Selectivity factor species specificity

Protein G. This vitamin K-dependent glycoproteia serine protease zymogen is produced ia the Hver. It is an anticoagulant with species specificity (19—21). Proteia C is activated to Proteia by thrombomodulin, a proteia that resides on the surface of endothefial cells, plus thrombin ia the presence of calcium. In its active form, Proteia selectively iaactivates, by proteolytic degradation. Factors V, Va, VIII, and Villa. In this reaction the efficiency of Proteia is enhanced by complex formation with free Proteia S. la additioa, Proteia activates tissue plasminogen activator, which... 

In the following text, various studies will be described, which attempt to establish a scientific rationale for the selection of the interspecies assessment factor. Based on these studies, it can be concluded that a species-specific default factor based on differences in caloric requirement (see Table 5.4) should be used for interspecies extrapolation regarding metabolic size. The remaining interspecies differences should preferentially be described probabilistically, or a deterministic default factor of 2.5 could be used for extrapolation of data from rat studies to the human situation. 

Biopharmaceuticals represent a broad but discrete class of large molecular weight therapeutic entities that are characterized by their specific pharmacological activities and distinctive pharmacokinetics. The selection of an appropriate animal model is dependent on a combination of PD and PK factors. As described in this chapter, it is essential to understand the relationship of the basic pharmacology of a biopharmaceutical (signaling, receptor presence, binding properties, etc.) and the associated PK properties to that expected in humans, in order to select animal species that will have the most predictive value in safety assessments. 

An essential factor required for accurate RNA Pol I transcription is the selectivity factor SL1 (SL1 Clos et al., 1986a Learned et al., 1985). As mentioned earlier, SL1 is also a species-specific factor that directs promoter-specific transcription in the presence of its cognate template. SL1 does not bind specifically to the rRNA promoter however, in the presence of UBF, it forms a strong cooperative DNA-binding complex at the ribosomal DNA promoter that is critical for initiation of transcription (Bell et al., 1988, 1989 Learned et al., 1986). Mutations in the promoter sequences that affect either the binding of UBF to the DNA template or the interaction of UBF with SL1 result in drastic reduction of transcription activity (Bell et al., 1988). These findings indicate that the interactions between UBF and its DNA recognition sequence, and between UBF and SL1, play a major role in RNA Pol I transcription. For many years the molecular identification of SL1 has proven a difficult task. The... 

A key factor in obtaining binding support for aquaculture is development of a sound business plan. The plan needs to demonstrate that the prospective culturist has identified all costs associated with estabhshment of the faciUty and its day-to-day operation. One or more suitable sites should have been identified and the species to be cultured selected before the business plan is submitted. Cost estimates should be verifiable. Having actual bids for a specific task at a specific location eg, pond constmction, well drilling, building constmction, and vehicle costs helps strengthen the business plan. 

Other factors which have a significant influence on process selection iaclude absolute quantity of sulfur present, concentration of various sulfur species, the quantity and concentration of other components ia the stream to be treated, quantity and conditions (temperature and pressure) of the stream to be treated, and, the location-specific environmental regulations governing overall sulfur recovery and allowable sulfur dioxide emissions (3). 

The identification of a specific nitrating species can be approached by comparing selectivity with that of nitration under conditions known to involve the nitronium ion. Examination of part B of Table 10.7 shows that the position selectivity exhibited by acetyl nitrate toward toluene and ethylbenzene is not dramatically different from that observed with nitronium ion. The data for i-propylbenzene suggest a lower ortho para ratio for acetyl nitrate nitrations. This could indicate a larger steric factor for nitration by acetyl nitrate. 

As discussed earlier, selectivity is the consequence of the interplay between toxicokinetic and toxicodynamic factors. Some examples are given in Table 2.8, which will now be briefly discussed (data from Walker and Oesch 1983, and Walker 1994a,b). These and other examples will be described in more detail under specific pollutants later in the text. In the table, comparisons are made between the median lethal doses or concentrations for different species or strains. Comparisons are made of data obtained in lethal toxicity tests where the same route of administration was used for species or strains that are compared. The degree of selectivity is expressed... 

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