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Despite the lifting of COVID-19 restrictions, the COVID-19 pandemic and its effects remain a global challenge including the sub-Saharan Africa (SSA) region. Knowledge of the COVID-19 dynamics and its potential trends amidst variations in COVID-19 vaccine coverage is therefore crucial for policy makers in the SSA region where vaccine uptake is generally lower than in high-income countries. Using a compartmental epidemiological model, this study aims to forecast the potential COVID-19 trends and determine how long a wave could be, taking into consideration the current vaccination rates. The model is calibrated using South African reported data for the first four waves of COVID-19, and the data for the fifth wave are used to test the validity of the model forecast. The model is qualitatively analysed by determining equilibria and their stability, calculating the basic reproduction number R0 and investigating the local and global sensitivity analysis with respect to R0. The impact of vaccination and control interventions are investigated via a series of numerical simulations. Based on the fitted data and simulations, we observed that massive vaccination would only be beneficial (deaths averting) if a highly effective vaccine is used, particularly in combination with non-pharmaceutical interventions. Furthermore, our forecasts demonstrate that increased vaccination coverage in SSA increases population immunity leading to low daily infection numbers in potential future waves. Our findings could be helpful in guiding policy makers and governments in designing vaccination strategies and the implementation of other COVID-19 mitigation strategies.

The mathematical interpretation of interventions for the mitigation of epidemics in the literature often involves finding the optimal time to initiate an intervention and/or the use of the number of infections to manage impact. Whilst these methods may work in theory, in order to implement effectively they may require information which is not likely to be available in the midst of an epidemic, or they may require impeccable data about infection levels in the community. In reality, testing and cases data can only be as good as the policy of implementation and the compliance of the individuals, which implies that accurately estimating the levels of infections becomes difficult or complicated from the data that is provided. In this paper, we demonstrate a different approach to the mathematical modelling of interventions, not based on optimality or cases, but based on demand and capacity of hospitals who have to deal with the epidemic on a day to day basis. In particular, we use data-driven modelling to calibrate a susceptible-exposed-infectious-recovered-died type model to infer parameters that depict the dynamics of the epidemic in several regions of the UK. We use the calibrated parameters for forecasting scenarios and understand, given a maximum capacity of hospital healthcare services, how the timing of interventions, severity of interventions, and conditions for the releasing of interventions affect the overall epidemic-picture. We provide an optimisation method to capture when, in terms of healthcare demand, an intervention should be put into place given a maximum capacity on the service. By using an equivalent agent-based approach, we demonstrate uncertainty quantification on the likelihood that capacity is not breached, by how much if it does, and the limit on demand that almost guarantees capacity is not breached.

Despite the lifting of COVID-19 restrictions, the COVID-19 pandemic and its effects remain a global challenge including the sub-Saharan Africa (SSA) region. Knowledge of the COVID-19 dynamics and its potential trends amidst variations in COVID-19 vaccine coverage is therefore crucial for policy makers in the SSA region where vaccine uptake is generally lower than in high-income countries. Using a compartmental epidemiological model, this study aims to forecast the potential COVID-19 trends and determine how long a wave could be, taking into consideration the current vaccination rates. The model is calibrated using South African reported data for the first four waves of COVID-19, and the data for the fifth wave are used to test the validity of the model forecast. The model is qualitatively analysed by determining equilibria and their stability, calculating the basic reproduction number R0 and investigating the local and global sensitivity analysis with respect to R0. The impact of vaccination and control interventions are investigated via a series of numerical simulations. Based on the fitted data and simulations, we observed that massive vaccination would only be beneficial (deaths averting) if a highly effective vaccine is used, particularly in combination with non-pharmaceutical interventions. Furthermore, our forecasts demonstrate that increased vaccination coverage in SSA increases population immunity leading to low daily infection numbers in potential future waves. Our findings could be helpful in guiding policy makers and governments in designing vaccination strategies and the implementation of other COVID-19 mitigation strategies.

