MATHEMATICAL MODELING AND BIFURCATION ANALYSIS FOR A BIOLOGICAL MECHANISM OF CANCER DRUG RESISTANCE

Drug resistance is one of the most intractable issues in targeted therapy for cancer diseases.It has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell populations.Focusing on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune setting.We analyze the local geometric properties of the equilibria of the model.Numerical simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant population.Moreover,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation strength.Sensitivity analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.

Aggravation of Cancer,Heart Diseases and Diabetes Subsequent to COVID-19 Lockdown via Mathematical Modeling

The global populationhas beenandwill continue to be severely impacted by theCOVID-19 epidemic.The primary objective of this research is to demonstrate the future impact of COVID-19 on those who suffer from other fatal conditions such as cancer,heart disease,and diabetes.Here,using ordinary differential equations(ODEs),two mathematical models are developed to explain the association between COVID-19 and cancer and between COVID-19 and diabetes and heart disease.After that,we highlight the stability assessments that can be applied to these models.Sensitivity analysis is used to examine how changes in certain factors impact different aspects of disease.The sensitivity analysis showed that many people are still nervous about seeing a doctor due to COVID-19,which could result in a dramatic increase in the diagnosis of various ailments in the years to come.The correlation between diabetes and cardiovascular illness is also illustrated graphically.The effects of smoking and obesity are also found to be significant in disease compartments.Model fitting is also provided for interpreting the relationship between real data and the results of thiswork.Diabetic people,in particular,need tomonitor their health conditions closely and practice heart health maintenance.People with heart diseases should undergo regular checks so that they can protect themselves from diabetes and take some precautions including suitable diets.The main purpose of this study is to emphasize the importance of regular checks,to warn people about the effects of COVID-19(including avoiding healthcare centers and doctors because of the spread of infectious diseases)and to indicate the importance of family history of cancer,heart diseases and diabetes.The provision of the recommendations requires an increase in public consciousness.

Modellings of Infectious Diseases and Cancers under Wars and Pollution Impacts in Iraq with Reference to a Novel Mathematical Model and Literature Review

Microbial pathogens include bacteria, viruses, fungi, and parasites and together account for a significant percentage of acute and chronic human diseases. In addition to understanding the mechanisms by which various pathogens cause human disease, research in microbial pathogenesis also addresses mechanisms of antimicrobial resistance and the development of new antimicrobial agents and vaccines. Answering fundamental questions regarding host-microbe interactions requires an interdisciplinary approach, including microbiology, genomics, informatics, molecular and cellular biology, biochemistry, immunology, epidemiology, environment and interaction between host and microbe. Studies investigating the direct effects of pollutants on respiratory tract infections are very vast, but those interested in the role of a pre-existing disease and effects of the exposure on the response to secondary stresses are few. In an experimental study at concentrations of air pollutants found in urban environments, frank toxicological responses are rarely observed, however, exposure to secondary stress like the respiratory challenge with infectious bacteria can exacerbate the response of the experimental host. The models like experimental, mechanical, and mathematical are the most abstract, but they allow analysis and logical proofs in a way that other approaches do not permit. The present review is mostly concerned with these model representations particularly with a novel mathematical model explaining the interaction between pathogen and immunity including the equivalence point.

Mathematical Modeling of Cell Polarity Establishment of Budding Yeast

The budding yeast Saccharomyces cerevisiae is a powerful model system for studying the cell polarity establishment.The cell polarization process is regulated by signaling molecules,which are initially distributed in the cytoplasm and then recruited to a proper location on the cell membrane in response to spatial cues or spontaneously.Polarization of these signaling molecules involves complex regulation,so the mathematical models become a useful tool to investigate the mechanism behind the process.In this review,we discuss how mathematical modeling has shed light on different regulations in the cell polarization.We also propose future applications for the mathematical modeling of cell polarization and morphogenesis.

A framework for dynamic modelling of railway track switches considering the switch blades,actuators and control systems

The main contribution of this paper is the development and demonstration of a novel methodology that can be followed to develop a simulation twin of a railway track switch system to test the functionality in a digital environment.This is important because,globally,railway track switches are used to allow trains to change routes;they are a key part of all railway networks.However,because track switches are single points of failure and safety-critical,their inability to operate correctly can cause significant delays and concomitant costs.In order to better understand the dynamic behaviour of switches during operation,this paper has developed a full simulation twin of a complete track switch system.The approach fuses finite element for the rail bending and motion,with physics-based models of the electromechanical actuator system and the control system.Hence,it provides researchers and engineers the opportunity to explore and understand the design space around the dynamic operation of new switches and switch machines before they are built.This is useful for looking at the modification or monitoring of existing switches,and it becomes even more important when new switch concepts are being considered and evaluated.The simulation is capable of running in real time or faster meaning designs can be iterated and checked interactively.The paper describes the modelling approach,demonstrates the methodology by developing the system model for a novel“REPOINT”switch system,and evaluates the system level performance against the dynamic performance requirements for the switch.In the context of that case study,it is found that the proposed new actuation system as designed can meet(and exceed)the system performance requirements,and that the fault tolerance built into the actuation ensures continued operation after a single actuator failure.

