scholarly journals A hybrid PDE–ABM model for viral dynamics with application to SARS-CoV-2 and influenza

2021 ◽  
Vol 8 (11) ◽  
Author(s):  
Sadegh Marzban ◽  
Renji Han ◽  
Nóra Juhász ◽  
Gergely Röst
Keyword(s):  
Continuous Variable ◽  
Virus Concentration ◽  
Viral Dynamics ◽  
Agent Based ◽  
Ode System ◽  
Infection Dynamics ◽  
A Cell ◽  
Spatio Temporal ◽  
Insight Into

We propose a hybrid partial differential equation–agent-based (PDE–ABM) model to describe the spatio-temporal viral dynamics in a cell population. The virus concentration is considered as a continuous variable and virus movement is modelled by diffusion, while changes in the states of cells (i.e. healthy, infected, dead) are represented by a stochastic ABM. The two subsystems are intertwined: the probability of an agent getting infected in the ABM depends on the local viral concentration, and the source term of viral production in the PDE is determined by the cells that are infected. We develop a computational tool that allows us to study the hybrid system and the generated spatial patterns in detail. We systematically compare the outputs with a classical ODE system of viral dynamics, and find that the ODE model is a good approximation only if the diffusion coefficient is large. We demonstrate that the model is able to predict SARS-CoV-2 infection dynamics, and replicate the output of in vitro experiments. Applying the model to influenza as well, we can gain insight into why the outcomes of these two infections are different.

scholarly journals A hybrid PDE–ABM model for viral dynamics with application to SARS–CoV–2 and influenza

2021 ◽  
Author(s):  
Sadegh Marzban ◽  
Renji Han ◽  
Nóra Juhász ◽  
Gergely Röst
Keyword(s):  
Continuous Variable ◽  
Virus Concentration ◽  
Viral Dynamics ◽  
Agent Based ◽  
Ode System ◽  
Infection Dynamics ◽  
A Cell ◽  
Spatio Temporal ◽  
Insight Into

We propose a hybrid partial differential equation - agent-based (PDE-ABM) model to describe the spatio-temporal viral dynamics in a cell population. The virus concentration is considered as a continuous variable and virus movement is modeled by diffusion, while changes in the states of cells (i.e. healthy, infected, dead) are represented by a stochastic agent-based model. The two subsystems are intertwined: the probability of an agent getting infected in the ABM depends on the local viral concentration, and the source term of viral production in the PDE is determined by the cells that are infected. We develop a computational tool that allows us to study the hybrid system and the generated spatial patterns in detail. We systematically compare the outputs with a classical ODE system of viral dynamics and find that the ODE model is a good approximation only if the diffusion coefficient is large. We demonstrate that the model is able to predict SARS-CoV-2 infection dynamics and replicate the output of in vitro experiments. Applying the model to influenza as well, we can gain insight into why the outcomes of these two infections are different.

scholarly journals Polyacrylamide Bead Sensors for in vivo Quantification of Cell-Scale Stress in Zebrafish Development

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
N. Träber ◽  
K. Uhlmann ◽  
S. Girardo ◽  
G. Kesavan ◽  
K. Wagner ◽  
...  
Keyword(s):  
Computational Analysis ◽  
Tissue Level ◽  
Quantitative Investigation ◽  
Pulsatile Pressure ◽  
Spatio Temporal ◽  
Stress Sensing ◽  
Living Organisms ◽  
Insight Into

AbstractMechanical stress exerted and experienced by cells during tissue morphogenesis and organ formation plays an important role in embryonic development. While techniques to quantify mechanical stresses in vitro are available, few methods exist for studying stresses in living organisms. Here, we describe and characterize cell-like polyacrylamide (PAAm) bead sensors with well-defined elastic properties and size for in vivo quantification of cell-scale stresses. The beads were injected into developing zebrafish embryos and their deformations were computationally analyzed to delineate spatio-temporal local acting stresses. With this computational analysis-based cell-scale stress sensing (COMPAX) we are able to detect pulsatile pressure propagation in the developing neural rod potentially originating from polarized midline cell divisions and continuous tissue flow. COMPAX is expected to provide novel spatio-temporal insight into developmental processes at the local tissue level and to facilitate quantitative investigation and a better understanding of morphogenetic processes.

