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50, 65, or 74)-to-acceptor (pHA 74) transport, and the other denoted by the superscript (A!D), corresponding to the reverse-direction transport The two equivalent ux relationships can be reduced to an ordinary differential equation in CD t , following a route similar to that in Section 7521 The gradient pH (2-Pe) model developed here implies that some back ux (A ! D) is possible As far as we know, reported literature studies generally considered back ux to be nil under gradient pH conditions That is, either Eq (710) or (711) were used to interpret the membrane transport under a pH gradient conditions If it can be assumed that CA t in Eq (726) represents a fully charged (ie, impermeable) form of the solute, then its contribution to back ux may be neglected, and an effective sink condition would prevail; that is, the concentration of the uncharged form of the solute, cA t , is used in place of CA t , where cA t % 0 Under such circumstances, the generic sink equation, Eq (722), may be used to determine an apparent permeability coef cient, Pa apparent so as to draw attention to hidden assumptions (ie, no reverse ux) However, valid use of Eq (722) is restricted to strictly maintained sink conditions and presumes the absence of membrane retention of solute This is a rather impractical constraint in high-throughput applications, where molecules with potentially diverse transport properties may be assayed at the same time A more general analysis requires the use of two effective permeability coef cients, one for each pH, each of which would be valid in the espective iso-pH conditions Since fewer limiting assumptions are made, the more general method may be more suitable for high-throughput applications We continue to derive the appropriate new model The donor acceptor membrane mass balance is molTOT VD CD 0 VA CA 1 VD CD 1 VM CM 1 7:28 .

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2 Stopping condition for the while-loop: In most of the discussed AIS models, the stopping condition is based on convergence of the ALC population or a preset number of iterations 3 Selecting a subset, S, of ALCs: The selected subset S can be the entire set P or a number of randomly selected ALCs from P Selection of S can also be based on the stimulation level (as discussed below) 4 Calculating the antigen affinity: The antigen a nity is the measurement of similarity or dissimilarity between an ALC and an antigen pattern The most commonly used measures of a nity in existing AIS models are the Euclidean distance, r-continuous matching rule, hamming distance and cosine similarity 5 Selecting a subset, H, of ALCs: In some of the AIS models, the selection of highest affinity ALCs is based on a preset a nity threshold Thus, the selected subset H can be the entire set S, depending on the preset a nity threshold 6 Calculating the network affinity: This is the measurement of affinity between two ALCs The di erent measures of network a nity are the same as those for antigen affinity A preset network a nity threshold determines whether two or more ALCs are linked to form a network 7 dapting the ALCs in subset H: Adaptation of ALCs can be seen as the maturation process of the ALC, supervised or unsupervised Some of the selection methods that can be used are negative selection (or positive selection), clonal selection and/or some evolutionary technique with mutation operators ALCs that form a network can in uence each other to adapt to an antigen These selection methods are discussed for each of the discussed AIS models in the chapter 8 Updating the stimulation of an ALC: The stimulation level is calculated in di erent ways in existing AIS models In some AIS models, the stimulation level is seen as the summation of antigen a nities, which determines the resource.

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