Mathematical Modeling of the Co-Infection Dynamics of HIV and Tuberculosis Incorporating Inconsistency in HIV Treatment

A non-linear HIV-TB co-infection has been formulated and analyzed. The positivity and invariant region has been established. The disease free equilibrium and its stability has been determined. The local stability was determined and found to be stable under given conditions. The basic reproduction number was obtained and according to findings, co-infection diminishes when this number is less than unity, and persists when the number is greater than unity. The global stability of the endemic equilibrium was calculated. The impact of HIV on TB was established as well as the impact of TB on HIV. Numerical solution was also done and the findings indicate that when the rate of HIV treatment increases the latent TB increases while the co-infected population decreases. When the rate of HIV treatment decreases the latent TB population decreases and the co-infected population increases. Encouraging communities to prioritize the consistent treatment of HIV infected individuals must be emphasized in order to reduce the scourge of HIV-TB co-infection.

Mathematical Modeling of HIV Investigating the Effect of Inconsistent Treatment

HIV is a retrovirus that infects and impairs the cells and functions of the immune system. It has caused a great challenge to global public health systems and leads to Acquired Immunodeficiency Syndrome (AIDS), if not attended to in good time. Antiretroviral therapy is used for managing the virus in a patient’s lifetime. Some of the symptoms of the disease include lean body mass and many opportunistic infections. This study has developed a SIAT mathematical model to investigate the impact of inconsistency in treatment of the disease. The arising non-linear differential equations have been obtained and analyzed. The DFE and its stability have been obtained and the study found that it is locally asymptotically stable when the basic reproduction number is less than unity. The endemic equilibrium has been obtained and found to be globally asymptotically stable when the basic reproduction number is greater than unity. Numerical solutions have been obtained and analyzed to give the trends in the spread dynamics. The inconsistency in treatment uptake has been analyzed through the numerical solutions. The study found that when the treatment rate of those infected increases, it leads to an increase in treatment population, which slows down the spread of HIV and vice versa. An increase in the rate of treatment of those with AIDS leads to a decrease in the AIDS population, the reverse happens when this rate decreases. The study recommends that the community involvement in advocating for consistent treatment of HIV to curb the spread of the disease.

A continuous and high-efficiency process to separate coal bed methane with porous ZIF-8 slurry:Experimental study and mathematical modelling

Coal bed methane has been considered as an important energy resource.One major difficulty of purifying coal bed methane comes from the similar physical properties of CH_4 and N_2.The ZIF-8/water-glycol slurry was used as a medium to separate coal bed methane by fluidifying the solid adsorbent material.The sorption equilibrium experiment of binary mixture(CH_4/N_2)and slurry was conducted.The selectivity of CH_4 to N_2 is within the range of 2-6,which proved the feasibility of the slurry separation method.The modified Langmuir equation was used to describe the gas-slurry phase equilibrium behavior,and the calculated results were in good agreement with the experimental data.A continuous absorption-adsorption and desorption process on the separation of CH_4/N_2 in slurry is proposed and its mathematical model is also developed.Sensitivity analysis is conducted to determine the operation conditions and the energy performance of the proposed process was also evaluated.Feed gas contains 30 mol%of methane and the methane concentration in product gas is 95.46 mol%with the methane recovery ratio of 90.74%.The total energy consumption for per unit volume of product gas is determined as 1.846 kWh Nm^(-3).Experimental results and process simulation provide basic data for the design and operation of pilot and industrial plant.

