Understanding European cross-border cooperation: a framework for analysis

European integration has had a dual impact on border regions. On the one hand, borders were physically dismantled across most of the EU’s internal territory. On the other hand, they have become a fertile ground for territorial co-operation and institutional innovation. The degree of cross-border co-operation and organization achieved varies considerably from one region to another depending on a combination of various facilitating factors for effective cross-border co-operation, more specifically, economic, political leadership, cultural/identity and state formation, and geographical factors. This article offers a conceptual framework to understand the growth and diversity of cross-border regionalism within the EU context by focusing on the levels of and drives for co-operation

Digital pathology workflow implementation at ipatimup

The advantages of the digital methodology are well known. In this paper, we provide a detailed description of the process for the digital transformation of the pathology laboratory at IPATIMUP, the major modifications that operate throughout the processing pipeline, and the advantages of its implementation. The model of digital workflow implementation at IPATIMUP demonstrates that careful planning and adoption of simple measures related to time, space, and sample management can be adopted by any pathology laboratory to achieve higher quality and easy digital transformation

Toward a common aggregation mechanism for a β-barrel protein family: insights derived from a stable dimeric species

Δ78Δ is a second generation functional all-β sheet variant of IFABP (intestinal fatty acid binding protein) corresponding to the fragment 29-106 of the parent protein. This protein and its predecessor, Δ98Δ (segment 29-126 of IFABP), were initially uncovered by controlled proteolysis. Remarkably, although IFABP and Δ98Δ are monomers in solution, Δ78Δ adopts a stable dimeric structure. With the aim of identifying key structural features that modulate the aggregation of β-proteins, we evaluate here the structure and aggregation propensity of Δ78Δ. The 2,2,2-trifluoroethanol (TFE) induced aggregation of this protein shows a primary nucleation-elongation mechanism, characterized by the stabilization of a dimeric nucleus. Its rate of production from the co-solvent induced aggregation prone state governs the kinetics of polymerization. In this context, the value of Δ78Δ lies in the fact that - being a stable dimeric species - it reduces an otherwise bimolecular reaction to a unimolecular one. Interestingly, even though Δ78Δ and IFABP display similar conformational stability, the abrogated form of IFABP shows an enhanced aggregation rate, revealing the ancillary role played on this process by the free energy of the native proteins. Δ78Δ share with IFABP and Δ98Δ a common putative aggregation-prone central peptide. Differences in the exposure/accessibility of this segment dictated by the environment around this region might underlie the observed variations in the speed of aggregation. Lessons learnt from this natural dimeric protein might shed light on the early conformational events leading to β-conversion from barrels to amyloid aggregates.Fil: Angelani, Carla Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Curto, Lucrecia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Cabanas, Inés S. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; ArgentinaFil: Caramelo, Julio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Uversky, Vladimir N. Russian Academy of Sciences. Institute for Biological Instrumentation; Rusia. University of South Florida. Department of Molecular Medicine; Estados UnidosFil: Delfino, Jose Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Fisicoquímica Biológicas; Argentin

Anticoagulant Activity of a Unique Sulfated Pyranosic (133) - ß - L - Arabinan through Direct Interaction with Thrombin

Fernández, Paula Virginia. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Química de Biomoléculas. Buenos Aires, Argentina.Quintana, Irene. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Hemostasia y Trombosis. Buenos Aires, Argentina.Cerezo, Alberto S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica. Subsede del Centro de Investigación de Hidratos de Carbono (CIHIDECAR). Ciudad Universitaria, Buenos Aires, Argentina.Caramelo, Julio J. CONICET - Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA). Buenos Aires, Argentina.Pol Fachin, Laercio. Universidade Federal do Rio Grande do Sul. Faculdade de Farmácia. Programa de Pos-Graduação em Biologia Celular e Molecular. Centro de Biotecnologia. Rio Grande do Sul, Brasil.Verli, Hugo. Universidade Federal do Rio Grande do Sul.Centro de Biotecnologia. Programa de Pos-Graduação em Biologia Celular e Molecular. Rio Grande do Sul, Brasil.Estevez, José Manuel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE). Buenos Aires, Argentina.Ciancia, Marina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Biología Aplicada y Alimentos. Cátedra de Química de Biomoléculas. Buenos Aires, Argentina.223–233Background: Many seaweed polysaccharides have anticoagulant activity, but the mechanism of action was elucidated in a few cases. Results: A highly sulfated pyranosic ß-arabinan exerts its activity through direct and indirect inhibition of thrombin. Conclusion: The structure and mechanism of action of the arabinan are different from those found for other polysaccharides. Significance: This arabinan could be an alternative anticoagulant in certain specific cases

