SARS-CoV-2 Nsp5 Protein Causes Acute Lung Inflammation: A Mathematical Model

2020 ◽  
Author(s):  
José Díaz ◽  
Elena R. Álvarez-Buylla ◽  
Antonio Bensussen
Keyword(s):  
Mathematical Model ◽  
Lung Inflammation ◽  
Threshold Value ◽  
Point Of View ◽  
Lung Cells ◽  
Acute Lung Inflammation ◽  
Translation Rate ◽  
Immune State ◽  
Critical Patients ◽  
Nf Kappab

In the present work we propose a mathematical model of the process of inflammation in lung cells in response to SARS-CoV-2 infection from which a plausible scenario for the dynamics of this process arise. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kappaB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. When in presence of the virus the translation rates of NF kappaB and IkB are increased to a high constant value, and the translation rate of IL-6 is increased above the threshold value of 7 nM s-1, the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. This over stimulated immune state becomes autonomous of the signals from other immune cells like macrophages and lymphocytes, and does not shut down by itself. Dexamethasone or Nimesulide have little effect on this state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5 with drugs like Saquinavir. In this form, our model suggests that Nsp5 is effectively the cause of the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. From an evolutive point of view, the use of Nsp5 as the switch to start inflammation, and the consequent overproduction of the ACE2 receptor, is the probable reason of the increased dangerousness of SARS-CoV-2 with respect to SARS-CoV.

scholarly journals SARS-CoV-2 Nsp5 Protein Causes Acute Lung Inflammation: A Dynamical Mathematical Model

2021 ◽  
Author(s):  
José Díaz ◽  
Elena R. Álvarez-Buylla ◽  
Antonio Bensussen
Keyword(s):  
Mathematical Model ◽  
Lung Inflammation ◽  
Threshold Value ◽  
Lung Cells ◽  
Acute Lung Inflammation ◽  
Translation Rate ◽  
Immune State ◽  
Central Node ◽  
Main Protease ◽  
Critical Patients

In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 also increases above the threshold value of 7 pg mL-1 s-1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5.To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 is effectively a central node underlying the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. Nsp5 seems to be the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.

scholarly journals SARS-CoV-2 Nsp5 Protein Causes Acute Lung Inflammation, A Dynamical Mathematical Model

2021 ◽  
Vol 1 ◽  
Author(s):  
Antonio Bensussen ◽  
Elena R. Álvarez-Buylla ◽  
José Díaz
Keyword(s):  
Mathematical Model ◽  
Lung Inflammation ◽  
Threshold Value ◽  
Lung Cells ◽  
Acute Lung Inflammation ◽  
Translation Rate ◽  
Immune State ◽  
Central Node ◽  
Main Protease ◽  
Critical Patients

In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 also increases above the threshold value of 7 pg mL−1 s−1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5. To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 is effectively a central node underlying the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. Nsp5 seems to be the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.

scholarly journals SARS CoV 2 Nsp5 Protein Causes Acute Lung Inflammation, a Dynamical Mathematical Model

2021 ◽  
Author(s):  
Antonio Bensussen ◽  
José Díaz ◽  
Elena R. Álvarez Buylla
Keyword(s):  
Mathematical Model ◽  
Immune Cells ◽  
Lung Inflammation ◽  
Inflammatory Process ◽  
Reference State ◽  
Lung Cells ◽  
Acute Lung Inflammation ◽  
Immune State ◽  
Main Protease ◽  
External Signals

Abstract In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario, our model suggests that the main protease Nsp5 enhances the inflammatory process by increasing the levels of NF κB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. This overstimulated immune state becomes autonomous of the signals from other immune cells, and does not shut down by itself neither when the external signals are turned off. Our model suggests that Nsp5 is effectively the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.