scholarly journals Geospatially Referenced Demographic Agent-Based Modeling of SARS-CoV-2-Infection (COVID-19) Dynamics and Mitigation Effects in a Real-world Community

2020 ◽  
Author(s):  
SO Adler ◽  
O Bodeit ◽  
L Bonn ◽  
B Goldenbogen ◽  
X Escalera-Fanjul ◽  
...  
Keyword(s):  
Real World ◽  
Policy Development ◽  
Household Composition ◽  
Mitigation Strategies ◽  
List Type ◽  
Human Beings ◽  
School Closures ◽  
Agent Based ◽  
Infection Dynamics ◽  
Spatio Temporal

AbstractRe-opening societies and economies across the globe following the initial wave of the severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) pandemic requires scientifically-guided decision processes and policy development. Public health authorities now consider it highly likely that transmission of SARS-CoV-2 and COVID-19 will follow a pattern of seasonal circulation globally. To guide mitigation strategies and tactics in a location-specific manner, accurate simulation of prolonged or intermittent patterns of social/physical distancing is required in order to prevent healthcare systems and communities from collapsing. It is equally important to capture the stochastic appearance of individual transmission events. Traditional epidemiological/statistical models cannot make predictions in a geospatial temporal manner based on human individuals in a community. Thus, the challenge is to conduct spatio-temporal simulations of transmission chains with real-world geospatial and georeferenced information of the dynamics of the disease and the effect of different mitigation strategies such as isolation of infected individuals or location closures. Here, we present a stochastic, geospatially referenced and demography-specific agent-based model with agents representing human beings and include information on age, household composition, daily occupation and schedule, risk factors, and other relevant properties. Physical encounters between humans are modeled in a time-dependent georeferenced network of the population. The model (GERDA-1) can predict infection dynamics under normal conditions and test the effect of different mitigation scenarios such as school closures, reduced social contacts as well as closure or reopening of public/work spaces. Specifically, it also includes the fate and influence of health care workers and their access to protective gear. Key predictions so far entail:the effect of specific groups on the spreading, specifically that children in school contribute substantially to distribution.the result of reopening society depends crucially on how strict the measures have been during lock-down.the outcome of reopening is a stochastic process - in the majority of cases, we must expect a second wave, in some cases not. To the best of our best knowledge, the GERDA-1 model is the first model able to predict a bimodal behavior of SARS-Cov-2 infection dynamics.Given the criticality of the global situation, informing the scientific community, decision makers and the general public seems prudent. Therefore, we here provide a pre-print of the GERDA-1 model together with a first set of predictions and analyses as work in progress.

scholarly journals In vitro Modeling of Embryonal Tumors

2021 ◽  
Vol 9 ◽  
Author(s):  
Lars Custers ◽  
Irene Paassen ◽  
Jarno Drost
Keyword(s):  
Time Window ◽  
Gene Signature ◽  
Developmental Time ◽  
Fetal Life ◽  
Embryonal Tumors ◽  
Cells Of Origin ◽  
A Cell ◽  
Insight Into

A subset of pediatric tumors affects very young children and are thought to arise during fetal life. A common theme is that these embryonal tumors hijack developmental programs, causing a block in differentiation and, as a consequence, unrestricted proliferation. Embryonal tumors, therefore typically maintain an embryonic gene signature not found in their differentiated progeny. Still, the processes underpinning malignant transformation remain largely unknown, which is hampering therapeutic innovation. To gain more insight into these processes, in vitro and in vivo research models are indispensable. However, embryonic development is an extremely dynamic process with continuously changing cellular identities, making it challenging to define cells-of-origin. This is crucial for the development of representative models, as targeting the wrong cell or targeting a cell within an incorrect developmental time window can result in completely different phenotypes. Recent innovations in in vitro cell models may provide more versatile platforms to study embryonal tumors in a scalable manner. In this review, we outline different in vitro models that can be explored to study embryonal tumorigenesis and for therapy development.