A potential signature for muscle-invasive tumors

Funding: This work was supported by the Astellas European Foundation Uro-Oncology Grant 2014; JABA RECORDATI Urology 2011 - Portuguese Society of Urology; Portuguese Foundation for Science and Technology (Strategic Project: PEst-C/SAU/UI3282/2013 and UID/NEU/04539/2013); GAI/FMUC and Santander Totta (Ref. FreitasGomes04.01.13) and Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Portugal (Ref. 14/12). Margarida FerreiraTeixeira benefits from a PhD scholarship from the Portuguese Foundation for Science and Technology (Reference SFRH/BD/77314/2011).Striking evidence associates cancer stem cells (CSCs) to the high recurrence rates and poor survival of patients with muscle-invasive bladder cancer (BC). However, the prognostic implication of those cells in risk stratification is not firmly established, mainly due to the functional and phenotypic heterogeneity of CSCs populations, as well as, to the conflicting data regarding their identification based on a single specific marker. This emphasizes the need to exploit putative CSC-related molecular markers with potential prognostic significance in BC patients. This study aimed to isolate and characterize bladder CSCs making use of different functional and molecular approaches. The data obtained provide strong evidence that muscle-invasive BC is enriched with a heterogeneous stem-like population characterized by enhanced chemoresistance and tumor initiating properties, able to recapitulate the heterogeneity of the original tumor. Additionally, a logistic regression analysis identified a 2-gene stem-like signature (SOX2 and ALDH2) that allows a 93% accurate discrimination between non-muscle-invasive and invasive tumors. Our findings suggest that a stemness-related gene signature, combined with a cluster of markers to more narrowly refine the CSC phenotype, could better identify BC patients that would benefit from a more aggressive therapeutic intervention targeting CSCs population.publishersversionpublishe

Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon's Syndrome of Unknown Cause

BACKGROUND: The association that exists between livedo reticularis (LR) and stroke is known as Sneddon's syndrome (SnS). The disorder is classified as primary SnS (PSnS), if the cause remains unknown and secondary SnS. The condition is rare and it occurs mainly sporadically. In 2014, 2 independent teams described a new genetic disorder with childhood-onset, which was called deficiency of adenosine deaminase 2 (DADA2), characterized by recurrent fevers and vascular pathologic features that included LR and stroke. All the patients carried recessively inherited mutations in cat eye syndrome chromosome region candidate 1 gene (CECR1), encoding the adenosine deaminase 2 (ADA2) protein. Genetic testing is the standard for the diagnosis of DADA2. However, the diagnostic accuracy of more affordable laboratorial analysis in CECR1-mutated individuals remains to be established. We aim to determine whether plasma ADA2 activity and serum immunoglobulin M (IgM) levels can distinguish (1) DADA2 from other adult patients within the SnS spectrum, and (2) healthy CECR1 heterozygous (HHZ) from healthy controls (HC). METHODS: ADA2 activity in plasma and serum IgM concentrations was measured in adult patients within the SnS spectrum, healthy first-degree relatives and HC. Genetic results were used as the reference standard. The primary outcome measures were sensitivity and specificity derived from receiver operating curve analysis. RESULTS: A total of 73 participants were included in the study: 26 patients with PSnS with no CECR1 mutation (PSnS), 6 bi-allelic (DADA2 patients) and 7 HHZ CECR1 mutations and 34 HC. Plasma ADA2 activity and serum IgM levels were significantly lower in DADA2 patients than in PSnS. With the use of the best indexes, plasma ADA2 activity differentiated PSnS from DADA2 with a sensitivity and specificity of 100.0% and HHZ from HC with a sensitivity of 97.1% and specificity of 85.7%. Serum IgM levels also differentiated PSnS from DADA2 with a sensitivity of 85.2% and specificity of 83.3%. CONCLUSION: Serum IgM levels might be used as a triage tool and plasma ADA2 activity performs perfectly as a diagnostic test for DADA2 in adult patients within the SnS spectrum. ADA2 activity in plasma also reliably distinguishes HHZ from HC.info:eu-repo/semantics/publishedVersio

Is the chlorophyll derivative Zn(II)e6Me a good photosensitizer to be used in root canal disinfection?

