571 research outputs found
Simulation of stochastic network dynamics via entropic matching
The simulation of complex stochastic network dynamics arising, for instance,
from models of coupled biomolecular processes remains computationally
challenging. Often, the necessity to scan a models' dynamics over a large
parameter space renders full-fledged stochastic simulations impractical,
motivating approximation schemes. Here we propose an approximation scheme which
improves upon the standard linear noise approximation while retaining similar
computational complexity. The underlying idea is to minimize, at each time
step, the Kullback-Leibler divergence between the true time evolved probability
distribution and a Gaussian approximation (entropic matching). This condition
leads to ordinary differential equations for the mean and the covariance matrix
of the Gaussian. For cases of weak nonlinearity, the method is more accurate
than the linear method when both are compared to stochastic simulations.Comment: 23 pages, 6 figures; significantly revised versio
Hotspots and Coldspots: Household and village-level variation in orphanhood prevalence in rural Malawi
We explore the spatial distribution of orphans in two areas of Malawi. We first review pertinent themes in qualitative data collected in our research sites. Then, using spatial analysis, we show how positive and negative clusters of orphansĂąâŹâwhich we term orphanhood "hotspots" and "coldspots"ĂąâŹâcan be found at the village and sub-village levels. In the third and longest section of the paper, and using multilevel analyses with both simple and complex variance structures, we evaluate the relationship between the presence of orphans and a range of individual, household and village-level characteristics, including households' spatial relationship to each other and to other local sites of significance. This series of analyses shows that the most important covariates of orphan presence are the density of settlement, household size, and religious characteristics, with the latter measured simultaneously at both household and village-level. Other characteristics like education, reported mortality levels and HIV infection, are wholly unrelated to orphan prevalence at all analytic levels. Wealth and various spatial characteristics are only marginally associated with orphan prevalence. We conclude by reviewing some difficulties in explaining causal mechanisms underlying these observed relationships, and discussing conceptual, theoretical and programmatic implications.Africa, AIDS/HIV, Malawi, multilevel model, orphan prevalence, orphans, spatial analysis
The prebiotic evolutionary advantage of transferring genetic information from RNA to DNA.
In the early 'RNA world' stage of life, RNA stored genetic information and catalyzed chemical reactions. However, the RNA world eventually gave rise to the DNA-RNA-protein world, and this transition included the 'genetic takeover' of information storage by DNA. We investigated evolutionary advantages for using DNA as the genetic material. The error rate of replication imposes a fundamental limit on the amount of information that can be stored in the genome, as mutations degrade information. We compared misincorporation rates of RNA and DNA in experimental non-enzymatic polymerization and calculated the lowest possible error rates from a thermodynamic model. Both analyses found that RNA replication was intrinsically error-prone compared to DNA, suggesting that total genomic information could increase after the transition to DNA. Analysis of the transitional RNA/DNA hybrid duplexes showed that copying RNA into DNA had similar fidelity to RNA replication, so information could be maintained during the genetic takeover. However, copying DNA into RNA was very error-prone, suggesting that attempts to return to the RNA world would result in a considerable loss of information. Therefore, the genetic takeover may have been driven by a combination of increased chemical stability, increased genome size and irreversibility
Dynamics of Competitive Evolution on a Smooth Landscape
We study competitive DNA sequence evolution directed by {\it in vitro}
protein binding. The steady-state dynamics of this process is well described by
a shape-preserving pulse which decelerates and eventually reaches equilibrium.
We explain this dynamical behavior within a continuum mean-field framework.
Analytical results obtained on the motion of the pulse agree with simulations.
Furthermore, finite population correction to the mean-field results are found
to be insignificant.Comment: 4 pages, 2 figures, revised, to appear in Phys. Rev. Let
Kinetic Accessibility of Buried DNA Sites in Nucleosomes
Using a theoretical model for spontaneous partial DNA unwrapping from
histones, we study the transient exposure of protein-binding DNA sites within
nucleosomes. We focus on the functional dependence of the rates for site
exposure and reburial on the site position, which is measurable experimentally
and pertinent to gene regulation. We find the dependence to be roughly
described by a random walker model. Close inspection reveals a surprising
physical effect of flexibility-assisted barrier crossing, which we characterize
within a toy model, the "semiflexible Brownian rotor."Comment: final version as published in Phys. Rev. Let
Modeling J /Psi production and absorption in a microscopic nonequilibrium approach
Charmonium production and absorption in heavy ion collisions is studied with the Ultrarelativisitic Quantum Molecular Dynamics model. We compare the scenario of universal and time independent color-octet dissociation cross sections with one of distinct color-singlet J/psi, psi 2 and CHIc states, evolving from small, color transparent configurations to their asymptotic sizes. The measured J/psi production cross sections in pA and AB collisions at SPS energies are consistent with both purely hadronic scenarios. The predicted rapidity dependence of J/psi suppression can be used to discriminate between the two experimentally. The importance of interactions with secondary hadrons and the applicability of thermal reaction kinetics to J/psi absorption are in- vestigated. We discuss the e ect of nuclear stopping and the role of leading hadrons. The dependence of the 2/J/psi ratio on the model assumptions and the possible influence of refeeding processes is also studied
Target search on a dynamic DNA molecule
We study a protein-DNA target search model with explicit DNA dynamics
applicable to in vitro experiments. We show that the DNA dynamics plays a
crucial role for the effectiveness of protein "jumps" between sites distant
along the DNA contour but close in 3D space. A strongly binding protein that
searches by 1D sliding and jumping alone, explores the search space less
redundantly when the DNA dynamics is fast on the timescale of protein jumps
than in the opposite "frozen DNA" limit. We characterize the crossover between
these limits using simulations and scaling theory. We also rationalize the slow
exploration in the frozen limit as a subtle interplay between long jumps and
long trapping times of the protein in "islands" within random DNA
configurations in solution.Comment: manuscript and supplementary material combined into a single documen
Translocation of structured polynucleotides through nanopores
We investigate theoretically the translocation of structured RNA/DNA
molecules through narrow pores which allow single but not double strands to
pass. The unzipping of basepaired regions within the molecules presents
significant kinetic barriers for the translocation process. We show that this
circumstance may be exploited to determine the full basepairing pattern of
polynucleotides, including RNA pseudoknots. The crucial requirement is that the
translocation dynamics (i.e., the length of the translocated molecular segment)
needs to be recorded as a function of time with a spatial resolution of a few
nucleotides. This could be achieved, for instance, by applying a mechanical
driving force for translocation and recording force-extension curves (FEC's)
with a device such as an atomic force microscope or optical tweezers. Our
analysis suggests that with this added spatial resolution, nanopores could be
transformed into a powerful experimental tool to study the folding of nucleic
acids.Comment: 9 pages, 5 figure
Dissociation rates of J / psi's with comoving mesons : thermal versus nonequilibrium scenario.
We study J/psi dissociation processes in hadronic environments. The validity of a thermal meson gas ansatz is tested by confronting it with an alternative, nonequilibrium scenario. Heavy ion collisions are simulated in the frame- work of the microscopic transport model UrQMD, taking into account the production of charmonium states through hard parton-parton interactions and subsequent rescattering with hadrons. The thermal gas and microscopic transport scenarios are shown to be very dissimilar. Estimates of J/psi survival probabilities based on thermal models of comover interactions in heavy ion collisions are therefore not reliable
The origin of transverse flow at the SPS
We study the transverse expansion in central Pb+Pb collisions at the CERN SPS. Strong collective motion of hadrons can be created. This flow is mainly due to meson baryon rescattering. It allows to study the angular distribution of intermediate mass meson baryon interactions
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