Modeling of Computer Virus Propagation with Fuzzy Parameters

Typically,a computer has infectivity as soon as it is infected.It is a reality that no antivirus programming can identify and eliminate all kinds of viruses,suggesting that infections would persevere on the Internet.To understand the dynamics of the virus propagation in a better way,a computer virus spread model with fuzzy parameters is presented in this work.It is assumed that all infected computers do not have the same contribution to the virus transmission process and each computer has a different degree of infectivity,which depends on the quantity of virus.Considering this,the parametersβandγbeing functions of the computer virus load,are considered fuzzy numbers.Using fuzzy theory helps us understand the spread of computer viruses more realistically as these parameters have fixed values in classical models.The essential features of the model,like reproduction number and equilibrium analysis,are discussed in fuzzy senses.Moreover,with fuzziness,two numerical methods,the forward Euler technique,and a nonstandard finite difference(NSFD)scheme,respectively,are developed and analyzed.In the evidence of the numerical simulations,the proposed NSFD method preserves the main features of the dynamic system.It can be considered a reliable tool to predict such types of solutions.

Hopf Bifurcation of Nonresident Computer Virus Model with Age Structure and Two Delays Effects

This paper constructed and studied a nonresident computer virus model with age structure and two delays effects. The non-negativity and boundedness of the solution of the model have been discussed, and then gave the basic regeneration number, and obtained the conditions for the existence and the stability of the virus-free equilibrium and the computer virus equilibrium. Theoretical analysis shows the conditions under which the model undergoes Hopf bifurcation in three different cases. The numerical examples are provided to demonstrate the theoretical results.

Animal models for the study of hepatitis B virus infection

Even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis B virus （HBV） worldwide. Current antiviral therapies, including interferon and nucleot（s）ide analogues, rarely cure chronic hepatitis B. Animal models are very crucial for understanding the pathogenesis of chronic hepatitis B and developing new therapeutic drugs or strategies. HBV can only infect humans and chimpanzees, with the use of chimpanzees in HBV research strongly restricted. Thus, most advances in HBV research have been gained using mouse models with HBV replication or infection or models with HBV-related hepadnaviral infection. This review summarizes the animal models currently available for the study of HBV infection.

Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein-Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma

Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.

Modified model for end-stage liver disease improves shortterm prognosis of hepatitis B virus-related acute-on-chronic liver failure

AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.

HBsAg/HBsAb Double Positive Hepatitis B Virus Infection Model in vitro and in vivo

The pathogenesis of HBsAg （＋）/HBsAb （＋） double positive hepatitis B virus infection was investigated by simulating HBsAg/HBsAb coexistence in vitro and establishing HBsAg/HBsAb double positive model in vivo. Eukaryotic expression plasmids PCI-SY, PCI-adw, PCI-adr, PCI-ayw, which expressed S gene product of different serotypes, were constructed and transfected into HepG2 cells. Recombinant proteins were purified from the transfected cells. At the same time, HBsAg mouse antiserum was obtained by immunizing mice with PCI-SY plasmid. HBsAg/HBsAb coexistence was simulated using these antigens and antiserum. Furthermore, the expression plasmids expressing different serotypes of S gene product including PCI-adw, PCI-adr, and PCI-ayw were injected into mice via tail vein. HBsAg and HBsAb in mice sera were tested at the first and 7th day respectively after antigen plasmids injection. Both in vitro simulation and in vivo animal models demonstrated that HBsAg antigen and HBsAb of the same serotypes Could not coexist, but HBsAg antigen and HBsAb of different serotype could coexist. HBsAg/HBsAb double positive hepatitis B virus infection could be due to infection of viruses of different serotypes.

Hepatocellular carcinoma mouse models:Hepatitis B virusassociatedhepatocarcinogenesis and haploinsufficienttumor suppressor genes

The multifactorial and multistage pathogenesis of hepatocellular carcinoma(HCC)has fascinated a wide spectrum of scientists for decades.While a number of major risk factors have been identified,their mechanistic roles in hepatocarcinogenesis still need to be elucidated.Many tumor suppressor genes(TSGs)have been identified as being involved in HCC.These TSGs can be classified into two groups depending on the situation with respect to allelic mutation/loss in the tumors:the recessive TSGs with two required mutated alleles and the haploinsufficient TSGs with one required mutated allele.Hepatitis B virus(HBV)is one of the most important risk factors associated with HCC.Although mice cannot be infected with HBV due to the narrow host range of HBV and the lack of a proper receptor,one advantage of mouse models for HBV/HCC research is the numerous and powerfulgenetic tools that help investigate the phenotypic effects of viral proteins and allow the dissection of the dose-dependent action of TSGs.Here,we mainly focus on the application of mouse models in relation to HBV-associated HCC and on TSGs that act either in a recessive or in a haploinsufficient manner.Discoveries obtained using mouse models will have a great impact on HCC translational medicine.