Mathematical Modelling of Particle Movement Ahead of the Solid-liquid Interface in Continuous Casting

Whether the particle will be trapped by the solid-liquid interface or not is dependent on its moving behavior ahead of the interface, so a mathematical model has been developed to investigate the movement of the particle ahead of the solid-liquid interface. Based on the theory for the boundary layer, the fluid velocity field near the solid-liquid interface was obtained, and the trajectories of particles were calculated by the equations of motion for particles. In this model, the drag force, the added mass force, the buoyance force, the gravitational force, the Saffman force and the Basset history force are considered. The results show that the behavior of the particle ahead of the solid-liquid interface is affected by the physical property of the particle and fluid flow. And in the continuous casting process, if it moves in the stream directed upward or downward near vertical solid-liquid interface or in the horizontal flow under the solid-liquid interface, the particle with the diameter from 5 um to 60um can reach the solid-liquid interface. But if it moves in horizontal flow above the solid-liquid interface, only the particle with the diameter from 5 um to 10 um can reach the solid-liquid interface.

Mathematical Modelling of Carbonitride Precipitation during Hot Working in Nb Microalloyed Steels

Based on thermodynamics and kinetics, precipitation behavior of microalloyed steels was analyzed. Deformation greatly promotes isothermal carbonitride precipitation and makes C-curve shift leftwards. The position and shape of C-curve also depend on the content of Nb and N. C-curve shifts leftwards a little when N content increases and the nose temperature is raised with increasing Nb content. Deformation shortened precipitation start time during continuous cooling, raised precipitation start temperature, accelerated precipitation kinetics of carbonitrides. With decreasing the finishing temperature and coiling temperature, the precipitates volume fraction increases and strength increment is raised during hot rolling. The simulated results are in agreement with experiment results.

Mathematical analysis of corneal remodelling after intracorneal ring surgery in keratoconus

AIM：To represent mathematically the intersection between the ectatic corneal geometry and the plane of intracorneal ring implants（ICRS）in order to determine the corneal response to ICRS surgery in keratoconus（KC）.Thereafter,to present the concept and early results of a newly derived topography-guided nomogram for ICRS surgery for the treatment of keratectasia. METHODS：The corneal rings plane intersection was modelled to a conic section. Ring effect was the result of：the ring size,position（steep vs flat）,location（distance from the geometric centre of the cornea）,and the discrepancy between the ring＇s curvature and the tunnel＇s curvature.Femtosecond laser was used to create the tunnels and the incision sites were chosen according to the nomogram in order to place the thickest ring in the steepest portion of the cornea regardless of the astigmatism axis of refraction.RESULTS：The conic section had a more prolate shape in the steep area of the cornea than in the flat area,depending on the corneal sagittal curvature. Equal ring size had more flattening effect in the steep area than in the flat area. Thick segment should be implanted under the steep portion of the cornea regardless of the cylinder axis of refraction. Single segment in the steep area was sufficient in early and moderate cases of KC. The new nomogram provided more topographic regularity with significant reduction of astigmatism and better improvement in uncorrected visual acuity（UCVA）and best-corrected visual acuity（BCVA）than the conventional nomogram. CONCLUSION：The newly derived nomogram can produce better results than the conventional nomogram. Moreover,based on this concept,a new nomogram can be integrated into the femtosecond laser software to create topography-guided,customized,elliptical tunnels with modified focal asphericity that allows for customized focal flattening of the irregularly steepened ectatic cornea.

Reducing the Range of Cancer Risk on BI-RADS 4 Subcategories via Mathematical Modelling

Breast Imaging Reporting and Data System,also known as BI-RADS is a universal system used by radiologists and doctors.It constructs a comprehensive language for the diagnosis of breast cancer.BI-RADS 4 category has a wide range of cancer risk since it is divided into 3 categories.Mathematicalmodels play an important role in the diagnosis and treatment of cancer.In this study,data of 42 BI-RADS 4 patients taken fromthe Center for Breast Health,Near East University Hospital is utilized.Regarding the analysis,a mathematical model is constructed by dividing the population into 4 compartments.Sensitivity analysis is applied to the parameters with the desired outcome of a reduced range of cancer risk.Numerical simulations of the parameters are demonstrated.The results of the model have revealed that an increase in the lactation rate and earlymenopause have a negative correlation with the chance of being diagnosed with BI-RADS 4 whereas a positive correlation increase in age,the palpable mass,and family history is distinctive.Furthermore,the negative effects of smoking and late menopause on BI-RADS 4C diagnosis are vehemently outlined.Consequently,the model showed that the percentages of parameters play an important role in the diagnosis of BI-RADS 4 subcategories.All things considered,with the assistance of the most effective parameters,the range of cancer risks in BI-RADS 4 subcategories will decrease.

