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.

Explosion resistance performance of reinforced concrete box girder coated with polyurea:Model test and numerical simulation

To study the anti-explosion protection effect of polyurea coating on reinforced concrete box girder,two segmental girder specimens were made at a scale of 1:3,numbered as G(without polyurea coating)and PCG(with polyurea coating).The failure characteristics and dynamic responses of the specimens were compared through conducting explosion tests.The reliability of the numerical simulation using LS-DYNA software was verified by the test results.The effects of different scaled distances,reinforcement ratios,concrete strengths,coating thicknesses and ranges of polyurea were studied.The results show that the polyurea coating can effectively enhance the anti-explosion performance of the girder.The top plate of middle chamber in specimen G forms an elliptical penetrating hole,while that in specimen PCG only shows a very slight local dent.The peak vertical displacement and residual displacement of PCG decrease by 74.8% and 73.7%,respectively,compared with those of specimen G.For the TNT explosion with small equivalent,the polyurea coating has a more significant protective effect on reducing the size of fracture.With the increase of TNT equivalent,the protective effect of polyurea on reducing girder displacement becomes more significant.The optimal reinforcement ratio,concrete strength,thickness and range of polyurea coating were also drawn.

Study on theoretical model for electrical explosion resistivity of Al/Ni reactive multilayer foil

Al/Ni reactive multilayer foil(RMF)possesses excellent comprehensive properties as a promising substitute for traditional Cu bridge.A theoretical resistivity model of Al/Ni RMF was developed to guide the optimization of EFIs.Al/Ni RMF with different bilayer thicknesses and bridge dimensions were prepared by MEMS technology and electrical explosion tests were carried out.According to physical and chemical reactions in bridge,the electrical explosion process was divided into 5 stages:heating of condensed bridge,vaporization and diffusion of Al layers,intermetallic combination reaction,intrinsic explosion,ionization of metal gases,which are obviously shown in measured voltage curve.Effects of interface and grain boundary scattering on the resistivity of film metal were considered.Focusing on variations of substance and state,the resistivity was developed as a function of temperature at each stage.Electrical explosion curves were calculated by this model at different bilayer thicknesses,bridge dimensions and capacitor voltages,which showed an excellent agreement with experimental ones.

Water resistant features of high-risk outburst coal seams and standard discriminant model of mining under water-pressure

It is important to emphasize the value of research in safe mining technology of high-risk water outburst coal seams. We describe briefly current conditions abroad and in China. Based on an Ordovician limestone aquifer with high-risk water outburst seams in the Feicheng coal field, we analyzed the water-resistant characteristics of a coal floor aquifuge and the behavior of water head intrusion of a confined aquifer and propose a safe criterion model and relevant technology of mining above aquifers. This has brought satisfactory results in engineering practice.

Efficacy of Pudilan Xiaoyan Oral Liquid in the treatment of pneumonia induced by drug-resistant Pseudomonas aeruginosa

Background:Pudilan Xiaoyan Oral Liquid(PDL)is a Chinese patent medicine with notable pharmacological properties,including anti-inflammatory and antibacterial effects.Drug-resistant Pseudomonas aeruginosa infection is a common and refractory bacterial infection in clinical practice.Due to its high drug resistance,it brings great challenges to treatment.This study aimed to assess the therapeutic efficacy of PDL in a murine model of pneumonia induced by drug-resistant Pseudomonas aeruginosa.Methods:Three different doses of PDL(11 mL/kg/d,5.5 mL/kg/d,2.75 mL/kg/d)were used to observe lung tissue pathology and inflammatory cytokine levels in pneumonia mouse models induced by multidrug-resistant Pseudomonas aeruginosa(MDR-PA).Additionally,the protective efficacy of PDL against mortality in infected mice was evaluated using a death model caused by MDR-PA.Finally sub-MIC concentration of levofloxacin was used to induce drug-resistant mice pneumonia model to evaluate the role of PDL in reversing drug resistance.Experimental data are expressed as mean±standard deviation.Statistical significance was determined by one-way analysis of variance followed by Tukey’s multiple-comparisons test.Results:Treatment effect of PDL on MDR-PA pneumonia:the medium and small doses of PDL can significantly reduce the lung index of multi-drug resistant bacteria infected pneumonia model mice(P<0.05),the lung index inhibition rates for these groups were 55.09%and 58.43%,and improve the degree of lung tissue lesions of mice;The expression of serum cytokines keratinocyte chemoattractant,tumor necrosis factor-αand monocyte chemoattractant protein-1 could be decreased in the three dosage groups of PDL(P<0.01).PDL treatment not only lowered the mortality but also extended the survival duration in mice infected with MDR-PA.It was found after sub-MIC concentration of levofloxacin induced resistance of Pseudomonas aeruginosa to pneumonia in mice.Compared with the model group,the lung index of mice in high and medium PDL doses was significantly reduced(P<0.05),with inhibition rates of 32.16%and 37.73%,respectively.Conclusion:PDL demonstrates protective effects against MDR-PA infection pneumonia,notably decreasing serum inflammatory factor levels.It shows promise in mitigating antibiotic resistance and offers potential for treating pneumonia resulting from Pseudomonas aeruginosa resistance.

