scholarly journals The impact of experimental design choices on parameter inference for models of growing cell colonies

2018 ◽  
Vol 5 (8) ◽  
pp. 180384 ◽  
Author(s):  
Andrew Parker ◽  
Matthew J. Simpson ◽  
Ruth E. Baker

To better understand development, repair and disease progression, it is useful to quantify the behaviour of proliferative and motile cell populations as they grow and expand to fill their local environment. Inferring parameters associated with mechanistic models of cell colony growth using quantitative data collected from carefully designed experiments provides a natural means to elucidate the relative contributions of various processes to the growth of the colony. In this work, we explore how experimental design impacts our ability to infer parameters for simple models of the growth of proliferative and motile cell populations. We adopt a Bayesian approach, which allows us to characterize the uncertainty associated with estimates of the model parameters. Our results suggest that experimental designs that incorporate initial spatial heterogeneities in cell positions facilitate parameter inference without the requirement of cell tracking, while designs that involve uniform initial placement of cells require cell tracking for accurate parameter inference. As cell tracking is an experimental bottleneck in many studies of this type, our recommendations for experimental design provide for significant potential time and cost savings in the analysis of cell colony growth.

2017 ◽  
Author(s):  
Andrew Parker ◽  
Matthew J. Simpson ◽  
Ruth E. Baker

AbstractTo better understand development, repair and disease progression it is useful to quantify the behaviour of proliferative and motile cell populations as they grow and expand to fill their local environment. Inferring parameters associated with mechanistic models of cell colony growth using quantitative data collected from carefully designed experiments provides a natural means to elucidate the relative contributions of various processes to the growth of the colony. In this work we explore how experimental design impacts our ability to infer parameters for simple models of the growth of proliferative and motile cell populations. We adopt a Bayesian approach, which allows us to characterise the uncertainty associated with estimates of the model parameters. Our results suggest that experimental designs that incorporate initial spatial heterogeneities in cell positions facilitate parameter inference without the requirement of cell tracking, whilst designs that involve uniform initial placement of cells require cell tracking for accurate parameter inference. As cell tracking is an experimental bottleneck in many studies of this type, our recommendations for experimental design provide for significant potential time and cost savings in the analysis of cell colony growth.


Processes ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 27 ◽  
Author(s):  
René Schenkendorf ◽  
Xiangzhong Xie ◽  
Moritz Rehbein ◽  
Stephan Scholl ◽  
Ulrike Krewer

In the field of chemical engineering, mathematical models have been proven to be an indispensable tool for process analysis, process design, and condition monitoring. To gain the most benefit from model-based approaches, the implemented mathematical models have to be based on sound principles, and they need to be calibrated to the process under study with suitable model parameter estimates. Often, the model parameters identified by experimental data, however, pose severe uncertainties leading to incorrect or biased inferences. This applies in particular in the field of pharmaceutical manufacturing, where usually the measurement data are limited in quantity and quality when analyzing novel active pharmaceutical ingredients. Optimally designed experiments, in turn, aim to increase the quality of the gathered data in the most efficient way. Any improvement in data quality results in more precise parameter estimates and more reliable model candidates. The applied methods for parameter sensitivity analyses and design criteria are crucial for the effectiveness of the optimal experimental design. In this work, different design measures based on global parameter sensitivities are critically compared with state-of-the-art concepts that follow simplifying linearization principles. The efficient implementation of the proposed sensitivity measures is explicitly addressed to be applicable to complex chemical engineering problems of practical relevance. As a case study, the homogeneous synthesis of 3,4-dihydro-1H-1-benzazepine-2,5-dione, a scaffold for the preparation of various protein kinase inhibitors, is analyzed followed by a more complex model of biochemical reactions. In both studies, the model-based optimal experimental design benefits from global parameter sensitivities combined with proper design measures.


2019 ◽  
Vol 2019 (1) ◽  
pp. 331-338 ◽  
Author(s):  
Jérémie Gerhardt ◽  
Michael E. Miller ◽  
Hyunjin Yoo ◽  
Tara Akhavan

In this paper we discuss a model to estimate the power consumption and lifetime (LT) of an OLED display based on its pixel value and the brightness setting of the screen (scbr). This model is used to illustrate the effect of OLED aging on display color characteristics. Model parameters are based on power consumption measurement of a given display for a number of pixel and scbr combinations. OLED LT is often given for the most stressful display operating situation, i.e. white image at maximum scbr, but having the ability to predict the LT for other configurations can be meaningful to estimate the impact and quality of new image processing algorithms. After explaining our model we present a use case to illustrate how we use it to evaluate the impact of an image processing algorithm for brightness adaptation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie Zhu ◽  
Blanca Gallego

