Integrating glycolysis, citric acid cycle, pentose phosphate pathway, and fatty acid beta-oxidation into a single computational model.

The metabolic network of a living cell is highly intricate and involves complex interactions between various pathways. In this study, we propose a computational model that integrates glycolysis, the pentose phosphate pathway (PPP), the fatty acids beta-oxidation, and the tricarboxylic acid cycle (TCA cycle) using queueing theory. The model utilizes literature data on metabolite concentrations and enzyme kinetic constants to calculate the probabilities of individual reactions occurring on a microscopic scale, which can be viewed as the reaction rates on a macroscopic scale.

Deep Reinforcement Learning for Articulatory Synthesis in a Vowel-to-Vowel Imitation Task.

Articulatory synthesis is one of the approaches used for modeling human speech production. In this study, we propose a model-based algorithm for learning the policy to control the vocal tract of the articulatory synthesizer in a vowel-to-vowel imitation task. Our method does not require external training data, since the policy is learned through interactions with the vocal tract model.

Conversion of fat to cellular fuel-Fatty acids β-oxidation model.

β-oxidation of fatty acids plays a significant role in the energy metabolism of the cell. This paper presents a β-oxidation model of fatty acids based on queueing theory. It uses Michaelis-Menten enzyme kinetics, and literature data on metabolites' concentration and enzymatic constants.

Queueing theory model of mTOR complexes' impact on Akt-mediated adipocytes response to insulin.

A queueing theory based model of mTOR complexes impact on Akt-mediated cell response to insulin is presented in this paper. The model includes several aspects including the effect of insulin on the transport of glucose from the blood into the adipocytes with the participation of GLUT4, and the role of the GAPDH enzyme as a regulator of mTORC1 activity. A genetic algorithm was used to optimize the model parameters.

Modeling an immune response to influenza A virus infection in alveolar epithelial cells.

Influenza A viruses (IAV) have been the cause of several influenza pandemics in history and are a significant threat for the next global pandemic. Hospitalized influenza patients often have excess interferon production and a dysregulated immune response to the IAV infection. Obtaining a better understanding of the mechanisms of IAV infection that induce these harmful effects would help drug developers and health professionals create more effective treatments for IAV infection and improve patient outcomes.

Queueing theory model of pentose phosphate pathway.

Due to its role in maintaining the proper functioning of the cell, the pentose phosphate pathway (PPP) is one of the most important metabolic pathways. It is responsible for regulating the concentration of simple sugars and provides precursors for the synthesis of amino acids and nucleotides. In addition, it plays a critical role in maintaining an adequate level of NADPH, which is necessary for the cell to fight oxidative stress.

Queueing theory model of Krebs cycle.

Motivation: Queueing theory can be effective in simulating biochemical reactions taking place in living cells, and the article paves a step toward development of a comprehensive model of cell metabolism. Such a model could help to accelerate and reduce costs for developing and testing investigational drugs reducing number of laboratory animals needed to evaluate drugs.

Results: The article presents a Krebs cycle model based on queueing theory.

Modeling 3-D diffusion using queueing networks.

The objective of this paper is to propose and then validate a new method for simulating molecular diffusion in a 3-D environment. Diffusion governing principles of Brownian motion have been discovered by Einstein and Smoluchowski. In a classical approach, diffusion is modeled using partial differential equations.

The mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic outcomes for long-acting antiretroviral therapy.

During studies to extend the half-life of crystalline nanoformulated antiretroviral therapy (nanoART) the mixed lineage kinase-3 inhibitor URMC-099, developed as an adjunctive neuroprotective agent was shown to facilitate antiviral responses. Long-acting ritonavir-boosted atazanavir (nanoATV/r) nanoformulations co-administered with URMC-099 reduced viral load and the numbers of HIV-1 infected CD4+ T-cells in lymphoid tissues more than either drug alone in infected humanized NOD/SCID/IL2Rγc-/- mice. The drug effects were associated with sustained ART depots.

Identifying Intracellular pDNA Losses From a Model of Nonviral Gene Delivery.

Nonviral gene delivery systems are a type of nanocommunication system that transmit plasmid packets (i.e., pDNA packets) that are programmed at the nanoscale to biological systems at the microscopic cellular level.

Integrating mitosis, toxicity, and transgene expression in a telecommunications packet-switched network model of lipoplex-mediated gene delivery.

Gene delivery systems transport exogenous genetic information to cells or biological systems with the potential to directly alter endogenous gene expression and behavior with applications in functional genomics, tissue engineering, medical devices, and gene therapy. Nonviral systems offer advantages over viral systems because of their low immunogenicity, inexpensive synthesis, and easy modification but suffer from lower transfection levels. The representation of gene transfer using models offers perspective and interpretation of complex cellular mechanisms,including nonviral gene delivery where exact mechanisms are unknown.

Endosomal trafficking of nanoformulated antiretroviral therapy facilitates drug particle carriage and HIV clearance.

Unlabelled: Limitations of antiretroviral therapy (ART) include poor patient adherence, drug toxicities, viral resistance, and failure to penetrate viral reservoirs. Recent developments in nanoformulated ART (nanoART) could overcome such limitations. To this end, we now report a novel effect of nanoART that facilitates drug depots within intracellular compartments at or adjacent to the sites of the viral replication cycle.