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Article ; Online: A mathematical model to study low-dose metronomic scheduling for chemotherapy.

Arora, Garhima / Bairagi, Nandadulal / Chatterjee, Samrat

2024 Volume 372, Page(s) 109186

Abstract: Metronomic chemotherapy refers to the frequent administration of chemotherapeutic agents at a lower dose and presents an attractive alternative to conventional chemotherapy with encouraging response rates. However, the schedule of the therapy, including ... ...

Abstract	Metronomic chemotherapy refers to the frequent administration of chemotherapeutic agents at a lower dose and presents an attractive alternative to conventional chemotherapy with encouraging response rates. However, the schedule of the therapy, including the dosage of the drug, is usually based on empiricism. The confounding effects of tumor-endothelial-immune interactions during metronomic administration of drugs have not yet been explored in detail, resulting in an incomplete assessment of drug dose and frequency evaluations. The present study aimed to gain a mechanistic understanding of different actions of metronomic chemotherapy using a mathematical model. We have established an analytical condition for determining the dosage and frequency of the drug depending on its clearance rate for complete tumor elimination. The model also brings forward the immune-mediated clearance of the tumor during the metronomic administration of the chemotherapeutic agent. The results from the global sensitivity analysis showed an increase in the sensitivity of drug and immune-mediated killing factors toward the tumor population during metronomic scheduling. Our results emphasize metronomic scheduling over the maximum tolerated dose (MTD) and define a model-based approach for approximating the optimal schedule of drug administration to eliminate tumors while minimizing harm to the immune cells and the patient's body.
Language	English
Publishing date	2024-04-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	1126-5
ISSN	1879-3134 ; 0025-5564
ISSN (online)	1879-3134
ISSN	0025-5564
DOI	10.1016/j.mbs.2024.109186
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Article ; Online: Demand-induced regime shift in fishery: A mathematical perspective.

Bairagi, Nandadulal / Bhattacharya, Santanu / Sarkar, Biswajit

Mathematical biosciences

2023 Volume 361, Page(s) 109008

Abstract: Though overfishing and climate change are the primary reasons for a regime shift in the fishery, we demonstrate here a different reason for the regime shift, not reported earlier to the best of our knowledge. We show that high demand for fish may cause a ...

Abstract	Though overfishing and climate change are the primary reasons for a regime shift in the fishery, we demonstrate here a different reason for the regime shift, not reported earlier to the best of our knowledge. We show that high demand for fish may cause a regime shift in a fishery in a shorter time. For this, a four-dimensional bioeconomic fishery model is considered and analyzed to explore the system's dynamic behavior. The objective is to demonstrate how increasing demand may cause a catastrophic change in the fish and fishery. We provide the local and global stabilities of different equilibrium points, guaranteeing the stable coexistence of ecological and economic states. Our bifurcation analysis revealed that the demand parameter might play positive and negative roles in the system dynamics. Demand can make an unstable fishery stable. It can also help remove the infection from the system. On the flip side, high demand may cause a regime shift from a harvested state to a non-harvested state, making the price unbounded. Using Pontryagin's maximum principle, we further discussed optimal revenue generation.
MeSH term(s)	Animals ; Fisheries ; Conservation of Natural Resources ; Fishes
Language	English
Publishing date	2023-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1126-5
ISSN	1879-3134 ; 0025-5564
ISSN (online)	1879-3134
ISSN	0025-5564
DOI	10.1016/j.mbs.2023.109008
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Article ; Online: Multimodal distribution of transient time of predator extinction in a three-species food chain.

Pattanayak, Debarghya / Mishra, Arindam / Bairagi, Nandadulal / Dana, Syamal K

Chaos (Woodbury, N.Y.)

2023 Volume 33, Issue 4

Abstract: The transient dynamics capture the time history in the behavior of a system before reaching an attractor. This paper deals with the statistics of transient dynamics in a classic tri-trophic food chain with bistability. The species of the food chain model ...

