A macroscopic kinetic model for DNA polymerase elongation and high-fidelity nucleotide election

The enzymatically catalyzed template-directed extension of ssDNA/primer complex is an impor-tant reaction of extraordinary complexity. The DNA polymerase does not merely facilitate the insertion of dNMP, but it also performs rapid screening of substrates to ensure a high degree of fidelity. Several kinetic studies have determined rate constants and equilibrium constants for the elementary steps that make up the overall pathway. The information is used to develop a macro-scopic kinetic model, using an approach described by Ninio [Ninio J., 1987. Alternative to the steady-state method: derivation of reaction rates from first-passage times and pathway probabili-ties. Proc. Natl. Acad. Sci. U.S.A. 84, 663–667]. The principle idea of the Ninio approach is to track a single template/primer complex over time and to identify the expected behavior. The average time to insert a single nucleotide is a weighted sum of several terms, in-cluding the actual time to insert a nucleotide plus delays due to polymerase detachment from ei-ther the ternary (template-primer-polymerase) or quaternary (+nucleotide) complexes and time delays associated with the identification and ultimate rejection of an incorrect nucleotide from the binding site. The passage times of all events and their probability of occurrence are ex-pressed in terms of the rate constants of the elementary steps of the reaction pathway. The model accounts for variations in the average insertion time with different nucleotides as well as the in-fluence of G+C content of the sequence in the vicinity of the insertion site. Furthermore the model provides estimates of error frequencies. If nucleotide extension is recognized as a compe-tition between successful insertions and time delaying events, it can be described as a binomial process with a probability distribution. The distribution gives the probability to extend a primer/template complex with a certain number of base pairs and in general it maps annealed complexes into extension products.

'Beheading', Rule Manipulation and Fraud: The Approval of Election Results in Brazil, 1894-1930

Studies of electoral fraud tend to focus their analyses only on the pre-electoral or electoral phases. By examining the Brazilian First Republic (1889-1930), this article shifts the focus to a later phase, discussing a particular type of electoral fraud that has been little explored by the literature, namely, that perpetrated by the legislatures themselves during the process of giving final approval to election results. The Brazilian case is interesting because of a practice known as degola ('beheading') whereby electoral results were altered when Congress decided on which deputies to certify as duly elected. This has come to be seen as a widespread and standard practice in this period. However, this article shows that this final phase of rubber-stamping or overturning election results was important not because of the number of degolas, which was actually much lower than the literature would have us believe, but chiefly because of their strategic use during moments of political uncertainty. It argues that the congressional certification of electoral results was deployed as a key tool in ensuring the political stability of the Republican regime in the absence of an electoral court.

Congressional Endorsements in the Presidential Nomination Process: Democratic Superdelegates in the 2008 Election

Examining congressional superdelegate endorsements in the 2008 Democratic presidential nomination, the authors show that changes in the political context affected the balance of factors in members’ decisions to endorse Clinton or Obama. Specifically, the national standing of the candidates became increasingly important—and local opinion less important—to Obama endorsements even as constituency views became a stronger influence over Clinton endorsements. The findings reveal how constituency considerations affect the elite endorsement choices that shape the presidential nominating process. In addition, the analysis highlights the ways in which members of Congress balance conflicting considerations in a changing political context when an issue plays out over an extended period.

Congressional Endorsements in the Presidential Nomination Process: Democratic Superdelegates in the 2008 Election

Examining congressional superdelegate endorsements in the 2008 Democratic presidential nomination, the authors show that changes in the political context affected the balance of factors in members' decisions to endorse Clinton or Obama. Specifically, the national standing of the candidates became increasingly important-and local opinion less important-to Obama endorsements even as constituency views became a stronger influence over Clinton endorsements. The findings reveal how constituency considerations affect the elite endorsement choices that shape the presidential nominating process. In addition, the analysis highlights the ways in which members of Congress balance conflicting considerations in a changing political context when an issue plays out over an extended period.