scholarly journals Existence of a Conserved Quantity and Stability of In Vitro Virus Infection Dynamics Models with Absorption Effect

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Celia Martínez-Lázaro ◽  
Marco Antonio Taneco-Hernández ◽  
Ramón Reyes-Carreto ◽  
Cruz Vargas-De-León
Keyword(s):  
Experimental Data ◽  
Equilibrium Points ◽  
First Integral ◽  
Conserved Quantity ◽  
Target Cells ◽  
Estimation Of Parameters ◽  
Infection Dynamics ◽  
A Cell ◽  
Dynamics Models

The estimation of parameters in biomathematical models is useful to characterize quantitatively the dynamics of biological processes. In this paper, we consider some systems of ordinary differential equations (ODEs) modelling the viral dynamics in a cell culture. These models incorporate the loss of viral particles due to the absorption into target cells. We estimated the parameters of models by least-squares minimization between numerical solution of the system and experimental data of cell cultures. We derived a first integral or conserved quantity, and we proved the use of experimental data in order to test the conservation law. The systems have nonhyperbolic equilibrium points, and the conditions for their stability are obtained by using a Lyapunov function. We complemented these theoretical results with some numerical simulations.

scholarly journals NSun2 Promotes Cell Growth via Elevating Cyclin-Dependent Kinase 1 Translation

2015 ◽  
Vol 35 (23) ◽  
pp. 4043-4052 ◽  
Author(s):  
Junyue Xing ◽  
Jie Yi ◽  
Xiaoyu Cai ◽  
Hao Tang ◽  
Zhenyun Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Division Cycle ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Cyclin Dependent Kinase ◽  
A Cell ◽  
Cycle Dependent ◽  
Insight Into

The tRNA methytransferase NSun2 promotes cell proliferation, but the molecular mechanism has not been elucidated. Here, we report that NSun2 regulates cyclin-dependent kinase 1 (CDK1) expression in a cell cycle-dependent manner. Knockdown of NSun2 decreased the CDK1 protein level, while overexpression of NSun2 elevated it without alteringCDK1mRNA levels. Further studies revealed that NSun2 methylatedCDK1mRNAin vitroand in cells and that methylation by NSun2 enhanced CDK1 translation. Importantly, NSun2-mediated regulation of CDK1 expression had an impact on the cell division cycle. These results provide new insight into the regulation of CDK1 during the cell division cycle.

scholarly journals The Role of Biofilms, Bacterial Phenotypes, and Innate Immune Response in Mycobacterium avium Colonization to Infection

2021 ◽  
Author(s):  
Catherine Weathered ◽  
Kelly Pennington ◽  
Patricio Escalante ◽  
Elsje Pienaar
Keyword(s):  
Pulmonary Disease ◽  
Mycobacterium Avium ◽  
Three Dimensional ◽  
Published Data ◽  
Agent Based ◽  
Macrophage Recruitment ◽  
Infection Dynamics ◽  
Phenotype Distribution

