Messenger RNA Fluctuations and Regulatory RNAs Shape the Dynamics of Negative Feedback Loop

Single cell experiments of simple regulatory networks can markedly differ from cell population experiments. Such differences arise from stochastic events in individual cells that are averaged out in cell populations. For instance, while individual cells may show sustained oscillations in the concentrations of some proteins, such oscillations may appear damped in the population average. In this paper we investigate the role of RNA stochastic fluctuations as a leading force to produce a sustained excitatory behavior at the single cell level. Opposed to some previous models, we build a fully stochastic model of a negative feedback loop that explicitly takes into account the RNA stochastic dynamics. We find that messenger RNA random fluctuations can be amplified during translation and produce sustained pulses of protein expression. Motivated by the recent appreciation of the importance of non--coding regulatory RNAs in post--transcription regulation, we also consider the possibility that a regulatory RNA transcript could bind to the messenger RNA and repress translation. Our findings show that the regulatory transcript helps reduce gene expression variability both at the single cell level and at the cell population level.Comment: 87.18.Vf --> Systems biology 87.10.Mn --> Stochastic models in biological systems 87.18.Tt --> Noise in biological systems http://www.ncbi.nlm.nih.gov/pubmed/20365787 http://www.weizmann.ac.il/complex/tlusty/papers/PhysRevE2010.pd

Master Equation for Hydrogen Recombination on Grain Surfaces

Recent experimental results on the formation of molecular hydrogen on astrophysically relevant surfaces under conditions similar to those encountered in the interstellar medium provided useful quantitative information about these processes. Rate equation analysis of experiments on olivine and amorphous carbon surfaces provided the activation energy barriers for the diffusion and desorption processes relevant to hydrogen recombination on these surfaces. However, the suitability of rate equations for the simulation of hydrogen recombination on interstellar grains, where there might be very few atoms on a grain at any given time, has been questioned. To resolve this problem, we introduce a master equation that takes into account both the discrete nature of the H atoms and the fluctuations in the number of atoms on a grain. The hydrogen recombination rate on microscopic grains, as a function of grain size and temperature, is then calculated using the master equation. The results are compared to those obtained from the rate equations and the conditions under which the master equation is required are identified.Comment: Latex document. 14 pages of text. Four associated figs in in PS format on separate files that are "called-in" the LaTeX documen

Molecular Hydrogen Formation on Astrophysically Relevant Surfaces

Recent experimental results about the formation of molecular hydrogen on astrophysically relevant surfaces under conditions close to those encountered in the interstellar medium are analyzed using rate equations. The parameters of the rate equation model are fitted to temperature-programmed desorption curves obtained in the laboratory. These parameters are the activation energy barriers for atomic hydrogen diffusion and desorption, the barrier for molecular hydrogen desorption, and the probability of spontaneous desorption of a hydrogen molecule upon recombination. The model is a generalization of the Polanyi-Wigner equation and provides a description of both first and second order kinetic processes within a single model. Using the values of the parameters that fit best the experimental results, the efficiency of hydrogen recombination on olivine and amorphous carbon surfaces is obtained for a range of hydrogen flux and surface temperature pertinent to a wide range of interstellar conditions

Transient transcriptional responses to stress are generated by opposing effects of mRNA production and degradation

The state of the transcriptome reflects a balance between mRNA production and degradation. Yet how these two regulatory arms interact in shaping the kinetics of the transcriptome in response to environmental changes is not known. We subjected yeast to two stresses, one that induces a fast and transient response, and another that triggers a slow enduring response. We then used microarrays following transcriptional arrest to measure genome-wide decay profiles under each condition. We found condition-specific changes in mRNA decay rates and coordination between mRNA production and degradation. In the transient response, most induced genes were surprisingly destabilized, whereas repressed genes were somewhat stabilized, exhibiting counteraction between production and degradation. This strategy can reconcile high steady-state level with short response time among induced genes. In contrast, the stress that induces the slow response displays the more expected behavior, whereby most induced genes are stabilized, and repressed genes are destabilized. Our results show genome-wide interplay between mRNA production and degradation, and that alternative modes of such interplay determine the kinetics of the transcriptome in response to stress