AbstractEpidemic models are being used by governments to inform public health strategies to reduce the spread of SARS-CoV-2. They simulate potential scenarios by manipulating model parameters that control processes of disease transmission and recovery. However, the validity of these parameters is challenged by the uncertainty of the impact of public health interventions on disease transmission, and the forecasting accuracy of these models is rarely investigated during an outbreak. We fitted a stochastic transmission model on reported cases, recoveries and deaths associated with SARS-CoV-2 infection across 101 countries. The dynamics of disease transmission was represented in terms of the daily effective reproduction number ($$R_t$$ R t ). The relationship between public health interventions and $$R_t$$ R t was explored, firstly using a hierarchical clustering algorithm on initial $$R_t$$ R t patterns, and secondly computing the time-lagged cross correlation among the daily number of policies implemented, $$R_t$$ R t , and daily incidence counts in subsequent months. The impact of updating $$R_t$$ R t every time a prediction is made on the forecasting accuracy of the model was investigated. We identified 5 groups of countries with distinct transmission patterns during the first 6 months of the pandemic. Early adoption of social distancing measures and a shorter gap between interventions were associated with a reduction on the duration of outbreaks. The lagged correlation analysis revealed that increased policy volume was associated with lower future $$R_t$$ R t (75 days lag), while a lower $$R_t$$ R t was associated with lower future policy volume (102 days lag). Lastly, the outbreak prediction accuracy of the model using dynamically updated $$R_t$$ R t produced an average AUROC of 0.72 (0.708, 0.723) compared to 0.56 (0.555, 0.568) when $$R_t$$ R t was kept constant. Monitoring the evolution of $$R_t$$ R t during an epidemic is an important complementary piece of information to reported daily counts, recoveries and deaths, since it provides an early signal of the efficacy of containment measures. Using updated $$R_t$$ R t values produces significantly better predictions of future outbreaks. Our results found variation in the effect of early public health interventions on the evolution of $$R_t$$ R t over time and across countries, which could not be explained solely by the timing and number of the adopted interventions.


Hydrology ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 102
Author(s):  
Frauke Kachholz ◽  
Jens Tränckner

Land use changes influence the water balance and often increase surface runoff. The resulting impacts on river flow, water level, and flood should be identified beforehand in the phase of spatial planning. In two consecutive papers, we develop a model-based decision support system for quantifying the hydrological and stream hydraulic impacts of land use changes. Part 1 presents the semi-automatic set-up of physically based hydrological and hydraulic models on the basis of geodata analysis for the current state. Appropriate hydrological model parameters for ungauged catchments are derived by a transfer from a calibrated model. In the regarded lowland river basins, parameters of surface and groundwater inflow turned out to be particularly important. While the calibration delivers very good to good model results for flow (Evol =2.4%, R = 0.84, NSE = 0.84), the model performance is good to satisfactory (Evol = −9.6%, R = 0.88, NSE = 0.59) in a different river system parametrized with the transfer procedure. After transferring the concept to a larger area with various small rivers, the current state is analyzed by running simulations based on statistical rainfall scenarios. Results include watercourse section-specific capacities and excess volumes in case of flooding. The developed approach can relatively quickly generate physically reliable and spatially high-resolution results. Part 2 builds on the data generated in part 1 and presents the subsequent approach to assess hydrologic/hydrodynamic impacts of potential land use changes.


Water ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 463
Author(s):  
Gopinathan R. Abhijith ◽  
Leonid Kadinski ◽  
Avi Ostfeld

The formation of bacterial regrowth and disinfection by-products is ubiquitous in chlorinated water distribution systems (WDSs) operated with organic loads. A generic, easy-to-use mechanistic model describing the fundamental processes governing the interrelationship between chlorine, total organic carbon (TOC), and bacteria to analyze the spatiotemporal water quality variations in WDSs was developed using EPANET-MSX. The representation of multispecies reactions was simplified to minimize the interdependent model parameters. The physicochemical/biological processes that cannot be experimentally determined were neglected. The effects of source water characteristics and water residence time on controlling bacterial regrowth and Trihalomethane (THM) formation in two well-tested systems under chlorinated and non-chlorinated conditions were analyzed by applying the model. The results established that a 100% increase in the free chlorine concentration and a 50% reduction in the TOC at the source effectuated a 5.87 log scale decrement in the bacteriological activity at the expense of a 60% increase in THM formation. The sensitivity study showed the impact of the operating conditions and the network characteristics in determining parameter sensitivities to model outputs. The maximum specific growth rate constant for bulk phase bacteria was found to be the most sensitive parameter to the predicted bacterial regrowth.