ON GLOBAL STABILITY OF A NONRESIDENT COMPUTER VIRUS MODEL

In this paper, we establish new sufficient conditions for the infected equilibrium of a nonresident computer virus model to be globally asymptotically stable. Our results extend two kind of known results in recent literature.

Diagnostic non-invasive model of large risky esophageal varices in cirrhotic hepatitis C virus patients

AIM To build a diagnostic non-invasive model for screening of large varices in cirrhotic hepatitis C virus(HCV) patients. METHODS This study was conducted on 124 post-HCV cirrhotic patients presenting to the clinics of the Endemic Medicine Department at Mansoura University Hospital for evaluation before HCV antiviral therapy: 78 were Child A and 46 were Child B(score ≤ 8). Inclusion criteria for patients enrolled in this study was presence of cirrhotic HCV(diagnosed by either biopsy or fulfillment of clinical basis). Exclusion criteria consisted of patients with other etiologies of liver cirrhosis, e.g., hepatitis B virus and patients with high MELD score on transplant list. All patients were subjected to full medical record, full basic investigations, endoscopy, and computed tomography(CT), and then divided into groups with no varices, small varices, or large risky varices. In addition, values of Fibrosis-4 score(FIB-4), aminotransferase-to-platelet ratio index(APRI), and platelet count/splenic diameter ratio(PC/SD) were also calculated.RESULTS Detection of large varies is a multi-factorial process, affected by many variables. Choosing binary logistic regression, dependent factors were either large or small varices while independent factors included CT variables such coronary vein diameter, portal vein(PV) diameter, lieno-renal shunt and other laboratory noninvasive variables namely FIB-4, APRI, and platelet count/splenic diameter. Receiver operating characteristic(ROC) curve was plotted to determine the accuracy of non-invasive parameters for predicting the presence of large esophageal varices and the area under the ROC curve for each one of these parameters was obtained. A model was established and the best model for prediction of large risky esophageal varices used both PC/SD and PV diameter(75% accuracy), while the logistic model equation was shown to be(PV diameter ×-0.256) plus(PC/SD ×-0.006) plus(8.155). Values nearing 2 or more denote large varices.CONCLUSION This model equation has 86.9% sensitivity and 57.1% specificity, and would be of clinical applicability with 75% accuracy.

A Stochastic Numerical Analysis for Computer Virus Model with Vertical Transmission Over the Internet

We are presenting the numerical analysis for stochastic SLBR model of computer virus over the internet in this manuscript.We are going to present the results of stochastic and deterministic computer virus model.Outcomes of the threshold number C∗hold in stochastic computer virus model.If C∗<1 then in such a condition virus controlled in the computer population while C∗>1 shows virus spread in the computer population.Unfortunately,stochastic numerical techniques fail to cope with large step sizes of time.The suggested structure of the stochastic non-standard finite difference scheme(SNSFD)maintains all diverse characteristics such as dynamical consistency,bounded-ness and positivity as well-defined by Mickens.On this basis,we can suggest a collection of plans for eradicating viruses spreading across the internet effectively.

Application of hepatitis B virus replication mouse model

AIM:To evaluate the value of the hepatitis B virus(HBV) replication mouse model with regard to several aspects of the study of HBV biology.METHODS:To evaluate the HBV replication mouse model in detecting the efficacy of anti-HBV agents,the interferon inducer polyinosinic-polytidylin acid(polyIC) and nucleotide analogues adefovir and entecavir were administered to mice injected with wild type pHBV4.1,and the inhibiting effect of these agents on HBV DNA replication was evaluated.To identify the model's value in a replication ability study of HBV drug-resistant mutants and a HBx-minus mutant,telbivudine resistance mutants(rtM204I,ayw subtype),adefovir resistance mutants(rtA181V + rtN236T,ayw subtype) and HBxminus mutants were injected respectively,and their corresponding HBV DNA replication intermediates in mouse liver were assessed.RESULTS:Compared with the wild type HBV replication mouse model without antiviral agent treatment,the HBV DNA replication intermediates of the polyICtreated group were decreased 1-fold;while in the entecavir-and adefovir-treated groups,the levels of HBV DNA replication intermediates were inhibited 13.6-fold and 1.4-fold,respectively.For the mouse models injected with telbivudine resistance mutant,adefovir resistance mutant and HBx-minus mutant,HBV DNA replication intermediates could still be detected,but the levels of HBV DNA replication intermediates of these mutants decreased 4.5-fold,5.6-fold and 2.9-fold respectively,compared with the mouse model with wild type HBV plasmid.CONCLUSION:The HBV replication mouse model we established was a useful and convenient tool to detect the efficacy of antiviral agents and to study the replication ability of HBV mutants in vivo.