An Evolutionarily Conserved Mechanism for Controlling the Efficiency of Protein Translation

SummaryRecent years have seen intensive progress in measuring protein translation. However, the contributions of coding sequences to the efficiency of the process remain unclear. Here, we identify a universally conserved profile of translation efficiency along mRNAs computed based on adaptation between coding sequences and the tRNA pool. In this profile, the first ∼30–50 codons are, on average, translated with a low efficiency. Additionally, in eukaryotes, the last ∼50 codons show the highest efficiency over the full coding sequence. The profile accurately predicts position-dependent ribosomal density along yeast genes. These data suggest that translation speed and, as a consequence, ribosomal density are encoded by coding sequences and the tRNA pool. We suggest that the slow “ramp” at the beginning of mRNAs serves as a late stage of translation initiation, forming an optimal and robust means to reduce ribosomal traffic jams, thus minimizing the cost of protein expression.PaperFlic

Epitaxial growth of Cu on Cu(001): experiments and simulations

A quantitative comparison between experimental and Monte Carlo simulation results for the epitaxial growth of Cu/Cu(001) in the submonolayer regime is presented. The simulations take into account a complete set of hopping processes whose activation energies are derived from semi-empirical calculations using the embedded-atom method. The island separation is measured as a function of the incoming flux and the temperature. A good quantitative agreement between the experiment and simulation is found for the island separation, the activation energies for the dominant processes, and the exponents that characterize the growth. The simulation results are then analyzed at lower coverages, which are not accessible experimentally, providing good agreement with theoretical predictions as well.Comment: Latex document. 7 pages. 3 embedded figures in separate PS files. One bbl fil

Effects of Small Island Mobility on Growth in Molecular Beam Epitaxy

The effects of mobility of small islands on island growth in molecular beam epitaxy are studied. It is shown that small island mobility affects both the scaling and morphology of islands during growth. Three microscopic models are considered, in which the critical island sizes are $i^*=1,2$ and 3 (such that islands of size $s \le i^*$ are mobile while islands of size $s \ge i^{\ast}+1$ are immobile). As i^* increases, islands become more compact, while the exponent $\gamma$ which relates the island density to deposition rate increases. The morphological changes are quantified by using fractal analysis. It is shown that the fractal dimensions are rather insensitive to changes in i^*. However, the prefactors provide a quantitative measure of the changing morphologies.Comment: 25 pages of text, RevTeX, additional 8 figures in 10 PS files. Replaced version include some minor changes, notation, etc. To be published in: Phys. Rev B, Vol. 55 (1997

A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE

This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model

Snowmass Neutrino Frontier: DUNE Physics Summary

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment with a primary physics goal of observing neutrino and antineutrino oscillation patterns to precisely measure the parameters governing long-baseline neutrino oscillation in a single experiment, and to test the three-flavor paradigm. DUNE's design has been developed by a large, international collaboration of scientists and engineers to have unique capability to measure neutrino oscillation as a function of energy in a broadband beam, to resolve degeneracy among oscillation parameters, and to control systematic uncertainty using the exquisite imaging capability of massive LArTPC far detector modules and an argon-based near detector. DUNE's neutrino oscillation measurements will unambiguously resolve the neutrino mass ordering and provide the sensitivity to discover CP violation in neutrinos for a wide range of possible values of δCP. DUNE is also uniquely sensitive to electron neutrinos from a galactic supernova burst, and to a broad range of physics beyond the Standard Model (BSM), including nucleon decays. DUNE is anticipated to begin collecting physics data with Phase I, an initial experiment configuration consisting of two far detector modules and a minimal suite of near detector components, with a 1.2 MW proton beam. To realize its extensive, world-leading physics potential requires the full scope of DUNE be completed in Phase II. The three Phase II upgrades are all necessary to achieve DUNE's physics goals: (1) addition of far detector modules three and four for a total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary muon spectrometer with a magnetized, high-pressure gaseous argon TPC and calorimeter