Simulation mechanistic

The time-dependent Schrddinger equation governs the evolution of a quantum mechanical system from an initial wavepacket. In the case of a semiclassical simulation, this wavepacket must be translated into a set of initial positions and momenta for the pseudoparticles. What the initial wavepacket is depends on the process being studied. This may either be a physically defined situation, such as a molecular beam experiment in which the paiticles are defined in particular quantum states moving relative to one another, or a theoretically defined situation suitable for a mechanistic study of the type what would happen if. .. 

These, such as the black box that was the receptor at the turn of the century, usually are simple input/output functions with no mechanistic description (i.e., the drug interacts with the receptor and a response ensues). Another type, termed the Parsimonious model, is also simple but has a greater number of estimatable parameters. These do not completely characterize the experimental situation completely but do offer insights into mechanism. Models can be more complex as well. For example, complex models with a large number of estimatable parameters can be used to simulate behavior under a variety of conditions (simulation models). Similarly, complex models for which the number of independently verifiable parameters is low (termed heuristic models) can still be used to describe complex behaviors not apparent by simple inspection of the system. 

A kinetic model which accounts for a multiplicity of active centres on supported catalysts has recently been developed. Computer simulations have been used to mechanistically validate the model and examine the effects on Its parameters by varying the nature of the distrlbultons, the order of deactivation, and the number of site types. The model adequately represents both first and second order deactivating polymerizations. Simulation results have been used to assist the interpretation of experimental results for the MgCl /EB/TlCl /TEA catalyst suggesting that... 

The initial set of simulations were used to mechanistically validate the kinetic model so it could be used in meaningful kinetic Investigations. By pre-determining the distribution of active sites, actual (theoretical) values of 9j and 02 can be... 

For this reason, process-based whole-farm simulators have been developed. The simulators comprise modules containing semiempirical equations and mechanistic models that account for soil type, crops grovm, climate, herd size, manure handling, and other factors for a variety of farms as well as modules that calculate GHG emissions, other types of... 

A valid mechanistic model can be very useful, not only in that it can appreciably add to our process understanding, but also in that it can be successfully employed in many aspects of emulsion polymerization reactor technology, ranging from latex reactor simulation to on-line state estimation and control. A general model framework has been presented and then it was shown how it can be applied in a few of these areas. The model, being very flexible and readily expandable, was further extended to cover several monomer and comonomer systems, in an effort to illustrate some of its capabilities. 

Physiologically based mechanistic gastrointestinal simulation can be used for identification and ranking of drug discovery candidates with regard to their lib-... 

Tab. 18.1. Comparison of rule-based ranking to mechanistic simulation-based ranking of 138 common drugs.

Mechanistic Simulation (ACAT models) in Early Discovery... 

The mechanistic simulation ACAT model was modified to account automatically for the change in small intestinal and colon k as a function of the local (pH-dependent) log D of the drug molecule. The rank order of %HIA from GastroPlus was directly compared with rank order experimental %HIA with this correction for the log D of each molecule in each of the pH environments of the small intestine. A significant Spearman rank correlation coefficient for the mechanistic simulation-based method of 0.58 (p < 0.001) was found. The mechanistic simulation produced 71% of %HIA predictions within 25% of the experimental values. 

In addition to the mechanistic simulation of absorptive and secretive saturable carrier-mediated transport, we have developed a model of saturable metabolism for the gut and liver that simulates nonlinear responses in drug bioavailability and pharmacokinetics [19]. Hepatic extraction is modeled using a modified venous equilibrium model that is applicable under transient and nonlinear conditions. For drugs undergoing gut metabolism by the same enzymes responsible for liver metabolism (e.g., CYPs 3A4 and 2D6), gut metabolism kinetic parameters are scaled from liver metabolism parameters by scaling Vmax by the ratios of the amounts of metabolizing enzymes in each of the intestinal enterocyte compart-... 

Application of ultra-high-throughput in silico estimation of biopharmaceutical properties to the generation of rule-based computational alerts has the potential to improve compound selection to those drug candidates that are likely to prove less troublesome in their development. The extension of purely in silico methods to the realm of mechanistic simulation further enhances our ability to predict the impact of physiological and biochemical process on drug absorption and bioavailability. 

The detailed kinetic description of a chemical process is a primary feature for both the industrial practice and the comprehension of the reaction mechanism. The development of a kinetic model able to predict at the same time the reactants conversion and the products distribution (i.e., a detailed kinetic model) is a prerequisite for the design, optimization, and simulation of the industrial process. Also, the detailed description of process kinetics allows the ex post evaluation of the goodness of the mechanistic scheme on the basis of which the model itself is developed, making possible the collection of further insight in the chemistry of the process. 

Recently, Orosz et al. [136] reviewed and critically reevaluated some of the known mechanistic studies. Detailed mathematical expressions for rate constants were presented, and these are used to derive relationships, which can then be used as guidelines in the optimization procedure of the POCL response. A model based on the time-window concept, which assumes that only a fraction of the exponential light emission curve is captured and integrated by the detector, was presented. Existing data were used to simulate the detector response for different reagent concentrations and flow rates. 

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