McFarland model

Special cases of such bilinear models are the McFarland model [McFarland, 1970], where b2 = 2b and p = 1 and the Higuchi-Davis model [Higuchi and Davis, 1970], where 2 = 1 and P = Vup / Vaq, which is the ratio between the volume of the lipid phase Viip and the volume of the aqueous phase Vaq. 

The bilinear model (eq. 93) (Figure 14) was derived from a reconsideration of the McFarland model, taking into account the different volumes of aqueous and organic... 

Sustaining the transport model, further non-linear representations of the observed structure-activity relationships were derived. According to the McFarland model (Seydel and Schaper, 1979 Kubinyi 1993), the probability of a drug reaching the receptor after passing several membranes depends on its lipophilicity in a symmetrical manner with linearly increasing and decreasing sides of the curve ... 

The term a gives the slope of the left-hand ascending side of the curve and (a - b) that of the right-hand descending side. The non-linear parameter jS, which must be estimated by a stepwise iteration procedure, relates to the volume ratio of the aqueous and lipid phases in the system. Setting jS = 1 and b 2a produces the original McFarland model. Kubiny s bilinear model can be derived from kinetically controlled model systems as well as from equilibrium models, indicating that it is valid under diffusion control as well as under equilibrium or pseudo-equilibrium conditions. For many data sets, the bilinear function aptly fits the experimental observations. Difficulties in calculations may arise from unbalanced data sets, which often occur in environ-... 

Decision analytic models have been constmcted to compare the costs of TCAs with those of SSRIs and other compounds. These comparisons have included imipramine or amitriptyline versus paroxetine or sertraline (Stewart, 1994) imipramine versus paroxetine Qonsson and Bebbington, 1994 McFarland, 1994 Lapierre et al, 1995) fluoxetine versus amitriptyline, clomipramine, doxepin and imipramine (Le Pen et al, 1994) venlafaxine versus amitriptyline, desipramine. 

With few exceptions, models find in favour of newer compounds Qonsson and Bebbington, 1994 Le Pen et al, 1994 McFarland, 1994 Stewart, 1994 Einarson et al, 1995 Lapierre et al, 1995 Nuitjen et al, 1995 Montgomeiy et al, 1996). One study (CCOHTA, 1997) did make allowances for variations in practice and patient behaviour. The results indicated that in the short term treatment was likely to be more successful with an SSRI than with a TCA, but at a higher cost. However, when treatment dropout rates found in naturalistic studies were substituted for drop-out rates found in controlled trials, the cost differences became smaller. When cost-utility analysis was applied, this increased cost was offset by improvements in quality of life for the patients. 

Raevsky, O. A., Schaper, K.-J., Van de Waterbeemd, H., McFarland, J. Hydrogen bond contribution to properties and activities of chemicals and drugs. In Molecular Modeling and Prediction of Bioactivity, Gundertofte, K., Jorgensen,... 

IPCC (Intergovernmental Panel on Climate Change), Aviation and the Global Atmosphere, 1999, J.E.Penner, D. H. Lister, D. 1. Griggs, D.J. Dokken, M. McFarland (Eds), Chapter 4 Modelling the Chemical Composition of the Atmosphere, I.S.A. Isaksen and C. Jackman, Cambridge University Press. 

Andersen, M.E., H.J. Clewell III, and H.A. Barton (1998). A pharmacodynamic model of atrazine effects on estrous cycle characteristics in the Sprague-Dawley rat. In L.G. Ballantine, J.E. McFarland, and D.S. Hackett, eds., Triazine Herbicides Risk Assessment. Washington, DC American Chemical Society, pp. 432-477. 

Another cutoff model, which deals with nonlinearity in biological systems, is one defined by McFarland (191). It attempts to elucidate the dependency of drug transport on hydrophobicity in multicompartment models. McFarland addressed the probability of drug molecules traversing several aqueous lipid barriers from the first aqueous compartment to a distant, final aqueous compartment. The probability of a drug molecule to access the final compartment n of a biological system was used to define the drug concentration in this compartment. 

McFarland, J.W., Raevsky, O.A. and Wilkerson, W.W. (1999) Hydrogen bond acceptor and donor factors, Ca and Q new QSAR descriptors, in Molecular Modeling and Prediction of Bioactivity (eds K. Gundertofte and K. Jorgensen), Kluwer Academic/Plenum Publishers, USA, pp. 280-281. 

Theoretical approaches were followed by others, the first one laying the foundation for all other theoretical models. McFarland considered the rate constants k (transport from the aqueous phase into an organic phase) and I (transport in the reverse direction) to be related to the probabilities of a molecule to enter either the lipid phase (eq. 87) or the aqueous phase (eq. 88) from an aqueous/lipid interface (Pi,j = probabilities) [436]. 

Figure 13 McFarland probability model (eqs. 87 — 90). Symmetrical curves with linear ascending and descending sides result from eq. 90 (reproduced from Figure 1 and redrawn from Figure 3 of ref. [436] with permission from the American Chemical Society, Washington, DC, USA).

Successful discriminant analysis is based on the assumption that the data in each class are normally distributed and all classes have the same covariance matrix (McFarland and Cans, 1990). Discriminant analysis is extremely sensitive to collinearities among descriptors and the ratio of the number of chemicals in the data set to the number of descriptors in the model should exceed 10 1. For the training-set selection, the data quality, the statistical significance, the type of descriptors and the limitations of the model range, the same restrictions apply for discriminant analysis as explained for classical regression analysis (section 3.2.1) ... 

Michael C. McFarland, S.J., Mathematical Models for Formal Verification in a Design Automation System, PhD Thesis, Dept, of Electrical Engineering, Carnegie Mellon University, July 1981. 

Our joint work with Miriam Leeser on automaton models for scheduling started at the Fourth International Workshop on High-Level Synthesis our work with Miriam on BFSMs is central to PUBSS. Thanks to Mike McFarland and Raul Camposano for valuable feedback on a variety of problems. 

The development of toxicity equivalent factors (TEFs) for halogenated aromatic compounds, as proposed by Safe [34], is based on the observed common receptor-mediated mechanism of action of toxic halogenated aromatics. The relative toxicity of 2,3,7,8-TCDD is taken as unity on the TEF scale, and individual TEF values have been derived for the other stereoisomers including PCBs [38]. Recendy, a thermodynamic model for calculating the TEF values for PCBs was reported by Kafafi et al. [39] their model permitted calculation of the dissociation constants of complexes formed between the aryl hydrocarbon receptor and a PCB molecule. McFarland and Clarke [40] have argued that, as the toxicity of individual congeners varies over a range of 10, the determination of total PCB content is of... 

C. W. McFarland, The Finite Difference Method for Modeling Potential and Current Distributions in Electroplating Cells, in Electroplating Engineering and Waste Recycle New Developments, Dexter Snyder, Uziel Landau, and R, Sard, 1982 Symposium Proceedings, The Electrochemical Society, Inc., Pennington, NJ, 1983. 

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