ATP allosterically activates the human 5-lipoxygenase molecular mechanism of arachidonic acid and 5(S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid.

5-Lipoxygenase (5-LOX) reacts with arachidonic acid (AA) to first generate 5(S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid [5(S)-HpETE] and then an epoxide from 5(S)-HpETE to form leukotriene A4, from a single polyunsaturated fatty acid. This work investigates the kinetic mechanism of these two processes and the role of ATP in their activation. Specifically, it was determined that epoxidation of 5(S)-HpETE (dehydration of the hydroperoxide) has a rate of substrate capture (Vmax/Km) significantly lower than that of AA hydroperoxidation (oxidation of AA to form the hydroperoxide); however, hyperbolic kinetic parameters for ATP activation indicate a similar activation for AA and 5(S)-HpETE. Solvent isotope effect results for both hydroperoxidation and epoxidation indicate that a specific step in its molecular mechanism is changed, possibly because of a lowering of the dependence of the rate-limiting step on hydrogen atom abstraction and an increase in the dependency on hydrogen bond rearrangement. Therefore, changes in ATP concentration in the cell could affect the production of 5-LOX products, such as leukotrienes and lipoxins, and thus have wide implications for the regulation of cellular inflammation

Evaluation of Boundary Conditions for the Gust-Cascade Problem

Using a high-order accuracy finite-difference time-domain algorithm, the acoustic scattering from a flat-plate cascade is computed. Keeping the grid and time step fixed, the effect of four different boundary conditions on the accuracy and stability of the computed solution is compared

Three-dimensional Structure in a Supersonic Jet: Behavior near Centerline

The unsteady structure of a supersonic jet is highly three dimensional, though the mean flow is axisymmetric. In simulating a circular jet, the centerline represents a computational boundary. As such, spurious modes can be generated near centerline, unless special attention is given to the behavior of the 3D structure near the centerline. Improper treatment of the dependent variables near the centerline results in the solution diverging or being suitable only for small amplitude excitation. With a careful treatment of the centerline formation, no spurious mode is generated. The results show that a near-linear disturbance growth is obtained, as the linear stability theory indicates. At high levels of excitation, nonlinear development of disturbances is evident and saturation is reached downstream

Effect of Coannular Flow on Linearized Euler Equation Predictions of Jet Noise

An improved version of a previously validated linearized Euler equation solver is used to compute the noise generated by coannular supersonic jets. Results for a single supersonic jet are compared to the results from both a normal velocity profile and an inverted velocity profile supersonic jet

Comparison of Numerical Schemes for a Realistic Computational Aeroacoustics Benchmark Problem

In this work, a nonlinear structured-multiblock CAA solver, the NASA GRC BASS code, will be tested on a realistic CAA benchmark problem. The purpose of this test is to ascertain what effect the high-accuracy solution methods used in CAA have on a realistic test problem, where both the mean flow and the unsteady waves are simultaneously computed on a fully curvilinear grid from a commercial grid generator. The proposed test will compare the solutions obtained using several finite-difference methods on identical grids to determine whether high-accuracy schemes have advantages for this benchmark problem

Evaluation of Boundary Conditions for Computational Aeroacoustics

The performance of three boundary conditions for aeroacoustics were investigated, namely, (1) Giles-1990; (2) Tam and Webb-1993, and (3) Thompson-1987. For each boundary condition, various implementations were tested to study the sensitivity of their performance to the implementation procedure. Details of all implementations are given. Results are shown for the acoustic field of a monopole in a uniform freestream

Unsteady Validation of a Mean Flow Boundary Condition for Computational Aeroacoustics

In this work, a previously developed mean flow boundary condition will be validated for unsteady flows. The test cases will be several reference benchmark flows consisting of vortical gusts convecting in a uniform mean flow, as well as the more realistic case of a vortical gust impinging on a loaded 2D cascade. The results will verify that the mean flow boundary condition both imposes the desired mean flow as well as having little or no effect on the instantaneous unsteady solution

On the Use of Linearized Euler Equations in the Prediction of Jet Noise

Linearized Euler equations are used to simulate supersonic jet noise generation and propagation. Special attention is given to boundary treatment. The resulting solution is stable and nearly free from boundary reflections without the need for artificial dissipation, filtering, or a sponge layer. The computed solution is in good agreement with theory and observation and is much less CPU-intensive as compared to large-eddy simulations

Direct Computation of Sound Radiation by Jet Flow Using Large-scale Equations

Jet noise is directly predicted using large-scale equations. The computational domain is extended in order to directly capture the radiated field. As in conventional large-eddy-simulations, the effect of the unresolved scales on the resolved ones is accounted for. Special attention is given to boundary treatment to avoid spurious modes that can render the computed fluctuations totally unacceptable. Results are presented for a supersonic jet at Mach number 2.1