Role of Intracellular Stochasticity in Biofilm Growth. Insights from Population Balance Modeling.

There is increasing recognition that stochasticity involved in gene regulatory processes may help cells enhance the signal or synchronize expression for a group of genes. Thus the validity of the traditional deterministic approach to modeling the foregoing processes cannot be without exception. In this study, we identify a frequently encountered situation, i.e., the biofilm, which has in the past been persistently investigated with intracellular deterministic models in the literature. We show in this paper circumstances in which use of the intracellular deterministic model appears distinctly inappropriate. In Enterococcus faecalis, the horizontal gene transfer of plasmid spreads drug resistance. The induction of conjugation in planktonic and biofilm circumstances is examined here with stochastic as well as deterministic models. The stochastic model is formulated with the Chemical Master Equation (CME) for planktonic cells and Reaction-Diffusion Master Equation (RDME) for biofilm. The results show that although the deterministic model works well for the perfectly-mixed planktonic circumstance, it fails to predict the averaged behavior in the biofilm, a behavior that has come to be known asstochastic focusing. A notable finding from this work is that the interception of antagonistic feedback loops to signaling, accentuates stochastic focusing. Moreover, interestingly, increasing particle number of a control variable could lead to an even larger deviation. Intracellular stochasticity plays an important role in biofilm and we surmise by implications from the model, that cell populations may use it to minimize the influence from environmental fluctuation

Using atmospheric trace gas vertical profiles to evaluate model fluxes: a case study of Arctic-CAP observations and GEOS simulations for the ABoVE domain

Accurate estimates of carbon&ndash;climate feedbacks require an independent means for evaluating surface flux models at regional scales. The altitude-integrated enhancement (AIE) derived from the Arctic Carbon Atmospheric Profiles (Arctic-CAP) project demonstrates the utility of this bulk quantity for surface flux model evaluation. This bulk quantity leverages background mole fraction values from the middle free troposphere, is agnostic to uncertainties in boundary layer height, and can be derived from model estimates of mole fractions and vertical gradients. To demonstrate the utility of the bulk quantity, six airborne profiling surveys of atmospheric carbon dioxide (CO2), methane (CH4), and carbon monoxide (CO) throughout Alaska and northwestern Canada between April and November&nbsp;2017 were completed as part of NASA's Arctic&ndash;Boreal Vulnerability Experiment (ABoVE). The Arctic-CAP sampling strategy involved acquiring vertical profiles of CO2, CH4, and CO from the surface to 5&thinsp;km altitude at 25 sites around the ABoVE domain on a 4- to 6-week time interval. All Arctic-CAP measurements were compared to a global simulation using the Goddard Earth Observing System (GEOS) modeling system. Comparisons of the AIE bulk quantity from aircraft observations and GEOS simulations of atmospheric CO2, CH4, and CO highlight the fidelity of the modeled surface fluxes. The model&ndash;data comparison over the ABoVE domain reveals that while current state-of-the-art models and flux estimates are able to capture broad-scale spatial and temporal patterns in near-surface CO2 and CH4 concentrations, more work is needed to resolve fine-scale flux features that are captured in CO observations. &nbsp;</p

Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

Antioxidant starch-based films with encapsulated eugenol. Application to sunflower oil preservation

[EN] Starch films containing eugenol, which was added to the film-forming dispersion in free form or encapsulated with different wall materials (whey protein or lecithin), were obtained by casting. The physical and the antioxidant properties of the films, the release kinetics of eugenol in different food simulants and their performance at preventing sunflower oil oxidation during storage were evaluated. Encapsulated eugenol modified the film microstructure, yielding less stretchable films with reduced water affinity, transparency and oxygen permeability as compared to films formulated with non-encapsulated eugenol. The addition of eugenol microcapsules containing oleic acid promoted the eugenol retention in the starch matrix during film formation and thus, these films exhibited the greatest antioxidant activity. Films developed with encapsulated eugenol powder containing lecithin and oleic acid were highly effective at preventing sunflower oil oxidation even throughout 53 days of storage at 30¿°C, maintaining low and almost constant values of peroxide index, conjugated dienes and trienes in comparison with the control samples.The authors acknowledge the financial support provided by the Spanish Ministerio de Educacion y Ciencia (Projects AGL2013-42989-R and AGL2016-76699-R). Author Emma Talon thanks the Universitat Politecnica de Valencia for a FPI Grant (99/2011). The authors also thank the services rendered by the Electron Microscopy Service of the UPV.Talón-Argente, E.; Vargas, M.; Chiralt, A.; González Martínez, MC. (2019). Antioxidant starch-based films with encapsulated eugenol. Application to sunflower oil preservation. LWT - Food Science and Technology. 113:1-10. https://doi.org/10.1016/j.lwt.2019.108290S11011

Bistability versus Bimodal Distributions in Gene Regulatory Processes from Population Balance

