Dr. Antoaneta Dimitrova spreekt over de Europese Unie en de crisis

Antoaneta Dimitrova is werkzaam bij het Instituut Bestuurskunde van de Universiteit Leiden. In een interview geeft zij haar op visie op de Europese Unie en de perikelen rondom de euro

Commissie BookBilders

De commissie Bestuurskundige Berichten 2011-2012 ‘‘BookBilders” stelt zich aan u voor

Chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates migration to bone marrow stromal cell-produced monocyte chemotactic proteins MCP-1, -2 and -3

The restricted bone marrow (BM) localisation of multiple myeloma (MM) cells most likely results from a specific homing influenced by chemotactic factors, combined with the proper signals for growth and survival provided by the BM microenvironment. In analogy to the migration and homing of normal lymphocytes, one can hypothesise that the BM homing of MM cells is mediated by a multistep process, involving the concerted action of adhesion molecules and chemokines. In this study, we report that primary MM cells and myeloma derived cell lines (Karpas, LP-1 and MM5.1) express the chemokine receptor CCR2. In addition, we found that the monocyte chemotactic proteins (MCPs) MCP-1, -2 and -3, three chemokines acting as prominent ligands for CCR2, are produced by stromal cells, cultured from normal and MM BM samples. Conditioned medium (CM) from BM stromal cells, as well as MCP-1, -2 and -3, act as chemoattractants for human MM cells. Moreover, a blocking antibody against CCR2, as well as a combination of neutralizing antibodies against MCP-1, -2 and -3, significantly reduced the migration of human MM cells to BM stromal cell CM. The results obtained in this study indicate the involvement of CCR2 and the MCPs in the BM homing of human MM cells. (C) 2003 Cancer Research UK

Endograft apposition and infrarenal neck enlargement after endovascular aortic aneurysm repair

BACKGROUND: Sufficient apposition and oversizing of the endograft in the aortic neck are both essential for durable endovascular aneurysm repair (evar). These measures are however not regularly stated on post-evar computed tomography angiography (CTa) scan reports. in this study endograft apposition and neck enlargement (NE) after EVAR with an Endurant II(s) endograft were analyzed and associated with supra- and infrarenal aortic neck morphology. MeThods: in 97 consecutive elective patients, the aortic neck morphology was measured on the pre-evar CTa scan on a 3mensio vascular workstation. The distance between the lowest renal artery and the proximal edge of the fabric (shortest fabric distance, sfd), and the shortest length of circumferential apposition between endograft and aortic wall (shortest apposition length, sal) were determined on the early postEVAR CTA scan. NE, defined as the aortic diameter change between pre- and post-EVAR CTA scan, was determined at eight levels: +40, +30, +20, +15, +10, 0, -5 and -10 mm relative to the lowest renal artery baseline. The aortic neck diameter and preoperative oversizing were correlated to NE with the Pearson correlation coefficient. The effective post-EVAR endograft oversizing is calculated from the nominal endograft diameter and the post-evar neck diameter where the endograft is circumferentially apposed. resulTs: The median time (interquartile range, iQr) between the evar procedure and the pre- and post-evar CTa scan was 40 (25, 71) days and 36 (30, 46) days, respectively. The endurant ii(s) endograft was deployed with a median (iQr) sfd of 1.0 (0.0, 3.0) mm. The sal was <10 mm in 9% of patients and significantly influenced by the pre-EVAR aortic neck length (P=0.001), hostile neck shape (P=0.017), and maximum curvature at the suprarenal aorta (P=0.039). The median (interquartile range) SAL was 21.0 (15.0, 27.0) mm with a median (IQR) pre-evar infrarenal neck length of 23.5 (13.0, 34.8) mm. The median (iQr) difference between the sal and neck length was -5.0 (-12.0, 2.8) mm. Significant (P<0.001) NE of 1.7 (0.9, 2.5) mm was observed 5 mm below the renal artery baseline, which resulted in an effective post-EVAR endograft oversizing <10% in 43% of the patients. No correlation was found between NE and aortic neck diameter or preoperative oversizing. ConClusions: Circumferential apposition between an endograft and the infrarenal aortic neck, sal, and ne can be derived from standard postoperative CT scans. These variables provide essential information about the post-procedural endograft and aortic neck morphology regardless of the preoperative measurements. Patients with SAL<10 mm or effective oversizing <10% due to NE may benefit from intensified followup, but clinical consequences of sal and ne should be evaluated in future longitudinal studies with longer term follow-up

Smeared versus localised sources in flux compactifications

We investigate whether vacuum solutions in flux compactifications that are obtained with smeared sources (orientifolds or D-branes) still survive when the sources are localised. This seems to rely on whether the solutions are BPS or not. First we consider two sets of BPS solutions that both relate to the GKP solution through T-dualities: (p+1)-dimensional solutions from spacetime-filling Op-planes with a conformally Ricci-flat internal space, and p-dimensional solutions with Op-planes that wrap a 1-cycle inside an everywhere negatively curved twisted torus. The relation between the solution with smeared orientifolds and the localised version is worked out in detail. We then demonstrate that a class of non-BPS AdS_4 solutions that exist for IASD fluxes and with smeared D3-branes (or analogously for ISD fluxes with anti-D3-branes) does not survive the localisation of the (anti) D3-branes. This casts doubts on the stringy consistency of non-BPS solutions that are obtained in the limit of smeared sources.Comment: 23 pages; v2: minor corrections, added references, version published in JHE

Cloning and functional characterization of a fructan 1-exohydrolase (1-FEH) in edible burdock (Arctium lappa L.)