Characterization and Modelling of High Temperature Flow Behaviour of V Modified 2.25Cr-1Mo Heat Resistant Steel Plate

In order to study the high temperature flow behaviour of the V modified 2.25Cr-1Mo steel plate to guide the industrial rolling practice, the hot compression tests were carried out at the temperatures from 900 ℃ to 1150 ℃ and the strain rates from 0.01s^-1 to 1 s^-1 on Thermecmastor-Z equipment. Based on the experimental data of the hot compression tests, a kind of Arrhenius-type constitutive equation was developed.The equation can accurately show the relationship between the flow stress and the deformation temperature, the strain and the strain rate. The measured true stress-true strain curves exhibit two kinds of flow stress curves. Moreover, the forming mechanisms of these two types curves were explained by softening, wok hardening theory as well as metallographic and hardness experimental results. The accuracy of the developed Arrheniustype constitutive equation was identified by three kinds of statistic parameters and also by comparison of the measured and predicted data. The reasonable value of the three types of statistic parameters and the good agreement between the experimental and predicted data can confirm the validity of the developed Arrheniustype constitutive equation for V modified 2.25 Cr-1 Mo heat resistant steel plate.

An Improved Heat Transfer Model for Flame Resistant Fabric Used in Thermal Protective Clothing

An improved numerical heat transfer model considering pyrolysis effect is proposed to predict thermal performance of heat-resistant fabric subjected to radiant heat flux. The model incorporates the heat-induced changes in fabric thermophysical properties. The new model has been validated with data from modified Radiant Protective Performance (RPP) tests of flame-resistant cotton fabrics. Comparison with experimental data shows that the predictions of mass loss rates and temperature profiles within the charring material and skin simulant are in reasonably good agreement with the experiments. Results from the numerical model contribute to a better understanding of the heat transfer process within flame-resistant fabrics under high heat flux conditions, and also to establish a systematic method for analyzing heat transfer in other fibrous materials applications.

Three-dimensional forward modeling of DC resistivity using the aggregation-based algebraic multigrid method

To speed up three-dimensional （3D） DC resistivity modeling, we present a new multigrid method, the aggregation-based algebraic multigrid method （AGMG）. We first discretize the differential equation of the secondary potential field with mixed boundary conditions by using a seven-point finite-difference method to obtain a large sparse system of linear equations. Then, we introduce the theory behind the pairwise aggregation algorithms for AGMG and use the conjugate-gradient method with the V-cycle AGMG preconditioner （AGMG-CG） to solve the linear equations. We use typical geoelectrical models to test the proposed AGMG-CG method and compare the results with analytical solutions and the 3DDCXH algorithm for 3D DC modeling （3DDCXH）. In addition, we apply the AGMG-CG method to different grid sizes and geoelectrical models and compare it to different iterative methods, such as ILU-BICGSTAB, ILU-GCR, and SSOR-CG. The AGMG-CG method yields nearly linearly decreasing errors, whereas the number of iterations increases slowly with increasing grid size. The AGMG-CG method is precise and converges fast, and thus can improve the computational efficiency in forward modeling of three-dimensional DC resistivity.

Forward modeling of marine DC resistivity method for a layered anisotropic earth

Since the ocean bottom is a sedimentary environment wherein stratification is well developed, the use of an anisotropic model is best for studying its geology. Beginning with Maxwell＇s equations for an anisotropic model, we introduce scalar potentials based on the divergence-free characteristic of the electric and magnetic （EM） fields. We then continue the EM fields down into the deep earth and upward into the seawater and couple them at the ocean bottom to the transmitting source. By studying both the DC apparent resistivity curves and their polar plots, we can resolve the anisotropy of the ocean bottom. Forward modeling of a high-resistivity thin layer in an anisotropic half-space demonstrates that the marine DC resistivity method in shallow water is very sensitive to the resistive reservoir but is not influenced by airwaves. As such, it is very suitable for oil and gas exploration in shallowwater areas but, to date, most modeling algorithms for studying marine DC resistivity are based on isotropic models. In this paper, we investigate one-dimensional anisotropic forward modeling for marine DC resistivity method, prove the algorithm to have high accuracy, and thus provide a theoretical basis for 2D and 3D forward modeling.