In recent times, stochastic treatments of gene regulatory processes have appeared in the literature in which a cell exposed to a signaling molecule in its environment triggers the synthesis of a specific protein through a network of intracellular reactions. The stochastic nature of this process leads to a distribution of protein levels in a population of cells as determined by a Fokker-Planck equation. Often instability occurs as a consequence of two (stable) steady state protein levels, one at the low end representing the “off” state, and the other at the high end representing the “on” state for a given concentration of the signaling molecule within a suitable range. A consequence of such bistability has been the appearance of bimodal distributions indicating two different populations, one in the “off” state and the other in the “on” state. The bimodal distribution can come about from stochastic analysis of a single cell. However, the concerted action of the population altering the extracellular concentration in the environment of individual cells and hence their behavior can only be accomplished by an appropriate population balance model which accounts for the reciprocal effects of interaction between the population and its environment. In this study, we show how to formulate a population balance model in which stochastic gene expression in individual cells is incorporated. Interestingly, the simulation of the model shows that bistability is neither sufficient nor necessary for bimodal distributions in a population. The original notion of linking bistability with bimodal distribution from single cell stochastic model is therefore only a special consequence of a population balance model

TI in the presence of RNAP pause sites.

<p><b>(A)</b> Mechanistic representation of RNAP collision in presence of two pause sites in the sense strand at positions 160 bp (x_k/L = 0.4) and 320 bp (x_k/L = 0.8). Pause times are 2 s. Increased production of truncated RNA at the pause sites due to enhanced probability of collision is indicated by arrows. <b>(B)</b> Switch response in <i>x</i> levels maintains sharpness as pause time increases but the dynamic range of <i>x</i> is widened more than one order of magnitude. <i>H</i> denotes the value of Hill coefficient (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133873#sec002" target="_blank">Methods</a>). <b>(C)</b> Expression maps for truncated and full-length RNA from pX at different pause times. Truncated RNA production increases as pause time increases. <b>(D)</b> Expression maps for truncated and full-length RNA from pY at different pause times.</p

Algorithm for discrete TI model.

<p><b>(A)</b> A pair of convergent promoters pX (present on sense/top DNA strand) and pY (present on antisense/bottom DNA strand) separated by overlapping DNA of length L is shown. Promoters pX and pY drive expression of genes <i>X</i> and <i>Y</i> respectively, which produce full-length transcripts <i>x</i> and <i>y</i> (denoted by bold arrows) respectively. For each i^th and j^th round of transcription from pX and pY promoters respectively, RNAP (denoted by large grey ovals) form DNA-bound RNAP complexes at the respective promoter region following a binding (τ_BX and τ_BY) and initiation (τ_IX and τ_IY) process. After firing, the center of RNAP moves to first position of the overlapping region to form an elongation complex (EC, denoted by smaller grey ovals). The time taken for each i^th EC (fired from pX) to reach k^th position on sense strand (t_X,i,k) as well as the time taken for each j^th EC (fired from pY) to reach h^th position on the antisense (t_Y,j,h) strand along the overlapping DNA are tracked. The footprint of an EC is denoted by <i>fp</i>. <b>(B)</b> For each i^th and j^th rounds of transcription, the model calculates the outcome of TI depending on the region where opposing RNAPs meet. Occlusion and sitting duck interference occur at the promoters pX (left panels) or pY (right panels), and RNAP collisions between ECs occur along the overlapping DNA (middle panel) following the mathematical constraints shown. Upon RNAP collision, one or both ECs on the sense and antisense strand fall off the DNA and result in production of truncated transcripts <i>x</i>_<i>k</i> and <i>y</i>_<i>h</i> (denoted by dashed arrows) from pX and pY respectively. In absence of any kind of TI, transcription is successful, producing a full-length transcript (<i>x</i>, <i>y</i>). Once 30,000 rounds of transcription from the stronger promoter have been calculated the net rate of production of full-length (<i>k</i>_<i>x</i> and <i>k</i>_<i>y</i>) and truncated RNA (<math><mrow><msub><mi>k</mi><mrow><msub><mi>x</mi><mi>k</mi></msub></mrow></msub></mrow></math> and <math><mrow><msub><mi>k</mi><mrow><msub><mi>y</mi>h</msub></mrow></msub></mrow></math>) are obtained.</p

Antisense transcription coupled with protein feedback gives rise to bistability.

<p><b>(A)</b> Successful full-length <i>x</i> and <i>y</i> transcripts that do not undergo antisense interaction are free to be translated into proteins X and Y respectively. Production of inducer molecule, Z, is indirectly activated by protein Y. Protein X implements a negative feed-back loop by binding to operator site O_Y and repressing promoter pY. Z binds to X and relieves the repression of pY promoter. <b>(B-D)</b> These multiple regulatory layers enable cells to demonstrate a higher-order a bistable switch response to different rates of production of W (denoted by k_WZ). ON state is characterized by production of proteins Y and Z while OFF state is characterized by production of protein X. Threshold k_WZ value to switch between OFF to ON states is 11.5 nM/s whereas the threshold for the inverse switch between ON to OFF states occurs at k_WZ = 8.8 nM/s.</p