AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human...AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.展开更多
Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pa...Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pathophysiological conditions, various biophysiological and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc., may influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of atherosclerotic plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and its major complication, the acute vascular syndromes.展开更多
The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on eluc...The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE technologies and point out their limitations. We will then discuss the major discoveries and the new biological insightsthat have emerged from their applications to cardiovascular diseases. Finally we will touch upon potential challenges and future developments in this area.展开更多
New classes of functions namely (V, ρ)_(h,φ)-type I, quasi (V, ρ)_(h,φ)-type I and pseudo (V, ρ)_(h,φ)-type I functions are defined for multiobjective programming problem by using BenTal's generalized algebr...New classes of functions namely (V, ρ)_(h,φ)-type I, quasi (V, ρ)_(h,φ)-type I and pseudo (V, ρ)_(h,φ)-type I functions are defined for multiobjective programming problem by using BenTal's generalized algebraic operation. The examples of (V, ρ)_(h,φ)-type I functions are given. The sufficient optimality conditions are obtained for multi-objective programming problem involving above new generalized convexity.展开更多
Cholangiocytes-the epithelial cells which line the bileducts-are increasingly recognized as importanttransporting epithelia actively involved in the absorptionand secretion of water,ions,and solutes.Thisrecognition is...Cholangiocytes-the epithelial cells which line the bileducts-are increasingly recognized as importanttransporting epithelia actively involved in the absorptionand secretion of water,ions,and solutes.Thisrecognition is due in part to the recent development ofnew experimental models.New biologic concepts haveemerged including the identification and topography ofreceptors and flux proteins on the apical and/orbasolateral membrane which are involved in the molecularmechanisms of ductal bile secretion.Individually isolatedand/or perfused bile duct units from livers of rats andmice serve as new,physiologically relevant in vitromodels to study cholangiocyte transport.Biliary treedimensions and novel insights into anatomic remodeling ofproliferating bile ducts have emerged from three-dimensional reconstruction using CT scanning andsophisticated software.Moreover,new pathologicconcepts have arisen regarding the interaction ofcholangiocytes with pathogens such as Cryptosporidiumparvum.These concepts and associated methodologiesmay provide the framework to develop new therapies forthe cholangiopathies,a group of important hepatobiliarydiseases in which cholangiocytes are the target cell.展开更多
The mast cell is an enigmatic cell type whose physiological function has preoccupied large numbers of investigators for decadest. Some have concluded that the absence of mast cells is incompatible with life, at least ...The mast cell is an enigmatic cell type whose physiological function has preoccupied large numbers of investigators for decadest. Some have concluded that the absence of mast cells is incompatible with life, at least in humans, because no human conditions have been documented where these cells are absent from the body. On the other hand, mice harboring specific mutations in certain growth factors, or their receptors, that展开更多
The increasing integration of variable wind generation has aggravated the imbalance between electricity supply and demand. Power-to-hydrogen(P2H) is a promising solution to balance supply and demand in a variable powe...The increasing integration of variable wind generation has aggravated the imbalance between electricity supply and demand. Power-to-hydrogen(P2H) is a promising solution to balance supply and demand in a variable power grid, in which excess wind power is converted into hydrogen via electrolysis and stored for later use. In this study, an energy hub(EH) with both a P2H facility(electrolyzer) and a gas-to-power(G2P) facility(hydrogen gas turbine) is proposed to accommodate a high penetration of wind power. The EH is modeled and integrated into a security-constrained unit commitment(SCUC) problem, and this optimization problem is solved by a mixed-integer linear programming(MILP) method with the Benders decomposition technique. Case studies are presented to validate the proposed model and elaborate on the technological potential of integrating P2H into a power system with a high level of wind penetration(HWP).展开更多
文摘AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.
文摘Apoptosis is a form of genetically programmed cell death, which plays a key role in regulation of cellularity in a variety of tissue and cell types including the cardiovascular tissues. Under both physiological and pathophysiological conditions, various biophysiological and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc., may influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of atherosclerotic plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and its major complication, the acute vascular syndromes.
基金Part of studies cited in this review was in partsupported by Johns Hopkins Institutional ResearchGrant(Ye,SQ),a pilot project(Ye,SQ)in The Hop-kins DK Center for the Analysis of Gene Expres-sion(R24DK58757-01,NIDDK)and Dorothy WallisWagner Charitable Tru
文摘The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE technologies and point out their limitations. We will then discuss the major discoveries and the new biological insightsthat have emerged from their applications to cardiovascular diseases. Finally we will touch upon potential challenges and future developments in this area.
基金Supported by the NSF of Shaanxi Provincial Educational Department(06JK152)
文摘New classes of functions namely (V, ρ)_(h,φ)-type I, quasi (V, ρ)_(h,φ)-type I and pseudo (V, ρ)_(h,φ)-type I functions are defined for multiobjective programming problem by using BenTal's generalized algebraic operation. The examples of (V, ρ)_(h,φ)-type I functions are given. The sufficient optimality conditions are obtained for multi-objective programming problem involving above new generalized convexity.
基金grants DK24031 and DK57993(N.F.LaRusso)from the National Institutes of Healththe Mayo Foundation
文摘Cholangiocytes-the epithelial cells which line the bileducts-are increasingly recognized as importanttransporting epithelia actively involved in the absorptionand secretion of water,ions,and solutes.Thisrecognition is due in part to the recent development ofnew experimental models.New biologic concepts haveemerged including the identification and topography ofreceptors and flux proteins on the apical and/orbasolateral membrane which are involved in the molecularmechanisms of ductal bile secretion.Individually isolatedand/or perfused bile duct units from livers of rats andmice serve as new,physiologically relevant in vitromodels to study cholangiocyte transport.Biliary treedimensions and novel insights into anatomic remodeling ofproliferating bile ducts have emerged from three-dimensional reconstruction using CT scanning andsophisticated software.Moreover,new pathologicconcepts have arisen regarding the interaction ofcholangiocytes with pathogens such as Cryptosporidiumparvum.These concepts and associated methodologiesmay provide the framework to develop new therapies forthe cholangiopathies,a group of important hepatobiliarydiseases in which cholangiocytes are the target cell.
基金Supported by the grants from the National Institutes of Health,USA (DK33491 and AT01180) and the Crohn's and Colitis Foundation of America
文摘The mast cell is an enigmatic cell type whose physiological function has preoccupied large numbers of investigators for decadest. Some have concluded that the absence of mast cells is incompatible with life, at least in humans, because no human conditions have been documented where these cells are absent from the body. On the other hand, mice harboring specific mutations in certain growth factors, or their receptors, that
基金supported by National Natural Science Foundation of China(No.51377035)NSFC-RCUK_EPSRC(No.51361130153)
文摘The increasing integration of variable wind generation has aggravated the imbalance between electricity supply and demand. Power-to-hydrogen(P2H) is a promising solution to balance supply and demand in a variable power grid, in which excess wind power is converted into hydrogen via electrolysis and stored for later use. In this study, an energy hub(EH) with both a P2H facility(electrolyzer) and a gas-to-power(G2P) facility(hydrogen gas turbine) is proposed to accommodate a high penetration of wind power. The EH is modeled and integrated into a security-constrained unit commitment(SCUC) problem, and this optimization problem is solved by a mixed-integer linear programming(MILP) method with the Benders decomposition technique. Case studies are presented to validate the proposed model and elaborate on the technological potential of integrating P2H into a power system with a high level of wind penetration(HWP).