Mathematically modelling and controlling prostate cancer under intermittent hormone therapy

In this review, we summarize our recently developed mathematical models that predict the effects of intermittent androgen suppression therapy on prostate cancer （PCa）. Although hormone therapy for PCa shows remarkable results at the beginning of treatment, cancer cells frequently acquire the ability to grow without androgens during long-term therapy, resulting in an eventual relapse. To circumvent hormone resistance, intermittent androgen suppression was investigated as an alternative treatment option. However, at the present time, it is not possible to select an optimal schedule of on- and off-treatment cycles for any given patient. In addition, clinical trials have revealed that intermittent androgen suppression is effective for some patients but not for others. To resolve these two problems, we have developed mathematical models for PCa under intermittent androgen suppression. The mathematical models not only explain the mechanisms of intermittent androgen suppression but also provide an optimal treatment schedule for the on- and off-treatment periods.

MATHEMATICAL MODELLING OF FLOW PHENOMENA IN METAL BATH COVERED WITH MOLTEN SLAG

By use of the two-component LDA and high speed camera,the water model of the flow field in metal bath under molten slag layer has been tested.On the basis of experimental results,the flow boundary conditions of liquid metal at the slag-metal interface of a gas injecting bath were deduced.The flow field and the turbulent parameters of the metal bath covered with slag were solved by the vorticity-stream function method.The results reveal that the flow velocity, turbulent energy and circulating rate of the melt under slag are lower than that of without slagcover.Another one “dead zone” of the lowest turbulent energy is formed in the top layer under cover of slag near the ladle linning.

Mathematical and Numerical Modelling of Copper Tube Extrusion after Optimizing Geometrical and Operating Parameters

This study aimed to optimize cross-sectional area of the extruder and the flow rate of the material through the extruder. Extrusion process was first modelized using the continuum mechanics method before being simulated with the commercial software LS-DYNA using the Johnson-Cook model based on the finite element method after optimization of the factors with simplex algorithm. The study was carried out on a connecting rod: diameter of 145 mm, cross-section of 1.65 m2, length of 0.25 m, volume of 0.41 m3 and a mass of 37 kg. Optimum parameters obtained were temperature of 850℃, flow rate of 0.237 m/s, die diameter of 19.2 mm, pin diameter of 14 mm, extrusion strength of 565.6 kN and press pressure of 245 GPa. From these factors, a blank was obtained with external and internal diameters of 19.2 and 14 mm respectively over a length of 28 m with a thickness of 2.6 mm. Simulation using LS-DYNA software resulted in a difference in values of 7.4% between optimization and simulation when the difference of 2.4% was found between modelling and simulation. These values make the process optimal for industrial application to improve the extrusion requirements of copper tubes.

Refined mathematical model for the breaching of concrete-face sand-gravel dams due to overtopping failure

Overtopping is one of the main reasons for the breaching of concrete-face sand-gravel dams(CFSGDs).In this study,a refined mathematical model was established based on the characteristics of the overtopping breaching of CFSGDs.The model characteristics were as follows:(1)Based on the Renormailzation Group(RNG)k-εturbulence theory and volume of fluid(VOF)method,the turbulent characteristics of the dam-break flow were simulated,and the erosion surface of the water and soil was tracked;(2)In consideration of the influence of the change in the sediment content on the dam-break flow,the dam material transport equation,which could reflect the characteristics of particle settlement and entrainment motion,was used to simulate the erosion process of the sand gravels;(3)Based on the bending moment balance method,a failure equation of the concrete face slab under dead weight and water load was established.The proposed model was verified through a case study on the failure of the Gouhou CFSGD.The results showed that the proposed model could well simulate the erosion mode of the special vortex flow of the CFSGD scouring the support body of the concrete face slab inward and reflect the mutual coupling relationship between the dam-break flow,sand gravels,and concrete face slabs.Compared with the measured values,the relative errors of the peak discharge,final breach average width,dam breaching duration,and maximum failure length of the face slab calculated using the proposed model were all less than 12%,thus verifying the rationality of the model.The proposed model was demonstrated to perform better and provide more detailed results than three selected parametric models and three simplified mathematical models.The study results can aid in establishing the risk level and devising early warning strategies for CFSGDs.

