Models for Screening

At the outset of the study of a new reaction very little is known with certainty. At this stage, we are not interested in very precise descriptions. It is sufficient to know whether or not the variables influence, what magnitude and direction these influences have, and whether there are important interaction effects. 

Response models which are useful in this context are the linear models 

The linear models will approximate the response surface by a plane. The estimated linear coefficients, bh describe the slope of the plane and hence, the sensitivity of the response to a variation of the corresponding variable settings. A slope close to zero (of the same order as the experimental error) indicates that the variable does not have a significant influence, whereas a slope distinctly different from zero shows a significant influence. 

In the second-order interaction model cross-product terms have also been included. A significant estimated cross-product coefficient, bVj, shows that the influence of variable X is dependent on the settings of variable xp i.e. there is an interaction effect between these variables. Geometrically this corresponds to a twist of the response surface over the xi x3 plane. 

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Santos FA, Rao VSN (1998) Inflammatory edema induced by 1,8-cineole in the hindpaw of rats a model for screening antiallergic and anti-inflammatory compounds. Phytomedicine 5(2) 115-119... 

Comparing only the results at low pH, one would expect both formulations to perform equally in the clinic. However, as would be expected from the dissolution profiles at both pH values, formulation B produced far less variability of absorption in the clinical studies and was also better absorbed than formulation A. This example illustrates clearly the value of the hypochlorhydic model for screening formulations prior to taking them into the clinic. 

Zebrafish A Vertebrate Model for Screening Thyroid Gland Function Disrupters.. 421... 

Thienpont B, Tingaud-Sequeira A, Prats E, Barata C, Babin PJ, Raldua D (2011) Zebrafish eleutheroembryos provide a suitable vertebrate model for screening chemicals that impair thyroid hormone synthesis. Environ Sci Technol 45 7525-7532... 

Table 14.3 Characteristics of an effective cell model for screening for sublethal cytotoxicity [4, 11, 33, 36].

Reinhardt CA (1993) Neurodevelopmental toxicity in vitro Primary cell culture models for screening and risk assessment. Reprod Toxicol, 7(Suppl 1) 165-170. 

As observed in all our GBPM applications, the first raw7 model, due to the large number of its features, was often not usable as a pharmacophore model for screening. As shown in Fig. 7.6, our approach was able to recognize cor-... 

Catalyst HypoGenf pharmacophore and GOLDb docking were used to develop the composite model for screening potential thymidine monophosphate kinase inhibitors... 

Yi, B. (2002). Nonparametric, parametric and semiparametric models for screening and decoding pools of chemical compounds. Unpublished PhD dissertation. North Carolina State University, Department of Statistics. 

Franke et al. (1999) have described an in vitro model for screening of drug entry into the brain using primary cultures of porcine brain capillary endothelial cells (PBCEC). By using serum-free culture conditions... 

Based on simple models for screening a relation between Kd, molecular size and water regain may be derived (Porath, 1962b). 

Abelson MB, Butrus SI, KJitnan GH, et al. Topical arachidonic acid a model for screening anti-inflammatory agents. J Ocul Pharmacol 1987 3 63-75. 

T.A., and Diller, D.J. (2002) Use of catalyst pharmacophore models for screening of large combinatorial libraries. Journal of Chemical Information and Computer Sciences, 42, 1204-1211. 

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