<p>Abstract</p> <p>Background</p> <p>We have previously reported on the variation of total fructooligosaccharides (FOS), total inulooligosaccharides (IOS) and inulin in the roots of burdock stored at different temperatures. During storage at 0°C, an increase of FOS as a result of the hydrolysis of inulin was observed. Moreover, we suggested that an increase of IOS would likely be due to the synthesis of the IOS by fructosyltransfer from 1-kestose to accumulated fructose and elongated fructose oligomers which can act as acceptors for fructan:fructan 1-fructosyltransferase (1-FFT). However, enzymes such as inulinase or fructan 1-exohydorolase (1-FEH) involved in inulin degradation in burdock roots are still not known. Here, we report the isolation and functional analysis of a gene encoding burdock 1-FEH.</p> <p>Results</p> <p>A cDNA, named <it>aleh1</it>, was obtained by the RACE method following PCR with degenerate primers designed based on amino-acid sequences of FEHs from other plants. The <it>aleh1 </it>encoded a polypeptide of 581 amino acids. The relative molecular mass and isoelectric point (<it>pI</it>) of the deduced polypeptide were calculated to be 65,666 and 4.86. A recombinant protein of <it>aleh1 </it>was produced in <it>Pichia pastoris</it>, and was purified by ion exchange chromatography with DEAE-Sepharose CL-6B, hydrophobic chromatography with Toyopearl HW55S and gel filtration chromatography with Toyopearl HW55S. Purified recombinant protein showed hydrolyzing activity against β-2, 1 type fructans such as 1-kestose, nystose, fructosylnystose and inulin. On the other hand, sucrose, neokestose, 6-kestose and high DP levan were poor substrates.</p> <p>The purified recombinant protein released fructose from sugars extracted from burdock roots. These results indicated that <it>aleh1 </it>encoded 1-FEH.</p

Opportunistic screening models for high-risk men and women to detect diastolic dysfunction and heart failure with preserved ejection fraction in the community

Background: The prevalence of undetected left ventricular diastolic dysfunction is high, especially in the elderly with comorbidities. Left ventricular diastolic dysfunction is a prognostic indicator of heart failure, in particularly of heart failure with preserved ejection fraction and of future cardiovascular and all-cause mortality. Therefore we aimed to develop sex-specific diagnostic models to enable the early identification of men and women at high-risk of left ventricular diastolic dysfunction with or without symptoms of heart failure who require more aggressive preventative strategies. Design: Individual patient data from four primary care heart failure-screening studies were analysed (1371 participants, excluding patients classified as heart failure and left ventricular ejection fraction <50%). Methods: Eleven candidate predictors were entered into logistic regression models to be associated with the presence of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in men and women separately. Internal-external cross-validation was performed to develop and validate the models. Results: Increased age and b-blocker therapy remained as predictors in both the models for men and women. The model for men additionally consisted of increased body mass index, moderate to severe shortness of breath, increased pulse pressure and history of ischaemic heart disease. The models performed moderately and similarly well in men (c-statistics range 0.60–0.75) and women (c-statistics range 0.51–0.76) and the performance improved significantly following the addition of N-terminal pro b-type natriuretic peptide (c-statistics range 0.61–0.80 in women and 0.68–0.80 in men). Conclusions: We provide an easy-to-use screening tool for use in the community, which can improve the early detection of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in high-risk men and women and optimise tailoring of preventive interventions

Chronic Helminth Infections Protect Against Allergic Diseases by Active Regulatory Processes

Developed countries are suffering from an epidemic rise in immunologic disorders, such as allergy-related diseases and certain autoimmunities. Several studies have demonstrated a negative association between helminth infections and inflammatory diseases (eg, allergy), providing a strong case for the involvement of helminth infections in this respect. However, some studies point in the opposite direction. The discrepancy may be explained by differences in frequency, dose, time, and type of helminth. In this review, new studies are discussed that may support the concept that chronic helminth infections in particular—but not acute infections—are associated with the expression of regulatory networks necessary for downmodulating allergic immune responses to harmless antigens. Furthermore, different components of regulatory networks are highlighted, such as the role of regulatory T and B cells, modulation of dendritic cells, early innate signals from structural cells (eg, epithelial cells), and their individual contributions to protection against allergic diseases. It is of great interest to define and characterize specific helminth molecules that have profound immunomodulatory capacities as targets for therapeutic application in the treatment or prophylaxis of allergic manifestations