Tight gas charging and accumulation mechanisms and mathematical model

The gas-water distribution and production heterogeneity of tight gas reservoirs have been summarized from experimental and geological observations, but the charging and accumulation mechanisms have not been examined quantitatively by mathematical model. The tight gas charging and accumulation mechanisms were revealed from a combination of physical simulation of nuclear magnetic resonance coupling displacement, numerical simulation considering material and mechanical equilibria, as well as actual geological observation. The results show that gas migrates into tight rocks to preferentially form a gas saturation stabilization zone near the source-reservoir interface. When the gas source is insufficient, gas saturation reduction zone and uncharged zone are formed in sequence from the source-reservoir interface. The better the source rock conditions with more gas expulsion volume and higher overpressure, the thicker the gas saturation stabilization and reduction zones, and the higher the overall gas saturation. When the source rock conditions are limited, the better the tight reservoir conditions with higher porosity and permeability as well as larger pore throat, the thinner the gas saturation stabilization and reduction zones, but the gas saturation is high. The sweet spot of tight gas is developed in the high-quality reservoir near the source rock, which often corresponds to the gas saturation stabilization zone. The numerical simulation results by mathematical model agree well with the physical simulation results by nuclear magnetic resonance coupling displacement, and reasonably explain the gas-water distribution and production pattern of deep reservoirs in the Xujiaweizi fault depression of the Songliao Basin and tight gas reservoirs in the Linxing-Huangfu area of the Ordos Basin.

Quantification of Ride Comfort Using Musculoskeletal Mathematical Model Considering Vehicle Behavior

This research aims to quantify driver ride comfort due to changes in damper characteristics between comfort mode and sport mode,considering the vehicle’s inertial behavior.The comfort of riding in an automobile has been evaluated in recent years on the basis of a subjective sensory evaluation given by the driver.However,reflecting driving sensations in design work to improve ride comfort is abstract in nature and difficult to express theoretically.Therefore,we evaluated the human body’s effects while driving scientifically by quantifying the driver’s behavior while operating the steering wheel and the behavior of the automobile while in motion using physical quantities.To this end,we collected driver and vehicle data using amotion capture system and vehicle CAN and IMU sensors.We also constructed a three-dimensional musculoskeletal mathematical model to simulate driver movements and calculate the power and amount of energy per unit of time used for driving the joints and muscles of the human body.Here,we used comfort mode and sport mode to compare damper characteristics in terms of hardness.In comfort mode,damper characteristics are soft and steering stability is mild,but vibration from the road is not easily transmitted to the driver making for a lighter load on the driver.In sport mode,on the other hand,damper characteristics are hard and steering stability is comparatively better.Still,vibration from the road is easily transmitted to the driver,whichmakes it easy for a load to be placed on the driver.As a result of this comparison,it was found that a load was most likely to be applied to the driver’s neck.This result in relation to the neck joint can therefore be treated as an objective measure for quantifying ride comfort.

The Reconstruction Technique of Multi-Product Production and MINLP Mathematical Modelling

Low efficiency, negative impacts on the environment and non-profitable operations are the main shortcomings of out-dated industrial processes. Such systems can be reconstructed and improved in the direction of multi-product operations. The study of this article focuses on the development of a method for multi-product operations by reconstructing out-dated industrial processes. This article contains the theory of a developed method that enables the updating of existing process units and integrated systems on the basis of reconstruction scenarios and pathways. The goals of the set out method are: 1) to maintain the existing process units and chemical plants to a greater extent, 2) to enable the potential for finding new process alternatives and technological solutions, 3) to provide a streamlined operation for all subsystems and total systems, 4) to promote environmental and social responsibilities, and 5) to apply the concept of the presented reconstruction method to non-profitable industrial processes. In regard to multi-product operations, a conceptual model is a suitable tool for the reconstruction of industrial processes. It connects several software tools and so enables quick decision-making between process alternatives. A reconstruction method provides foresight into the possible improvements to existing industrial processes. In comparison with the indirect synthesis of DME (simple reconstruction pathway), the lower operating costs from the direct synthesis of DME (complex reconstruction pathway) were confirmed.

Simulation Analysis of New Energy Vehicle Engine Cooling System Based on K-E Turbulent Flow Mathematical Model

New energy vehicles have better clean and environmental protection characteristics than traditional fuel vehicles.The new energy engine cooling technology is critical in the design of new energy vehicles.This paper used oneand three-way joint simulation methods to simulate the refrigeration system of new energy vehicles.Firstly,a k-εturbulent flow model for the cooling pump flow field is established based on the principle of computational fluid dynamics.Then,the CFD commercial fluid analysis software FLUENT is used to simulate the flow field of the cooling pump under different inlet flow conditions.This paper proposes an optimization scheme for new energy vehicle engines’“boiling”phenomenon under high temperatures and long-time climbing conditions.The simulation results show that changing the radiator’s structure and adjusting the thermostat’s parameters can solve the problem of a“boiling pot.”The optimized new energy vehicle engine can maintain a better operating temperature range.The algorithm model can reference each cryogenic system component hardware selection and control strategy in the new energy vehicle’s engine.