Entropy ◽  
2021 ◽  
Vol 23 (4) ◽  
pp. 387
Author(s):  
Yiting Liang ◽  
Yuanhua Zhang ◽  
Yonggang Li

A mechanistic kinetic model of cobalt–hydrogen electrochemical competition for the cobalt removal process in zinc hydrometallurgical was proposed. In addition, to overcome the parameter estimation difficulties arising from the model nonlinearities and the lack of information on the possible value ranges of parameters to be estimated, a constrained guided parameter estimation scheme was derived based on model equations and experimental data. The proposed model and the parameter estimation scheme have two advantages: (i) The model reflected for the first time the mechanism of the electrochemical competition between cobalt and hydrogen ions in the process of cobalt removal in zinc hydrometallurgy; (ii) The proposed constrained parameter estimation scheme did not depend on the information of the possible value ranges of parameters to be estimated; (iii) the constraint conditions provided in that scheme directly linked the experimental phenomenon metrics to the model parameters thereby providing deeper insights into the model parameters for model users. Numerical experiments showed that the proposed constrained parameter estimation algorithm significantly improved the estimation efficiency. Meanwhile, the proposed cobalt–hydrogen electrochemical competition model allowed for accurate simulation of the impact of hydrogen ions on cobalt removal rate as well as simulation of the trend of hydrogen ion concentration, which would be helpful for the actual cobalt removal process in zinc hydrometallurgy.


2020 ◽  
Vol 2020 (1) ◽  
Author(s):  
Shuai Yang ◽  
Haijun Jiang ◽  
Cheng Hu ◽  
Juan Yu ◽  
Jiarong Li

Abstract In this paper, a novel rumor-spreading model is proposed under bilingual environment and heterogenous networks, which considers that exposures may be converted to spreaders or stiflers at a set rate. Firstly, the nonnegativity and boundedness of the solution for rumor-spreading model are proved by reductio ad absurdum. Secondly, both the basic reproduction number and the stability of the rumor-free equilibrium are systematically discussed. Whereafter, the global stability of rumor-prevailing equilibrium is explored by utilizing Lyapunov method and LaSalle’s invariance principle. Finally, the sensitivity analysis and the numerical simulation are respectively presented to analyze the impact of model parameters and illustrate the validity of theoretical results.


Symmetry ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 617
Author(s):  
Jianpeng Ma ◽  
Shi Zhuo ◽  
Chengwei Li ◽  
Liwei Zhan ◽  
Guangzhu Zhang

When early failures in rolling bearings occur, we need to be able to extract weak fault characteristic frequencies under the influence of strong noise and then perform fault diagnosis. Therefore, a new method is proposed: complete ensemble intrinsic time-scale decomposition with adaptive Lévy noise (CEITDALN). This method solves the problem of the traditional complete ensemble intrinsic time-scale decomposition with adaptive noise (CEITDAN) method not being able to filter nonwhite noise in measured vibration signal noise. Therefore, in the method proposed in this paper, a noise model in the form of parameter-adjusted noise is used to replace traditional white noise. We used an optimization algorithm to adaptively adjust the model parameters, reducing the impact of nonwhite noise on the feature frequency extraction. The experimental results for the simulation and vibration signals of rolling bearings showed that the CEITDALN method could extract weak fault features more effectively than traditional methods.


Energies ◽  
2020 ◽  
Vol 14 (1) ◽  
pp. 72
Author(s):  
Sergiu Spataru ◽  
Peter Hacke ◽  
Dezso Sera

An in-situ method is proposed for monitoring and estimating the power degradation of mc-Si photovoltaic (PV) modules undergoing thermo-mechanical degradation tests that primarily manifest through cell cracking, such as mechanical load tests, thermal cycling and humidity freeze tests. The method is based on in-situ measurement of the module’s dark current-voltage (I-V) characteristic curve during the stress test, as well as initial and final module flash testing on a Sun simulator. The method uses superposition of the dark I-V curve with final flash test module short-circuit current to account for shunt and junction recombination losses, as well as series resistance estimation from the in-situ measured dark I-Vs and final flash test measurements. The method is developed based on mc-Si standard modules undergoing several stages of thermo-mechanical stress testing and degradation, for which we investigate the impact of the degradation on the modules light I-V curve parameters, and equivalent solar cell model parameters. Experimental validation of the method on the modules tested shows good agreement between the in-situ estimated power degradation and the flash test measured power loss of the modules, of up to 4.31 % error (RMSE), as the modules experience primarily junction defect recombination and increased series resistance losses. However, the application of the method will be limited for modules experiencing extensive photo-current degradation or delamination, which are not well reflected in the dark I-V characteristic of the PV module.


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