Mycobacterium avium complex (MAC), is known for colonizing and infecting humans following inhalation of the bacteria. MAC pulmonary disease is notoriously difficult to treat and prone to recurrence. Both the incidence and prevalence MAC pulmonary disease have been increasing globally. MAC is well known to form biofilms in the environment, and in vitro, these biofilms have been shown to aid MAC in epithelial cell invasion, protect MAC from phagocytosis, and cause premature apoptosis in macrophages. In vivo, the system of interactions between MAC, biofilms and host macrophages is complex, difficult to replicate in vitro and in animal models, has not been fully characterized. Here we present a three-dimensional agent-based model of a lung airway to help understand how these interactions evolve in the first 14 days post-bacterial inhalation. We parameterized the model using published data and performed uncertainty analysis to characterize outcomes and parameters effects on those outcomes. Model results show diverse outcomes, including wide ranges of macrophage recruitment levels, and bacterial loads and phenotype distribution. Though most bacteria are phagocytosed by macrophages and remain intracellular, there are also many simulations in which extracellular bacteria continue to drive the colonization and infection. Initial parameters dictating host immune levels, bacterial loads introduced to the airway, and biofilm conditions have significant and lasting impacts on the course of these results. Additionally, though macrophage recruitment is key for suppressing bacterial loads, there is evidence of significant excess recruitment that fail to impact bacterial numbers. These results highlight a need and identify a path for further exploration into the inhalation events in MAC infection. Early infection dynamics could have lasting impacts on the development of nodular bronchiectatic or fibrocavitary disease as well as inform possible preventative and treatment intervention targeting biofilm-macrophage interactions.

scholarly journals Polyacrylamide Bead Sensors for in vivo Quantification of Cell-Scale Stress in Zebrafish Development

2018 ◽  
Author(s):  
N. Träber ◽  
K. Uhlmann ◽  
S. Girardo ◽  
G. Kesavan ◽  
K. Wagner ◽  
...  
Keyword(s):  
Computational Analysis ◽  
Tissue Level ◽  
Quantitative Investigation ◽  
Pulsatile Pressure ◽  
Spatio Temporal ◽  
Stress Sensing ◽  
Living Organisms ◽  
Insight Into

ABSTRACTMechanical stress exerted and experienced by cells during tissue morphogenesis and organ formation plays an important role in embryonic development. While techniques to quantify mechanical stresses in vitro are available, few methods exist for studying stresses in living organisms. Here, we describe and characterize cell-like polyacrylamide (PAAm) bead sensors with well-defined elastic properties and size for in vivo quantification of cell-scale stresses. The beads were injected into developing zebrafish embryos and their deformations were computationally analyzed to delineate spatio-temporal local acting stresses. With this computational analysis-based cell-scale stress sensing (COMPAX) we are able to detect pulsatile pressure propagation in the developing neural rod potentially originating from polarized midline cell divisions and continuous tissue flow. COMPAX is expected to provide novel spatiotemporal insight into developmental processes at the local tissue level and to facilitate quantitative investigation and a better understanding of morphogenetic processes.

Ultrastructure of melanocyte-keratinocyte interactions and pigment transfer in vitro

1978 ◽  
Vol 36 (2) ◽  
pp. 650-651
Author(s):  
Raul I. Garcia ◽  
Evelyn A. Flynn ◽  
George Szabo
Keyword(s):  
Direct Injection ◽  
Skin Pigmentation ◽  
Freeze Fracture ◽  
Pigment Granule ◽  
Time Lapse ◽  
Ultrastructural Level ◽  
Lanthanum Tracer ◽  
A Cell

Skin pigmentation in mammals involves the interaction of epidermal melanocytes and keratinocytes in the structural and functional unit known as the Epidermal Melanin Unit. Melanocytes(M) synthesize melanin within specialized membrane-bound organelles, the melanosome or pigment granule. These are subsequently transferred by way of M dendrites to keratinocytes(K) by a mechanism still to be clearly defined. Three different, though not necessarily mutually exclusive, mechanisms of melanosome transfer have been proposed: cytophagocytosis by K of M dendrite tips containing melanosomes, direct injection of melanosomes into the K cytoplasm through a cell-to-cell pore or communicating channel formed by localized fusion of M and K cell membranes, release of melanosomes into the extracellular space(ECS) by exocytosis followed by K uptake using conventional phagocytosis. Variability in methods of transfer has been noted both in vivo and in vitro and there is evidence in support of each transfer mechanism. We Have previously studied M-K interactions in vitro using time-lapse cinemicrography and in vivo at the ultrastructural level using lanthanum tracer and freeze-fracture.

Sign in / Sign up

Export Citation Format

Share Document