Nonmodular oscillator and switch based on RNA decay drive regeneration of multimodal gene expression

Periodic gene expression dynamics are key to cell and organism physiology. Studies of oscillatory expression have focused on networks with intuitive regulatory negative feedback loops, leaving unknown whether other common biochemical reactions can produce oscillations. Oscillation and noise have been proposed to support the capacity of mammalian progenitor cells to restore heterogenous, multimodal expression from extreme subpopulations, but underlying networks and specific roles of noise remained elusive. We use mass-action-based models to show that regulated RNA degradation involving as few as two RNA species, applicable to nearly half of human protein-coding genes, can generate sustained oscillations without imposed feedback. Diverging oscillation periods synergize with noise to robustly restore bimodal expression in cell populations. The global bifurcation organizing this divergence relies on an oscillator and bistable switch which cannot be decomposed into two structural modules. Our work reveals surprisingly rich dynamics of post-transcriptional reactions and a potentially widespread mechanism useful for development and regeneration.

Generalized Poisson-Nernst-Planck-Based Physical Model of the O2|LSM|YSZ Electrode

The paper presents a generalized Poisson-Nernst-Planck model of an yttria-stabilized zirconia electrolyte developed from first principles of nonequilibrium thermodynamics which allows for spatial resolution of the space charge layer. It takes into account limitations in oxide ion concentrations due to the limited availability of oxygen vacancies. The electrolyte model is coupled with a reaction kinetic model describing the triple phase boundary with electron conducting lanthanum strontium manganite and gaseous phase oxygen. By comparing the outcome of numerical simulations based on different formulations of the kinetic equations with the results of EIS and CV measurements we attempt to discern the existence of separate surface lattice sites for oxygen adatoms and surface oxides from the assumption of shared ones. Moreover, we show that the mass-action kinetics model is sensitive to oxygen partial pressure unlike exponential kinetics models. The resulting model is fitted to a dataset of EIS and CVs spanning multiple temperatures and pressures, using various relative weights of EIS and CV data in the fitness function. The model successfully describes the physics of the interface around the OCV.

A numerical approach for detecting switch-like bistability in mass action chemical reaction networks with conservation laws

Background Theoretical analysis of signaling pathways can provide a substantial amount of insight into their function. One particular area of research considers signaling pathways capable of assuming two or more stable states given the same amount of signaling ligand. This phenomenon of bistability can give rise to switch-like behavior, a mechanism that governs cellular decision making. Investigation of whether or not a signaling pathway can confer bistability and switch-like behavior, without knowledge of specific kinetic rate constant values, is a mathematically challenging problem. Recently a technique based on optimization has been introduced, which is capable of finding example parameter values that confer switch-like behavior for a given pathway. Although this approach has made it possible to analyze moderately sized pathways, it is limited to reaction networks that presume a uniterminal structure. It is this limited structure we address by developing a general technique that applies to any mass action reaction network with conservation laws. Results In this paper we developed a generalized method for detecting switch-like bistable behavior in any mass action reaction network with conservation laws. The method involves (1) construction of a constrained optimization problem using the determinant of the Jacobian of the underlying rate equations, (2) minimization of the objective function to search for conditions resulting in a zero eigenvalue, (3) computation of a confidence level that describes if the global minimum has been found and (4) evaluation of optimization values, using either numerical continuation or directly simulating the ODE system, to verify that a bistability region exists. The generalized method has been tested on three motifs known to be capable of bistability. Conclusions We have developed a variation of an optimization-based method for the discovery of bistability, which is not limited to uniterminal chemical reaction networks. Successful completion of the method provides an S-shaped bifurcation diagram, which indicates that the network acts as a bistable switch for the given optimization parameters.

The Action Potential simulated by Mass Action Law Modelación de Potenciales de Acción generados mediante la Ley de Acción de Masas

En este trabajo se presenta un modelo matemático para potenciales de acción (PA), similar al modelo de Hodgkin y Huxley, utilizando la Ley de Acción de Masas para determinar las corrientes iónicas que atraviesan la membrana en cada célula excitable. Este modelo permite visualizar que la cinética de los canales iónicos (las velocidades de transición de un estado a otro), determina el curso temporal de las corrientes. Además, resalta que los tipos y la intensidad de las corrientes activadas en la membrana celular, determinan la morfología de los PA. Por lo anterior, a cada potencial de acción se le asociaron corrientes iónicas especificas, con esta condición, el modelo generó un sistema de ecuaciones diferenciales cuya solución es la función V=V(t), los resultados mostraron que esta función simula a los PA registrados experimentalmente.

Multiscale model for forecasting Sabin 2 vaccine virus household and community transmission

Since the global withdrawal of Sabin 2 oral poliovirus vaccine (OPV) from routine immunization, the Global Polio Eradication Initiative (GPEI) has reported multiple circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks. Here, we generated an agent-based, mechanistic model designed to assess OPV-related vaccine virus transmission risk in populations with heterogeneous immunity, demography, and social mixing patterns. To showcase the utility of our model, we present a simulation of mOPV2-related Sabin 2 transmission in rural Matlab, Bangladesh based on stool samples collected from infants and their household contacts during an mOPV2 clinical trial. Sabin 2 transmission following the mOPV2 clinical trial was replicated by specifying multiple, heterogeneous contact rates based on household and community membership. Once calibrated, the model generated Matlab-specific insights regarding poliovirus transmission following an accidental point importation or mass vaccination event. We also show that assuming homogeneous contact rates (mass action), as is common of poliovirus forecast models, does not accurately represent the clinical trial and risks overestimating forecasted poliovirus outbreak probability. Our study identifies household and community structure as an important source of transmission heterogeneity when assessing OPV-related transmission risk and provides a calibratable framework for expanding these analyses to other populations. Trial Registration: ClinicalTrials.gov This trial is registered with clinicaltrials.gov, NCT02477046.

