Origin of the Problem

It is always best to understand a biological problem before trying to find ways to avoid it. The reason that action potential duration is important is that repolarization is a fragile process. It can fail, and when it does so, the action potential is followed by one or many oscillations. These are called early after-depolarizations (EADs). We will also encounter late after-depolarizations (DADs) later in this chapter. 

The long-lasting cardiac action potential is a consequence of such an evolutionary compromise in the development of potassium currents in the heart. Early work on these channels [5] showed that they could be divided into two classes channels that close on depolarization, Iki, and channels that open during depolarization, including the various components of Ik and the transient outward current, it0. At rest, Iki is switched on and holds the resting potential at a very negative level, where the other K+ currents are switched off. On depolarization iki rapidly switches off, while the other currents take time to activate and cause repolarization. This analysis of the potassium channels in cardiac muscle formed the basis of the first biophysically detailed model [6] and remains the basis of all subsequent models [7-9]. 

The bad side is that one of the proteins (hERG, that forms the main component of ik) is highly promiscuous. The channel can be blocked by many pharmaceutical compounds. When that happens, repolarization fails and the action potential is followed by one or more waves of depolarization (Fig. 9.1). These can trigger cardiac arrhythmia that in some cases is fatal. 

Many factors can interact with dmgs to make this problem worse. These include genetic factors, such as mutations in sodium, potassium and calcium channel genes that predispose people to repolarization failure [11-13]. This is the main explanation for the fact that dmgs with this side-effect have it in only a small fraction of the population. In principle, it should become possible to screen for such genetic predispositions to exclude such patients in clinical trials and to avoid treating them with drugs that interact in this way (Fig. 9.2). 

Early after depolarization without mutation Re polarization failure with mutation  

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While sharing of electrons, i.e., covalent bonding, is the major component of the cohesive force in intermetallics, rationalization of their structure formation based on such chemical bonding is not trivial, because of the failure of the common electron counting rules that chemists have developed over the years from the studies of covalent compounds. The origin of the problem is the well-delo-... 

Pierce J (1994) Color in textile effluents the origins of the problem. J Soc Dyers Color 110 131-134... 

Both of these conditions result in weakened bones but the origins of the problems are different. 

To summarize, the results presented for five representative examples of nonadiabatic dynamics demonstrate the ability of the MFT method to account for a qualitative description of the dynamics in case of processes involving two electronic states. The origin of the problems to describe the correct long-time relaxation dynamics as well as multi-state processes will be discussed in more detail in Section VI. Despite these problems, it is surprising how this simplest MQC method can describe complex nonadiabatic dynamics. Other related approximate methods such as the quantum-mechanical TDSCF approximation have been found to completely fail to account for the long-time behavior of the electronic dynamics (see Fig. 10). This is because the standard Hartree ansatz in the TDSCF approach neglects all correlations between the dynamical DoF, whereas the ensemble average performed in the MFT treatment accounts for the static correlation of the problem. 

Pierce, J. Colour in textile effluents - the origins of the problem. J. Soc. Dyers Colour. 1994, 110, 131-133. 

The chemical engineer has traditionally been the guardian of process knowledge. So, one would suppose that if fundamental process knowledge is vanishing, the origin of the problem may lie in our universities. Perhaps, there is less of that, hands-on approach, ... 

To isolate the origin of the problem due to the detector, the chromatographer may perform the dry cell test by disconnecting the detector from the column and then blowing the cell dry with dry nitrogen. Under these conditions no drift should be observed. 

Giddings (9,10) argued that the origin of the problem rests with a basic conjecture of the van Deemter concept the assumption that the different contributions to the HETP are independent of each other and that therefore the variances of these different contributions can be summed up ... 

For the development of applications for superconductors, two obstacles in particular have to be surmounted. The first is that the material must be cooled to low temperatures to attain 7),. As higher temperature superconductors are developed, this has become less of a major drawback, but still militates against the use of superconductors in conventional settings. The second problem is one of fabrication. When prepared as a bulk material, the cuprate superconductors have unacceptably low critical current densities, i.e. the superconductivity is lost after the material has carried only a limited amount of current. The origin of the problem is the presence of grain boundaries in the solid... 

The Origin of the Problems with PM3 Core Repulsion Function ... 

High temperature and pressure steam in the Pressmized Water Reactor s (PWR) system are below the temperature and pressure of the primary coolant, on another word, to have better efficiency, we are obliged to increase the temperature and pressure of the primary system. This is the origin of the problem, where to handle complication come up, as a result of reactor operating conditions, the system becomes sophisticated, and in the same time, safety and safety related items increase and the choice of material used becomes more and more difficult. 

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