AIM: To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma (HCC). METHODS: We performed a retrospective analysis of all patients w...AIM: To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma (HCC). METHODS: We performed a retrospective analysis of all patients with HCC who were treated with thalido- mide for at least two months. The medical records of patients with HCC who were treated at our institution between April 2003 and March 2008 were reviewed. Image studies performed before and after treatment, tumor response, overall survival, and the decrease in o-fetoprotein (AFP) levels were evaluated. RESULTS: A total of 53 patients with HCC received either 100 or 200 mg/d of thalidomide. The patient population consisted of 9 women and 44 men with a median age of 61 years. Thirty patients (56.6%) were classified as Child-Pugh A, and 12 patients (22.6%) were classified as Child-Pugh B. Twenty-six patients had portal vein thrombosis (49.1%), and 25 patients had extrahepatic metastasis (47.1%). The median duration of thalidomide treatment was 6.0 mo. Six of the 53 patients achieved a confirmed response (11.3%), one achieved a complete response (1.9%) and 5 achieved a partial response (9.4%). The disease control rate (CR + PR + SD) was 28.3% (95% CI: 17.8-42.4), and the median overall survival rate was 10.5 too. The 1- and 2-year survival rates were 45% and 20%, respectively. Only one complete response patient showed an im- proved overall survival rate of 66.8 mo. Sixteen patients (30.2%) showed more than a 50% decrease in their serum AFP levels from baseline, indicating a better re- sponse rate (31.3%), disease control rate (43.8%), and overall survival time (20.7 mo). The therapy was well tolerated, and no significant toxicities were observed. CONCLUSION: Thalidomide was found to be safe for advanced HCC patients, demonstrating anti-tumor ac- tivity including response, survival, and AFP decreases of greater than 50% from baseline.展开更多
As a critical apoptosis executioner, caspase-3 becomes activated and then enters into the nucleus to exert its function. However, the molecular mechanism of this nuclear entry of active caspase-3 is still unknown. In ...As a critical apoptosis executioner, caspase-3 becomes activated and then enters into the nucleus to exert its function. However, the molecular mechanism of this nuclear entry of active caspase-3 is still unknown. In this study, we revealed that easpase-3 harbors a crm-l-independent nuclear export signal (NES) in its small subunit. Using reversecaspase-3 as the study model, we found that the function of the NES in caspase-3 was not disturbed by the conformational changes during induced caspase-3 activation. Mutations disrupting the cleavage activity or p3-recognition site resulted in a defect in the nuclear entry of active caspase-3. We provide evidence that the p3-mediated specific cleavage activity of active caspase-3 abrogated the function of the NES. In conclusion, our results demonstrate that during caspase-3 activation, NES is constitutively present, p3-mediated specific cleavage activity abrogates the NES function in caspase-3, thus facilitating the nuclear entry of active caspase-3.展开更多
For material nonlinear problem,elements derived with the flexibility-based method are more accurate than classical elements derived with the stiffness-based method. A review of the current state of the art of the flex...For material nonlinear problem,elements derived with the flexibility-based method are more accurate than classical elements derived with the stiffness-based method. A review of the current state of the art of the flexibility-based finite element method is provided to enhance the robustness of structure analysis. The research on beam-column elements is the mainstream in the research on flexibility-based finite element method at present. The original development of flexibility-based finite element method is reviewed, and the further development of this method is then presented in several specific aspects, such as geometrically nonlinear analysis and dynamic analysis. The further research needed to be carried out in the future is finally discussed.展开更多
In order to quantitate the bovine immunodeficiency virus line (BIVL) was established by transfecting baby hamster kidney (BIV) cells infection in vitro, a BIV indicator cell with reporter plasmids containing the f...In order to quantitate the bovine immunodeficiency virus line (BIVL) was established by transfecting baby hamster kidney (BIV) cells infection in vitro, a BIV indicator cell with reporter plasmids containing the firefly luciferase gene driven by a BIV long terminal repeat promoter. The BIV activates promoter activity of the LTR to express luciferase upon infection. BIV infection could therefore by quantified by detection of luciferase activity. Compared to standard assays used to detect BIV infection, the BIVL-based assay is 10 times more sensitive than the the CPE-based assay, and has similar sensitivity with the viral capsid protein Western blot assay BIV indicator cell line could detect BIV infection specifically. Luciferase activity of BIV infected BIVL cells showed a time dependent manner, and 60 h post infection is the optimal time to detect BIV infection. Luciferase activity of BIVL cells correlates with the BIV capsid protein expression. Moreover, a linear relationship was found between MOI and the activated intensity of luciferase expression. In brief, the BIV indicator cell line is an easy, robust and quantitive method for monitoring BIV infection.展开更多
