Rationale for employment

For the vibrational frequencies and rotational constants, density functional theory calculations with the relatively modest 6-31IG basis set generally suffice. However, for accurate estimates of the lowest frequency modes it is occasionally necessary to include diffuse functions in the vibrational analyses and so it is perhaps better to employ the 6-311++G basis. Truhlar and coworkers have recently noted the related importance of diffuse functions in estimating relative conformational energies with density functional theory [47]. For density functional calculations there appears to be little rationale for employing the more expensive correlation-consistent basis sets, since the results are essentially converged with the 6-311-H-G basis set and since the limited accuracy of the density functional methods does not warrant extrapolation to the infinite basis set limit. 

Composite endpoints are used in these cardiovascular outcome safety trials since the occurrence of individual events is typically low. The statistical rationale for employment of these endpoints is explained. 

Almost all larger FT and HP boiler plants employ some form of external capital equipment for MU water and FW treatment. The rationale for installing capital equipment is to eliminate (or at least minimize) the level of mineral impurities, process contaminants, and noncondensable gases entering the boiler via the FW system to reduce the potential for the development of waterside deposition, corrosion, steam contamination, and other waterside problems. 

Phosphate is critical to normal bone mineralization when phosphate stores are deficient, a clinical and pathologic picture resembling vitamin D-deficient rickets develops. However, such children fail to respond to the usual doses of vitamin D employed in the treatment of nutritional rickets. A defect in l,25(OH)2D production by the kidney has also been noted, because the serum l,25(OH)2D levels tend to be low relative to the degree of hypophosphatemia observed. This combination of low serum phosphate and low or low-normal serum l,25(OH)2D provides the rationale for treating such patients with oral phosphate (1-3 g daily) and calcitriol (0.25-2 Mg daily). Reports of such combination therapy are encouraging in this otherwise debilitating disease. 

In the following we present an application of laser induced fluorescence to a study of the chemistry of sulfur in rich hydrogen/oxygen/nitrogen (H2/O2/N2) flames and demonstrate a simple rationale for taking quench effects into account. Fluorescence measurements for S2, SH, S02, SO, and OH along with measurements of flame temperature and H-atom (in sulfur free flames) have been employed to develop a kinetic model for the highly coupled flame chemistry of sulfur. The kinetic aspects of the study already have been presented in considerable detail (6). 

Arindam Bose (Pfizer Central Research) further discussed the ICH documents and presented a rationale for the recommended combination of test procedures and process clearance validations required to demonstrate that marketed biopharmaceuticals are free of adventitious agents. He showed that testing of Pre-Seed Stock (PSS), the Master Cell Bank (MCB), and the Working Cell Bank (WCB) is required to demonstrate that they are free from contamination by mycoplasma, bacteria, molds, and yeasts. In addition, viral clearance validation studies must be performed on scaled down versions of each chromatographic step and the viral inactivation/removal step employed in the product purification scheme. Finally, clearance studies must be conducted with a panel of relevant and model viruses (typically three to four) to establish that the purification scheme will indeed purge any viruses that may be inadvertently introduced during processing. 

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