scholarly journals Modeling and Simulation of a miRNA Regulatory Network of the PTEN Gene

Mathematics ◽  
2021 ◽  
Vol 9 (15) ◽  
pp. 1803
Author(s):  
Gionmattia Carancini ◽  
Margherita Carletti ◽  
Giulia Spaletta
Keyword(s):  
Regulatory Network ◽  
Species Interactions ◽  
Initial Conditions ◽  
Reaction Rates ◽  
Suppressor Gene ◽  
Mass Action ◽  
Pten Gene ◽  
Dimensional System ◽  
Competitive Endogenous Rnas ◽  
Proposed Model

The PTEN onco-suppressor gene is likely to play an important role in the onset of brain cancer, namely glioblastoma multiforme. Consequently, the PTEN regulatory network, involving microRNAs and competitive endogenous RNAs, becomes a crucial tool for understanding the mechanism related to low levels of expression in cancer patients. This paper introduces a novel model for the regulation of PTEN whose solution is approximated by a high-dimensional system of ordinary differential equations under the assumption that the Law of Mass Action applies. Extensive numerical simulations are presented that mirror parts of the biological subtext that lies behind various alterations. Given the complexity of processes involved in the acquisition of empirical data, initial conditions and reaction rates were inferred from the literature. Despite this, the proposed model is shown to be capable of capturing biologically reasonable behaviors of inter-species interactions, thus representing a positive result, which encourages pursuing the possibility of experimenting on data hopefully provided by omics disciplines.

Ignition and flame quenching of quiescent fuel mists

1978 ◽  
Vol 364 (1717) ◽  
pp. 277-294 ◽  
Keyword(s):  
Reaction Rates ◽  
Ignition Energy ◽  
Minimum Ignition Energy ◽  
Proposed Model ◽  
Theoretical Predictions ◽  
Quenching Distance ◽  
Experimental Values ◽  
Sole Criterion ◽  
Fuel Vapour ◽  
Level Of Agreement

A model is proposed for the ignition of quiescent multidroplet fuel mists which assumes that chemical reaction rates are infinitely fast, and that the sole criterion for successful ignition is the generation, by the spark, of an adequate concentration of fuel vapour in the ignition zone. From analysis of the relevant heat transfer and evaporation processes involved, ex­pressions are derived for the prediction of quenching distance and minimum ignition energy. Support for the model is demonstrated by a close level of agreement between theoretical predictions of minimum ignition energy and the corresponding experimental values obtained using a specially designed ignition apparatus in which ignition energies are measured for several different fuels, over wide ranges of pressure, mixture composition and mean drop size. The results show that both quenching distance and mini­mum ignition energy are strongly dependent on droplet size, and are also dependent, but to a lesser extent, on air density, equivalence ratio and fuel volatility. An expression is derived to indicate the range of drop sizes over which the proposed model is valid.

Kinetic Model of Adiabatic Temperature Rise of Mass Concrete

2021 ◽  
Vol 13 (5) ◽  
pp. 771-780
Author(s):  
Shou-Kai Chen ◽  
Bo-Wen Xu
Keyword(s):  
Temperature Field ◽  
Temperature Rise ◽  
Initial Conditions ◽  
Dynamic Change ◽  
Adiabatic Temperature ◽  
Model Parameters ◽  
Hydration Reaction ◽  
Mass Concrete ◽  
Adiabatic Temperature Rise ◽  
Proposed Model

The adiabatic temperature rise model of mass concrete is very important for temperature field simulation, same to crack resistance capacity and temperature control of concrete structures. In this research, a thermal kinetics analysis was performed to study the exothermic hydration reaction process of concrete, and an adiabatic temperature rise model was proposed. The proposed model considers influencing factors, including initial temperature, temperature history, activation energy, and the completion degree of adiabatic temperature rise and is theoretically mature and definitive in physical meaning. It was performed on different initial temperatures for adiabatic temperature rise test; the data were employed in a regression analysis of the model parameters and initial conditions. The same function was applied to describe the dynamic change of the adiabatic temperature rise rates for different initial temperatures and different temperature changing processes and subsequently employed in a finite element analysis of the concrete temperature field. The test results indicated that the proposed model adequately fits the data of the adiabatic temperature rise test, which included different initial temperatures, and accurately predicts the changing pattern of adiabatic temperature rise of concrete at different initial temperatures. Compared with the results using the traditional age-based adiabatic temperature rise model, the results of a calculation example revealed that the simulated calculation results using the proposed model can accurately reflect the temperature change pattern of concrete in heat dissipation conditions.

