116 research outputs found
Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy
Governance Conditions for Improving Quality Drinking Water Resources: the Need for Enhancing Connectivity
Realising the water quality objectives of the European Water Framework Directive have appeared to stagnate over the last decade all across Europe because of their highly complex nature. In the literature, interactive governance approaches tend to be regarded as the best way of dealing with complex water issues, but so far little empirical evidence has been reported on this perspective in regard to water quality issues. In this paper we have analysed how conditions of governance contribute to the realisation of water quality objectives at different types of drinking water resources in the Netherlands. The analysis demonstrates the importance of addressing different hydrological scales, institutional levels and sectors and thus enhance connectivity in order to improve water quality. The two other important conditions of governance approaches for water quality improvement which were identified are the use of joint fact-finding to gain a shared perception of risks, and the use of explicit decision-making and close monitoring of outcomes (re. water quality improvement), both of which contribute to this enhanced connectivity
Effects of Dual Targeting of Tumor Cells and Stroma in Human Glioblastoma Xenografts with a Tyrosine Kinase Inhibitor against c-MET and VEGFR2
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118357.pdf (publisher's version ) (Open Access)Anti-angiogenic treatment of glioblastoma with Vascular Endothelial Growth Factor (VEGF)- or VEGF Receptor 2 (VEGFR2) inhibitors normalizes tumor vessels, resulting in a profound radiologic response and improved quality of life. This approach however does not halt tumor progression by diffuse infiltration, as this phenotype is less angiogenesis dependent. Combined inhibition of angiogenesis and diffuse infiltrative growth would therefore be a more effective treatment approach in these tumors. The HGF/c-MET axis is important in both angiogenesis and cell migration in several tumor types including glioma. We therefore analyzed the effects of the c-MET- and VEGFR2 tyrosine kinase inhibitor cabozantinib (XL184, Exelixis) on c-MET positive orthotopic E98 glioblastoma xenografts, which routinely present with angiogenesis-dependent areas of tumor growth, as well as diffuse infiltrative growth. In cultures of E98 cells, cabozantinib effectively inhibited c-MET phosphorylation, concomitant with inhibitory effects on AKT and ERK1/2 phosphorylation, and cell proliferation and migration. VEGFR2 activation in endothelial cells was also effectively inhibited . Treatment of BALB/c nu/nu mice carrying orthotopic E98 xenografts resulted in a significant increase in overall survival. Cabozantinib effectively inhibited angiogenesis, resulting in increased hypoxia in angiogenesis-dependent tumor areas, and induced vessel normalization. Yet, tumors ultimately escaped cabozantinib therapy by diffuse infiltrative outgrowth via vessel co-option. Of importance, in contrast to the results from experiments, blockade of c-MET activation was incomplete, possibly due to multiple factors including restoration of the blood-brain barrier resulting from cabozantinib-induced VEGFR2 inhibition. In conclusion, cabozantinib is a promising therapy for c-MET positive glioma, but improving delivery of the drug to the tumor and/or the surrounding tissue may be needed for full activity
El narcoperiodismo de GarcĂa Márquez: uma análise dos aspectos da narcoliteratura no livro-reportagem NotĂcia de um sequestro
Desde os anos 1970, a cobertura da mĂdia tradicional sobre o narcotráfico caracterizou-se pela superficialidade de suas narrativas cujo processo impossibilita a profundidade de análise. PorĂ©m, alguns repĂłrteres foram bem-sucedidos ao aproximar o narcotráfico e o jornalismo literário, rompendo com essa barreira limitante, principalmente, a partir da produção de livros-reportagem. O tema influenciou a literatura do continente (originando termos como narcoliteratura, narconarrativa e narcocultura), bem como o contexto do tráfico de drogas proporcionou a produção editorial de obras de nĂŁo ficção, a partir dos final dos anos 80, atingindo o ápice nos anos 90 e 2000. Desta forma, este artigo discute o papel do livro-reportagem para a produção cultural da narcoliteratura, a partir de uma análise de seus aspectos dentro da obra jornalĂstica NotĂcia de um sequestro (1996), de Gabriel GarcĂa Márquez. O artigo está apoiado nos conceitos de livro-reportagem, de Edvaldo Pereira Lima e nas discussões sobre narcocultura, de Omar RincĂłn e de Diana Palaversich
Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
The Banff 2022 Kidney Meeting Work Plan:Data-driven refinement of the Banff Classification for renal allografts
The XVIth Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from September 19 to 23, 2022, as a joint meeting with the Canadian Society of Transplantation. In addition to a key focus on the impact of microvascular inflammation and biopsy-based transcript analysis on the Banff Classification, further sessions were devoted to other aspects of kidney transplant pathology, in particular T cell–mediated rejection, activity and chronicity indices, digital pathology, xenotransplantation, clinical trials, and surrogate endpoints. Although the output of these sessions has not led to any changes in the classification, the key role of Banff Working Groups in phrasing unanswered questions, and coordinating and disseminating results of investigations addressing these unanswered questions was emphasized. This paper summarizes the key Banff Meeting 2022 sessions not covered in the Banff Kidney Meeting 2022 Report paper and also provides an update on other Banff Working Group activities relevant to kidney allografts.</p
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