Helicase Loading at Chromosomal Origins of Replication

Loading of the replicative DNA helicase at origins of replication is of central importance in DNA replication. As the first of the replication fork proteins assemble at chromosomal origins of replication, the loaded helicase is required for the recruitment of the rest of the replication machinery. In this work, we review the current knowledge of helicase loading at Escherichia coli and eukaryotic origins of replication. In each case, this process requires both an origin recognition protein as well as one or more additional proteins. Comparison of these events shows intriguing similarities that suggest a similar underlying mechanism, as well as critical differences that likely reflect the distinct processes that regulate helicase loading in bacterial and eukaryotic cells.Howard Hughes Medical InstituteNational Institutes of Health (U.S.) (Grant RO1 GM052339

Multiple Functions for Mcm2–7 ATPase Motifs during Replication Initiation

The Mcm2–7 replicative helicase is central to all steps of eukaryotic DNA replication. The hexameric ring of Mcm subunits forms six essential ATPases whose contributions to replication initiation remain unclear. Mcm2–7 complexes containing ATPase-motif mutations showed Mcm2–7 ATP binding and hydrolysis are required for helicase loading. Loading-defective Mcm2–7 mutant complexes were defective in initial Mcm2–7 recruitment or Cdt1 release. Comparison with Cdc6 ATPase mutants showed that Cdc6 ATP hydrolysis is not required for helicase loading but instead drives removal of Mcm2–7 complexes that cannot complete loading. A subset of Mcm2–7 ATPase-site mutants completed helicase loading but could not initiate replication. Individual mutants were defective in distinct events during helicase activation, including maintenance of DNA association, recruitment of the GINS helicase activator, and DNA unwinding. Consistent with its heterohexameric structure, our findings show that the six Mcm2–7 ATPase active sites are specialized for different functions during helicase loading and activation.United States. National Institutes of Health (GM052339)United States. National Institutes of Health (GM007287)National Science Foundation (U.S.) (1122374

Strategic Operations Research and the Edelman Prize Finalist Applications 1989-1998

In an earlier study we examined the available evidence on the Edelman Prize finalist applications 1989-1998. This study concluded that 13 of the 42 private sector applications provide examples of strategic operations research (SOR) when SOR is defined as operations research that creates a sustainable competitive advantage. In a follow-up study we tested our classifications, gathering longitudinal information on the continued success of the Edelman applications. We contacted people who were familiar with all the private sector applications that were Edelman finalists 1989-1996 and had at least five years of history since the competition. We describe the post-Edelman history of these applications and use this data to reassess their strategic role. We found that the longitudinal data provides evidence to support our original classification, but also suggests that several additional applications were more strategic than was originally apparent. We conclude that almost 60% (20 of 34) of these applications created a sustainable competitive advantage for their firms and provide examples of SOR

Evolution of Giant Planets in Eccentric Disks

We investigate the interaction between a giant planet and a viscous circumstellar disk by means of high-resolution, two-dimensional hydrodynamical simulations. We consider planet masses that range from 1 to 3 Jupiter masses (Mjup) and initial orbital eccentricities that range from 0 to 0.4. We find that a planet can cause eccentricity growth in a disk region adjacent to the planet's orbit, even if the planet's orbit is circular. Disk-planet interactions lead to growth in a planet's orbital eccentricity. The orbital eccentricities of a 2 Mjup and a 3 Mjup planet increase from 0 to 0.11 within about 3000 orbits. Over a similar time period, the orbital eccentricity of a 1 Mjup planet grows from 0 to 0.02. For a case of a 1 Mjup planet with an initial eccentricity of 0.01, the orbital eccentricity grows to 0.09 over 4000 orbits. Radial migration is directed inwards, but slows considerably as a planet's orbit becomes eccentric. If a planet's orbital eccentricity becomes sufficiently large, e > ~0.2, migration can reverse and so be directed outwards. The accretion rate towards a planet depends on both the disk and the planet orbital eccentricity and is pulsed over the orbital period. Planet mass growth rates increase with planet orbital eccentricity. For e~0.2 the mass growth rate of a planet increases by approximately 30% above the value for e=0. For e > ~0.1, most of the accretion within the planet's Roche lobe occurs when the planet is near the apocenter. Similar accretion modulation occurs for flow at the inner disk boundary which represents accretion toward the star.Comment: 20 pages 16 figures, 3 tables. To appear in The Astrophysical Journal vol.652 (December 1, 2006 issue

