Screening hierarchical

In order to address these challenges, a hierarchical approach may be adopted. This approach focuses on the big picture first, then adds details to promising solutions. Therefore, preliminary screening ought to be conducted first to identify overall reaction alternatives that meet process requirements in terms of desired product, cost effectiveness, environmental acceptability, and thermodynamic feasibility. At this stage, minimum details are to be invoked. The problem of synthesizing environmentally acceptable reactions EARs has been introduced by Crabtree and El-Halwagi (1994) and can be stated as follows ... 

DeWitte, R.S. and Robins, R.H. 2006.A hierarchical screening methodology for physicochemical/ ADME/Tox profiling. Expert Opin. Drug Metab. Toxicol. 2 805. 

Fig. 10.1 Hierarchical and horizontal in vitro screening sequences. In each phase only compounds possessing certain criteria would move to the next phase. In the hierarchical model...

It is interesting to note that this approach can be implemented as either a parallel or hierarchical screening approach depending on whether or not the data on failed compounds is required Figure 1.2. For example, when screening a focused library for... 

Figure 1.2 Comparison of parallel and hierarchical screening strategies.ln the parallel screen the first three assays are run in parallel followed by a manual decision to reduce the candidate compounds down for the subsequent set of three assays. The use of real-time data QC steps and feedback in the hierarchical approach supports the filtering out of failed compounds prior to submission to the next assay. Both strategies...

Table 8.2 S ummary of the hierarchical filtering of a database of small molecules using the pharmacophore described in Fig. 8.9 (screening 1) and Fig. 8.12 (screening 2)...

Todeschini R, Consonni V (2000) Handbook of molecular descriptors. In Mannhold R, Kubinyi H, Timmerman H (eds), Methods and principles in medicinal chemistry 11. WILEY-VCH, Weinheim. Walters WP, Stahl MT, Murcko MA (1998) Virtual screening — and overview. Drug Discov Today 3 160—178. Ward JH (1963) Hierarchical grouping to optimize an objective function. J Am Stat Assoc 58 236—244. Warmuth MK, Liao J, Ratsch G et al. (2003) Active learning with support vector machines in the drug discovery process. J Chem Inf Comput Sci 43 667—673. 

Generation or use of existing rule-based screens Refinement of known rule-based screens Use of hierarchical models, discriminant functions or decision trees to classify data Generation of QSPkR models (replacing complex or 3D parameters with more rapidly calculable 1D and 2D parameters wherever possible)... 

Current generally applicable biodegradation models focus on the estimation of readily and nonreadily biodegradability in screening tests. This is because most experimental data are from such tests (e.g., MITI-I). There are far fewer data that are both quantitative and environmentally relevant (i.e., measured half-lives or rate constants). However, individual transformations and pathways are well documented in the literature. This allows for development of explicitly mechanistic models, making use of established group-contribution approaches, hierarchic rule-based expert systems, and probabilistic evaluation of possible transformation pathways. 

Once a complete flowsheet has been developed, the operability and control of the process can be considered. Moreover, the economic incentive for modifying the flowsheet to improve the control can be considered. Then a (hierarchical) procedure for the synthesis of a control system for the complete plant can be used as an additional tool for screening the process alternatives, and a preliminary hazardous operations study can be initiated. The results of this conceptual design study then provides an estimate of the economic incentive for initiating a more rigorous design study. 

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