The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM) for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1). We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101) is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody). Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu). The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier) benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.
The effects of platinum addition to gold and indium addition to a gold-platinum alloy on their optical properties were investigated using a computer-controlled spectrophotometer. Spectral reflectance data from a polished sample for the incident CIE standard illuminant D65 was collected as a function of the wavelength at 10 nm intervals from 360 to 740 nm. Three coordinates, L* (lightness), a* (red-green), b* (yellow-blue), in the CIE 1976 L*a*b* colour space, were determined to quantify the colour of experimental binary Au-Pt and ternary Au-Pt-In alloys.The pronounced step near 520 nm (approximately 2.4 eV) in the spectral reflectance-wavelength curve for pure gold, which is responsible for the rich yellow colour of gold, became less pronounced with the addition of platinum. The decoloring effect of platinum was found to be due to this phenomenon. The addition of indium of up to ca 4 at% to a Au-10 at% Pt alloy increased both chromaticity indices, ie, a* and b* values, giving a gold tinge to the alloy: this effect was brought about by both the slight increase in reflectance in the long-wavelength range and the slight decrease in reflectance in the short-wavelength range of the visible spectrum.
Nine experimental Pd-free Ag-Au-Pt-Cu dental alloys containing 10 at.% Pt and 10 to 35 at.% Au were prepared and their optical properties and microstructures were investigated by means of spectrophotometric colorimetry, optical microscopy, and electron probe microanalysis. All the alloys were annealed at 850°C and mirror-polished to observe their reflectance curves in the visible spectrum and three-dimensional color coordinates. All the alloys were composed of a major phase of Ag-Au-rich matrix and a minor and almost colorless Pt-Cu-rich phase. It was found that the color of the alloys was substantially controlled by the Ag-Au-rich matrix and that with increasing Au/Ag atomic ratio from 0.130 to 0.996, the yellow-blue chromaticity index b* increased from 8.0 to 14.4, giving a pale yellow color. This systematic increase in yellowness was caused by a continuous shift of the absorption edge of reflectance curve towards longer wavelengths with increasing Au/Ag atomic ratio.
Microstructure observation of peeling plane of the fusing porcelain with titanium was performed by SEM EDX. From the results of the bend test, bonding strength of the degassed sample using bonding porcelain is higher than that of degassing free and bonding porcelain free sample. From SEM EDX observation of the peeling plane, the sample using the bonding porcelain shows good reactivity with the porcelain, and many hollows out of the porcelain side were observed. However, chemical composition of peeling plane indicates that peeling plane is formed by mainly titanium. Microstructures of the sample with and without bonding porcelain are obviously different, which indicates that the difference of reaction product in interface region. From the result of the cross sectional observation of the fused porcelain/titanium interface, it was suggested that the peeling at interface between titanium and porcelain causes at the oxygen dissolved titanium and/or titanium oxide phase which diffuses to the porcelain side.
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