AIM： To culture human pancreatic tissue obtained from small resection specimens as a pre-clinical model for examining virus-host interactions. METHODS： Human pancreatic tissue samples （malignant and normal） were o...AIM： To culture human pancreatic tissue obtained from small resection specimens as a pre-clinical model for examining virus-host interactions. METHODS： Human pancreatic tissue samples （malignant and normal） were obtained from surgical specimens and processed immediately to tissue slices. Tissue slices were cultured ex vivo for 1-6 d in an incubator using 95% 02. Slices were subsequently analyzed for viability and morphology. In addition the slices were incubated with different viral vectors expressing the reporter genes GFP or DsRed. Expression of these reporter genes was measured at 72 h after infection.RESULTS： With the Krumdieck tissue slicer, uniform slices could be generated from pancreatic tissue but only upon embedding the tissue in 3% low melting agarose. Immunohistological examination showed the presence of all pancreatic cell types. Pancreatic normal and cancer tissue slices could be cultured for up to 6 d, while retaining viability and a moderate to good morphology. Reporter gene expression indicated that the slices could be infected and transduced efficiently by adenoviral vectors and by adeno associated viral vectors, whereas transduction with lentiviral vectors was limited. For the adenoviral vector, the transduction seemed limited to the peripheral layers of the explants. CONCLUSION： The presented system allows reproducible processing of minimal amounts of pancreatic tissue into slices uniform in size, suitable for pre-clinical evaluation of gene therapy vectors.展开更多
The digital development rights in developing countries are based on establishing a new international economic order and ensuring equal participation in the digital globalization process to achieve people's well-ro...The digital development rights in developing countries are based on establishing a new international economic order and ensuring equal participation in the digital globalization process to achieve people's well-rounded development in the digital society.The relationship between cross-border data flows and the realization of digital development rights in developing countries is quite complex.Currently,developing countries seek to safeguard their existing digital interests through unilateral regulation to protect data sovereignty and multilateral regulation for cross-border data cooperation.However,developing countries still have to face internal conflicts between national digital development rights and individual and corporate digital development rights during the process of realizing digital development rights.They also encounter external contradictions such as developed countries interfering with developing countries'data sovereignty,developed countries squeezing the policy space of developing countries through dominant rules,and developing countries having conflicts between domestic and international rules.This article argues that balancing openness and security on digital trade platforms is the optimal solution for developing countries to realize their digital development rights.The establishment of WTO digital trade rules should inherently reflect the fundamental demands of developing countries in cross-border data flows.At the same time,given China's dual role as a digital powerhouse and a developing country,it should actively promote the realization of digital development rights in developing countries.展开更多
We present qualitative data from a study in Ghana （2011）, where the National Health Insurance Scheme （NHIS） was introduced to improve access to health care. In 2011 membership enrolment and retention in the scheme...We present qualitative data from a study in Ghana （2011）, where the National Health Insurance Scheme （NHIS） was introduced to improve access to health care. In 2011 membership enrolment and retention in the scheme was stalling. To obtain better insights into socio-cultural factors that influence utilization of healthcare services and the NHIS this study compared Explanatory Models of healthcare clients with those of primary healthcare providers and the NHIS regarding illness, the need for, the quality of, and the control over heaithcare and health insurance services. We found critical disparities in socio-cultural beliefs and perceptions of healthcare and health insurance between these three stakeholder groups, such as the clients＇ holistic view on illness versus healthcare providers＇ bio-medical view; the clients＇ inter-relational focus in perceiving quality of services versus the providers＇ medical technical focus. These differences are leading to misconceptions, blame practice, poor services, non-adherence and low trust. The findings increase our understanding of clients＇ behavior and that of their service providers. We conclude with key messages for policy leaders and operational managers that can guide them in improving services and facilitating client trust and interest to participate in health insurance and utilize healthcare services.展开更多