scholarly journals Computational Design of Sensitized Combustion Chemistry Experiments

2021 ◽  
Vol 7 ◽  
Author(s):  
Cody Ising ◽  
Pedro Rodriguez ◽  
Daniel Lopez ◽  
Jeffrey Santner
Keyword(s):  
Shock Tube ◽  
Initial Conditions ◽  
Computational Design ◽  
Reaction Rates ◽  
Oxidation Reactions ◽  
Combustion Chemistry ◽  
Experimental Conditions ◽  
As Species ◽  
User Friendly

In combustion chemistry experiments, reaction rates are often extracted from complex experiments using detailed models. To aid in this process, experiments are performed such that measurable quantities, such as species concentrations, flame speed, and ignition delay, are sensitive to reaction rates of interest. In this work, a systematic method for determining such sensitized experimental conditions is demonstrated. An open-source python script was created using the Cantera module to simulate thousands of 0D and hundreds of 1D combustion chemistry experiments in parallel across a broad, user-defined range of mixture conditions. The results of the simulation are post-processed to normalize and compare sensitivity values among reactions and across initial conditions for time-varying and steady-state simulations, in order to determine the “most useful” experimental conditions. This software can be utilized by researchers as a fast, user-friendly screening tool to determine the thermodynamic and mixture parameters for an experimental campaign. We demonstrate this software through two case studies comparing results of the 0D script against a shock tube experiment and results of the 1D script against a spherical flame experiment. In the shock tube case study we present mixture conditions compared to those used in the literature to study H + O2 (+M)→HO2(+M). In the flame case study, we present mixture conditions compared to those in the literature to study formyl radical (HCO) decomposition and oxidation reactions. The systematically determined experimental conditions identified in the present work are similar to the conditions chosen in the literature.

scholarly journals Phase Separation Can Increase Enzyme Activity by Concentration and Molecular Organization

2020 ◽  
Author(s):  
William Peeples ◽  
Michael K. Rosen
Keyword(s):  
Phase Separation ◽  
Enzymatic Reaction ◽  
Reaction Rates ◽  
Quantitative Model ◽  
Mass Action ◽  
Molecular Organization ◽  
Scaffolding Proteins ◽  
Enzyme Cascade ◽  
Separation Threshold ◽  
Liquid Liquid Phase Separation

AbstractBiomolecular condensates concentrate macromolecules into discrete cellular foci without an encapsulating membrane. Condensates are often presumed to increase enzymatic reaction rates through increased concentrations of enzymes and substrates (mass action), although this idea has not been widely tested and other mechanisms of modulation are possible. Here we describe a synthetic system where the SUMOylation enzyme cascade is recruited into engineered condensates generated by liquid-liquid phase separation of multidomain scaffolding proteins. SUMOylation rates can be increased up to 36-fold in these droplets compared to the surrounding bulk, depending on substrate KM. This dependency produces substantial specificity among different substrates. Analyses of reactions above and below the phase separation threshold lead to a quantitative model in which reactions in condensates are accelerated by mass action and by changes in substrate KM, likely due to scaffold-induced molecular organization. Thus, condensates can modulate reaction rates both by concentrating molecules and by physically organizing them.

scholarly journals A Multidimensional and Multiscale Model for Pressure Analysis in a Reservoir-Pipe-Valve System

2019 ◽  
Vol 141 (5) ◽  
Author(s):  
Feng Jie Zheng ◽  
Chao Yong Zong ◽  
William Dempster ◽  
Fu Zheng Qu ◽  
Xue Guan Song
Keyword(s):  
Large Scale ◽  
Pressure Fluctuations ◽  
Three Dimensional ◽  
Multiscale Model ◽  
Computational Time ◽  
Small Scale ◽  
Dimensional System ◽  
Cfd Model ◽  
Computationally Efficient ◽  
Proposed Model

Reservoir-pipe-valve (RPV) systems are widely used in many industrial processes. The pressure in an RPV system plays an important role in the safe operation of the system, especially during the sudden operations such as rapid valve opening or closing. To investigate the pressure response, with particular interest in the pressure fluctuations in an RPV system, a multidimensional and multiscale model combining the method of characteristics (MOC) and computational fluid dynamics (CFD) method is proposed. In the model, the reservoir is modeled as a zero-dimensional virtual point, the pipe is modeled as a one-dimensional system using the MOC, and the valve is modeled using a three-dimensional CFD model. An interface model is used to connect the multidimensional and multiscale model. Based on the model, a transient simulation of the turbulent flow in an RPV system is conducted in which not only the pressure fluctuation in the pipe but also the detailed pressure distribution in the valve is obtained. The results show that the proposed model is in good agreement when compared with a high fidelity CFD model used to represent both large-scale and small-scale spaces. As expected, the proposed model is significantly more computationally efficient than the CFD model. This demonstrates the feasibility of analyzing complex RPV systems within an affordable computational time.