Global Stability of SEIQRS Computer Virus Propagation Model with Non-Linear Incidence Function

In this paper, we present an SEIQRS epidemic model with non-linear incidence function. The proposed model exhibits two equilibrium points, the virus free equilibrium and viral equilibrium. The model stability is connected with the basic reproduction number R0. If R0 R0 > 1, then the model is locally and globally stable at viral equilibrium point. Numerical methods are used for supporting the analytical work.

Simulation modelling of potato virus Y spread in relation to initial inoculum and vector activity

Potato virus Y(PVY)is a non-persistent virus that is transmitted by many aphid species and causes significant damage to potato production.We constructed a spatially-explicit model simulating PVY spread in a potato field and used it to investigate possible effects of transmission efficiency,initial inoculum levels,vector behavior,vector abundance,and timing of peak vector activity on PVY incidence at the end of a simulated growing season.Lower PVY incidence in planted seed resulted in lower virus infection at the end of the season.However,when populations of efficient PVY vectors were high,significant PVY spread occurred even when initial virus inoculum was low.Non-colonizing aphids were more important for PVY spread compared to colonizing aphids,particularly at high densities.An early-season peak in the numbers of noncolonizing aphids resulted in the highest number of infected plants in the end of the season,while mid-and late-season peaks caused relatively little virus spread.Our results highlight the importance of integrating different techniques to prevent the number of PVY-infected plants from exceeding economically acceptable levels instead of trying to control aphids within potato fields.Such management plans should be implemented very early in a growing season.

Hepatitis B virus infection modeling using multi-cellular organoids derived from human induced pluripotent stem cells

Chronic infection with hepatitis B virus(HBV)remains a global health concern despite the availability of vaccines.To date,the development of effective treatments has been severely hampered by the lack of reliable,reproducible,and scalable in vitro modeling systems that precisely recapitulate the virus life cycle and represent virus-host interactions.With the progressive understanding of liver organogenesis mechanisms,the development of human induced pluripotent stem cell(iPSC)-derived hepatic sources and stromal cellular compositions provides novel strategies for personalized modeling and treatment of liver disease.Further,advancements in three-dimensional culture of self-organized liver-like organoids considerably promote in vitro modeling of intact human liver tissue,in terms of both hepatic function and other physiological characteristics.Combined with our experiences in the investigation of HBV infections using liver organoids,we have summarized the advances in modeling reported thus far and discussed the limitations and ongoing challenges in the application of liver organoids,particularly those with multi-cellular components derived from human iPSCs.This review provides general guidelines for establishing clinical-grade iPSC-derived multi-cellular organoids in modeling personalized hepatitis virus infection and other liver diseases,as well as drug testing and transplantation therapy.

Numerical Simulations for Stochastic Computer Virus Propagation Model

We are presenting the numerical simulations for the stochastic computer virus propagation model in this manuscript.We are comparing the solutions of stochastic and deterministic computer virus models.Outcomes of a threshold number R0 hold in stochastic computer virus model.If R_(0)<1 then in such a condition virus controlled in the computer population while R_(0)>1 shows virus rapidly spread in the computer population.Unfortunately,stochastic numerical techniques fail to cope with large step sizes of time.The suggested structure of the stochastic non-standard finite difference technique can never violate the dynamical properties.On this basis,we can suggest a collection of strategies for removing virus’s propagation in the computer population.

Hopf Bifurcation of a Nonresident Computer Virus Model with Delay

In this paper, a delayed nonresident computer virus model with graded infection rate is considered in which the following assumption is imposed: latent computers have lower infection ability than infectious computers. With the aid of the bifurcation theory, sufficient conditions for stability of the infected equilibrium of the model and existence of the Hopf bifurcation are established. In particular, explicit formulae which determine direction and stability of the Hopf bifurcation are derived by means of the normal form theory and the center manifold reduction for functional differential equations. Finally, a numerical example is given in order to show the feasibility of the obtained theoretical findings.