Abstract	The transient dynamics capture the time history in the behavior of a system before reaching an attractor. This paper deals with the statistics of transient dynamics in a classic tri-trophic food chain with bistability. The species of the food chain model either coexist or undergo a partial extinction with predator death after a transient time depending upon the initial population density. The distribution of transient time to predator extinction shows interesting patterns of inhomogeneity and anisotropy in the basin of the predator-free state. More precisely, the distribution shows a multimodal character when the initial points are located near a basin boundary and a unimodal character when chosen from a location far away from the boundary. The distribution is also anisotropic because the number of modes depends on the direction of the local of initial points. We define two new metrics, viz., homogeneity index and local isotropic index, to characterize the distinctive features of the distribution. We explain the origin of such multimodal distributions and try to present their ecological implications.
MeSH term(s)	Animals ; Food Chain ; Models, Biological ; Population Dynamics ; Predatory Behavior ; Ecosystem
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1472677-4
ISSN	1089-7682 ; 1054-1500
ISSN (online)	1089-7682
ISSN	1054-1500
DOI	10.1063/5.0136372
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Diffusive instability in hyperbolic reaction-diffusion equation with different inertia.

Ghorai, Santu / Poria, Swarup / Bairagi, Nandadulal

Chaos (Woodbury, N.Y.)

2022 Volume 32, Issue 1, Page(s) 13101

Abstract: This work considers a two-dimensional hyperbolic reaction-diffusion system with different inertia and explores criteria for various instabilities, like a wave, Turing, and Hopf, both theoretically and numerically. It is proven that wave instability may ... ...

Abstract	This work considers a two-dimensional hyperbolic reaction-diffusion system with different inertia and explores criteria for various instabilities, like a wave, Turing, and Hopf, both theoretically and numerically. It is proven that wave instability may occur in a two-species hyperbolic reaction-diffusion system with identical inertia if the diffusion coefficients of the species are nonidentical but cannot occur if diffusion coefficients are identical. Wave instability may also arise in a two-dimensional hyperbolic reaction-diffusion system if the diffusivities of the species are equal, which is never possible in a parabolic reaction-diffusion system, provided the inertias are different. Interestingly, Turing instability is independent of inertia, but the stability of the corresponding local system depends on the inertia. Theoretical results are demonstrated with an example where the local interaction is represented by the Schnakenberg system.
Language	English
Publishing date	2022-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1472677-4
ISSN	1089-7682 ; 1054-1500
ISSN (online)	1089-7682
ISSN	1054-1500
DOI	10.1063/5.0071959
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Article ; Online: The effect of noise in an HIV infection model with cytotoxic T-lymphocyte impairment.

Majumder, Abhijit / Sardar, Shibani / Bairagi, Nandadulal

Chaos (Woodbury, N.Y.)

2022 Volume 32, Issue 11, Page(s) 113131

Abstract: The human immunodeficiency virus (HIV) interacts with the immune cells within the human body, where the environment is uncertain and noisy. Stochastic models can successfully encapsulate the effect of such a noisy environment compared to their ... ...

Abstract	The human immunodeficiency virus (HIV) interacts with the immune cells within the human body, where the environment is uncertain and noisy. Stochastic models can successfully encapsulate the effect of such a noisy environment compared to their deterministic counterparts. The human immune system is complex but well-coordinated with various immune cells like C D
MeSH term(s)	Humans ; T-Lymphocytes, Cytotoxic ; HIV Infections ; Cell Communication ; Computer Simulation ; Uncertainty
Language	English
Publishing date	2022-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1472677-4
ISSN	1089-7682 ; 1054-1500
ISSN (online)	1089-7682
ISSN	1054-1500
DOI	10.1063/5.0105770
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Article ; Online: Covid-19 disease dynamics with vaccination: The effect of uncertainty

Bairagi, Nandadulal / Majumder, Abhijiit

medRxiv

Abstract: Rate parameters are critical in estimating the covid burden using mathematical models. In the Covid-19 mathematical models, these parameters are assumed to be constant. However, uncertainties in these rate parameters are almost inevitable. In this paper, ...