AIM:To generate an adenoviral vector specifically targeting the EphA2 receptor(EphA2R) highly expressed on pancreatic cancer cells in vivo.METHODS:YSA,a small peptide ligand that binds the EphA2R with high affinity,wa...AIM:To generate an adenoviral vector specifically targeting the EphA2 receptor(EphA2R) highly expressed on pancreatic cancer cells in vivo.METHODS:YSA,a small peptide ligand that binds the EphA2R with high affinity,was inserted into the HI loop of the adenovirus serotype 5 fiber knob.To further increase the specificity of this vector,binding sites for native adenoviral receptors,the coxsackie and adenovirus receptor(CAR) and integrin,were ablated from the viral capsid.The ablated retargeted adenoviral vector was produced on 293T cells.Specifi c targeting of this novel adenoviral vector to pancreatic cancer was investigated on established human pancreatic cancer cell lines.Upon demonstrating specifi c in vitro targeting,in vivo targeting to subcutaneous growing human pancreatic cancer was tested by intravenous and intraperitoneal administration of the ablated adenoviral vector.RESULTS:Ablation of native cellular binding sites reduced adenoviral transduction at least 100-fold.Insertion of the YSA peptide in the HI loop restored adenoviral transduction of EphA2R-expressing cells but not of cells lacking this receptor.YSA-mediated transduction was inhibited by addition of synthetic YSA peptide.The transduction specificity of the ablated retargeted vector towards human pancreatic cancer cells was enhanced almost 10-fold in vitro.In a subsequent in vivo study in a nude(nu/nu) mouse model however,no increased adenoviral targeting to subcutaneously growing human pancreas cancer nodules was seen upon injection into the tail vein,nor upon injection into the peritoneum.CONCLUSION:Targeting the EphA2 receptor increases specificity of adenoviral transduction of human pancreatic cancer cells in vitro but fails to enhance pancreatic cancer transduction in vivo.展开更多
This article will briefly discuss the implications of recognition of ecological justice in relation to environmental education(EE) and education for sustainable development(ESD).It is argued that the present conceptio...This article will briefly discuss the implications of recognition of ecological justice in relation to environmental education(EE) and education for sustainable development(ESD).It is argued that the present conception of environment taught through EE and ESD negates the subjectivity of non-human species and ignores the ethical imperatives of ecological justice.Evocating environmental ethics,major directions integrating ecological justice into EE and ESD are proposed.展开更多
基金Supported by The Dutch Cancer Society(grant.UvA2002-2604)
文摘AIM： To culture human pancreatic tissue obtained from small resection specimens as a pre-clinical model for examining virus-host interactions. METHODS： Human pancreatic tissue samples （malignant and normal） were obtained from surgical specimens and processed immediately to tissue slices. Tissue slices were cultured ex vivo for 1-6 d in an incubator using 95% 02. Slices were subsequently analyzed for viability and morphology. In addition the slices were incubated with different viral vectors expressing the reporter genes GFP or DsRed. Expression of these reporter genes was measured at 72 h after infection.RESULTS： With the Krumdieck tissue slicer, uniform slices could be generated from pancreatic tissue but only upon embedding the tissue in 3% low melting agarose. Immunohistological examination showed the presence of all pancreatic cell types. Pancreatic normal and cancer tissue slices could be cultured for up to 6 d, while retaining viability and a moderate to good morphology. Reporter gene expression indicated that the slices could be infected and transduced efficiently by adenoviral vectors and by adeno associated viral vectors, whereas transduction with lentiviral vectors was limited. For the adenoviral vector, the transduction seemed limited to the peripheral layers of the explants. CONCLUSION： The presented system allows reproducible processing of minimal amounts of pancreatic tissue into slices uniform in size, suitable for pre-clinical evaluation of gene therapy vectors.
