Robust tolerance toward

The constmction of aromatic C—S bonds has traditionally been of prime synthetic interest to medicinal chemists engaged in the preparation of natural and unnatural products. In this regard, the metal-catalyzed cross-coupling strategies to build C—S bonds have found a wide range of applications in the pharmaceutical industry for their robustness and tolerance toward other functional groups. " ... 

Proteins are surprisingly resilient toward mutation. Tolerance is defined as the ability of a protein to undergo mutation without disrupting its fitness or structure. Within a protein, there is a distribution of tolerances. Some sites that are essential for function may not accept any mutations, while other positions can accept almost all amino acid substitutions with little effect. We can speak of both structural and functional tolerance, depending on the property that is robust to mutation. There is some connection between structural and functional tolerance because mutations that tend to be bad for structure also are bad for function. It is not expected that the overlap between structure and function is exact, however, since structural perturbations can conceivably retain function and, conversely, mutations that do not effect the structure could destroy function [such as mutations of essential catalytic residues (Hellinga et al., 1992 Shoichet et al., 1995 Suzuki et al., 1996b)]. 

One fundamental choice is the selection of a packed or capillary column. Packed columns generally tolerate misuse better than do capillary columns they certainly are much less expensive, and they require simpler instrumentation to enable them to deliver all of their potential resolution. However, they do not cover as wide application or operating condition ranges, nor do they deliver the potential for speed of analysis with capillary columns. In certain areas, such as instrumentation for operation outside a controlled lab environment, the higher robustness of packed columns often makes them the primary choice. Some applications, such as many gas analyses, are frequently better served by packed columns with application-specific phases and supports, such as porous polymers or molecular sieves, although great strides have been made toward suitable capillary columns since the early 1990s. 

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