Objective:The aim of our study was to evaluate the in vitro antitumor activity of two novel platinum-based(II) complexes(2.3-pyridinedicarboxylic acid dehydrate platinum and 2.3-pyrazinedicarboxylic acid dehydrate pla...Objective:The aim of our study was to evaluate the in vitro antitumor activity of two novel platinum-based(II) complexes(2.3-pyridinedicarboxylic acid dehydrate platinum and 2.3-pyrazinedicarboxylic acid dehydrate platinum),which were concurrently provided with hydrophilic carboxyl group and lipophilic pyrazinyl or pyridyl group,on SW620 colorectal cancer cell line and the impact of the two compounds on the cell cycle and apoptosis of the cells when compared with the oxaliplatin,desiring the new ligand combined with hydrophilic and lipophilic properties would facilitate the transportation and transmembrane of the drugs,showing a better antitumor activity.Methods:After SW620 cells were treated with different doses of the three platinum-based agents for 24,48 and 72 h,the cell proliferation inhibition rate was determined using methyl thiazolyl tetrazolium(MTT) assay;the morphology of cells were evaluated under inverted microscope;the changes in cell cycle were determined using flow cytometry;the percent apoptosis was measured using Annexin V/PI double staining and the micromorphology of the cells after drug exposure was evaluated using scanning electron microscopy.Results:The evaluation on the proliferation inhibition rate revealed that the three platinum-based agents inhibited the SW620 cells in a time-and dose-dependent manner and showed different strengths as pyridine > pyrazine > Oxa.Under optical microscope,the morphological changes such as cell shrinkage,round cells and dead cells were frequently observed after drug exposure.Cell cycle determination showed that all of the three agents could function to block the cells converting from phase S to phase G2M.Apoptosis evaluation revealed that the three agents promoted the apoptosis of SW620 cells in a time-and dose-dependent manner and showed different strengths as pyridine > pyrazine > Oxa.Typical early and late apoptotic morphological changes could be detected during electron microscopy.Conclusion:The two novel platinum-based(II) complexes showed a stronger antitumor effect on SW620 cells than oxaliplatin,with the targeted site at a certain phase of cell cycle and apoptosis.展开更多
In recent years the evolution of highly developed and complicated computerization has boosted the importance to business of IT infrastructure. Enhancement of business agility is not possible unless greater flexibility...In recent years the evolution of highly developed and complicated computerization has boosted the importance to business of IT infrastructure. Enhancement of business agility is not possible unless greater flexibility is built into IT infrastructure. More often than not, MIS's today are not flexible enough in this sense to agilely accommodate demands for system change incessantly confronting them. We have been focusing our research on MIS flexibility, its evaluation and the development of methodology for its enhancement. This paper aims to present a comparative evaluation via future oriented POC (penalty of change) analysis of system alternatives involving a case of new technology implementation. To start with, we will define the concept of MIS flexibility. We will then describe an actual case of technology implementation and define the problem it involved and go on to illustrate the evaluation procedure of MIS flexibility via future oriented POC analysis.展开更多
Large-scale national disasters have recently occurred worldwide, causing tremendous damage to life and property. Therefore, urban safety has become a critical issue, and disaster prevention and mitigation are also con...Large-scale national disasters have recently occurred worldwide, causing tremendous damage to life and property. Therefore, urban safety has become a critical issue, and disaster prevention and mitigation are also considered in urban development and infrastructure construction. When earthquake disasters occur, road networks play major roles in rescue activity for responding to urban damage. The urban-disaster prevention spatial system attempts to mitigate hazards by considering shelters, routes for evacuation and rescue and necessary logistics. A literature review shows numerous studies related to a disaster-prevention shelter survey before or after hazards, however, they are less concerned with the reliability of shelter evaluation. This study assesses shelter evaluation by considering road networks. The authors construct 10 selected indices individually related to road networks. Three integrated composite indices are established to explain planned-shelter risks using the Arc GIS diagram of a spatial concept of an urban-planning review process. The relationship between shelters and evacuation/rescue routes is important for disaster-prevention planning. This survey investigates the factors of road networks, fire engine rescue routes, fire station location and road/population density for vulnerability evaluations.展开更多