Demonstrative protest crime: the limits of criminological analysis

Classical and network protest always assumes mass character. In this regard, the study of protest movements should assume: a) The analysis of many protest actions; b) the analysis of each individual protest action as a manifestation of the phenomenon of collective behavior. At the same time, the first level is important in the context of ensuring the representativeness of the second type of research. «Collective action» and «action of a team member» are fundamentally important. The regulatory system always deals with the assessment of the behavior of a particular person. In this regard, criminology and criminal law should not focus on the protest actions themselves, but on the behavior of individuals within the framework of these actions. In the theoretical analysis of the behavior of these individual participants of mass actions, it is necessary to distinguish: a) actions performed during a mass action, and actions that ensure the protest action itself, which can be performed both before and after it; b) actions of organizers, inspirers, leaders of protest actions, and actions of ordinary participants of the protest action; c) actions related to the organization and participation in mass actions coordinated by the official authorities, and in those not coordinated by the official authorities; d) lawful actions and illegal actions, and among the latter - criminally illegal and administratively illegal; e) intellectual, informational actions, and physical actions. To describe these actions, the article suggests using the term «demonstrative protest crimes». They are: a) associated with a well-defined sphere of public relations that arise in the process of interaction between a person, society and the authorities; b) they are imbued with the unity of motivational factors and the characteristics of the personality of the participants; c) they have a common determinative complex and a common mechanism for their commission; d) they have a distinct separation by the place and time of their commission; e) they assume a specific type and mechanism for the implementation of preventive measures. These signs allow us to consider demonstrative protest crimes as a separate, independent type of crime.

Increasing the efficiency of rare earth metal recovery from technological solutions during processing of apatite raw materials

The issues of complex processing of mineral resources are relevant due to the depletion of available raw materials. So, it is necessary to involve technological waste, generated during the processing of raw materials, to obtain valuable components. In the process flow of apatite concentrate treatment using the sulfuric acid method, a large amount of phosphogypsum is produced with an average content of light rare earth metals (REMs) reaching 0.032-0.45 %. When phosphogypsum is treated with sulfuric acid solutions, a part of REMs is transferred to the sulfate solution, from which it can be extracted by means of ion exchange method. The study focuses on sorption recovery of light REMs (praseodymium, neodymium and samarium) in the form of anionic sulfate complexes of the composition [ln(SO4)2]– on polystyrene anion exchanger AN-31. The experiments were performed under static conditions at a liquid-to-solid ratio of 1:1, pH value of 2, temperature of 298 K and initial REM concentration in the solutions ranging from 0.83 to 226.31 mmol/kg. Thermodynamic description of sorption isotherms was carried out by the method based on linearization of the mass action equation, modified for the ion exchange reaction. As a result of performed calculations, the authors obtained the constants of ion exchange equilibrium for Pr, Nd and Sm, as well as the values of the change in the Gibbs energy for the ion exchange of REM sulfate complexes on the AN-31 anion exchanger and the values of total capacity of the anion exchanger. Calculated separation factors indicated low selectivity of AN-31 anionite exchanger for light REMs; however, the anion exchanger is suitable for effective recovery of a sum of light REMs. Based on the average value of ion exchange equilibrium constant for light REMs, parameters of a sorption unit with a fluidized bed of anion exchanger were estimated.

A different approach for the fractional chemical model

This article analyzes and compares the two algorithms for the numerical solutions of the fractional isothermal chemical equations (FICEs) based on mass action kinetics for autocatalytic feedback, involving the conversion of a reactant in the Liouville-Caputo sense. The first method is based upon the spectral collocation method (SCM), where the properties of Legendre polynomials are utilized to reduce the FICEs to a set of algebraic equations. We then use the well-known method like Newton-Raphson method (NRM) to solve the set of algebraic equations. The second method is based upon the properties of Newton polynomial interpolation (NPI) and the fundamental theorem of fractional calculus. We utilize these methods to construct the numerical solutions of the FICEs. The accuracy and effectiveness of these methods is satisfied graphically by combining the numerical results and plotting the absolute error. Also, the absolute errors are tabulated, and a good agreementfound in all cases.

HillTau: A fast, compact abstraction for model reduction in biochemical signaling networks

Signaling networks mediate many aspects of cellular function. The conventional, mechanistically motivated approach to modeling such networks is through mass-action chemistry, which maps directly to biological entities and facilitates experimental tests and predictions. However such models are complex, need many parameters, and are computationally costly. Here we introduce the HillTau form for signaling models. HillTau retains the direct mapping to biological observables, but it uses far fewer parameters, and is 100 to over 1000 times faster than ODE-based methods. In the HillTau formalism, the steady-state concentration of signaling molecules is approximated by the Hill equation, and the dynamics by a time-course tau. We demonstrate its use in implementing several biochemical motifs, including association, inhibition, feedforward and feedback inhibition, bistability, oscillations, and a synaptic switch obeying the BCM rule. The major use-cases for HillTau are system abstraction, model reduction, scaffolds for data-driven optimization, and fast approximations to complex cellular signaling.