Habitatge i espais intermediaris: de porteries i porters a Barcelona

En aquest article volem posar en relleu algunes de les maneres com es poden analitzar els porters i les porteries, en qualitat d'institució i d'espai a través dels quals es poden copsar un conjunt de contradiccions i tensions de la modernitat. És a dir, volem fer veure com aquests espais i aquestes persones morals se situen en el centre d'una sèrie d'oposicions clàssiques a la Modernitat. El que analitzarem aquí és com els porters i les porteries sorgeixen històricament com a institucions dintre de la ciutat i se situen en el llindar de les oposicions següents: 1) públic / privat; 2) comunitat / contracte; 3) formal / informal; 4) ordre / desordre; 5) coneixement / secret

Human Macrophages and Dendritic Cells Can Equally Present MART-1 Antigen to CD8+ T Cells after Phagocytosis of Gamma-Irradiated Melanoma Cells

Dendritic cells (DC) can achieve cross-presentation of naturally-occurring tumor-associated antigens after phagocytosis and processing of dying tumor cells. They have been used in different clinical settings to vaccinate cancer patients. We have previously used gamma-irradiated MART-1 expressing melanoma cells as a source of antigens to vaccinate melanoma patients by injecting irradiated cells with BCG and GM-CSF or to load immature DC and use them as a vaccine. Other clinical trials have used IFN-gamma activated macrophage killer cells (MAK) to treat cancer patients. However, the clinical use of MAK has been based on their direct tumoricidal activity rather than on their ability to act as antigen-presenting cells to stimulate an adaptive antitumor response. Thus, in the present work, we compared the fate of MART-1 after phagocytosis of gamma-irradiated cells by clinical grade DC or MAK as well as the ability of these cells to cross present MART-1 to CD8+ T cells. Using a high affinity antibody against MART-1, 2A9, which specifically stains melanoma tumors, melanoma cell lines and normal melanocytes, the expression level of MART-1 in melanoma cell lines could be related to their ability to stimulate IFN-gamma production by a MART-1 specific HLA-A*0201-restricted CD8+ T cell clone. Confocal microscopy with Alexa Fluor®647-labelled 2A9 also showed that MART-1 could be detected in tumor cells attached and/or fused to phagocytes and even inside these cells as early as 1 h and up to 24 h or 48 h after initiation of co-cultures between gamma-irradiated melanoma cells and MAK or DC, respectively. Interestingly, MART-1 was cross-presented to MART-1 specific T cells by both MAK and DC co-cultured with melanoma gamma-irradiated cells for different time-points. Thus, naturally occurring MART-1 melanoma antigen can be taken-up from dying melanoma cells into DC or MAK and both cell types can induce specific CD8+ T cell cross-presentation thereafter

Bridges over Convulsing Waters: the EU aspiring Eastern Partners' Role in the Regional Governance

Abstract The enlargement of the European Union (EU) to the East in 2004 and 2007 so as to include ten former communist countries and two small Mediterranean islands has triggered new questions on the nature of EU governance. We argue that the accession of Central and Eastern European countries (CEECs) to the EU has affected governance patterns in the EU and beyond. Undeniably, the most recent waves of enlargement have had feed-back effects on Europeanisation mechanisms (Grabb

Habitatge i espais intermediaris: de porteries i porters a Barcelona

En aquest article volem posar en relleu algunes de les maneres com es poden analitzar els porters i les porteries, en qualitat d¿institució i d¿espai a través dels quals es poden copsar un conjunt de contradiccions i tensions de la modernitat. És a dir, volem fer veure com aquests espais i aquestes persones morals se situen en el centre d¿una sèrie d'oposicions clàssiques a la Modernitat. El que analitzarem aquí és com els porters i les porteries sorgeixen històricament com a institucions dintre de la ciutat i se situen en el llindar de les oposicions següents: 1) públic / privat; 2) comunitat / contracte; 3) formal / informal; 4) ordre / desordre; 5) coneixement / secret

What determines demand for European Union referendums?