Higher education and science determine the intellectual potential of a society, train new specialists, and consolidate and change citizenship values. Consumer citizenship education for sustainable development is an im...Higher education and science determine the intellectual potential of a society, train new specialists, and consolidate and change citizenship values. Consumer citizenship education for sustainable development is an important function of higher education with a significant moral, social, political, economic, ecological and legal capacity. Consumer citizenship education plays an important role in ensuring the stability and sustainable development of any society. These approaches make it possible to develop the multi-scale thinking of future specialists and enhance their ability to analyse critically the main dilemmas created by the processes of social, legal, environmental, and economic development. The article is devoted to the experience of the Latvian system of higher education in consumer citizenship education within the context of sustainable development. It focuses more specifically on cooperation as a form of voluntary interaction between the partners involved in ensuring sustainable development. The aim of the research is to analyse the experience of consumer citizenship education in Latvian higher education within the context of sustainable development emphasizing the role of various forms of studies. Mostly theoretical research methods have been used in the present study. The starting point of for this research is a theoretical framework. There are both legal underpinnings and practical implementation aspects in this task. The features outlined above are emphasized in the normative acts referring to the Latvian higher education, the documents of the institutions of higher education, and particularly in the study programmes. The results of the research show that consumer citizenship education can be acquired as an interdisciplinary system. The goals and objectives of consumer citizenship education involve training young specialists possessing broad professional knowledge, developed critical thinking, the ability to organize and manage work in a modem way, understanding of the ethical, civic and patriotic values, as well as the ability and skills to engage in various social activities. Consumer citizenship education needs transdisciplinary knowledge if it is to solve the problems of humanity, the problems aggravated by unsustainable, unethical, even immoral consumption. The link between consumer citizenship education and sustainable development is ensured by shared common values, which reveal the sense and importance of both consumer citizenship and ethical sustainability.展开更多
This paper examines an empirical evidence of a frame continuation performed by KAMMI alumni, a contemporary Indonesian Islamic social movement organization. The concepts of "frame continuation" and "value-based ide...This paper examines an empirical evidence of a frame continuation performed by KAMMI alumni, a contemporary Indonesian Islamic social movement organization. The concepts of "frame continuation" and "value-based identity" can be used as theoretical foundation to explore and explain the phenomena of dakwah movement performed by the alumni of KAMMI. Field research on KAMMI alumni role provides the primary empirical foundation for investigating frame continuation, a sustainability of the dakwah movement beyond students' movement organization. Discussion about KAMMI alumni's role provides empirical evidences about how they have strong commitment on either political or religious activities (or both) as their strategies to maintain and continue their previous identity as both political and religious activists. The main foundation for their activism is a value of dakwah (proselytizing), in which Islamic values are believed to be a suitable vehicle for constructing a sacred society in democratic era of Indonesia. The KAMMI alumni believe their movement is a significant religious duty.展开更多