Review of Air Dispersion Modelling Approaches to Assess the Risk of Wind-Borne Spread of Foot-and-Mouth Disease Virus

Foot-and-mouth disease virus (FMDV) is one of the most economically serious veterinary pathogens due to its negative effects on livestock and its highly infectious nature via a variety of transmission paths through oral and inhalation routes. Measures to enhance outbreak management can be designed according to analytical results predicted by mathematical models for wind-borne dispersion, an important path of virus transmission. Accurate atmospheric dispersion models are useful tools for properly determining risk management plans, while inaccurate models may conversely lead to accidental loss in two possible ways. Overly strict measures, e.g., slaughter for too wide an area, can cause severe economic difficulties, including irreversible loss of business operations for a number of farms. On the contrary, inestimable loss potentially caused by lax controls is a persistent threat. In this paper, available modelling procedures for forecasting the spread of FMDV, which have been used since the 1970s, each having its advantages and limitations, are reviewed for the purpose of ensuring suitable application in various conditions of any future emergency cases.

Research on viral dynamic models of hepatitis B virus infection

A mathematical model with cytotoxic cells of hepatitis B virus (HBV)infection is set up based on a basic model of virus dynamics without cytotoxic cells andexperimental observation of anti-viral drag therapy for HBV infection patients. A quantitativeanalysis of dynamic behaviors shows that the model has three kinds of equilibrium points, whichrepresent the patient's complete recovery without immune ability, complete recovery with immuneability, and HBV persistent infection at the end of the treatment with drag lamivudine,respectively. Our model may provide possible quantitative interpretations for the treatments ofchronic HBV infections with the drag lamivudine, in particularly explain why the plasma virus ofNowak et al. 's patients turnover the original level after stopping the lamivudine treatment.

Modelling the prevalence of hepatitis C virus amongst blood donors in Libya:An investigation of providing a preventive strategy

AIM: To determine hepatitis C virus(HCV) seroprevalence among the Libyan population using blood donors and applying the autoregressive integrated moving average(ARIMA) model to predict future trends and formulate plans to minimize the burden of HCV infection.METHODS: HCV positive cases were collected from 1008214 healthy blood donors over a 6-year period from 2008 to 2013. Data were used to construct the ARIMA model to forecast HCV seroprevalence among blood donors. The validity of the model was assessed using the mean absolute percentage error between the observed and fitted seroprevalence. The fitted ARIMA model was used to forecast the incidence of HCV beyond the observed period for the year 2014 and further to 2055.RESULTS: The overall prevalence of HCV among blood donors was 1.8%, varying over the study period from 1.7% to 2.5%, though no significant variation was found within each calendar year. The ARIMA model showed a non-significant auto-correlation of the residuals, and the prevalence was steady within the last 3 years as expressed by the goodness-of-fit test. The forecast incidence showed an increase in HCV seropositivity in 2014, ranging from 500 to 700 per 10000 population, with an overall prevalence of 2.3%-2.7%. This may be extended to 2055 with minimal periodical variation within each 6-year period.CONCLUSION: The applied model was found to be valuable in evaluating the seroprevalence of HCV among blood donors, and highlighted the growing burden of such infection on the Libyan health care system. The model may help in formulating national policies to prevent increases in HCV infection and plan future strategies that target the consequences of the infection.

Integrated analysis of human influenza A(H1N1)virus infectionrelated genes to construct a suitable diagnostic model

The genome characteristics and structural functions of coding proteins correlate with the genetic diversity of the H1N1 virus,which aids in the understanding of its underlying pathogenic mechanism.In this study,analyses of the characteristic of the H1N1 virus infection-related genes,their biological functions,and infection-related reversal drugs were performed.Additionally,we used multi-dimensional bioinformatics analysis to identify the key genes and then used these to construct a diagnostic model for the H1N1 virus infection.There was a total of 169 differently expressed genes in the samples between 21 h before infection and 77 h after infection.They were used during the protein-protein interaction(PPI)analysis,and we obtained a total of 1725 interacting genes.Then,we performed a weighted gene co-expression network analysis(WGCNA)on these genes,and we identified three modules that showed significant potential for the diagnosis of the H1N1 virus infection.These modules contained 60 genes,and they were used to construct this diagnostic model,which showed an effective prediction value.Besides,these 60 genes were involved in the biological functions of this infectious virus,like the cellular response to type I interferon and in the negative regulation of the viral life cycle.However,20 genes showed an upregulated expression as the infection progressed.Other 36 upregulated genes were used to examine the relationship between genes,human influenza A virus,and infection-related reversal drugs.This study revealed numerous important reversal drug molecules on the H1N1 virus.They included rimantadine,interferons,and shikimic acid.Our study provided a novel method to analyze the characteristic of different genes and explore their corresponding biological function during the infection caused by the H1N1 virus.This diagnostic model,which comprises 60 genes,shows that a significant predictive value can be the potential biomarker for the diagnosis of the H1N1 virus infection.