Electromagnetics from a quasistatic perspective

Quasistatics is introduced so that it fits smoothly into the standard textbook presentation of electrodynamics. The usual path from statics to general electrodynamics is rather short and surprisingly simple. A closer look reveals however that it is not without confusing issues as has been illustrated by many contributions to this Journal. Quasistatic theory is conceptually useful by providing an intermediate level in between statics and the full set of Maxwell's equations. Quasistatics is easier than general electrodynamics and in some ways more similar to statics. It is however, in terms of interesting physics and important applications, far richer than statics. Quasistatics is much used in electromagnetic modeling, an activity that today is possible on a PC and which also has great pedagogical potential. The use of electromagnetic simulations in teaching gives additional support for the importance of quasistatics. This activity may also motivate some change of focus in the presentation of basic electrodynamics

Sequence-specific stalling of DNA polymerase gamma and the effects of mutations causing progressive ophthalmoplegia

Item does not contain fulltextA large number of mutations in the gene encoding the catalytic subunit of mitochondrial DNA polymerase gamma (POLgammaA) cause human disease. The Y955C mutation is common and leads to a dominant disease with progressive external ophthalmoplegia and other symptoms. The biochemical effect of the Y955C mutation has been extensively studied and it has been reported to lower enzyme processivity due to decreased capacity to utilize dNTPs. However, it is unclear why this biochemical defect leads to a dominant disease. Consistent with previous reports, we show here that the POLgammaA:Y955C enzyme only synthesizes short DNA products at dNTP concentrations that are sufficient for proper function of wild-type POLgammaA. In addition, we find that this phenotype is overcome by increasing the dNTP concentration, e.g. dATP. At low dATP concentrations, the POLgammaA:Y955C enzyme stalls at dATP insertion sites and instead enters a polymerase/exonuclease idling mode. The POLgammaA:Y955C enzyme will compete with wild-type POLgammaA for primer utilization, and this will result in a heterogeneous population of short and long DNA replication products. In addition, there is a possibility that POLgammaA:Y955C is recruited to nicks of mtDNA and there enters an idling mode preventing ligation. Our results provide a novel explanation for the dominant mtDNA replication phenotypes seen in patients harboring the Y955C mutation, including the existence of site-specific stalling. Our data may also explain why mutations that disturb dATP pools can be especially deleterious for mtDNA synthesis