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. However, it should be noted that the model has some limitations, including not accounting for all the reactions in which the metabolites are involved. Therefore, a genetic algorithm (GA) was used to estimate the impact of these external processes. Despite these limitations, our model achieved high accuracy and stability, providing real-time observation of changes in metabolite concentrations. This type of model can help in better understanding the mechanisms of biochemical reactions in cells, which can ultimately contribute to the prevention and treatment of aging, cancer, metabolic diseases, and neurodegenerative disorders.

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

ß-oxidation of fatty acids plays a significant role in the energy metabolism of the cell. This paper presents a ß-oxidation model of fatty acids based on queueing theory. It uses Michaelis-Menten enzyme kinetics, and literature data on metabolites' concentration and enzymatic constants. A genetic algorithm was used to optimize the parameters for the pathway reactions. The model enables real-time tracking of changes in the concentrations of metabolites with different carbon chain lengths. Another application of the presented model is to predict the changes caused by system disturbance, such as altered enzyme activity or abnormal fatty acid concentration. The model has been validated against experimental data. There are diseases that change the metabolism of fatty acids and the presented model can be used to understand the cause of these changes, analyze metabolites abnormalities, and determine the initial target of treatment.

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. It can be observed that mTORC1 activity is related to the amount of GLUT4 involved in glucose transport. The results show the relationship between the amount of GAPDH in the cell and mTORC1 activity. Moreover, obtained results suggest that mTORC1 inhibitors may be an effective agent in the fight against type 2 diabetes. However, these results are based on theoretical knowledge and appropriate experimental tests should be performed before making firm conclusions.

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. These reasons prompted the authors to develop a computational model, based on queueing theory, capable of simulating changes in PPP metabolites' concentrations. The model has been validated with empirical data from tumor cells. The obtained results prove the stability and accuracy of the model. By applying queueing theory, this model can be further expanded to include successive metabolic pathways. The use of the model may accelerate research on new drugs, reduce drug costs, and reduce the reliance on laboratory animals necessary for this type of research on which new methods are tested.

A Novel, Low Computational Complexity, Parallel Swarm Algorithm for Application in Low-Energy Devices.

In this work, we propose a novel metaheuristic algorithm that evolved from a conventional particle swarm optimization (PSO) algorithm for application in miniaturized devices and systems that require low energy consumption. The modifications allowed us to substantially reduce the computational complexity of the PSO algorithm, translating to reduced energy consumption in hardware implementation. This is a paramount feature in the devices used, for example, in wireless sensor networks (WSNs) or wireless body area sensors (WBANs), in which particular devices have limited access to a power source. Various swarm algorithms are widely used in solving problems that require searching for an optimal solution, with simultaneous occurrence of a different number of sub-optimal solutions. This makes the hardware implementation worthy of consideration. However, hardware implementation of the conventional PSO algorithm is challenging task. One of the issues is an efficient implementation of the randomization function. In this work, we propose novel methods to work around this problem. In the proposed approach, we replaced the block responsible for generating random values using deterministic methods, which differentiate the trajectories of particular particles in the swarm. Comprehensive investigations in the software model of the modified algorithm have shown that its performance is comparable with or even surpasses the conventional PSO algorithm in a multitude of scenarios. The proposed algorithm was tested with numerous fitness functions to verify its flexibility and adaptiveness to different problems. The paper also presents the hardware implementation of the selected blocks that modify the algorithm. In particular, we focused on reducing the hardware complexity, achieving high-speed operation, while reducing energy consumption.

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. The model allows for tracking of metabolites concentration changes in real time. To validate the model, a drug-induced inhibition affecting activity of enzymes involved in Krebs cycle was simulated and compared with available experimental data. AVAILABILITYAND IMPLEMENTATION: The source code is freely available for download at https://github.com/UTP-WTIiE/KrebsCycleUsingQueueingTheory, implemented in C# supported in Linux or MS Windows. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Components of Artificial Neural Networks Realized in CMOS Technology to be Used in Intelligent Sensors in Wireless Sensor Networks.

The article presents novel hardware solutions for new intelligent sensors that can be used in wireless sensor networks (WSN). A substantial reduction of the amount of data sent by the sensor to the base station in the WSN may extend the possible sensor working time. Miniature integrated artificial neural networks (ANN) applied directly in the sensor can take over the analysis of data collected from the environment, thus reducing amount of data sent over the RF communication block. A prototype specialized chip with components of the ANN was designed in the CMOS 130 nm technology. An adaptation mechanism and a programmable multi-phase clock generator-components of the ANN-are described in more detail. Both simulation and measurement results of selected blocks are presented to demonstrate the correctness of the design.

Analog Programmable Distance Calculation Circuit for Winner Takes All Neural Network Realized in the CMOS Technology.

This paper presents a programmable analog current-mode circuit used to calculate the distance between two vectors of currents, following two distance measures. The Euclidean (L2) distance is commonly used. However, in many situations, it can be replaced with the Manhattan (L1) one, which is computationally less intensive, whose realization comes with less power dissipation and lower hardware complexity. The presented circuit can be easily reprogrammed to operate with one of these distances. The circuit is one of the components of an analog winner takes all neural network (NN) implemented in the complementary metal-oxide-semiconductor 0.18- [Formula: see text] technology. The learning process of the realized NN has been successfully verified by the laboratory tests of the fabricated chip. The proposed distance calculation circuit (DCC) features a simple structure, which makes it suitable for networks with a relatively large number of neurons realized in hardware and operating in parallel. For example, the network with three inputs occupies a relatively small area of 3900 µm(2). When operating in the L2 mode, the circuit dissipates 85 [Formula: see text] of power from the 1.5 V voltage supply, at maximum data rate of 10 MHz. In the L1 mode, an average dissipated power is reduced to 55 [Formula: see text] from 1.2 V voltage supply, while data rate is 12 MHz in this case. The given data rates are provided for the worst case scenario, where input currents differ by 1%-2% only. In this case, the settling time of the comparators used in the DCC is quite long. However, that kind of situation is very rare in the overall learning process.

Realization of the conscience mechanism in CMOS implementation of winner-takes-all self-organizing neural networks.

This paper presents a complementary metal-oxide-semiconductor (CMOS) implementation of a conscience mechanism used to improve the effectiveness of learning in the winner-takes-all (WTA) artificial neural networks (ANNs) realized at the transistor level. This mechanism makes it possible to eliminate the effect of the so-called ¿dead neurons,¿ which do not take part in the learning phase competition. These neurons usually have a detrimental effect on the network performance, increasing the quantization error. The proposed mechanism comes as part of the analog implementation of the WTA neural networks (NNs) designed for applications to ultralow power portable diagnostic devices for online analysis of ECG biomedical signals. The study presents Matlab simulations of the network's model, discusses postlayout circuit level simulations and includes results of measurement completed for the physical realization of the circuit.