Multi-field dynamic modeling and numerical simulation of aluminum alloy resistance spot welding

In order to explore the influence of welding parameters and to investigate the Al alloy (AA) nugget formation process, a comprehensive model involving electrical-thermal-mechanical and metallurgical analysis was established to numerically display the resistance spot welding (RSW) process within multiple fields and understand the AA-RSW physics. A multi-disciplinary finite element method (FEM) framework and a empirical sub-model were built to analyze the affecting factors on weld nugget and the underlying nature of welding physics with dynamic simulation procedure. Specifically, a counter-intuitive phenomenon of the resistance time-variation caused by the transient inverse virtual variation (TIVV) effect was highlighted and analyzed on the basis of welding current and temperature distribution simulation. The empirical model describing the TIVV phenomenon was used for modifying the dynamic resistance simulation during the AA spot welding process. The numerical and experimental results show that the proposed multi-field FEM model agrees with the measured AA welding feature, and the modified dynamic resistance model captures the physics of nugget growth and the electrical-thermal behavior under varying welding current and fluctuating heat input.

Dynamic recrystallization behavior of burn resistant titanium alloy Ti-25V-15Cr-0.2Si

Dynamic recrystallization (DRX) behavior in β phase region for the burn resistant titanium alloy Ti?25V?15Cr?0.2Si was investigated with a compression test in the temperature range of 950?1100 °C and the strain rate of 0.001?1 s?1. The results show that deformation mechanism of this alloy in hot deformation is dominated by DRX, and new grains of DRX are evolved by bulging nucleation mechanism as a predominant mechanism. DRX occurs more easily with the decrease of strain rate and the increase of deformation temperature. Grain refinement is achieved due to DRX during the hot deformation at strain rate range of 0.01?0.1 s?1 and temperature range of 950?1050 °C. DRX grain coarsening is observed for the alloy deformed at the higher temperatures of 1100 °C and the lower strain rates of 0.001 s?1. Finally, in order to determine the recrystallized fraction and DRX grain size under different deformation conditions, the prediction models of recrystallization kinetics and recrystallized grain sizes were established.

HOT DUCTILITY OF 304HC STAINLESS STEEL AND THE MODEL OF RESISTANCE TO DEFORMATION

The ductility map of 304HC stainless was determined by using the Gleeble-1500 dynamic thermal-mechanical simulator. The effect of Cu on the hot ductility of 304HC stainless steel was analyzed and the mathematical model of resistance to deformation was established. The microstructure, inclusion and fracture surface were studied by using the method of micro structure analysis, scanning, energy spectrum and electron microscope. The results show that Cu has effect on the hot ductility, and the hot ductility of 304HC stainless steel decrease with the increase of content of Cu. The deformation temperature also has much effect on the hot ductility, the suitable deformation temperature are 1100-1200℃. The reason of it is that the Cu rich chemical compounds were precipitated from austenite phase during cooling. The Cu rich chemical compounds are brittle substance such as Cu2S, Cu2O and ε-Cu etc.

Development and characterization of multidrug resistant human hepatocarcinoma cell line in nude mice