The mathematical interpretation of interventions for the mitigation of epidemics in the literature often involves finding the optimal time to initiate an intervention and/or the use of the number of infections to manage impact. Whilst these methods may work in theory, in order to implement effectively they may require information which is not likely to be available in the midst of an epidemic, or they may require impeccable data about infection levels in the community. In reality, testing and cases data can only be as good as the policy of implementation and the compliance of the individuals, which implies that accurately estimating the levels of infections becomes difficult or complicated from the data that is provided. In this paper, we demonstrate a different approach to the mathematical modelling of interventions, not based on optimality or cases, but based on demand and capacity of hospitals who have to deal with the epidemic on a day to day basis. In particular, we use data-driven modelling to calibrate a susceptible-exposed-infectious-recovered-died type model to infer parameters that depict the dynamics of the epidemic in several regions of the UK. We use the calibrated parameters for forecasting scenarios and understand, given a maximum capacity of hospital healthcare services, how the timing of interventions, severity of interventions, and conditions for the releasing of interventions affect the overall epidemic-picture. We provide an optimisation method to capture when, in terms of healthcare demand, an intervention should be put into place given a maximum capacity on the service. By using an equivalent agent-based approach, we demonstrate uncertainty quantification on the likelihood that capacity is not breached, by how much if it does, and the limit on demand that almost guarantees capacity is not breached.

The process of revitalising quiescent cells in order for them to proliferate plays a pivotalrole in the repair of worn-out tissues as well as for tissue homeostasis. This process is also crucialin the growth, development and well-being of higher multi-cellular organisms such as mammals.Deregulation of proliferation-quiescence transition is related to many diseases, such as cancer. Recentstudies have revealed that this proliferation–quiescence process is regulated tightly by the Rb − E2Fbistable switch mechanism. Based on experimental observations, in this study, we formulate amathematical model to examine the effect of the growth factor concentration on the proliferation–quiescence transition in human cells. Working with a non-dimensionalised model, we prove thepositivity, boundedness and uniqueness of solutions. To understand model solution behaviour closeto bifurcation points, we carry out bifurcation analysis, which is further illustrated by the use ofnumerical bifurcation analysis, sensitivity analysis and numerical simulations. Indeed, bifurcationand numerical analysis of the model predicted a transition between bistable and stable states, whichare dependent on the growth factor concentration parameter (GF). The derived predictions confirmexperimental observations.

The process of revitalising quiescent cells in order for them to proliferate plays a pivotalrole in the repair of worn-out tissues as well as for tissue homeostasis. This process is also crucialin the growth, development and well-being of higher multi-cellular organisms such as mammals.Deregulation of proliferation-quiescence transition is related to many diseases, such as cancer. Recentstudies have revealed that this proliferation–quiescence process is regulated tightly by the Rb − E2Fbistable switch mechanism. Based on experimental observations, in this study, we formulate amathematical model to examine the effect of the growth factor concentration on the proliferation–quiescence transition in human cells. Working with a non-dimensionalised model, we prove thepositivity, boundedness and uniqueness of solutions. To understand model solution behaviour closeto bifurcation points, we carry out bifurcation analysis, which is further illustrated by the use ofnumerical bifurcation analysis, sensitivity analysis and numerical simulations. Indeed, bifurcationand numerical analysis of the model predicted a transition between bistable and stable states, whichare dependent on the growth factor concentration parameter (GF). The derived predictions confirmexperimental observations.

Compartmental models are popular in the mathematics of epidemiology for their simplicity and wide range of applications. Although they are typically solved as initial value problems for a system of ordinary differential equations, the observed data are typically akin to a boundary value-type problem: we observe some of the dependent variables at given times, but we do not know the initial conditions. In this paper, we reformulate the classical susceptible–infectious–recovered system in terms of the number of detected positive infected cases at different times to yield what we term the observational model. We then prove the existence and uniqueness of a solution to the boundary value problem associated with the observational model and present a numerical algorithm to approximate the solution. This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.

Compartmental models are popular in the mathematics of epidemiology for their simplicity and wide range of applications. Although they are typically solved as initial value problems for a system of ordinary differential equations, the observed data are typically akin to a boundary value-type problem: we observe some of the dependent variables at given times, but we do not know the initial conditions. In this paper, we reformulate the classical susceptible–infectious–recovered system in terms of the number of detected positive infected cases at different times to yield what we term the observational model. We then prove the existence and uniqueness of a solution to the boundary value problem associated with the observational model and present a numerical algorithm to approximate the solution. This article is part of the theme issue ‘Technical challenges of modelling real-life epidemics and examples of overcoming these’.

