Human domain

The predictive power of the luminescent PET sensor principle is again apparent here. Further, the benzocrown ether and the amine receptors would selectively bind Na" and H, respectively. A remarkable feature here is that no molecular wiring is needed to allow the human operation of this two-input molecular device. The device self-selects its own ion inputs into the appropriate signal channels by means of the chemoselective receptor modules. Since the output signal is fluorescence, even a single molecule can interface with detectors in the human domain, including the dark-adapted eye. Tanaka s 45 is another example where fluorescence quenching is achieved only when Ba and SCN are present. This was mentioned in Section 6. Similarly, several sensor systems—1,17, and 21—could be employed... 

The nature of expert systems and their development process presents particular difficulties for the application of the traditional method of validating software against comprehensive pre-specifications, since the final level of operation of an expert system is difficult to pre-determine. Testing by measuring the degree of comparability of the system s performance to the performance of human domain experts, by using a representative set of problem cases, is more practical and more in tune with the definition of expert systems. 

Slavin-Chiorini DC, Kashmiri SVS, Lee HS, Milenic DE, Poole DJ, Bemon E, Schlom J, Horan Hand P. A CDR-grafted (humanized) domain-deleted antitumor antibody. Cancer Biother Radiopharm 1997 12 305-316. 

However, the designed simulations still need to be configured with a set of system and plant parameters to justify the geometrical positions and shapes of components as well as required simulation time and precision. In addition, the generated simulations typically require a set of variables representing boundary conditions for the system under simulation (see Sect. 10.3). Furthermore, their output variables (i.e., simulated results) have to be saved and visualized in a form that is easy to be read and comprehended by human domain expert. These tasks are solved by the simulation integration approach, which is proposed in the first part of this chapter. 

Definition / An expert system is a computer program that manipulates large amounts of symboHc knowledge using quaUtative techniques, to solve problems that can otherwise be solved only by expert human problem solvers. Expert systems capture the human problem solver s expertise in the form of domain-specific knowledge and domain-independent problem-solving strategies. 

One of the main attractions of normal mode analysis is that the results are easily visualized. One can sort the modes in tenns of their contributions to the total MSF and concentrate on only those with the largest contributions. Each individual mode can be visualized as a collective motion that is certainly easier to interpret than the welter of information generated by a molecular dynamics trajectory. Figure 4 shows the first two normal modes of human lysozyme analyzed for their dynamic domains and hinge axes, showing how clean the results can sometimes be. However, recent analytical tools for molecular dynamics trajectories, such as the principal component analysis or essential dynamics method [25,62-64], promise also to provide equally clean, and perhaps more realistic, visualizations. That said, molecular dynamics is also limited in that many of the functional motions in biological molecules occur in time scales well beyond what is currently possible to simulate. 

Figure 4 DynDom [67] analysis of the first two normal modes of human lysozyme. Dark grey and white indicate the two dynamic domains, separated by the black hinge bending region. The vertical line represents a hinge axis that produces a closure motion in the first normal mode. The horizontal line represents a hinge axis that produces a twisting motion in the second normal mode. (Adapted from Ref. 68.) The DynDom program is available from the Internet at http //md. chem.rug.nl/ steve/dyndom.html.

Figure 13.19 Ribbon diagram of the stmcture of the extracellular domain of the human growth hormone. The hormone-binding region is formed by loops (yellow) at the hinge region between two fibronectin type III domains. (Adapted from J. Wells et al., Annu. Rev.

Figure 13.20 Ribbon diagram of the structure of a 1 2 complex between the human growth hormone and the extracellular domains of two receptor molecules. The two receptor molecules (blue) bind the hormone (red) with essentially the same loop regions (yellow).

De Vos, A.M., Ultsch, M., Kossiakoff, A.A. Human growth hormone and extracellular domain of its receptor crystal structure of the complex. Science 255 306-312,... 

Morton, C.J., et al. Solution structure and peptide binding of the SH3 domain from human Fyn. Structure 4 705-714, 1996. 

In this chapter we will discuss immunoglobulins of the IgG class, which is the major type of immunoglobulin in normal human serum, and which has the simplest structure. Each chain of an IgG molecule is divided into domains of about 110 amino acid residues. The light chains have two such domains, and the heavy chains have four. 

Wang, J., et al. Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains. Nature 348 411-418, 1990. 

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