scholarly journals A High-Throughput Screen with Isogenic PTEN+/+ and PTEN−/− Cells Identifies CID1340132 as a Novel Compound That Induces Apoptosis in PTEN and PIK3CA Mutant Human Cancer Cells

2011 ◽  
Vol 16 (4) ◽  
pp. 383-393 ◽  
Author(s):  
Hui-Fang Li ◽  
Adam Keeton ◽  
Michele Vitolo ◽  
Clinton Maddox ◽  
Lynn Rasmussen ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Tumor Suppressor Gene ◽  
High Throughput ◽  
Human Cancer ◽  
Genetic Difference ◽  
Suppressor Gene ◽  
Pten Gene ◽  
Target Cells ◽  
Mutant Cells

The PTEN tumor suppressor gene is one of the most commonly mutated genes in human cancer. Because inactivation of PTEN is a somatic event, PTEN mutations represent an important genetic difference between cancer cells and normal cells and therefore a potential anticancer drug target. However, it remains a substantial challenge to identify compounds that target loss-of-function events such as mutations of tumor suppressors. In an effort to identify small molecules that preferentially kill cells with mutations of PTEN, the authors developed and implemented a high-throughput, paired cell-based screen composed of parental HCT116 cells and their PTEN gene-targeted derivatives. From 138 758 compounds tested, two hits were identified, and one, N′-[(1-benzyl-1H-indol-3-yl)methylene]benzenesulfonohydrazide (CID1340132), was further studied using a variety of cell-based models, including HCT116, MCF10A, and HEC1A cells with targeted deletion of either their PTEN or PIK3CA genes. Preferential killing of PTEN and PIK3CA mutant cells was accompanied by DNA damage, inhibition of DNA synthesis, and apoptosis. Taken together, these data validate a cell-based screening approach for identifying lead compounds that target cells with specific tumor suppressor gene mutations and describe a novel compound with preferential killing activity toward PTEN and PIK3CA mutant cells.

PTEN Gene Deletions in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4889-4889
Author(s):  
Xiao Ying Qi ◽  
A. Keith Stewart ◽  
Hong Chang
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Myeloma Cell ◽  
Suppressor Gene ◽  
High Dose Chemotherapy ◽  
Pten Gene ◽  
Allelic Loss ◽  
High Dose ◽  
13Q Deletion

Abstract PTEN, a tumor suppressor gene, negatively regulates the anti-apoptotic action of akt phosphorylation. Allelic loss or mutation of this gene has been detected in many solid tumors and more recently in human myeloma cell lines (HMCLs). Expression of PTEN has resulted in growth inhibition and apoptosis of a HMCL, suggesting that it may play a role in the pathogenesis of multiple myeloma (MM). However, the PTEN status in tumor cells from patients with MM has not been determined. Using a triple staining method combining staining for cytoplasmic light chains and fluorescence in situ hybridization (FISH) with chromosome 10-centromere and PTEN-gene specific probes, we analyzed clonal plasma cells from 71 patients with MM, 10 with plasma cell leukemia (PCL) and 10 HMCLs. Hemizygous PTEN deletions were detected in 4 of 71 (5.6%) MM patients, 2 of 10 (20%) PCLs, and 2 of 10 (20%) HMCLs. The percentages of clonal plasma cells containing PTEN deletions ranged from 21–90% (median, 56%). Three of the 4 patients with PTEN deletions were detected at diagnosis with stage III disease (Duire-Salmon) and 1 was detected at relapse. Two patients had IgG kappa, 1 IgG lambda and 1 free lambda light chain. To correlate the PTEN status with other known genetic abnormalities in MM, we investigated 4 MM and 2 PCLs with PTEN deletions using FISH for chromosome13q, p53 status, translocations t(11;14), t(4;14) and t(14;16). One MM had a 13q deletion, 1 PCL had a t(11;14), and the other PCL had a t(14;16), a 13q deletion and a p53 deletion. All 4 MM patients with hemizygous PTEN deletions received melphalan based high-dose chemotherapy and autologous stem cell support. Their median overall survival (OS) was 48.1months, and progression free survival (PFS) was 42.8 months as compared to patients without PTEN deletions (OS, not reached, PFS, 25.8 months) (p=0.51 for OS, p=0.67 for PFS). Our results indicate that PTEN deletions are uncommon in MM patients and therefore unlikely represent a primary event for MM. PTEN deletions appear to occur in the advance stage of the disease, and are more frequently involved in PCL or HMCLs suggesting that deletions of PTEN may be associated with disease progression in a subset of MM.