Joint measurements of spin, operational locality and uncertainty

Joint, or simultaneous, measurements of non-commuting observables are possible within quantum mechanics, if one accepts an increase in the variances of the jointly measured observables. In this paper, we discuss joint measurements of a spin 1/2 particle along any two directions. Starting from an operational locality principle, it is shown how to obtain a bound on how sharp the joint measurement can be. We give a direct interpretation of this bound in terms of an uncertainty relation.Comment: Accepted for publication in Phys. Rev.

Joint measurements and Bell inequalities

Joint quantum measurements of non-commuting observables are possible, if one accepts an increase in the measured variances. A necessary condition for a joint measurement to be possible is that a joint probability distribution exists for the measurement. This fact suggests that there may be a link with Bell inequalities, as these will be satisfied if and only if a joint probability distribution for all involved observables exists. We investigate the connections between Bell inequalities and conditions for joint quantum measurements to be possible. Mermin's inequality for the three-particle Greenberger-Horne-Zeilinger state turns out to be equivalent to the condition for a joint measurement on two out of the three quantum systems to exist. Gisin's Bell inequality for three co-planar measurement directions, meanwhile, is shown to be less strict than the condition for the corresponding joint measurement

Applications of sensitivity analysis for probit stochastic network equilibrium

Network equilibrium models are widely used by traffic practitioners to aid them in making decisions concerning the operation and management of traffic networks. The common practice is to test a prescribed range of hypothetical changes or policy measures through adjustments to the input data, namely the trip demands, the arc performance (travel time) functions, and policy variables such as tolls or signal timings. Relatively little use is, however, made of the full implicit relationship between model inputs and outputs inherent in these models. By exploiting the representation of such models as an equivalent optimisation problem, classical results on the sensitivity analysis of non-linear programs may be applied, to produce linear relationships between input data perturbations and model outputs. We specifically focus on recent results relating to the probit Stochastic User Equilibrium (PSUE) model, which has the advantage of greater behavioural realism and flexibility relative to the conventional Wardrop user equilibrium and logit SUE models. The paper goes on to explore four applications of these sensitivity expressions in gaining insight into the operation of road traffic networks. These applications are namely: identification of sensitive, ‘critical’ parameters; computation of approximate, re-equilibrated solutions following a change (post-optimisation); robustness analysis of model forecasts to input data errors, in the form of confidence interval estimation; and the solution of problems of the bi-level, optimal network design variety. Finally, numerical experiments applying these methods are reported

Collapse models with non-white noises

We set up a general formalism for models of spontaneous wave function collapse with dynamics represented by a stochastic differential equation driven by general Gaussian noises, not necessarily white in time. In particular, we show that the non-Schrodinger terms of the equation induce the collapse of the wave function to one of the common eigenstates of the collapsing operators, and that the collapse occurs with the correct quantum probabilities. We also develop a perturbation expansion of the solution of the equation with respect to the parameter which sets the strength of the collapse process; such an approximation allows one to compute the leading order terms for the deviations of the predictions of collapse models with respect to those of standard quantum mechanics. This analysis shows that to leading order, the ``imaginary'' noise trick can be used for non-white Gaussian noise.Comment: Latex, 20 pages;references added and minor revisions; published as J. Phys. A: Math. Theor. {\bf 40} (2007) 15083-1509

Influence Functionals and the Accelerating Detector

The influence functional is derived for a massive scalar field in the ground state, coupled to a uniformly accelerating DeWitt monopole detector in $D+1$ dimensional Minkowski space. This confirms the local nature of the Unruh effect, and provides an exact solution to the problem of the accelerating detector without invoking a non-standard quantization. A directional detector is presented which is efficiently decohered by the scalar field vacuum, and which illustrates an important difference between the quantum mechanics of inertial and non-inertial frames. From the results of these calculations, some comments are made regarding the possibility of establishing a quantum equivalence principle, so that the Hawking effect might be derived from the Unruh effect.Comment: 32 page