Seismic gap method is one of the effective earthquake prediction methods using seismicity patterns. However, this method has some limitations and uncertainty when using it singly in predicting earthquakes. This paper ...Seismic gap method is one of the effective earthquake prediction methods using seismicity patterns. However, this method has some limitations and uncertainty when using it singly in predicting earthquakes. This paper puts forward the prediction method using the dynamic seismicity pattern with dynamic implications. This method considers the formation and evolution of the seismic gap on the basis of plate movement and structural characteristics. Through analysis of 26 cases of earthquakes of MS≥5.0 occurring in East China and South China, this paper obtains the relationship between the main shock with seismic gap and active fault's location, as well as the relationship between the seismic gap and location and strike of active faults. Meanwhile, this paper provides a dynamic explanation of the differences in the formation and evolution patterns of the seismic gap between the two regions, thus providing the physical basis for and reducing the uncertainty of predicting earthquakes using the seismic gap method.展开更多
文摘AIM: To evaluate the efficacy of thalidomide in com- bination with other therapies to treat patients with ad- vanced hepatocellular carcinoma (HCC). METHODS: We performed a retrospective analysis of all patients with HCC who were treated with thalido- mide for at least two months. The medical records of patients with HCC who were treated at our institution between April 2003 and March 2008 were reviewed. Image studies performed before and after treatment, tumor response, overall survival, and the decrease in o-fetoprotein (AFP) levels were evaluated. RESULTS: A total of 53 patients with HCC received either 100 or 200 mg/d of thalidomide. The patient population consisted of 9 women and 44 men with a median age of 61 years. Thirty patients (56.6%) were classified as Child-Pugh A, and 12 patients (22.6%) were classified as Child-Pugh B. Twenty-six patients had portal vein thrombosis (49.1%), and 25 patients had extrahepatic metastasis (47.1%). The median duration of thalidomide treatment was 6.0 mo. Six of the 53 patients achieved a confirmed response (11.3%), one achieved a complete response (1.9%) and 5 achieved a partial response (9.4%). The disease control rate (CR + PR + SD) was 28.3% (95% CI: 17.8-42.4), and the median overall survival rate was 10.5 too. The 1- and 2-year survival rates were 45% and 20%, respectively. Only one complete response patient showed an im- proved overall survival rate of 66.8 mo. Sixteen patients (30.2%) showed more than a 50% decrease in their serum AFP levels from baseline, indicating a better re- sponse rate (31.3%), disease control rate (43.8%), and overall survival time (20.7 mo). The therapy was well tolerated, and no significant toxicities were observed. CONCLUSION: Thalidomide was found to be safe for advanced HCC patients, demonstrating anti-tumor ac- tivity including response, survival, and AFP decreases of greater than 50% from baseline.
基金Supplementary information is linked to the online version of the paper on the Cell Research website.Acknowledgments We thank Prof Jian Wang (Shanghai University, Shanghai) for his valuable revision and discussion. This work was supported by grants from the National Natural Science Foundation of China (30700411), Shenzhen Bureau of Science Technology and Information (SZKJ-2006018, SZKJ-2007012), Shenzhen Nanshan Bureau of Science Technology and Information (2008036) and Shenzhen Key Laboratory Advancement Scheme.
文摘As a critical apoptosis executioner, caspase-3 becomes activated and then enters into the nucleus to exert its function. However, the molecular mechanism of this nuclear entry of active caspase-3 is still unknown. In this study, we revealed that easpase-3 harbors a crm-l-independent nuclear export signal (NES) in its small subunit. Using reversecaspase-3 as the study model, we found that the function of the NES in caspase-3 was not disturbed by the conformational changes during induced caspase-3 activation. Mutations disrupting the cleavage activity or p3-recognition site resulted in a defect in the nuclear entry of active caspase-3. We provide evidence that the p3-mediated specific cleavage activity of active caspase-3 abrogated the function of the NES. In conclusion, our results demonstrate that during caspase-3 activation, NES is constitutively present, p3-mediated specific cleavage activity abrogates the NES function in caspase-3, thus facilitating the nuclear entry of active caspase-3.
基金Sponsored by the National Natural Science Foundation of China (Grant No.90815014 and 90715021)
文摘For material nonlinear problem,elements derived with the flexibility-based method are more accurate than classical elements derived with the stiffness-based method. A review of the current state of the art of the flexibility-based finite element method is provided to enhance the robustness of structure analysis. The research on beam-column elements is the mainstream in the research on flexibility-based finite element method at present. The original development of flexibility-based finite element method is reviewed, and the further development of this method is then presented in several specific aspects, such as geometrically nonlinear analysis and dynamic analysis. The further research needed to be carried out in the future is finally discussed.
