Building Surrogates

Radial Basis functions (RBF) belong to the class of Artificial Neural Networks (ANNs) and are a popular choice for approximating nonlinear functions. RBF (f has its output symmetric around an associated centre p. 

A set of RBFs can serve as a basis for representing a wide class of functions that are expressible as linear combinations of the chosen RBFs 

Require Kmax (Maximum solutions used in creating surrogates Require 0 a 1 (Fraction of archive solutions used  

However, Eq. (5.9) is usually very expensive to implement if the number of the data points is large. Thus a generalized RBF network is usually adopted of the following form  

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Of course, men make much use of excuses for activities which lead to discovery, and the lure of unknown structures has in the past yielded a huge dividend of unsought fact, which has been of major importance in building organic chemistry as a science. Should a surrogate now be needed, we do not hesitate to advocate the case for synthesis. 

The variables used to build the necessary models need only to be sensitive to the critical processing parameters, in other words they can be surrogates of the actual variables (impurities, pH, etc.) being controlled. 

Alternatively to the DNA modifications in the previous two sections where the chromophore was attached to one of the four DNA bases, chromophores can be incorporated as artificial DNA bases substituting a natural base or even a whole base-pair. There is a large number of recently reported syntheses of chromophores as DNA base surrogates, e.g. flavine derivatives [26] and thiazole orange derivatives [42]. Additionally, a variety of phosphoramidites as DNA building blocks for the introduction of fluorophores into DNA are commercially available, e.g. acridine derivatives. Clearly, the synthetic protocols for this kind of DNA modification do not follow a principle strategy which can be applied in a versatile fashion, as is the case for the DNA base modifications mentioned in the previous sections. It is important to point out that in many cases it turned out to be useful to replace the 2 -deoxyribose moiety with acyclic linker systems. This was also the case during our attempts to synthesize ethidium-modified DNA, which will be described here briefly. 

P53 Normal p53 protein has an extremely short half-life and is found in small quantities inside cells. As such, p53 cannot be detected in normal cells using immuno-histochemistry. The p53 protein from abnormal p53 genes has a longer half-life than normal p53 protein, builds up inside cells, and can be detected with anti-p53 antibodies. In theory, p53 overexpression, as a surrogate marker for p53 gene mutations, is an immunohis-tochemical test for neoplasia (dysplasia). However, this is not the case in practice because correlation between staining and gene abnormalities is not precise. ... 

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