Gated rotation mechanism of site-specific recombination by ϕC31 integrase

Integrases, such as that of the Streptomyces temperate bacteriophage ϕC31, promote site-specific recombination between DNA sequences in the bacteriophage and bacterial genomes to integrate or excise the phage DNA. ϕC31 integrase belongs to the serine recombinase family, a large group of structurally related enzymes with diverse biological functions. It has been proposed that serine integrases use a “subunit rotation” mechanism to exchange DNA strands after double-strand DNA cleavage at the two recombining att sites, and that many rounds of subunit rotation can occur before the strands are religated. We have analyzed the mechanism of ϕC31 integrase-mediated recombination in a topologically constrained experimental system using hybrid “phes” recombination sites, each of which comprises a ϕC31 att site positioned adjacent to a regulatory sequence recognized by Tn3 resolvase. The topologies of reaction products from circular substrates containing two phes sites support a right-handed subunit rotation mechanism for catalysis of both integrative and excisive recombination. Strand exchange usually terminates after a single round of 180° rotation. However, multiple processive “360° rotation” rounds of strand exchange can be observed, if the recombining sites have nonidentical base pairs at their centers. We propose that a regulatory “gating” mechanism normally blocks multiple rounds of strand exchange and triggers product release after a single round

Animal Use and Acceptable Alternatives: A Report from the United States

No abstract availabl

On measuring alpha in B(t)-> rho^\pm pi^\mp

Defining a most economical parametrization of time-dependent B-> rho^\pm pi^\mp decays, including a measurable phase alpha_{eff} which equals the weak phase alpha in the limit of vanishing penguin amplitudes, we propose two ways for determining alpha in this processes. We explain the limitation of one method, assuming only that two relevant tree amplitudes factorize and that their relative strong phase, delta_t, is negligible. The other method, based on broken flavor SU(3), permits a determination of alpha in B^0-> rho^\pm pi^\mp in an overconstrained system using also rate measurements of B^{0,+}-> K^* pi and B^{0,+}->rho K. Current data are shown to restrict two ratios of penguin and tree amplitudes, r_\pm, to a narrow range around 0.2, and to imply an upper bound |alpha_{eff} - alpha| < 15 degrees. Assuming that delta_t is much smaller than 90 degrees, we find alpha =(93\pm 16) degrees and (102 \pm 20) degrees using BABAR and BELLE results for B(t)-> rho^\pm pi^mp. Avoiding this assumption for completeness, we demonstrate the reduction of discrete ambiguities in alpha with increased statistics, and show that SU(3) breaking effects are effectively second order in r_\pm.Comment: 23 pages, 2 figures, data and references updated, to be published in Phys. Rev.

Synchronizing Sequencing Software to a Live Drummer

Copyright 2013 Massachusetts Institute of Technology. MIT allows authors to archive published versions of their articles after an embargo period. The article is available at

Liquefaction Analysis of Lower San Fernando Darn Using Strength Ratios

Olson (2000) evaluated 33 liquefaction flow failure case histories to assess the yield strength ratio and liquefied strength ratio mobilized during the failures. Using back-analysis procedures developed by Olson (2000), yield and liquefied shear strengths are shown to be proportional to the pre-failure vertical effective stress and are related to standard and cone penetration resistances. This paper examines the triggering of liquefaction and subsequent flow failure of Lower San Fernando Dam using yield and liquefied strength ratios. The yield strength ratio is used to correctly predict the occurrence of liquefaction in the upstream hydraulic fill of the dam, and the liquefied shear strength ratio is used to correctly predict the subsequent flow failure of the upstream slope. The relationships for the yield and liquefied ratios are presented, and their application to existing or new structures is illustrated using the Lower San Fernando Dam case history

Preventing pain on injection of propofol: A comparison between lignocaine pre-treatment and lignocaine added to propofol

Publisher's copy made available with the permission of the publisherA randomized double-blind study compared two methods of preventing the pain from injection of propofol, lignocaine pre-treatment followed by propofol and lignocaine added to propofol. One hundred patients received a 4 ml solution intravenously with a venous tourniquet for 1 minute, followed by propofol mixed with 2 ml of solution. Patients were divided into two treatment groups of 50 patients each: 4 ml 1% lignocaine pre-treatment followed by propofol and 2 ml saline, or 4 ml saline followed by propofol and 2 ml 2% lignocaine. Pain was assessed with a 100 mm visual analogue scale after induction and in recovery. The incidence of injection pain was 8% in the propofol mixed with lignocaine group, and 28% in the lignocaine pre-treatment group. This difference is statistically significant (P=0.017). For those patients who had pain, the mean pain score was 26.5 on induction for the propofol with lignocaine group (n=4), while the mean score was 44.4 for the pre-treatment group (n=13). The difference was not statistically significant (P=0.25). None of the propofol mixed with lignocaine group recalled pain, while 13 of the pre-treatment group did so. Lignocaine pre-treatment does not improve the immediate or the recalled comfort of patients during propofol induction when compared to lignocaine added to propofol. It is recommended that lignocaine should be added to propofol for induction rather than given before induction.P. Lee, W. J. Russellhttp://www.aaic.net.au/Article.asp?D=200339

Dynamic model of gene regulation for the lac operon

Gene regulatory network is a collection of DNA which interact with each other and with other matter in the cell. The lac operon is an example of a relatively simple genetic network and is one of the best-studied structures in the Escherichia coli bacteria. In this work we consider a deterministic model of the lac operon with a noise term, representing the stochastic nature of the regulation. The model is written in terms of a system of simultaneous first order differential equations with delays. We investigate an analytical and numerical solution and analyse the range of values for the parameters corresponding to a stable solution