基金The General Foundation of Tianjin Science Committee for Applied Basic Research (08JCZDJC21000)Chinese Ministry of Education (30770081)
文摘In order to quantitate the bovine immunodeficiency virus line (BIVL) was established by transfecting baby hamster kidney (BIV) cells infection in vitro, a BIV indicator cell with reporter plasmids containing the firefly luciferase gene driven by a BIV long terminal repeat promoter. The BIV activates promoter activity of the LTR to express luciferase upon infection. BIV infection could therefore by quantified by detection of luciferase activity. Compared to standard assays used to detect BIV infection, the BIVL-based assay is 10 times more sensitive than the the CPE-based assay, and has similar sensitivity with the viral capsid protein Western blot assay BIV indicator cell line could detect BIV infection specifically. Luciferase activity of BIV infected BIVL cells showed a time dependent manner, and 60 h post infection is the optimal time to detect BIV infection. Luciferase activity of BIVL cells correlates with the BIV capsid protein expression. Moreover, a linear relationship was found between MOI and the activated intensity of luciferase expression. In brief, the BIV indicator cell line is an easy, robust and quantitive method for monitoring BIV infection.
基金Supported by a grant from the National Nature Sciences Foundation of China (No. 20671064)
文摘Objective:The aim of our study was to evaluate the in vitro antitumor activity of two novel platinum-based(II) complexes(2.3-pyridinedicarboxylic acid dehydrate platinum and 2.3-pyrazinedicarboxylic acid dehydrate platinum),which were concurrently provided with hydrophilic carboxyl group and lipophilic pyrazinyl or pyridyl group,on SW620 colorectal cancer cell line and the impact of the two compounds on the cell cycle and apoptosis of the cells when compared with the oxaliplatin,desiring the new ligand combined with hydrophilic and lipophilic properties would facilitate the transportation and transmembrane of the drugs,showing a better antitumor activity.Methods:After SW620 cells were treated with different doses of the three platinum-based agents for 24,48 and 72 h,the cell proliferation inhibition rate was determined using methyl thiazolyl tetrazolium(MTT) assay;the morphology of cells were evaluated under inverted microscope;the changes in cell cycle were determined using flow cytometry;the percent apoptosis was measured using Annexin V/PI double staining and the micromorphology of the cells after drug exposure was evaluated using scanning electron microscopy.Results:The evaluation on the proliferation inhibition rate revealed that the three platinum-based agents inhibited the SW620 cells in a time-and dose-dependent manner and showed different strengths as pyridine > pyrazine > Oxa.Under optical microscope,the morphological changes such as cell shrinkage,round cells and dead cells were frequently observed after drug exposure.Cell cycle determination showed that all of the three agents could function to block the cells converting from phase S to phase G2M.Apoptosis evaluation revealed that the three agents promoted the apoptosis of SW620 cells in a time-and dose-dependent manner and showed different strengths as pyridine > pyrazine > Oxa.Typical early and late apoptotic morphological changes could be detected during electron microscopy.Conclusion:The two novel platinum-based(II) complexes showed a stronger antitumor effect on SW620 cells than oxaliplatin,with the targeted site at a certain phase of cell cycle and apoptosis.
文摘In recent years the evolution of highly developed and complicated computerization has boosted the importance to business of IT infrastructure. Enhancement of business agility is not possible unless greater flexibility is built into IT infrastructure. More often than not, MIS's today are not flexible enough in this sense to agilely accommodate demands for system change incessantly confronting them. We have been focusing our research on MIS flexibility, its evaluation and the development of methodology for its enhancement. This paper aims to present a comparative evaluation via future oriented POC (penalty of change) analysis of system alternatives involving a case of new technology implementation. To start with, we will define the concept of MIS flexibility. We will then describe an actual case of technology implementation and define the problem it involved and go on to illustrate the evaluation procedure of MIS flexibility via future oriented POC analysis.
