Creative solutions, identification

The selection of an appropriate mobile phase is another aspect of concern. Most often the commonly used LC mobile phase is not compatible with thermospray LC/MS, for instance owing to the use of non-volatile buffers can be left out or replaced by volatile ones. In other cases the buffers are present for retention time reproducibility, which mostly is not very important for identification. In other applications however a correspondence between UV or fluorescence peaks and MS identification is obligatory, which makes mobile phase changes unattractive. In this respect it is often overlooked that LC-UV and LC/MS give different responses as a result of different detection principles. For not too complex samples a UV photo-diode array detector can be used to link up the chromatographic peaks obtained under different mobile phase conditions. To cut short, despite many successes also many potential problems are met in LC/MS to which tailor-made creative solutions are needed. 

The key to success in normative creativity lies in the identification of the precise nature and causes of the problem. You know what the deviation is it is a matter of discovering how to determine its cause and take the corrective action. The creative action needed will lead you down the well-trodden path of collecting data, analysis, diagnosis of causes until eventually you are in a position to generate ideas for solution. 

While micelles and bicelles have served as the membrane-mimetic solvent for the majority of solution NMR studies on integral membrane proteins, the identification of suitable NMR-compatible solvents remains a formidable challenge. With <30 unique multi-spanning membrane protein structures determined by solution NMR, there is a clear need to expand the current library of solubilization agents for this purpose. In response to this problem, creative approaches are currently being developed that may open the door to solution NMR for a wider range of membrane proteins in the future. Some of the systems that have started to yield promising results include nanodiscs, amphipols, and reverse micelles. 

Despite the obvious success of munerical methods for nonlinear mathematical programming, their weaknesses were discovered early on. Among them it should be highlighted the main one, namely, the absence of the physicochemical visualization. To some extent it relates also to Bellmann s dynamic programming method. Naturally, incomplete information about the nature of the studied process on a way to optimal result constrains strongly the creative capabilities of a researcher. In particular, identification of the most active control parameters from a variety of the candidates is complicated, thus also complicating the solution of the defined problem. 

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