Some pivotal observations

now let us stress and enlarge upon what this observation says. If one merely computes In,g using the single complete SDS for any one convenient isotopomer, say, for example, the normal isotopic species with the most abundant isotopes, the computed ratio Img Og 

Whether or not these approximate Watson In.S are useful for structural computations will be addressed in the next section. However, it might be observed here that Watson s [30, 32] r structure tended to be very good when only the I g values of a single SDS were needed. The observations noted above permit one to obtain near-equilibrium Ig values using only a single SDS, so perhaps one should not be surprised that the resulting structures are of rather high quality. 

Before moving on, we should address the issue of hydrogen-containing molecules. All of the conclusions above deal with heavy-atom systems. Consider now the data of Table 14 for HCN. For this molecule, data are available for some tritium as well as deuterium species and, because of this, one can obtain Ig (or Ij ) values for some isotopomers in more than one way, i.e., using different SDSs. Thus note, for example, that the Ig (or ,) value of the 2-12-14 parent molecule can be determined using either of the SDSs  

Overall, the variations of the I /Io values are several times greater than those observed for the heavy-atom molecules in Tables 12 and 13 where, incidentally, the O, S and Cl substitutions involve = 2 mass units. Actually, if one limits the observations to the species evaluated with H - D substitution and D H substitution, the range of variation is only about 6/10. In any case, Ig/Io is still fairly constant so that, even for the hydrogen atom species, I can be approximated to within a few parts/10 from the results for, say, just the normal isotopomer. The problem is that the true Watson values 

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In spite of the apparent inaccessibility of the distal site to the typical and traditional protein reagents, some progress has been made in delineating its properties. Pivotal to these developments was the observation by Heim et al. 110) that 3-amino-lH-l,2,4-triazole (AT) irreversibly in-... 

As already mentioned for rhodium carbene complexes, proof of the existence of electrophilic metal carbenoids relies on indirect evidence, and insight into the nature of intermediates is obtained mostly through reactivity-selectivity relationships and/or comparison with stable Fischer-type metal carbene complexes. A particularly puzzling point is the relevance of metallacyclobutanes as intermediates in cyclopropane formation. The subject is still a matter of debate in the literature. Even if some metallacyclobutanes have been shown to yield cyclopropanes by reductive elimination [15], the intermediacy of metallacyclobutanes in carbene transfer reactions is in most cases borne out neither by direct observation nor by clear-cut mechanistic studies and such a reaction pathway is probably not a general one. Formation of a metallacyclobu-tane requires coordination both of the olefin and of the carbene to the metal center. In many cases, all available evidence points to direct reaction of the metal carbenes with alkenes without prior olefin coordination. Further, it has been proposed that, at least in the context of rhodium carbenoid insertions into C-H bonds, partial release of free carbenes from metal carbene complexes occurs [16]. Of course this does not exclude the possibility that metallacyclobutanes play a pivotal role in some catalyst systems, especially in copper-and palladium-catalyzed reactions. 

Insulin resistance, in particular in skeletal muscle, plays a pivotal role in the pathogenesis of NIDDM. Several abnormalities of the insulin-signalling chain have been found. At the receptor level a decreased tyrosine kinase activity has been described which appears to be due to a regulatory event (reviewed by Haring, 1991). Relevant mutations of the insulin receptor were not found (reviewed by Haring and Mehnert, 1993). Abnormalities at the level of glycogen synthase were observed as discussed above. There is also some... 

Two pivotal discoveries enabled the full potential of Upo-somes to be realized. The first was the discovery in the late 1980s and early 1990s that the presence of additional molecnles snch as poly(oxyethylene) bonded onto the liposome snrface decreased their clearance by partially preventing liver and spleen nptake of i.v. injected liposomes. These are now often referred to as stealth liposomes as this effect enables them to escape recognition by the liver and spleen with the beneht of long drcnlation times. This observation was made almost in parallel with the discovery that polystyrene nanoparticles coated with a poly(oxyethylene) polymer also showed rednced liver and spleen nptake. It is likely that a reduction in the coating of these liposomes by plasma proteins (opsonization), and their rednced aggregation in the blood are responsible for the increased circnlation time of... 

Several known covalent modifications have been observed so far that can modify the amino acid residues in the histone tails. There include acetylation, phosphorylation, ubiquitination, and methylation. Although some of these modifications have been known for many years, only recently have functional roles for these modifications begun to surface (Workman and Kingston, 1998). Each histone can undergo numerous modifications, and the combinatorial effect of these serves to elicit a multitude of different responses. This combinatorial modification of histone tails has been referred to as the histone code (Jenuwein and Allis, 2001 Strahl and Allis, 2000) and has been proposed to play a pivotal role in the regulation of gene expression (Fig. 3). 

While the PyBroP-mediated bromination enabled the key C7 activation, its implementation on multiton scale still raised concerns, both due to the cost of this reagent and the quality of the commercial material (some significant differences in commercial supplies had been observed). Pyrrolidine was a potential contaminant, resulting in addition adduct 126 as an impurity (Scheme 36). With these considerations in mind, we began to investigate alternative methods for this pivotal transformation. 

Keeping in mind the importance of chitosan, as well as its economic value as an industrial product, we must pay attention to its key physical parameter, i.e., turbidity. Depending on source, a marked difference is observed in aqueous solutions of chitosan and its derivatives in terms of their turbidity [33]. Turbid aqueous solutions of chitosan and chitosan-derived products greatly lose their commercial value. Such chitosan cannot be used as a commercial product and in some cases may have to be discarded. Therefore, the selection of source plays a pivotal role in the production of chitin and chitosan. Shepherd et al. [20] reported the production of chitosan from New Zealand Arrow squid Notodarus sloani) pens as well as the evaluation of the functional properties of this squid chitosan compared with chitosan extracted from crustacean sources. Squid pen chitin and chitosan were visibly cleaner than chitin and chitosan obtained from crab and crayfish. In addition, due to the lower mineral content of squid pen as compared to cmstacean shells, the demineralization process can be skipped to extract chitin, which also makes the production cheaper. As shown in Table 4, the squid pen chitosan is similar in... 

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