文摘Large-scale national disasters have recently occurred worldwide, causing tremendous damage to life and property. Therefore, urban safety has become a critical issue, and disaster prevention and mitigation are also considered in urban development and infrastructure construction. When earthquake disasters occur, road networks play major roles in rescue activity for responding to urban damage. The urban-disaster prevention spatial system attempts to mitigate hazards by considering shelters, routes for evacuation and rescue and necessary logistics. A literature review shows numerous studies related to a disaster-prevention shelter survey before or after hazards, however, they are less concerned with the reliability of shelter evaluation. This study assesses shelter evaluation by considering road networks. The authors construct 10 selected indices individually related to road networks. Three integrated composite indices are established to explain planned-shelter risks using the Arc GIS diagram of a spatial concept of an urban-planning review process. The relationship between shelters and evacuation/rescue routes is important for disaster-prevention planning. This survey investigates the factors of road networks, fire engine rescue routes, fire station location and road/population density for vulnerability evaluations.
文摘Higher education and science determine the intellectual potential of a society, train new specialists, and consolidate and change citizenship values. Consumer citizenship education for sustainable development is an important function of higher education with a significant moral, social, political, economic, ecological and legal capacity. Consumer citizenship education plays an important role in ensuring the stability and sustainable development of any society. These approaches make it possible to develop the multi-scale thinking of future specialists and enhance their ability to analyse critically the main dilemmas created by the processes of social, legal, environmental, and economic development. The article is devoted to the experience of the Latvian system of higher education in consumer citizenship education within the context of sustainable development. It focuses more specifically on cooperation as a form of voluntary interaction between the partners involved in ensuring sustainable development. The aim of the research is to analyse the experience of consumer citizenship education in Latvian higher education within the context of sustainable development emphasizing the role of various forms of studies. Mostly theoretical research methods have been used in the present study. The starting point of for this research is a theoretical framework. There are both legal underpinnings and practical implementation aspects in this task. The features outlined above are emphasized in the normative acts referring to the Latvian higher education, the documents of the institutions of higher education, and particularly in the study programmes. The results of the research show that consumer citizenship education can be acquired as an interdisciplinary system. The goals and objectives of consumer citizenship education involve training young specialists possessing broad professional knowledge, developed critical thinking, the ability to organize and manage work in a modem way, understanding of the ethical, civic and patriotic values, as well as the ability and skills to engage in various social activities. Consumer citizenship education needs transdisciplinary knowledge if it is to solve the problems of humanity, the problems aggravated by unsustainable, unethical, even immoral consumption. The link between consumer citizenship education and sustainable development is ensured by shared common values, which reveal the sense and importance of both consumer citizenship and ethical sustainability.
文摘This paper examines an empirical evidence of a frame continuation performed by KAMMI alumni, a contemporary Indonesian Islamic social movement organization. The concepts of "frame continuation" and "value-based identity" can be used as theoretical foundation to explore and explain the phenomena of dakwah movement performed by the alumni of KAMMI. Field research on KAMMI alumni role provides the primary empirical foundation for investigating frame continuation, a sustainability of the dakwah movement beyond students' movement organization. Discussion about KAMMI alumni's role provides empirical evidences about how they have strong commitment on either political or religious activities (or both) as their strategies to maintain and continue their previous identity as both political and religious activists. The main foundation for their activism is a value of dakwah (proselytizing), in which Islamic values are believed to be a suitable vehicle for constructing a sacred society in democratic era of Indonesia. The KAMMI alumni believe their movement is a significant religious duty.
基金supported by the National Science and Technology Program of China Earthquake Administration (No. 2006BAC01B02-01-05)Anhui Provincial Science and Technique Foundation (No. 08010302204)Joint Earthquake Science Fundation (A08077)
文摘Seismic gap method is one of the effective earthquake prediction methods using seismicity patterns. However, this method has some limitations and uncertainty when using it singly in predicting earthquakes. This paper puts forward the prediction method using the dynamic seismicity pattern with dynamic implications. This method considers the formation and evolution of the seismic gap on the basis of plate movement and structural characteristics. Through analysis of 26 cases of earthquakes of MS≥5.0 occurring in East China and South China, this paper obtains the relationship between the main shock with seismic gap and active fault's location, as well as the relationship between the seismic gap and location and strike of active faults. Meanwhile, this paper provides a dynamic explanation of the differences in the formation and evolution patterns of the seismic gap between the two regions, thus providing the physical basis for and reducing the uncertainty of predicting earthquakes using the seismic gap method.