This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of wood...This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.展开更多
This review describes woodchucks chronically infected with the woodchuck hepatitis virus(WHV)as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma(HCC)induced by...This review describes woodchucks chronically infected with the woodchuck hepatitis virus(WHV)as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma(HCC)induced by the hepatitis B virus(HBV).Since laboratory animal models susceptible to HBV infection are limited,woodchucks experimentally infected with WHV,a hepatitis virus closely related to HBV,are increasingly used to enhance our understanding of virus-host interactions,immune response,and liver disease progression.A correlation of severe liver pathogenesis with high-level viral replication and deficient antiviral immunity has been established,which are present during chronic infection after WHV inoculation of neonatal woodchucks for modeling vertical HBV transmission in humans.HCC in chronic carrier woodchucks develops 17 to 36 mo after neonatal WHV infection and involves liver tumors that are comparable in size,morphology,and molecular gene signature to those of HBV-infected patients.Accordingly,woodchucks with WHV-induced liver tumors have been used for the improvement of imaging and ablation techniques of human HCC.In addition,drug efficacy studies in woodchucks with chronic WHV infection have revealed that prolonged treatment with nucleos(t)ide analogs,alone or in combination with other compounds,minimizes the risk of liver disease progression to HCC.More recently,woodchucks have been utilized in the delineation of mechanisms involved in innate and adaptive immune responses against WHV during acute,self-limited and chronic infections.Therapeutic interventions based on modulating the deficient host antiviral immunity have been explored in woodchucks for inducing functional cure in HBV-infected patients and for reducing or even delaying associated liver disease sequelae,including the onset of HCC.Therefore,woodchucks with chronic WHV infection constitute a well-characterized,fully immunocompetent animal model for HBV-induced liver cancer and for preclinical evaluation of the safety and efficacy of new modalities,which are based on chemo,gene,and immune therapy,for the prevention and treatment of HCC in patients for which current treatment options are dismal.展开更多
The antiretroviral action of dC14 in vitro has been proven in previous experiments. This paper deals with the effect of dC14 in vivo.Intraperitoneal inoculation of tumor cells into mice without dC14 treatment induced ...The antiretroviral action of dC14 in vitro has been proven in previous experiments. This paper deals with the effect of dC14 in vivo.Intraperitoneal inoculation of tumor cells into mice without dC14 treatment induced ascitic tumors after a latency of 6 days and death of the mice after 11 days. Both incidence and mortality of disease were 100%. In animals receiving dC14 treatment, the incidence and mortality were less, latency and survival periods were longer. Viral sequences could be detected in tumor cells and in spleens of tumor cell inoculated animals, receiving dC14 treatment or not but could not be detected in normal animals. Studied suggest that the suppressive action of dC14 on the development of mouse SRS ascitic tumor may be through blocking gene expression of virus.展开更多
Investigating flexibility and stability boosting transmission expansion planning(TEP)methods can increase the renewable energy(RE)consumption of the power systems.In this study,we propose a bi-level TEP method for vol...Investigating flexibility and stability boosting transmission expansion planning(TEP)methods can increase the renewable energy(RE)consumption of the power systems.In this study,we propose a bi-level TEP method for voltage-source-converter-based direct current(VSC-DC),focusing on flexibility and stability enhancement.First,we established the TEP framework of VSC-DC,by introducing the evaluation indices to quantify the power system flexibility and stability.Subsequently,we propose a bi-level VSC-DC TEP model:the upper-level model acquires the optimal VSC-DC planning scheme by using the improved moth flame optimization(IMFO)algorithm,and the lower-level model evaluates the flexibility through time-series production simulation.Finally,we applied the proposedVSC-DC TEPmethod to the modified IEEE-24 and IEEE-39 test systems,and obtained the optimalVSCDC planning schemes.The results verified that the proposed method can achieve excellent RE curtailment with high flexibility and stability.Furthermore,the well-designed IMFO algorithm outperformed the traditional particle swarm optimization(PSO)and moth flame optimization(MFO)algorithms,confirming the effectiveness of the proposed approach.展开更多
基金Supported by contract N01-AI-05399 to the College of Veterinary Medicine, Cornell University from the National Institute of Allergy and Infectious Diseases. PC and SM also have been supported by contract N01-AI-95390 to the Georgetown University Medical Center, Georgetown University from the National Institute of Allergy and Infectious Diseases
文摘This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes, and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, andfor the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and prevention of HBV disease sequelae.
