Microwave processing for sample preparation to evaluate mitochondrial ultrastructural damage in hemorrhagic shock.

This is a report of the adaptation of microwave processing in the preparation of liver biopsies for transmission electron microscopy (TEM) to examine ultrastructural damage of mitochondria in the setting of metabolic stress. Hemorrhagic shock was induced in pigs via 35% total blood volume bleed and a 90-min period of shock followed by resuscitation. Hepatic biopsies were collected before shock and after resuscitation. Following collection, biopsies were processed for TEM by a rapid method involving microwave irradiation (Giberson, 2001). Samples pre- and postshock of each of two animals were viewed and scored using the mitochondrial ultrastructure scoring system (Crouser et al., 2002), a system used to quantify the severity of ultrastructural damage during shock. Results showed evidence of increased ultrastructural damage in the postshock samples, which scored 4.00 and 3.42, versus their preshock controls, which scored 1.18 and 1.27. The results of this analysis were similar to those obtained in another model of shock (Crouser et al., 2002). However, the amount of time used to process the samples was significantly shortened with methods involving microwave irradiation.     

Chain-configurational properties of novolac phenol–formaldehyde resins

Rotational isomeric-state chain-configurational calculations have been applied to the novolac phenol–formaldehyde structure. Steric interference allows the chain to be considered with a twofold potential energy barrier model. Computations that fit the observed dipole-moment data over a range of molecular weights indicate that the conformational angle is near ±80°, with the g^±g⁼ states on the average being 155 cal/mole below the g^±g^± states. The limiting dipole-moment ratio is computed to be 1.47, compared to the experimental value of 1.48. A negative temperature coefficient agrees in sign with the experimental value, and the characteristic ratio of the end-to-end molecular dimensions is calculated to be 3.27, as compared to the experimental value of 4.76.     

Analysis of Enzyme Structure and Activity by Protein Engineering

Structure-activity relationships of enzymes can now be analyzed for the first time by the systematic alteration of protein structure. Recent developments in the chemical synthesis of DNA fragments and recombinant DNA technology enable the facile modification of proteins by highly specific mutagenesis of their genes. Kinetic analysis of the mutant enzymes combined with high-resolution structural data from protein X-ray crystallography allow direct measurements on the relationships between structure and function. In particular, the strength and nature of enzyme-substrate interactions and their detailed roles in catalysis and specificity can now be studied. We have developed such analysis of enzyme structure-function by site-directed mutagenesis of the tyrosyl-tRNA synthetase from Bacillus stearothermophilus, concentrating so far on the subtle role of hydrogen bonding in both substrate specificity and catalysis. We find that the energetics of tyrosine and ATP binding must be analyzed in terms of an exchange reaction with solvent water. Based on this idea and structural data, we have engineered an enzyme of improved enzyme-substrate affinity, and there thus appear to be real prospects of engineering proteins of new specificities, activities, and structural properties. We are also using protein engineering to gather direct information on the nature of enzyme catalysis. For example, we find the catalysis of formation of Tyr-AMP from Tyr and ATP is due largely to electrostatic and hydrogen bonding interactions that are stronger in the transition state than in the ground state—a “strain” mechanism rather than acid-base or covalent catalysis.     

Residual smallness in commutative algebra

In Oman and Salminen [19 Oman, G., Salminen, A. Residually small commutative rings. J. Commut. Algebra (17 pages as a preprint, to appear). [Google Scholar]], the authors introduce and study residually small rings, defined as follows: an infinite commutative ring R with identity is residually smallif for every r∈R?{0}, there exists an ideal I_r of R such that r?I_r and |R∕I_r|<|R|. The purpose of this note is to extend our study. In particular, we continue our investigation of residually small rings and then generalize this notion to modules.     

What Does Davidson Reject When He Rejects Conceptual Schemes?

According to a common line of criticism, Donald Davidson’s argument in “On the Very Idea of a Conceptual Scheme” is invalid because it moves illicitly from the relatively weak thesis that conceptual schemes cannot be incommensurable to the stronger thesis that the idea of a conceptual scheme itself is incoherent. I argue in this paper that such objections fail because they misunderstand the position that Davidson’s argument is intended to rule out. According to the “scheme-content dualism” Davidson targets, conceptual schemes differ only if they are incommensurable with one another. Thus, if Davidson has successfully shown the idea of incommensurability to be incoherent (as the critics in question grant), then he has shown “the very idea of a conceptual scheme” to be incoherent, as well.