STABILITY OF REGULATORY PROTEIN GRADIENTS INDUCED BY MORPHOGEN DPP IN DROSOPHILA WING DISC

2013 ◽  
Vol 23 (08) ◽  
pp. 1350138 ◽  
Author(s):  
HONGWEI YIN ◽  
XIAOYONG XIAO ◽  
XIAOQING WEN ◽  
TIANSHOU ZHOU
Keyword(s):  
Regulatory Network ◽  
Regulatory Protein ◽  
Reaction Rates ◽  
Wing Disc ◽  
Drosophila Wing ◽  
Major Reaction ◽  
Key Genes ◽  
Pattern Information ◽  
Protein Gradients ◽  
And Control

In the development of Drosophila wing disc, morphogen Dpp, which is a signaling molecule from a local region and disperses into anterior and posterior compartments, builds up a gradient with precise pattern information. Experiments have demonstrated that the key genes (brk, dad, omb and sal) and phosphorylated protein (pMad), which are activated by Dpp signaling molecules and form the gradients of the corresponding proteins of these genes, direct and control the spatial pattern of the wing disc. However, the regulatory network of these genes are in complex and nonlinear interaction with upstream regulators and downstream targets. In this paper, the mathematical model is built according to the regulatory relationships of these key genes. The stabilities of the gradients of these corresponding proteins are investigated. Furthermore, numerical simulations show that these gradients are robust with respect to some major reaction rates in this regulatory network.

scholarly journals Simulation of a stochastic multi-echelon distribution supply chain under a continuous inventory control policy

2020 ◽  
Vol 9 (2) ◽  
pp. 262
Author(s):  
Hamid Ech-cheikh ◽  
Abdessamad Douraid ◽  
Khalid El Had
Keyword(s):  
Distribution System ◽  
Initial Conditions ◽  
Discrete Event ◽  
Control Policy ◽  
Simulation Framework ◽  
Event Simulation ◽  
Proposed Model ◽  
Inventory Control Policy ◽  
Distribution Process ◽  
Key Variables

Multi Echelon Distribution System (MEDS) is a multifaceted system focusing on integration of all factors involved in the entire distribution process of finished goods to customers. This paper proposes a simulation framework at the operational level of MEDS. The proposed model includes three echelons, based on discrete-event simulation approach, where the performed operations within our system are depending on several key variables that often seem to have strong interrelationships. It is necessary to simulate such complicated system, in order to understand the whole mechanism, to analyze the interactions between various components and eventually to provide information without decomposing the system. The simulation framework is used to evaluate the performance of the considered system at initial conditions and to compare it with different scenarios generated by simulation running. The study concludes with an analysis of system performance and the finding results according to each scenario.   

scholarly journals Mathematical Model of Kinetics of Antigens Accumulation in the Process of Periodical Submerged Cultivation of Vibrio cholerae 569В Inaba with Limitation as Regards Carbonic Substrate

2014 ◽  
pp. 96-99
Author(s):  
A. V. Komissarov ◽  
A. K. Nikiforov ◽  
S. N. Zadokhin ◽  
S. A. Eremin ◽  
O. A. Volokh ◽  
...  
Keyword(s):  
Experimental Data ◽  
Mathematical Model ◽  
Model Comparison ◽  
Initial Conditions ◽  
Accumulation Rate ◽  
Submerged Cultivation ◽  
Maximum Output ◽  
Proposed Model ◽  
Cultivation Process ◽  
Kinetics Of

Presented is mathematical model of kinetics of the process of O-antigen and cholera toxin synthesis during periodical submerged cultivation of V. cholerae 569В Inaba with limitation as regards carbonic substrate. The proposed model is based upon analysis of experimental data on V. cholerae 569В Inaba biomass and antigens accumulation, rate of growth and antigens release, and glucose utilization. Using Mathcad 15.0 software calculated are coefficients of differential equations entering into the mathematical model. Comparison of predicted and experimental data demonstrates that relative error of determination of concentrations of the synthesized substances, glucose and cholera vibrio is between 5 and 20 %. The proposed model permits to determine maximum output of final products and specify the parameters of cultivation process performance at different initial conditions.

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