AIM： To establish a multidrug resistant （MDR） cell subline from the human hepatocardnoma cell line （HepG2） in nude mice. METHODS： HepG2 cell cultures were incubated with increasing concentrations of adriamycin （ADM） to develop an ADM-resistant cell subline （HepG2/ADM） with crossresistance to other chemotherapeutic agents. Twenty male athymic BALB/c-nu/nu mice were randomized into HepG2/nude and HepG2/ADM/nude groups （10 in each group）. A cell suspension （either HepG2 or HepG2/ADM） was injected subcutaneously into mice in each group. Tumor growth was recorded, and animals were sacrificed 4-5 wk after cell implantation. Tumors were prepared for histology, and viable tumor was dispersed into a single-cell suspension. The IC50 values for a number of chemotherapeutic agents were determined by 2, 3-bis （2-methoxy-4-nitro-5-sulfophenyl）-2H-tetrazolium-5-carboxanilide inner salt （MTT） assay. Rhodamine-123 retention/efflux and the level of resistance-associated proteins were determined by flow cytometry. The mRNA expression of mdr1, mrp and Irp genes was detected using reverse transcriptase polymerase chain reaction （RT-PCR） in HepG2/nude and HepG2/ADM/nude groups. RESULTS： The appearances of HepG2/nude cells were slightly different from those of HepG2/ADM/nude cells. Similar tumor growth curves were determined in both groups. A cross-resistance to ADM, vincristine, cisplatin and 5-fluorouracil was seen in HepG2/ADM/nude group. The levels of P-glycoprotein and multidrug resistanceassociated proteins were significantly increased. The mRNA expression levels of mdrl, mrp and/rp were higher in HepG2/ADM/nude cells. CONCLUSION： ADM-resistant HepG2 subline in nude mice has a cross resistance to chemotherapeutic drugs. It may be used as an in vivo model to investigate the mechanisms of MDR, and explore the targeted approaches to overcoming MDR.

Development of Wistar rat model of insulin resistance

AIM: To establish a simplified and reliable animal model of insulin resistance with low cost in Wistar rats. METHODS: Wistar rats were treated with a high fat emulsion by ig for 10 d. Changes of the diets, drinking and body weight were monitored every day and insulin resistance was evaluated by hyperinsulinemic-euglycemicclamp techniques and short insulin tolerance test using capillary blood glucose. Morphologic changes of liver, fat, skeletal muscles, and pancreatic islets were assessed under light microscope. mRNA expressions of GLUT2 and α-glucosidase in small intestine epithelium, GLUT4 in skeletal muscles and Kir6.2 in beta cell of islets were determined by in situ hybridization.RESULTS: KITT was smaller in treated animals (4.5±0.9)than in untreated control Wistar rats (6.8±1.5), and so was glucose injection rate. Both adipocyte hypertrophy and large pancreatic islets were seen in high fat fed rats,but no changes of skeletal muscles and livers wereobserved. mRNA levels of GLUT2, α-glucosidase in small intestinal epithelium and Kir6.2 mRNA in beta cells of islets increased, whereas that of GLUT4 in skeletal muscles decreased in high fat fed group compared with normal control group.CONCLUSION: An insulin resistance animal model in Wistar rats is established by ig special fat emulsion.

Establishing a predictive model for aspirin resistance in elderly Chinese patients with chronic cardiovascular disease

Background Resistance to anti-platelet therapy is detrimental to patients. Our aim was to establish a predictive model for aspirin resistance to identify high-risk patients and to propose appropriate intervention. Methods Elderly patients （n = 1130） with stable chronic coronary heart disease who were taking aspirin （75 mg） for 〉 2 months were included. Details of their basic characteristics, laboratory test results, and medications were collected. Logistic regression analysis was performed to establish a predictive model for aspirin resistance. Risk score was finally established according to coefficient B and type of variables in logistic regression. The Hosmer-Lemeshow （HL） test and receiver operating characteristic curves were performed to respectively test the calibration and discrimination of the model. Results Seven risk factors were included in our risk score. They were serum creatinine （〉 110 μmol/L, score of 1）; fasting blood glucose （〉 7.0 mmol/L, score of 1）; hyperlipidemia （score of 1）; number of coronary arteries （2 branches, score of 2; 〉 3 branches, score of 4）; body mass index （20-25 kg/m2, score of 2; 〉 25 kg/m2, score of 4）; percutaneous coronary intervention （score of 2）; and smoking （score of 3）. The HL test showed P ≥ 0.05 and area under the receiver operating characteristic curve ≥ 0.70. Conclusions We explored and quantified the risk factors for aspirin resistance. Our predictive model showed good calibration and discriminative power and therefore a good foundation for the further study of patients undergoing anti-platelet therapy.

