An objective of this work is to develop a validated computational model that can be used to estimate ratcheting accumulation behavior of granular soils due to high-cyclic loading. An accumulation model was proposed to...An objective of this work is to develop a validated computational model that can be used to estimate ratcheting accumulation behavior of granular soils due to high-cyclic loading. An accumulation model was proposed to describe only the envelope of the maximum plastic deformations generated during the cyclic loading process, which can calculate the accumulated deformation by means of relatively large load cycle increments. The concept of volumetric hardening was incorporated into the model and a so-called overstress formulation was employed to describe the evolution of the accumulated volumetric deformation as a state parameter. The model accounted for ratcheting shakedown and accumulation such as a pseudo-yield surface(a shakedown surface) associated with loading inside the current virgin yield surface which was implemented into the well-known modified Cam-clay model. Finally, the model was calibrated using data from the stress-controlled drained cyclic triaxial tests on homogeneous fine grained sands. It is seen that the model can successfully represent important features of the ratcheting accumulation of both volumetric and deviatoric deformation caused by repeated drained loading over a large number of cycles.展开更多
In studies of auditory perception, a dichotomy between envelope and temporal fine structure(TFS) has been emphasized. It has been shown that frequency-following responses(FFRs) in the rat inferior colliculus can be di...In studies of auditory perception, a dichotomy between envelope and temporal fine structure(TFS) has been emphasized. It has been shown that frequency-following responses(FFRs) in the rat inferior colliculus can be divided into the envelope component(FFREnv)and the temporal fine structure component(FFRTFS). However, the existing FFR models cannot successfully separate FFREnv and FFRTFS. This study was to develop a new FFR model to effectively distinguish FFREnv from FFRTFS by both combining the advantages of the two existing FFR models and simultaneously adding cellular properties of inferior colliculus neurons. To evaluate the validity of the present model, correlations between simulated FFRs and experimental data from the rat inferior colliculus were calculated. Different model parameters were tested, FFRs were calculated, and the parameters with highest prediction were chosen to establish an ideal FFR model. The results indicate that the new FFR model can provide reliable predictions for experimentally obtained FFREnv and FFRTFS.展开更多
AIM： In the present study, antibody and peripheral blood mononuclear cells （PBMC） proliferative responses against hepatitis C virus （HCV） antigens were evaluated in HCV chronically infected patients. METHODS： Pa...AIM： In the present study, antibody and peripheral blood mononuclear cells （PBMC） proliferative responses against hepatitis C virus （HCV） antigens were evaluated in HCV chronically infected patients. METHODS： Paired serum and PBMC samples were taken six months apart from 34 individuals, either treated or not, and tested by enzyme-linked immunosorbent assay （ELISA） and carboxyfluorescein succinimidyl ester staining. RSULTS： Over 70% of the patients showed specific IgG and IgM against capsid, E1 and NS3, while HVR-1 was recognized by half of the patients. An increase in the levels of the anti-capsid IgM （P = 0.027） and IgG （P = 0.0006） was observed in six-month samples, compared to baseline. Similarly, a significantly higher percent of patients had detectable IgA reactivity to capsid （P = 0.017） and NS3 （P = 0.005） after six months, compared to baseline. Particularly, IgA against structural antigens positively correlated with hepatic damage （P = 0.036）. IgG subclasses evaluation against capsid and NS3 revealed a positive recognition mediated by IgG1 in more than 80% of the individuals. On the contrary, less than 30% of the patients showed a positive proliferative response either of CD4＋ or CD8＋ T cells, being the capsid poorly recognized. CONCLUSION： These results confirm that while the cellular immune response is narrow and weak, a broad and vigorous humoral response occurs in HCV chronic infection. The observed correlation between IgA and hepatic damage may have diagnostic significance, although it warrants further confirmation.展开更多