Notwithstanding elite opposition to referendums as inconsistent with theories of representative democracy, the 27-nation European Election Study finds that 63 per cent of EU citizens want a vote on EU treaties. One explanation is that the majority want more popular participation in politics; another is that referendums are demanded by those negative about the performance of their governors at national and EU levels; a third is that demand is higher where referendums are part of the national context. Multi-level statistical analysis shows greater support for the hypotheses that citizens dissatisfied with government performance are more likely to want referendums to check their governors and that national context matters. However, dissatisfied EU citizens are a minority; most who endorse EU referendums are actually pro-EU. This lowers the risk of defeat if the EU consulted its citizens in a pan-European referendum

Housing and intermediate spaces: porters and porter’s lodges at Barcelona

En aquest article volem posar en relleu algunes de les maneres com es poden analitzar els porters i les porteries, en qualitat d’institució i d’espai a través dels quals es poden copsar un conjunt de contradiccions i tensions de la modernitat. És a dir, volem fer veure com aquests espais i aquestes persones morals se situen en el centre d’una sèrie d'oposicions clàssiques a la Modernitat. El que analitzarem aquí és com els porters i les porteries sorgeixen històricament com a institucions dintre de la ciutat i se situen en el llindar de les oposicions següents: 1) públic / privat; 2) comunitat / contracte; 3) formal / informal; 4) ordre / desordre; 5) coneixement / secret.This report is about analysing porters and porter’s lodges as institutions and spaces where tensions and contradictions of modernity can be shown. We would like to point out how theses intermediate spaces and moral persons are situated in the middle of a classical oppositions serie of modernity. The main purpose of this work is analyse how porters and porter’s lodges appear historically like institutions of the city, and how the are positioned within the following oppositions of modernity: 1) public / private; 2) community / contract; 3) formal / informal; 4) order / disorder; 5) connaissance / secret

Habitatge i espais intermediaris: de porteries i porters a Barcelona

En aquest article volem posar en relleu algunes de les maneres com es poden analitzar els porters i les porteries, en qualitat d'institució i d'espai a través dels quals es poden copsar un conjunt de contradiccions i tensions de la modernitat. És a dir, volem fer veure com aquests espais i aquestes persones morals se situen en el centre d'una sèrie d'oposicions clàssiques a la Modernitat. El que analitzarem aquí és com els porters i les porteries sorgeixen històricament com a institucions dintre de la ciutat i se situen en el llindar de les oposicions següents: 1) públic / privat; 2) comunitat / contracte; 3) formal / informal; 4) ordre / desordre; 5) coneixement / secret

Structure-based design and pre-clinical characterization of selective and orally bioavailable Factor XIa inhibitors: Demonstrating the power of an integrated S1 protease family approach

The serine protease Factor XI (FXI) is a prominent drug target as it holds promise to deliver efficacious anti-coagulation without an enhanced risk of major bleeds. Several efforts have been described targeting the active form of the enzyme, FXIa. Herein we disclose our efforts to identify potent, selective, and orally bioavailable inhibitors of FXIa. Compound 1, identified from a diverse library of internal serine protease inhibitors, was originally designed as a complement Factor D inhibitor and exhibited sub-micromolar FXIa activity and an encouraging ADME profile while being devoid of peptidomimetic architecture. Optimization of interactions in the S1, S1β, and S1` pockets of FXIa through a combination of structure-based drug design and traditional medicinal chemistry led to the discovery of compound 23 with sub-nanomolar potency on FXIa, enhanced selectivity over other coagulation proteases, and a pre-clinical PK profile consistent with bid dosing in patients

Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach

The serine protease Factor XI (FXI) is a prominent drug target as it holds promise to deliver efficacious anti-coagulation without an enhanced risk of major bleeds. Several efforts have been described targeting the active form of the enzyme, FXIa. Herein we disclose our efforts to identify potent, selective, and orally bioavailable inhibitors of FXIa. Compound 1, identified from a diverse library of internal serine protease inhibitors, was originally designed as a complement Factor D inhibitor and exhibited sub-micromolar FXIa activity and an encouraging ADME profile while being devoid of peptidomimetic architecture. Optimization of interactions in the S1, S1β, and S1` pockets of FXIa through a combination of structure-based drug design and traditional medicinal chemistry led to the discovery of compound 23 with sub-nanomolar potency on FXIa, enhanced selectivity over other coagulation proteases, and a pre-clinical PK profile consistent with bid dosing in patients