Characterization of inflammation and insulin resistance in high-fat diet-induced male C57BL/6J mouse model of obesity

Background: Animal models of diet-induced obesity(DIO) are commonly used in medical research for mimicking human diseases. There is no universal animal model, and careful evaluation of variety of factors needs to be considered when designing new experiments. Here, we investigated the effect of 9 weeks high-fat diet(HFD) intervention, providing 60% energy from fat, on parameters of inflammation and insulin resistance in male C57 BL/6 J mice.Methods: Six weeks old mice were initiated on regular diet(RD) or HFD providing 60 kcal energy from fat for 9 weeks. Fasting blood glucose levels were measured by glucometer, and fasting plasma levels of insulin and proinflammatory cytokines by Luminex assay. Insulin sensitivity was evaluated by using QUICKI and HOMA2 indexes.Results: HFD mice showed ~ 40% higher body weight and ~ 20% larger abdominal circumference, due to an increase in the white adipose tissue mass. Liver examination revealed increased size and higher hepatic lipid accumulation in livers from HFD mice compared to their RD counterparts. Animals from the HFD group were characterized with significantly higher presence of crown-like structures(CLS) in WAT and higher plasma levels of proinflammatory cytokines(TNF-α, IL-6, leptin, MCP-1, PAI-1, and resistin). HFD-fed mice also demonstrated impaired insulin sensitivity(lower QUICKI, higher HOMA-insulin resistance(HOMA-IR), and lower HOMA-percent sensitivity(HOMA-%S)) index values.Conclusion: Male C57 BL/6 J mice on 9 weeks HFD providing 60 kcal energy from fat display impaired insulin sensitivity and chronic inflammation, thus making this DIO mouse model appropriate for studies of early stages of obesity-related pathology.

Resistance Analysis of Unsymmetrical Trimaran Model with Outboard Sidehulls Configuration

The application of multi-hull ship or trimaran vessel as a mode of transports in both river and sea environments have grown rapidly in recent years.Trimaran vessels are currently of interest for many new high speed ship projects due to the high levels of hydrodynamic efficiency that can be achieved,compared to the mono-hull and catamaran hull forms.The purpose of this study is to identify the possible effects of using an unsymmetrical trimaran ship model with configuration（S/L） 0.1-0.3 and R/L=0.1-0.2.Unsymmetrical trimaran ship model with main dimensions： L=2000mm,B=200 mm and T=45 mm.Experimental methods（towing tank） were performed in the study using speed variations at Froude number 0.1-0.6.The ship model was pulled by an electric motor whose speed could be varied and adjusted.The ship model resistance was measured precisely by using a load cell transducer.The comparison of ship resistance for each configuration with mono-hull was shown on the graph as a function of the total resistance coefficient and Froude number.The test results found that the effective drag reduction could be achieved up to 17% at Fr=0.35 with configuration S/L=0.1.

Genetic Analysis of Stripe Disease Resistance in Rice Restorer Line C224 Using Major Gene plus Polygene Mixed Effect Model

The inheritance of stripe disease resistance in a rice restorer line C224 was analyzed using the mixed effect model of major gene plus polygene for quantitative traits.In addition,the resistance was investigated in seven crosses of C224 with maintainer lines.The results showed that the stripe resistance of C224 was controlled by two major genes with additive-dominance-epistasis effects plus polygenes with additive-dominance effects （E-1 model）.These two genes had additive effects of-12.47% and-24.75%,respectively,showing negative dominance effects.There were significant epistasis and interaction effects between the two major genes.The heritability of the two major genes was 92.12%,while that of polygenes was 2.74%,indicating that the stripe resistance had dominant major gene effect.Of the seven crosses,five displayed high or medium resistance to the stripe disease.

AN EFFICIENT NUMERICAL MODELING OF THE DC RESISTIVITY LOGGING: THEORY AND APPLICATIONS

The numerical solution of Green’s function for the potential in 2-D arbitrary in-homogeneous media with axial symmetry has been given by use of efficient half-analytical, half-numerical hybrid method. Then the logging responses of various kinds of the DC resistivity log with axisymmetric excitation have been obtained by using surface integral equation method to match the boundary conditions on the electrodes of the logging sonde. Comparing the results with that obtained by other methods, one can see good precision and efficiency of the given method. Some applications of the numerical modeling have been also discussed.

Interference Resistance of Pentamaran Ship Model With Asymmetric Outrigger Configurations

An experimental investigation is performed to assess the relation of interference performance on the total resistance of a pentamaran model advancing in calm water. For this motivation, the total drag of the ship is performed for several values of asymmetric outrigger configuration and hull separation, altering the Froude number in the range 0.3–0.9. Our results indicate that remarkable changes in resistance require notable changes in transverse distance values （hull separation） when wave interference may occur. In addition, there is no single configuration that consistently outperforms the other configurations across the entire speed range and the optimum interference factor -0.2 appears at a Froude number of 0.45 in S/L=0.33 with the outrigger outer position： asymmetric outboard for A3 configuration.