The development of a vaccine based on human immunodeficiency virus type 1(HIV-1) envelope glycoprotein(Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the a...The development of a vaccine based on human immunodeficiency virus type 1(HIV-1) envelope glycoprotein(Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen(HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations. Here, to elucidate the detailed roles of primary immunization in immune memory response formation and antibody production, we immunized C57BL/6 mice with each antigen and evaluated the development of T follicular helper(Tfh) cells, germinal centers,and the memory responses involved in prime and boost immunizations. We found that after prime immunization, compared with HBsAg, gp120 induced higher frequencies of Tfh cells and programmed death(PD)-1^+T cells, greater major histocompatibility complex II expression on B cells, comparable activated B cells, but weaker germinal center(GC)reactions and memory B cell responses in the draining lymph nodes, accompanied by slower antibody recall responses and poor immune memory responses. The above results suggested that more PD-1^+T cells arising in primary immunization may serve as major contributors to the slow antibody recall response elicited by HIV-1 Env.展开更多
Hepatitis C virus(HCV) infection is still a major public health problem worldwide since its first identification in 1989. At the start, HCV infection was post-transfusion viral infection, particularly in developing co...Hepatitis C virus(HCV) infection is still a major public health problem worldwide since its first identification in 1989. At the start, HCV infection was post-transfusion viral infection, particularly in developing countries. Recently, due to iv drug abuse, HCV infection became number one health problem in well-developed countries as well. Following acute HCV infection, the innateimmune response is triggered in the form of activated coordinated interaction of NK cells, dendritic cells and interferon α. The acquired immune response is then developed in the form of the antibody-mediated immune response(ABIR) and the cell-mediated immune response(CMIR). Both are responsible for clearance of HCV infection in about 15% of infected patients. However, HCV has several mechanisms to evade these antivirus immune reactions. The current review gives an overview of HCV structure, immune response and viral evasion mechanisms. It also evaluates the available preventive and therapeutic vaccines that induce innate, ABIR, CMIR. Moreover, this review highlights the progress in recent HCV vaccination studies either in preclinical or clinical phases. The unsatisfactory identification of HCV infection by the current screening system and the limitations of currently available treatments, including the ineligibility of some chronic HCV patients to such antiviral agents, mandate the development of an effective HCV vaccine.展开更多
基金Projects(41302219,41302076)supported by the National Natural Science Foundation of China
文摘An objective of this work is to develop a validated computational model that can be used to estimate ratcheting accumulation behavior of granular soils due to high-cyclic loading. An accumulation model was proposed to describe only the envelope of the maximum plastic deformations generated during the cyclic loading process, which can calculate the accumulated deformation by means of relatively large load cycle increments. The concept of volumetric hardening was incorporated into the model and a so-called overstress formulation was employed to describe the evolution of the accumulated volumetric deformation as a state parameter. The model accounted for ratcheting shakedown and accumulation such as a pseudo-yield surface(a shakedown surface) associated with loading inside the current virgin yield surface which was implemented into the well-known modified Cam-clay model. Finally, the model was calibrated using data from the stress-controlled drained cyclic triaxial tests on homogeneous fine grained sands. It is seen that the model can successfully represent important features of the ratcheting accumulation of both volumetric and deviatoric deformation caused by repeated drained loading over a large number of cycles.
基金supported by the National Natural Science Foundation of China(Grant No.31470987)the National Basic Research Development Program of China(Grant No.2015CB351800)“985”grants from Peking University for Physiological Psychology and China Postdoctoral Science Foundation(Grant No.2016M601066)
文摘In studies of auditory perception, a dichotomy between envelope and temporal fine structure(TFS) has been emphasized. It has been shown that frequency-following responses(FFRs) in the rat inferior colliculus can be divided into the envelope component(FFREnv)and the temporal fine structure component(FFRTFS). However, the existing FFR models cannot successfully separate FFREnv and FFRTFS. This study was to develop a new FFR model to effectively distinguish FFREnv from FFRTFS by both combining the advantages of the two existing FFR models and simultaneously adding cellular properties of inferior colliculus neurons. To evaluate the validity of the present model, correlations between simulated FFRs and experimental data from the rat inferior colliculus were calculated. Different model parameters were tested, FFRs were calculated, and the parameters with highest prediction were chosen to establish an ideal FFR model. The results indicate that the new FFR model can provide reliable predictions for experimentally obtained FFREnv and FFRTFS.