Abstract	Rate parameters are critical in estimating the covid burden using mathematical models. In the Covid-19 mathematical models, these parameters are assumed to be constant. However, uncertainties in these rate parameters are almost inevitable. In this paper, we study a stochastic epidemic model of the SARS-CoV-2 virus infection in the presence of vaccination in which some parameters fluctuate around its average value. Our analysis shows that if the stochastic basic reproduction number (SBRN) of the system is greater than unity, then there is a stationary distribution, implying the long-time disease persistence. A sufficient condition for disease eradication is also prescribed for which the exposed class goes extinct, followed by the infected class. The disease eradication criterion may not hold if the rate of vaccine-induced immunity loss increases or/and the force of infection increases. Using the Indian Covid-19 data, we estimated the model parameters and showed the future disease progression in the presence of vaccination. The disease extinction time is estimated under various conditions. It is revealed that the mean extinction time is an increasing function of both the force of infection and immunity loss rate and shows the lognormal distribution. We point out that disease eradication might not be possible even at a higher vaccination rate if the vaccine-induced immunity loss rate is high. Our observation thus indicates the endemicity of the disease for the existing vaccine efficacy. The disease eradication is possible only with a higher vaccine efficacy or a reduced infection rate.
Keywords	covid19
Language	English
Publishing date	2022-01-11
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.01.10.22269006
Database	COVID19

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Article ; Online: Identification of critical autophagy-related proteins in diabetic retinopathy: A multi-dimensional computational study

Sarmah, Dipanka Tanu / Gujjar, Sunil / Mathapati, Santosh / Bairagi, Nandadulal / Chatterjee, Samrat

Gene. 2023 May, v. 866 p.147339-

2023

Abstract: Diabetic retinopathy (DR) is a common consequence of diabetes mellitus and a primary cause of visual impairment in middle-aged and elderly individuals. DR is susceptible to cellular degradation facilitated by autophagy. In this study, we have employed a ... ...

Abstract	Diabetic retinopathy (DR) is a common consequence of diabetes mellitus and a primary cause of visual impairment in middle-aged and elderly individuals. DR is susceptible to cellular degradation facilitated by autophagy. In this study, we have employed a multi-layer relatedness (MLR) approach to uncover novel autophagy-related proteins involved in DR. The objective of MLR is to determine the relatedness of autophagic and DR proteins by incorporating both expression and prior-knowledge-based similarities. We constructed a prior knowledge-based network and identified the topologically significant novel disease-related candidate autophagic proteins (CAPs). Then, we evaluated their significance in a gene co-expression and a differentially-expressed gene (DEG) network. Finally, we investigated the proximity of CAPs to the known disease-related proteins. Leveraging this methodology, we identified three crucial autophagy-related proteins, TP53, HSAP90AA1, and PIK3R1, which can influence the DR interactome in various layers of heterogeneity of clinical manifestations. They are strongly related to multiple detrimental characteristics of DR, such as pericyte loss, angiogenesis, apoptosis, and endothelial cell migration, and hence may be used to prevent or delay the progression and development of DR. We evaluated one of the identified targets, TP53, in a cell-based model and found that its inhibition resulted in reduced angiogenesis in high glucose condition required to control DR.
Keywords	angiogenesis ; apoptosis ; autophagy ; cell movement ; diabetic retinopathy ; elderly ; endothelial cells ; genes ; glucose ; models ; vision disorders ; Network topology ; Protein-protein interaction network analysis ; WGCNA ; ARG ; ARP ; CAP ; DM ; DR ; DRP ; EBM ; HG ; HUVECs ; PFT-µ ; VEGF
Language	English
Dates of publication	2023-05
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2023.147339
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Identification of critical autophagy-related proteins in diabetic retinopathy: A multi-dimensional computational study.

Sarmah, Dipanka Tanu / Gujjar, Sunil / Mathapati, Santosh / Bairagi, Nandadulal / Chatterjee, Samrat

Gene

2023 Volume 866, Page(s) 147339

Abstract	Diabetic retinopathy (DR) is a common consequence of diabetes mellitus and a primary cause of visual impairment in middle-aged and elderly individuals. DR is susceptible to cellular degradation facilitated by autophagy. In this study, we have employed a multi-layer relatedness (MLR) approach to uncover novel autophagy-related proteins involved in DR. The objective of MLR is to determine the relatedness of autophagic and DR proteins by incorporating both expression and prior-knowledge-based similarities. We constructed a prior knowledge-based network and identified the topologically significant novel disease-related candidate autophagic proteins (CAPs). Then, we evaluated their significance in a gene co-expression and a differentially-expressed gene (DEG) network. Finally, we investigated the proximity of CAPs to the known disease-related proteins. Leveraging this methodology, we identified three crucial autophagy-related proteins, TP53, HSAP90AA1, and PIK3R1, which can influence the DR interactome in various layers of heterogeneity of clinical manifestations. They are strongly related to multiple detrimental characteristics of DR, such as pericyte loss, angiogenesis, apoptosis, and endothelial cell migration, and hence may be used to prevent or delay the progression and development of DR. We evaluated one of the identified targets, TP53, in a cell-based model and found that its inhibition resulted in reduced angiogenesis in high glucose condition required to control DR.
MeSH term(s)	Aged ; Middle Aged ; Humans ; Diabetic Retinopathy/genetics ; Diabetic Retinopathy/metabolism ; Autophagy-Related Proteins/genetics ; Gene Regulatory Networks ; Diabetes Mellitus
Chemical Substances	Autophagy-Related Proteins
Language	English
Publishing date	2023-03-05
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2023.147339
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Article ; Online: The interplay between DNA damage and autophagy in lung cancer: A mathematical study.

