A Council of Europe perspective on the European Union: Crucial and complex cooperation

The article addresses the institutional role of the EU in the Council of Europe, with particular emphasis on EU participation in Council of Europe treaties and EU accession to the ECHR. While recognising the joint effort to achieve greater unity in the region of Europe through respect for the shared core values of pluralist democracy, human rights and the rule of law, the concerns raised by non-Member States of the EU about the impact of EU law and policies on the Council of Europe’s standards are examined. It is argued that the Council of Europe and the EU have a shared responsibility for upholding the effectiveness of their respective frameworks and ensuring that any overlapping competences do not create conflict. This is particularly evident when it comes to the European system for the protection of fundamental rights, which is characterised by overlapping standards and procedures. The existing cooperation between the Council of Europe and the EU should be strengthened through a more rational, rules-based approach. In particular, it is suggested that the two systems should jointly agree on a series of basic principles on the treaty-making process, providing for horizontal application by the introduction of specific rules on, for example, voting and speaking rights of the EU, the sharing of reporting obligations between the EU and its Member States under Council of Europe monitoring mechanisms, and financial arrangements. The EU’s participation and financial contribution to monitoring follow-up should always be considered on a case-by-case basis, taking into account the specificities of each mechanism

Hygroscopic behavior of lyophilized bovine pericardium

Hygroscopic behavior of lyophilized products can be visualized starting from the construction of Moisture Sorption Isotherms (MSI). Such curves show the relationship between the maximum amount of absorbed water for a substance, with the equilibrium vapor pressure or water activity, at a given constant temperature. Aimed to study later the reconstitution and use of biological materials of lyophilized bovine pericardium, it was plot adsorption and desorption curves, at temperatures of 15, 25 and 35°C, on HydrosorbTM 1000 - water vapor sorption analyzer. The results showed MSI type II, according BET classification, typical reaction of hydrophilic surfaces with monolayer and multilayer formation. Histerese phenomenon was observed during the whole MSI interval. The mathematical models of BET and GAB fitted well the experimental data and allowed the water monolayer calculation, estimate the critical level of residual moisture that assures more stability to the product.O comportamento higroscópico de produtos desidratados pode ser visualizado a partir da construção de curvas denominadas Isotermas de Sorção de Umidade (ISU). Esse tipo de curva relaciona a quantidade máxima de água absorvida por uma substância, com a pressão de vapor de equilíbrio ou a atividade de água, numa dada temperatura mantida constante. Com o objetivo de estudar posteriormente a reconstituição, material de embalagem e utilização de implantes feitos a partir de pericárdio bovino liofilizado, foram traçadas curvas de adsorção e dessorção de umidade em um analisador de sorção de vapor de água, HydrosorbTM 1000, nas temperaturas de 15, 25 e 35°C. Os resultados obtidos mostraram ISU tendendo ao tipo II, segundo a classificação de BET, reação típica de superfícies hidrofílicas com formação de monocamada e multicamadas. O fenômeno da histerese foi observado durante todo o intervalo da ISU. Os modelos matemáticos de Brunauer-Emmett-Teller (BET) e Guggenheim-Anderson-de Boer (GAB) ajustaram bem os dados experimentais permitindo o cálculo do valor monomolecular, importante para a estimativa do nível crítico de umidade residual que confere maior estabilidade de armazenamento ao produto.31332

Survey of Activated FLT3 Signaling in Leukemia

Activating mutations of FMS-like tyrosine kinase-3 (FLT3) are found in approximately 30% of patients with acute myeloid leukemia (AML). FLT3 is therefore an attractive drug target. However, the molecular mechanisms by which FLT3 mutations lead to cell transformation in AML remain unclear. To develop a better understanding of FLT3 signaling as well as its downstream effectors, we performed detailed phosphoproteomic analysis of FLT3 signaling in human leukemia cells. We identified over 1000 tyrosine phosphorylation sites from about 750 proteins in both AML (wild type and mutant FLT3) and B cell acute lymphoblastic leukemia (normal and amplification of FLT3) cell lines. Furthermore, using stable isotope labeling by amino acids in cell culture (SILAC), we were able to quantified over 400 phosphorylation sites (pTyr, pSer, and pThr) that were responsive to FLT3 inhibition in FLT3 driven human leukemia cell lines. We also extended this phosphoproteomic analysis on bone marrow from primary AML patient samples, and identify over 200 tyrosine and 800 serine/threonine phosphorylation sites in vivo. This study showed that oncogenic FLT3 regulates proteins involving diverse cellular processes and affects multiple signaling pathways in human leukemia that we previously appreciated, such as Fc epsilon RI-mediated signaling, BCR, and CD40 signaling pathways. It provides a valuable resource for investigation of oncogenic FLT3 signaling in human leukemia

The arterial vascularization of the stomach fundus of human fetuses

We have investigated the existence, frequency and the course of arteries of the human stomach fundus by injection method. Our material obtained 52 human fetuses of the length range from 127 to 285 mm and the fetal age range from l5 to 28 weeks of gestation. It has been found, that the source of the arterial blood supply of this region are two arteries: the left gastric artery and splenic artery with its bigger branches: posterior gastric artery, superior polar artery and short gastric arteries. The source of arterial blood supply of the stomach fundus there have been two in 6 cases (11,5%) or three in 45 cases (86,6%) or four in 1 case (l,9%) of these arteries. We have analysed in detail the contribution and the range of the following arteries in the stomach quadrants. It has been shown, that the anterior medial quadrant has the best arterial blood supply and the anterior lateral has the worst one

Int. J. Cancer

Advanced and recurrent prostate tumors contain elevated levels of activated extracellular signal-regulated kinases I and 2 (ERK) in comparison to early-stage or benign specimens, and inhibition of ERK activation attenuates growth factor-dependent proliferation of prostate cells, suggesting a potential regulatory role for ERK in prostate tumorigenesis. Factors responsible for ERK activation in prostate cells are not well defined. Here, we show positive cooperative interaction between the G protein-coupled lysophosphatidic acid (LPA) and tyrosine kinase epidermal growth factor (EGF) receptors in androgen- insensitive prostate cancer PC-3 cells. Pre-treatment of the PC-3 cells with LPA decreases the dose of EGF required to elicit maximal activation of EGFR. Furthermore, treatment with LPA alone induces the rapid (maximal signal within 2 min) tyrosine phosphorylation of EGFR, and subsequent (maximal signal after 5 min) activation of ERK, suggesting that EGFR activation precedes ERK phosphorylation and may constitute a required component for signal relay from the LPA receptor to ERK. Accordingly, we show that inhibition of EGFR kinase activity attenuates the LPA-regulated ERK activation. In addition, we find that the LPA-regulated tyrosine phosphorylation of EGFR and activation of ERK are attenuated by batimastat, a generic inhibitor of matrix metalloproteinases (MMP). However, unlike the situation in fibroblasts, we find that the LPA-induced transactivation of EGFR in PC-3 cells is not mediated by shedding of heparin-binding EGF. Together, our data show that LPA and EGF cooperate to induce mitogenic signaling in prostate cancer cells in an MMP-regulated activation of the ERK pathway. (C) 2002 Wiley-Liss, Inc