基金Supported by Grant from Pan American Health Organization, held by Dr. Santiago Dueas-Carrera
文摘AIM： In the present study, antibody and peripheral blood mononuclear cells （PBMC） proliferative responses against hepatitis C virus （HCV） antigens were evaluated in HCV chronically infected patients. METHODS： Paired serum and PBMC samples were taken six months apart from 34 individuals, either treated or not, and tested by enzyme-linked immunosorbent assay （ELISA） and carboxyfluorescein succinimidyl ester staining. RSULTS： Over 70% of the patients showed specific IgG and IgM against capsid, E1 and NS3, while HVR-1 was recognized by half of the patients. An increase in the levels of the anti-capsid IgM （P = 0.027） and IgG （P = 0.0006） was observed in six-month samples, compared to baseline. Similarly, a significantly higher percent of patients had detectable IgA reactivity to capsid （P = 0.017） and NS3 （P = 0.005） after six months, compared to baseline. Particularly, IgA against structural antigens positively correlated with hepatic damage （P = 0.036）. IgG subclasses evaluation against capsid and NS3 revealed a positive recognition mediated by IgG1 in more than 80% of the individuals. On the contrary, less than 30% of the patients showed a positive proliferative response either of CD4＋ or CD8＋ T cells, being the capsid poorly recognized. CONCLUSION： These results confirm that while the cellular immune response is narrow and weak, a broad and vigorous humoral response occurs in HCV chronic infection. The observed correlation between IgA and hepatic damage may have diagnostic significance, although it warrants further confirmation.
基金supported by the Grant of National Natural Science Foundation of China (Grant number 81271824, 81772190, 81601755)the Grant of National Science and Technology Major Project (Grant number 2012ZX10001009-002003)
文摘The development of a vaccine based on human immunodeficiency virus type 1(HIV-1) envelope glycoprotein(Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen(HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations. Here, to elucidate the detailed roles of primary immunization in immune memory response formation and antibody production, we immunized C57BL/6 mice with each antigen and evaluated the development of T follicular helper(Tfh) cells, germinal centers,and the memory responses involved in prime and boost immunizations. We found that after prime immunization, compared with HBsAg, gp120 induced higher frequencies of Tfh cells and programmed death(PD)-1^+T cells, greater major histocompatibility complex II expression on B cells, comparable activated B cells, but weaker germinal center(GC)reactions and memory B cell responses in the draining lymph nodes, accompanied by slower antibody recall responses and poor immune memory responses. The above results suggested that more PD-1^+T cells arising in primary immunization may serve as major contributors to the slow antibody recall response elicited by HIV-1 Env.
文摘Hepatitis C virus(HCV) infection is still a major public health problem worldwide since its first identification in 1989. At the start, HCV infection was post-transfusion viral infection, particularly in developing countries. Recently, due to iv drug abuse, HCV infection became number one health problem in well-developed countries as well. Following acute HCV infection, the innateimmune response is triggered in the form of activated coordinated interaction of NK cells, dendritic cells and interferon α. The acquired immune response is then developed in the form of the antibody-mediated immune response(ABIR) and the cell-mediated immune response(CMIR). Both are responsible for clearance of HCV infection in about 15% of infected patients. However, HCV has several mechanisms to evade these antivirus immune reactions. The current review gives an overview of HCV structure, immune response and viral evasion mechanisms. It also evaluates the available preventive and therapeutic vaccines that induce innate, ABIR, CMIR. Moreover, this review highlights the progress in recent HCV vaccination studies either in preclinical or clinical phases. The unsatisfactory identification of HCV infection by the current screening system and the limitations of currently available treatments, including the ineligibility of some chronic HCV patients to such antiviral agents, mandate the development of an effective HCV vaccine.