The process of revitalising quiescent cells in order for them to proliferate plays a pivotalrole in the repair of worn-out tissues as well as for tissue homeostasis. This process is also crucialin the growth, development and well-being of higher multi-cellular organisms such as mammals.Deregulation of proliferation-quiescence transition is related to many diseases, such as cancer. Recentstudies have revealed that this proliferation–quiescence process is regulated tightly by the Rb − E2Fbistable switch mechanism. Based on experimental observations, in this study, we formulate amathematical model to examine the effect of the growth factor concentration on the proliferation–quiescence transition in human cells. Working with a non-dimensionalised model, we prove thepositivity, boundedness and uniqueness of solutions. To understand model solution behaviour closeto bifurcation points, we carry out bifurcation analysis, which is further illustrated by the use ofnumerical bifurcation analysis, sensitivity analysis and numerical simulations. Indeed, bifurcationand numerical analysis of the model predicted a transition between bistable and stable states, whichare dependent on the growth factor concentration parameter (GF). The derived predictions confirmexperimental observations.

The process of revitalising quiescent cells in order for them to proliferate plays a pivotalrole in the repair of worn-out tissues as well as for tissue homeostasis. This process is also crucialin the growth, development and well-being of higher multi-cellular organisms such as mammals.Deregulation of proliferation-quiescence transition is related to many diseases, such as cancer. Recentstudies have revealed that this proliferation–quiescence process is regulated tightly by the Rb − E2Fbistable switch mechanism. Based on experimental observations, in this study, we formulate amathematical model to examine the effect of the growth factor concentration on the proliferation–quiescence transition in human cells. Working with a non-dimensionalised model, we prove thepositivity, boundedness and uniqueness of solutions. To understand model solution behaviour closeto bifurcation points, we carry out bifurcation analysis, which is further illustrated by the use ofnumerical bifurcation analysis, sensitivity analysis and numerical simulations. Indeed, bifurcationand numerical analysis of the model predicted a transition between bistable and stable states, whichare dependent on the growth factor concentration parameter (GF). The derived predictions confirmexperimental observations.

The process of revitalising quiescent cells in order for them to proliferate plays a pivotalrole in the repair of worn-out tissues as well as for tissue homeostasis. This process is also crucialin the growth, development and well-being of higher multi-cellular organisms such as mammals.Deregulation of proliferation-quiescence transition is related to many diseases, such as cancer. Recentstudies have revealed that this proliferation–quiescence process is regulated tightly by the Rb − E2Fbistable switch mechanism. Based on experimental observations, in this study, we formulate amathematical model to examine the effect of the growth factor concentration on the proliferation–quiescence transition in human cells. Working with a non-dimensionalised model, we prove thepositivity, boundedness and uniqueness of solutions. To understand model solution behaviour closeto bifurcation points, we carry out bifurcation analysis, which is further illustrated by the use ofnumerical bifurcation analysis, sensitivity analysis and numerical simulations. Indeed, bifurcationand numerical analysis of the model predicted a transition between bistable and stable states, whichare dependent on the growth factor concentration parameter (GF). The derived predictions confirmexperimental observations.

BACKGROUND: The world is experiencing local/regional hotspots and spikes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19 disease. We aimed to formulate an applicable epidemiological model to accurately predict and forecast the impact of local outbreaks of COVID-19 to guide the local healthcare demand and capacity, policy-making and public health decisions. METHODS: The model utilized the aggregated daily COVID-19 situation reports (including counts of daily admissions, discharges and bed occupancy) from the local National Health Service (NHS) hospitals and COVID-19-related weekly deaths in hospitals and other settings in Sussex (population 1.7 million), Southeast England. These data sets corresponded to the first wave of COVID-19 infections from 24 March to 15 June 2020. A novel epidemiological predictive and forecasting model was then derived based on the local/regional surveillance data. Through a rigorous inverse parameter inference approach, the model parameters were estimated by fitting the model to the data in an optimal sense and then subsequent validation. RESULTS: The inferred parameters were physically reasonable and matched up to the widely used parameter values derived from the national data sets by Biggerstaff M, Cowling BJ, Cucunubá ZM et al. (Early insights from statistical and mathematical modeling of key epidemiologic parameters of COVID-19, Emerging infectious diseases. 2020;26(11)). We validate the predictive power of our model by using a subset of the available data and comparing the model predictions for the next 10, 20 and 30 days. The model exhibits a high accuracy in the prediction, even when using only as few as 20 data points for the fitting. CONCLUSIONS: We have demonstrated that by using local/regional data, our predictive and forecasting model can be utilized to guide the local healthcare demand and capacity, policy-making and public health decisions to mitigate the impact of COVID-19 on the loc

Investigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth. As a proof of concept, the effect of the glucocorticoid stress hormone, cortisol was tested on 66CL4 co-culture model. Results were comparable to 66CL4 syngeneic in vivo mouse model undergoing psychological stress. Furthermore, administration of glucocorticoid receptor antagonists demonstrated the use of this model to determine the effect of treatments on the immune-tumour interplay. In conclusion, we provide a method of quantifying the interaction between the immune system and cancer, which can become a screening tool in immunotherapy design.

BACKGROUND: The world is experiencing local/regional hotspots and spikes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19 disease. We aimed to formulate an applicable epidemiological model to accurately predict and forecast the impact of local outbreaks of COVID-19 to guide the local healthcare demand and capacity, policy-making and public health decisions. METHODS: The model utilized the aggregated daily COVID-19 situation reports (including counts of daily admissions, discharges and bed occupancy) from the local National Health Service (NHS) hospitals and COVID-19-related weekly deaths in hospitals and other settings in Sussex (population 1.7 million), Southeast England. These data sets corresponded to the first wave of COVID-19 infections from 24 March to 15 June 2020. A novel epidemiological predictive and forecasting model was then derived based on the local/regional surveillance data. Through a rigorous inverse parameter inference approach, the model parameters were estimated by fitting the model to the data in an optimal sense and then subsequent validation. RESULTS: The inferred parameters were physically reasonable and matched up to the widely used parameter values derived from the national data sets by Biggerstaff M, Cowling BJ, Cucunubá ZM et al. (Early insights from statistical and mathematical modeling of key epidemiologic parameters of COVID-19, Emerging infectious diseases. 2020;26(11)). We validate the predictive power of our model by using a subset of the available data and comparing the model predictions for the next 10, 20 and 30 days. The model exhibits a high accuracy in the prediction, even when using only as few as 20 data points for the fitting. CONCLUSIONS: We have demonstrated that by using local/regional data, our predictive and forecasting model can be utilized to guide the local healthcare demand and capacity, policy-making and public health decisions to mitigate the impact of COVID-19 on the loc

Investigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth. As a proof of concept, the effect of the glucocorticoid stress hormone, cortisol was tested on 66CL4 co-culture model. Results were comparable to 66CL4 syngeneic in vivo mouse model undergoing psychological stress. Furthermore, administration of glucocorticoid receptor antagonists demonstrated the use of this model to determine the effect of treatments on the immune-tumour interplay. In conclusion, we provide a method of quantifying the interaction between the immune system and cancer, which can become a screening tool in immunotherapy design.

In this work we present a novel bulk-surface virtual element method (BSVEM) for the numerical approximation of elliptic bulk-surface partial differential equations (BSPDEs) in three space dimensions. The BSVEM is based on the discretisation of the bulk domain into polyhedral elements with arbitrarily many faces. The polyhedral approximation of the bulk induces a polygonal approximation of the surface. Firstly, we present a geometric error analysis of bulk-surface polyhedral meshes independent of the numerical method. Then, we show that BSVEM has optimal second-order convergence in space, provided the exact solution is $H^{2+3/4}$ in the bulk and $H^2$ on the surface, where the additional $\frac{3}{4}$ is due to the combined effect of surface curvature and polyhedral elements close to the boundary. We show that general polyhedra can be exploited to reduce the computational time of the matrix assembly. To demonstrate optimal convergence results, a numerical example is presented on the unit sphere., Comment: 25 pages, 4 figures, 1 table. This replacement improves figures, updates references, and avoids redundancies. arXiv admin note: substantial text overlap with arXiv:2002.11748

Investigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth. As a proof of concept, the effect of the glucocorticoid stress hormone, cortisol was tested on 66CL4 co-culture model. Results were comparable to 66CL4 syngeneic in vivo mouse model undergoing psychological stress. Furthermore, administration of glucocorticoid receptor antagonists demonstrated the use of this model to determine the effect of treatments on the immune-tumour interplay. In conclusion, we provide a method of quantifying the interaction between the immune system and cancer, which can become a screening tool in immunotherapy design.