Sarmah, Dipanka Tanu / Bairagi, Nandadulal / Chatterjee, Samrat

Bio Systems

2021 Volume 206, Page(s) 104443

Abstract: The rising mortality in lung cancer, as well as the constraints of the existing drugs, have made it a major research topic. DNA damage marks the early onset of cancer as it often results from vulnerabilities due to UV rays, oxidative stress, ionizing ... ...

Abstract	The rising mortality in lung cancer, as well as the constraints of the existing drugs, have made it a major research topic. DNA damage marks the early onset of cancer as it often results from vulnerabilities due to UV rays, oxidative stress, ionizing radiation, and various types of genotoxic attacks. p53 plays an unequivocal role in the DNA repair process and has an abiding presence at the crossroads of the pathways linking DNA damage and cancer. p53 also regulates autophagy in a dual manner based on its cellular localization. The plexus of autophagy regulated by p53 includes AMPK and BCL2, which are positive and negative regulators of prime autophagy inducer beclin1, respectively. Although autophagy is a quintessential process, its levels need to be monitored as uncontrolled autophagy may lead to cell death. The association of p53 and autophagic cell death is very vital as the former acts whenever any threat comes to DNA while the latter may play a role in getting rid of the culprit cell. Therefore, in this paper, we have formulated a seven-dimensional mathematical model connecting p53, DNA damage, and autophagy in lung cancer. We performed both local and global sensitivity analysis along with parameter recalibration analysis to understand the system dynamics. We hypothesized that, by the modulation of beclin1 level, the regulation of AMPK and BCL2 could be a possible strategy to mitigate the progression of lung cancer.
MeSH term(s)	Autophagy/physiology ; DNA Damage/physiology ; Genes, p53/physiology ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Models, Theoretical ; Oxidative Stress/physiology
Language	English
Publishing date	2021-05-18
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	186234-0
ISSN	1872-8324 ; 0303-2647
ISSN (online)	1872-8324
ISSN	0303-2647
DOI	10.1016/j.biosystems.2021.104443
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Article ; Online: Persistence and extinction of species in a disease-induced ecological system under environmental stochasticity.

Majumder, Abhijit / Adak, Debadatta / Bairagi, Nandadulal

Physical review. E

2021 Volume 103, Issue 3-1, Page(s) 32412

Abstract: Population extinction is a serious issue both from the theoretical and practical points of view. We explore here how environmental noise influences persistence and extinction of interacting species in presence of a pathogen even when the populations ... ...

Abstract	Population extinction is a serious issue both from the theoretical and practical points of view. We explore here how environmental noise influences persistence and extinction of interacting species in presence of a pathogen even when the populations remain stable in its deterministic counterpart. Multiplicative white noise is introduced in a deterministic predator-prey-parasite system by randomly perturbing three biologically important parameters. It is revealed that the extinction criterion of species may be satisfied in multiple ways, indicating various routes to extinction, and disease eradication may be possible with the right environmental noise. Predator population cannot survive, even when its focal prey strongly persists if its growth rate is lower than some critical value, measured by half of the corresponding noise intensity. It is shown that the average extinction time of population decreases with increasing noise intensity and the probability distribution of the extinction time follows the log-normal density curve. A case study on red grouse (prey) and fox (predator) interaction in presence of the parasites trichostrongylus tenuis of grouse is presented to demonstrate that the model well fits the field data.
MeSH term(s)	Ecosystem ; Models, Biological ; Stochastic Processes
Language	English
Publishing date	2021-04-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.103.032412
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