On the displacements of the contours of the optic-electronic space images. Mathematical modeling of displacement

2017 ◽  
Vol 992 (4) ◽  
pp. 32-38 ◽  
Author(s):  
E.G. Voronin
Keyword(s):  
Mathematical Modeling ◽  
Remote Sensing ◽  
Mathematical Model ◽  
Point Of View ◽  
Design Features ◽  
Space Images ◽  
Electronic Imaging ◽  
Measuring Accuracy ◽  
Physical Laws

The article opens a cycle of three consecutive publications dedicated to the phenomenon of the displacement of the same points in overlapping scans obtained adjacent CCD matrices with opto-electronic imagery. This phenomenon was noticed by other authors, but the proposed explanation for the origin of displacements and the resulting estimates are insufficient, and developed their solutions seem controversial from the point of view of recovery of the measuring accuracy of opticalelectronic space images, determined by the physical laws of their formation. In the first article the mathematical modeling of the expected displacements based on the design features of a scanning opto-electronic imaging equipment. It is shown that actual bias cannot be forecast, because they include additional terms, which may be gross, systematic and random values. The proposed algorithm for computing the most probable values of the additional displacement and ways to address some of the systematic components of these displacements in a mathematical model of optical-electronic remote sensing.

scholarly journals Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 180
Author(s):  
Maud Weiss ◽  
Jiahui Fan ◽  
Mickaël Claudel ◽  
Luc Lebeau ◽  
Françoise Pons ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Lung Inflammation ◽  
Adverse Outcome ◽  
Cellular Responses ◽  
Target Cells ◽  
Inflammasome Activation ◽  
Adverse Outcome Pathway ◽  
Acute Lung Inflammation

With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

A note on design-based versus model-based variance estimation in stereology

2002 ◽  
Vol 34 (03) ◽  
pp. 484-490 ◽  
Author(s):  
Asger Hobolth ◽  
Eva B. Vedel Jensen
Keyword(s):  
Mathematical Model ◽  
Original Problem ◽  
Variance Estimation ◽  
Point Of View ◽  
Systematic Sampling ◽  
Variance Estimator ◽  
Shape Model ◽  
Model Based ◽  
Versus Model ◽  
Special Case

Recently, systematic sampling on the circle and the sphere has been studied by Gual-Arnau and Cruz-Orive (2000) from a design-based point of view. In this note, it is shown that their mathematical model for the covariogram is, in a model-based statistical setting, a special case of the p-order shape model suggested by Hobolth, Pedersen and Jensen (2000) and Hobolth, Kent and Dryden (2002) for planar objects without landmarks. Benefits of this observation include an alternative variance estimator, applicable in the original problem of systematic sampling. In a wider perspective, the paper contributes to the discussion concerning design-based versus model-based stereology.

scholarly journals Blockade of Secondary Lymphoid Tissue Chemokine ExacerbatesPropionibacterium acnes-Induced Acute Lung Inflammation

2001 ◽  
Vol 166 (3) ◽  
pp. 2071-2079 ◽  
Author(s):  
Meiji Itakura ◽  
Atsuko Tokuda ◽  
Hiroshi Kimura ◽  
Shigenori Nagai ◽  
Hiroyuki Yoneyama ◽  
...  
Keyword(s):  
Lymphoid Tissue ◽  
Lung Inflammation ◽  
Acute Lung Inflammation ◽  
Secondary Lymphoid Tissue

Effective Properties of Superconducting and Superfluid Composites

1998 ◽  
Vol 12 (29n31) ◽  
pp. 3063-3073 ◽  
Author(s):  
Leonid Berlyand
Keyword(s):  
Mathematical Model ◽  
Linear Problem ◽  
Effective Properties ◽  
Point Of View ◽  
Periodicity Cell ◽  
Unit Size ◽  
Composite Media ◽  
Homogenization Procedure

We consider a mathematical model which describes an ideal superfluid with a large number of thin insulating rods and an ideal superconductor reinforced by such rods. We suggest a homogenization procedure for calculating effective properties of both composite media. From the numerical point of view the procedure amounts to solving a linear problem in a periodicity cell of unit size.

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