Secondly, based on the nonlocal elasticity and the nonlinear von Karman beam theories, the nonlinear governing Equation of motion is derived. A class of nonlinear Mathieu–Hill Equation is established to determine the bifurcations and the regions of the nonlinear dynamic instability. The numerical results are performed while the emphasis is placed on investigating the effect of the parametric excitation, the thermo-magneto-mechanical loads, the viscoelastic foundation coefficients and the damping coefficient. The results emphasize that the outer layer of the nanobeam plays a significant role in the nonlinear instability of the system than the inner layer.

Steven A. Frank - One of the best experts on this subject based on the ideXlab platform.

  • Input-output relations in biological systems: Measurement, information and the Hill Equation
    Biology Direct, 2013
    Co-Authors: Steven A. Frank
    Abstract:

    UNLABELLED: Biological systems produce outputs in response to variable inputs. Input-output relations tend to follow a few regular patterns. For example, many chemical processes follow the S-shaped Hill Equation relation between input concentrations and output concentrations. That Hill Equation pattern contradicts the fundamental Michaelis-Menten theory of enzyme kinetics. I use the discrepancy between the expected Michaelis-Menten process of enzyme kinetics and the widely observed Hill Equation pattern of biological systems to explore the general properties of biological input-output relations. I start with the various processes that could explain the discrepancy between basic chemistry and biological pattern. I then expand the analysis to consider broader aspects that shape biological input-output relations. Key aspects include the input-output processing by component subsystems and how those components combine to determine the system's overall input-output relations. That aggregate structure often imposes strong regularity on underlying disorder. Aggregation imposes order by dissipating information as it flows through the components of a system. The dissipation of information may be evaluated by the analysis of measurement and precision, explaining why certain common scaling patterns arise so frequently in input-output relations. I discuss how aggregation, measurement and scale provide a framework for understanding the relations between pattern and process. The regularity imposed by those broader structural aspects sets the contours of variation in biology. Thus, biological design will also tend to follow those contours. Natural selection may act primarily to modulate system properties within those broad constraints.\n\nREVIEWERS: This article was reviewed by Eugene Koonin, Georg Luebeck and Sergei Maslov.