Investigational in vitro models that reflect the complexity of the interaction between the immune system and tumours are limited and difficult to establish. Herein, we present a platform to study the tumour-immune interaction using a co-culture between cancer spheroids and activated immune cells. An algorithm was developed for analysis of confocal images of the co-culture to evaluate the following quantitatively; immune cell infiltration, spheroid roundness and spheroid growth. As a proof of concept, the effect of the glucocorticoid stress hormone, cortisol was tested on 66CL4 co-culture model. Results were comparable to 66CL4 syngeneic in vivo mouse model undergoing psychological stress. Furthermore, administration of glucocorticoid receptor antagonists demonstrated the use of this model to determine the effect of treatments on the immune-tumour interplay. In conclusion, we provide a method of quantifying the interaction between the immune system and cancer, which can become a screening tool in immunotherapy design.

Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.

Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.

Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.

Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.

Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.

The main purpose of the current paper is to contribute towards the comprehension of the dynamics of the shadow system of a singular Gierer–Meinhardt model on an isotropically evolving domain. In the case where the inhibitor’s response to the activator’s growth is rather weak, then the shadow system of the Gierer–Meinhardt model is reduced to a single though non-local equation whose dynamics is thoroughly investigated throughout the manuscript. The main focus is on the derivation of blow-up results for this non-local equation, which can be interpreted as instability patterns of the shadow system. In particular, a diffusion-driven instability (DDI), or Turing instability, in the neighbourhood of a constant stationary solution, which then is destabilised via diffusion-driven blow-up, is observed. The latter indicates the formation of some unstable patterns, whilst some stability results of global-in-time solutions towards non-constant steady states guarantee the occurrence of some stable patterns. Most of the theoretical results are verified numerically, whilst the numerical approach is also used to exhibit the dynamics of the shadow system when analytical methods fail.

The main purpose of the current paper is to contribute towards the comprehension of the dynamics of the shadow system of a singular Gierer–Meinhardt model on an isotropically evolving domain. In the case where the inhibitor’s response to the activator’s growth is rather weak, then the shadow system of the Gierer–Meinhardt model is reduced to a single though non-local equation whose dynamics is thoroughly investigated throughout the manuscript. The main focus is on the derivation of blow-up results for this non-local equation, which can be interpreted as instability patterns of the shadow system. In particular, a diffusion-driven instability (DDI), or Turing instability, in the neighbourhood of a constant stationary solution, which then is destabilised via diffusion-driven blow-up, is observed. The latter indicates the formation of some unstable patterns, whilst some stability results of global-in-time solutions towards non-constant steady states guarantee the occurrence of some stable patterns. Most of the theoretical results are verified numerically, whilst the numerical approach is also used to exhibit the dynamics of the shadow system when analytical methods fail.

Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.

In this paper we consider a coupled bulk-surface PDE in two space dimensions. The model consists of a PDE in the bulk that is coupled to another PDE on the surface through general nonlinear boundary conditions. For such a system we propose a novel method, based on coupling a virtual element method [Beir\~ao da Veiga et al., 2013] in the bulk domain to a surface finite element method [Dziuk & Elliott, 2013] on the surface. The proposed method, which we coin the Bulk-Surface Virtual Element Method (BSVEM) includes, as a special case, the bulk-surface finite element method (BSFEM) on triangular meshes [Madzvamuse & Chung, 2016]. The method exhibits second-order convergence in space, provided the exact solution is $H^{2+1/4}$ in the bulk and $H^2$ on the surface, where the additional $\frac{1}{4}$ is required only in the simultaneous presence of surface curvature and non-triangular elements. Two novel techniques introduced in our analysis are (i) an $L^2$-preserving inverse trace operator for the analysis of boundary conditions and (ii) the Sobolev extension as a replacement of the lifting operator [Elliott & Ranner, 2013] for sufficiently smooth exact solutions. The generality of the polygonal mesh can be exploited to optimize the computational time of matrix assembly. The method takes an optimised matrix-vector form that also simplifies the known special case of BSFEM on triangular meshes [Madzvamuse & Chung, 2016]. Three numerical examples illustrate our findings., Comment: 39 pages, 9 figures, 5 tables