基金a preliminary result of the Chinese Government Scholarship High-level Graduate Program sponsored by China Scholarship Council(Program No.CSC202206310052)。
文摘The digital development rights in developing countries are based on establishing a new international economic order and ensuring equal participation in the digital globalization process to achieve people's well-rounded development in the digital society.The relationship between cross-border data flows and the realization of digital development rights in developing countries is quite complex.Currently,developing countries seek to safeguard their existing digital interests through unilateral regulation to protect data sovereignty and multilateral regulation for cross-border data cooperation.However,developing countries still have to face internal conflicts between national digital development rights and individual and corporate digital development rights during the process of realizing digital development rights.They also encounter external contradictions such as developed countries interfering with developing countries'data sovereignty,developed countries squeezing the policy space of developing countries through dominant rules,and developing countries having conflicts between domestic and international rules.This article argues that balancing openness and security on digital trade platforms is the optimal solution for developing countries to realize their digital development rights.The establishment of WTO digital trade rules should inherently reflect the fundamental demands of developing countries in cross-border data flows.At the same time,given China's dual role as a digital powerhouse and a developing country,it should actively promote the realization of digital development rights in developing countries.
文摘We present qualitative data from a study in Ghana （2011）, where the National Health Insurance Scheme （NHIS） was introduced to improve access to health care. In 2011 membership enrolment and retention in the scheme was stalling. To obtain better insights into socio-cultural factors that influence utilization of healthcare services and the NHIS this study compared Explanatory Models of healthcare clients with those of primary healthcare providers and the NHIS regarding illness, the need for, the quality of, and the control over heaithcare and health insurance services. We found critical disparities in socio-cultural beliefs and perceptions of healthcare and health insurance between these three stakeholder groups, such as the clients＇ holistic view on illness versus healthcare providers＇ bio-medical view; the clients＇ inter-relational focus in perceiving quality of services versus the providers＇ medical technical focus. These differences are leading to misconceptions, blame practice, poor services, non-adherence and low trust. The findings increase our understanding of clients＇ behavior and that of their service providers. We conclude with key messages for policy leaders and operational managers that can guide them in improving services and facilitating client trust and interest to participate in health insurance and utilize healthcare services.
基金Supported by Maurits en Anna de Kock fund to MA van Geer
文摘AIM:To generate an adenoviral vector specifically targeting the EphA2 receptor(EphA2R) highly expressed on pancreatic cancer cells in vivo.METHODS:YSA,a small peptide ligand that binds the EphA2R with high affinity,was inserted into the HI loop of the adenovirus serotype 5 fiber knob.To further increase the specificity of this vector,binding sites for native adenoviral receptors,the coxsackie and adenovirus receptor(CAR) and integrin,were ablated from the viral capsid.The ablated retargeted adenoviral vector was produced on 293T cells.Specifi c targeting of this novel adenoviral vector to pancreatic cancer was investigated on established human pancreatic cancer cell lines.Upon demonstrating specifi c in vitro targeting,in vivo targeting to subcutaneous growing human pancreatic cancer was tested by intravenous and intraperitoneal administration of the ablated adenoviral vector.RESULTS:Ablation of native cellular binding sites reduced adenoviral transduction at least 100-fold.Insertion of the YSA peptide in the HI loop restored adenoviral transduction of EphA2R-expressing cells but not of cells lacking this receptor.YSA-mediated transduction was inhibited by addition of synthetic YSA peptide.The transduction specificity of the ablated retargeted vector towards human pancreatic cancer cells was enhanced almost 10-fold in vitro.In a subsequent in vivo study in a nude(nu/nu) mouse model however,no increased adenoviral targeting to subcutaneously growing human pancreas cancer nodules was seen upon injection into the tail vein,nor upon injection into the peritoneum.CONCLUSION:Targeting the EphA2 receptor increases specificity of adenoviral transduction of human pancreatic cancer cells in vitro but fails to enhance pancreatic cancer transduction in vivo.
文摘This article will briefly discuss the implications of recognition of ecological justice in relation to environmental education(EE) and education for sustainable development(ESD).It is argued that the present conception of environment taught through EE and ESD negates the subjectivity of non-human species and ignores the ethical imperatives of ecological justice.Evocating environmental ethics,major directions integrating ecological justice into EE and ESD are proposed.