文摘This review describes woodchucks chronically infected with the woodchuck hepatitis virus(WHV)as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma(HCC)induced by the hepatitis B virus(HBV).Since laboratory animal models susceptible to HBV infection are limited,woodchucks experimentally infected with WHV,a hepatitis virus closely related to HBV,are increasingly used to enhance our understanding of virus-host interactions,immune response,and liver disease progression.A correlation of severe liver pathogenesis with high-level viral replication and deficient antiviral immunity has been established,which are present during chronic infection after WHV inoculation of neonatal woodchucks for modeling vertical HBV transmission in humans.HCC in chronic carrier woodchucks develops 17 to 36 mo after neonatal WHV infection and involves liver tumors that are comparable in size,morphology,and molecular gene signature to those of HBV-infected patients.Accordingly,woodchucks with WHV-induced liver tumors have been used for the improvement of imaging and ablation techniques of human HCC.In addition,drug efficacy studies in woodchucks with chronic WHV infection have revealed that prolonged treatment with nucleos(t)ide analogs,alone or in combination with other compounds,minimizes the risk of liver disease progression to HCC.More recently,woodchucks have been utilized in the delineation of mechanisms involved in innate and adaptive immune responses against WHV during acute,self-limited and chronic infections.Therapeutic interventions based on modulating the deficient host antiviral immunity have been explored in woodchucks for inducing functional cure in HBV-infected patients and for reducing or even delaying associated liver disease sequelae,including the onset of HCC.Therefore,woodchucks with chronic WHV infection constitute a well-characterized,fully immunocompetent animal model for HBV-induced liver cancer and for preclinical evaluation of the safety and efficacy of new modalities,which are based on chemo,gene,and immune therapy,for the prevention and treatment of HCC in patients for which current treatment options are dismal.
文摘The antiretroviral action of dC14 in vitro has been proven in previous experiments. This paper deals with the effect of dC14 in vivo.Intraperitoneal inoculation of tumor cells into mice without dC14 treatment induced ascitic tumors after a latency of 6 days and death of the mice after 11 days. Both incidence and mortality of disease were 100%. In animals receiving dC14 treatment, the incidence and mortality were less, latency and survival periods were longer. Viral sequences could be detected in tumor cells and in spleens of tumor cell inoculated animals, receiving dC14 treatment or not but could not be detected in normal animals. Studied suggest that the suppressive action of dC14 on the development of mouse SRS ascitic tumor may be through blocking gene expression of virus.
基金supported by the Science and Technology Project of Central China Branch of State Grid Corporation of China under Grant 52140023000T.
文摘Investigating flexibility and stability boosting transmission expansion planning(TEP)methods can increase the renewable energy(RE)consumption of the power systems.In this study,we propose a bi-level TEP method for voltage-source-converter-based direct current(VSC-DC),focusing on flexibility and stability enhancement.First,we established the TEP framework of VSC-DC,by introducing the evaluation indices to quantify the power system flexibility and stability.Subsequently,we propose a bi-level VSC-DC TEP model:the upper-level model acquires the optimal VSC-DC planning scheme by using the improved moth flame optimization(IMFO)algorithm,and the lower-level model evaluates the flexibility through time-series production simulation.Finally,we applied the proposedVSC-DC TEPmethod to the modified IEEE-24 and IEEE-39 test systems,and obtained the optimalVSCDC planning schemes.The results verified that the proposed method can achieve excellent RE curtailment with high flexibility and stability.Furthermore,the well-designed IMFO algorithm outperformed the traditional particle swarm optimization(PSO)and moth flame optimization(MFO)algorithms,confirming the effectiveness of the proposed approach.