The main purpose of the current paper is to contribute towards the comprehension of the dynamics of the shadow system of a singular Gierer–Meinhardt model on an isotropically evolving domain. In the case where the inhibitor’s response to the activator’s growth is rather weak, then the shadow system of the Gierer–Meinhardt model is reduced to a single though non-local equation whose dynamics is thoroughly investigated throughout the manuscript. The main focus is on the derivation of blow-up results for this non-local equation, which can be interpreted as instability patterns of the shadow system. In particular, a diffusion-driven instability (DDI), or Turing instability, in the neighbourhood of a constant stationary solution, which then is destabilised via diffusion-driven blow-up, is observed. The latter indicates the formation of some unstable patterns, whilst some stability results of global-in-time solutions towards non-constant steady states guarantee the occurrence of some stable patterns. Most of the theoretical results are verified numerically, whilst the numerical approach is also used to exhibit the dynamics of the shadow system when analytical methods fail.

Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.

The main purpose of the current paper is to contribute towards the comprehension of the dynamics of the shadow system of a singular Gierer–Meinhardt model on an isotropically evolving domain. In the case where the inhibitor’s response to the activator’s growth is rather weak, then the shadow system of the Gierer–Meinhardt model is reduced to a single though non-local equation whose dynamics is thoroughly investigated throughout the manuscript. The main focus is on the derivation of blow-up results for this non-local equation, which can be interpreted as instability patterns of the shadow system. In particular, a diffusion-driven instability (DDI), or Turing instability, in the neighbourhood of a constant stationary solution, which then is destabilised via diffusion-driven blow-up, is observed. The latter indicates the formation of some unstable patterns, whilst some stability results of global-in-time solutions towards non-constant steady states guarantee the occurrence of some stable patterns. Most of the theoretical results are verified numerically, whilst the numerical approach is also used to exhibit the dynamics of the shadow system when analytical methods fail.

The main purpose of the current paper is to contribute towards the comprehension of the dynamics of the shadow system of a singular Gierer–Meinhardt model on an isotropically evolving domain. In the case where the inhibitor’s response to the activator’s growth is rather weak, then the shadow system of the Gierer–Meinhardt model is reduced to a single though non-local equation whose dynamics is thoroughly investigated throughout the manuscript. The main focus is on the derivation of blow-up results for this non-local equation, which can be interpreted as instability patterns of the shadow system. In particular, a diffusion-driven instability (DDI), or Turing instability, in the neighbourhood of a constant stationary solution, which then is destabilised via diffusion-driven blow-up, is observed. The latter indicates the formation of some unstable patterns, whilst some stability results of global-in-time solutions towards non-constant steady states guarantee the occurrence of some stable patterns. Most of the theoretical results are verified numerically, whilst the numerical approach is also used to exhibit the dynamics of the shadow system when analytical methods fail.

Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics. Bifurcation analysis and numerical simulations predict a strong dependence of oscillatory system dynamics on the concentration of GEF-H1, an Lbc-type RhoGEF, which mediates the positive feedback amplification of Rho activity. This prediction is confirmed experimentally via optogenetic tuning of the effective GEF-H1 concentration in individual living cells. Numerical simulations show that pulse amplitude is most sensitive to external inputs into the myosin component at low GEF-H1 concentrations and that the spatial pulse width is dependent on GEF-H1 diffusion. Our study offers a theoretical framework to explain the emergence of local cell contraction pulses and their modulation by biochemical and mechanical signals.

In this study, we apply the Bayesian paradigm for parameter identification to a well-studied semi-linear reaction–diffusion system with activator-depleted reaction kinetics, posed on stationary as well as evolving domains. We provide a mathematically rigorous framework to study the inverse problem of finding the parameters of a reaction–diffusion system given a final spatial pattern. On the stationary domain the parameters are finite-dimensional, but on the evolving domain we consider the problem of identifying the evolution of the domain, i.e. a time-dependent function. Whilst others have considered these inverse problems using optimisation techniques, the Bayesian approach provides a rigorous mathematical framework for incorporating the prior knowledge on uncertainty in the observation and in the parameters themselves, resulting in an approximation of the full probability distribution for the parameters, given the data. Furthermore, using previously established results, we can prove well-posedness results for the inverse problem, using the well-posedness of the forward problem. Although the numerical approximation of the full probability is computationally expensive, parallelised algorithms make the problem solvable using high-performance computing.