The aim of this study was to assess antimicrobial efficacy and cytotoxic outcomes of a chlorophyll based photosensitizer (PS) Zn(II)chlorin e6 methyl ester (Zn(II)e6Me), when applied to human dentin discs and root blocks infected with 48 h biofilms. The results were compared with the ones obtained with FotoSan® (commercial Toluidine Blue O formulation) and 3% sodium hypochlorite (NaOCl).publishe

Cold atmospheric plasma, a novel approach against bladder cancer, with higher sensitivity for the high-grade cell line

Antitumor therapies based on Cold Atmospheric Plasma (CAP) are an emerging medical field. In this work, we evaluated CAP effects on bladder cancer. Two bladder cancer cell lines were used, HT-1376 (stage III) and TCCSUP (stage IV). Cell proliferation assays were performed evaluating metabolic activity (MTT assay) and protein content (SRB assay). Cell viability, cell cycle, and mitochondrial membrane potential (Δψm) were assessed using flow cytometry. Reactive oxygen and nitrogen species (RONS) and reduced glutathione (GSH) were evaluated by fluorescence. The assays were carried out with different CAP exposure times. For both cell lines, we obtained a significant reduction in metabolic activity and protein content. There was a decrease in cell viability, as well as a cell cycle arrest in S phase. The Δψm was significantly reduced. There was an increase in superoxide and nitric oxide and a decrease in peroxide contents, while GSH content did not change. These results were dependent on the exposure time, with small differences for both cell lines, but overall, they were more pronounced in the TCCSUP cell line. CAP showed to have a promising antitumor effect on bladder cancer, with higher sensitivity for the high-grade cell line.info:eu-repo/semantics/publishedVersio

Self-evaluation as a strategy of resistance to the ranking external evaluation

This article discusses the current meaning of the evaluation policies inand of school, presenting a study carried out by Brazilian and Portuguese researchers, with the participation of twenty public schools in the cities of São Paulo and Campinas (Brazil) and Porto (Portugal). Theoretically anchored in the Participatory Institutional Evaluation and Negotiated Quality approaches, the research involves the schools’ professionals and also sectors of education administration, through the study groups in each of the universities. The article critically addresses theexpertise function of the research that frequently legitimizes evaluations centered on products and thus lends credibility to standardized tests and to the proliferation of the so-calledevaluocracy, with consequent changes in the school inspection and management procedures, and also in the management of education systems. These changes corrupt/deform the concept of school autonomy and favor the proliferation of concession schools, stimulate the use of education vouchers, as well as the increase and naturalization of school inequalities and a certain representation of the Knowledge Society, which promotes vocational training for the working classes, recreating a dual education system. In contrast, this study argues for the possibilities of a virtuous circle between education, research and extension as a method of relation with public schools, starting from the concept of Negotiated Quality that, together with professionals and community in every school, initiates self-evaluation processes, with the intention of transformation and developing new relationships within and outside the school, reinforcing the strategic learning of a collective competence of social actors in favor of public school social quality.Este artigo discute o sentido atual das políticas de avaliaçãona e da escola ao apresentar a investigação realizada por pesquisadores brasileiros e portugueses, com a participação de vinte escolas públicas, nas cidades de São Paulo e Campinas (Brasil) e do Porto (Portugal). Referenciando-se na Avaliação Institucional Participativa e na Qualidade Negociada, a pesquisa se junta aos profissionais das escolas e de setores da administração educacional, com a formação de grupos de estudo em cada uma das universidades. O artigo aborda criticamente a função expertise da pesquisa que frequentemente legitima avaliações centradas nos produtos, portando credibilidade aos testes padronizados, à proliferação de uma avaliocracia, com consequente alteração de procedimentos de inspeção e direção escolares, além de mudanças na gestão dos sistemas educativos, corrompendo/deformando o conceito de autonomia escolar, favorecendo a proliferação de escolas administradas por concessão, o estímulo ao cheque-ensino, bem como o aumento e naturalização das desigualdades escolares e uma dada representação da sociedade do conhecimento, que refuncionaliza a formação profissional para as classes populares, recriando a dualidade do ensino. Em contraponto, a pesquisa argumenta as possibilidades de um circuito virtuoso do ensino, da pesquisa e da extensão como método na relação com escolas públicas, partindo de uma concepção de Qualidade Negociada que, em conjunto com profissionais e comunidade, em cada escola, inicia processos deautoavaliação, com intencionalidade de transformação e com a possibilidade de desenvolvimento de novas relações dentro e fora da escola, reforçando a aprendizagem estratégica da competência coletiva dos atores sociais em prol da escola pública de qualidade social