185 research outputs found

    Generation of a genetically modified chimeric plasmodium falciparum parasite expressing plasmodium vivax circumsporozoite protein for malaria vaccine development

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    Copyright © 2020 Miyazaki, Marin-Mogollon, Imai, Mendes, van der Laak, Sturm, Geurten, Miyazaki, Chevalley-Maurel, Ramesar, Kolli, Kroeze, van Schuijlenburg, Salman, Wilder, Reyes-Sandoval, Dechering, Prudencio, Janse, Khan and ̂ Franke-Fayard. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Chimeric rodent malaria parasites with the endogenous circumsporozoite protein (csp) gene replaced with csp from the human parasites Plasmodium falciparum (Pf) and P. vivax (Pv) are used in preclinical evaluation of CSP vaccines. Chimeric rodent parasites expressing PfCSP have also been assessed as whole sporozoite (WSP) vaccines. Comparable chimeric P. falciparum parasites expressing CSP of P. vivax could be used both for clinical evaluation of vaccines targeting PvCSP in controlled human P. falciparum infections and in WSP vaccines targeting P. vivax and P. falciparum. We generated chimeric P. falciparum parasites expressing both PfCSP and PvCSP. These Pf-PvCSP parasites produced sporozoite comparable to wild type P. falciparum parasites and expressed PfCSP and PvCSP on the sporozoite surface. Pf-PvCSP sporozoites infected human hepatocytes and induced antibodies to the repeats of both PfCSP and PvCSP after immunization of mice. These results support the use of Pf-PvCSP sporozoites in studies optimizing vaccines targeting PvCSP.CM-M was, in part, supported by Colciencias Ph.D. fellowship (Call 568 from 2012 Resolution 01218 Bogotá, Colombia). TI was, in part, supported by Uehara Memorial Foundation grant. Work performed at IMM was supported by Fundação para a Ciência e Tecnologia (FCT-Portugal)’s grants PTDC/BBB-BMD/2695/2014 and PTDC-SAU-INF-29550-2017. AR-S is supported by the MRC-DPFS grant MR/N019008/1.info:eu-repo/semantics/publishedVersio

    Governance Conditions for Improving Quality Drinking Water Resources: the Need for Enhancing Connectivity

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    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

    Robust Automated Tumour Segmentation on Histological and Immunohistochemical Tissue Images

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    Tissue microarray (TMA) is a high throughput analysis tool to identify new diagnostic and prognostic markers in human cancers. However, standard automated method in tumour detection on both routine histochemical and immunohistochemistry (IHC) images is under developed. This paper presents a robust automated tumour cell segmentation model which can be applied to both routine histochemical tissue slides and IHC slides and deal with finer pixel-based segmentation in comparison with blob or area based segmentation by existing approaches. The presented technique greatly improves the process of TMA construction and plays an important role in automated IHC quantification in biomarker analysis where excluding stroma areas is critical. With the finest pixel-based evaluation (instead of area-based or object-based), the experimental results show that the proposed method is able to achieve 80% accuracy and 78% accuracy in two different types of pathological virtual slides, i.e., routine histochemical H&E and IHC images, respectively. The presented technique greatly reduces labor-intensive workloads for pathologists and highly speeds up the process of TMA construction and provides a possibility for fully automated IHC quantification

    El narcoperiodismo de García Márquez: uma análise dos aspectos da narcoliteratura no livro-reportagem Notícia de um sequestro

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    Desde os anos 1970, a cobertura da mídia tradicional sobre o narcotráfico caracterizou-se pela superficialidade de suas narrativas cujo processo impossibilita a profundidade de análise. Porém, alguns repórteres 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 não 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 jornalística Notícia de um sequestro (1996), de Gabriel García Márquez. O artigo está apoiado nos conceitos de livro-reportagem, de Edvaldo Pereira Lima e nas discussões sobre narcocultura, de Omar Rincón e de Diana Palaversich
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