LONG-TERM MACRO ECONOMIC MODELLING OF THE BULGARIAN ECONOMY TO ANALYSE THE EFFECTS OF ANTICIPATED CHANGES IN THE ENERGY SECTOR

The middle and long-term forecasts of the economy for transition countries is an important challenge in order to understand better the effects of anticipated changes. During the accession negotiation between Bulgaria and the EU the continuation of the Kozloduy Nuclear Power Plant was a major stake both for Bulgaria and for the EU, such that various different options have been intensively discussed. In order to establish a transparent and factual basis different aspects have been analysed among which the consequences of the energy sector, in the local and over-regional economy, in social and environmental aspects. During the process of analysis it appeared appropriate and useful to analyse in-depth also the complex effects on the macro-economy of Bulgaria. In particular, negative and positive effects triggered in sectors others than the energy sector was to be evaluated. For this purpose a macroeconometric model INFORBG of the Bulgarian economy was developed. The model is disaggregated into 14 economic sectors. It represents the system of national accounts and describes the interdependent developments of some 250 macroeconomic variables. Thus it permits to set up consistent quantitative scenarios. In order to assess the macroeconomic consequences of an early closure two scenarios – one describing a deferred closure and the other one describing an early closure - were compared with each other. The model and its calculation results demonstrated a good example for practical use of macro-economic models in analysing anticipated changes in the economy of transition countries.Macro Economic, Bulgarian Economy, Energy

Zur Beruecksichtigung konkreter umweltpolitischer Massnahmen im Bielefelder Modell

Available from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Alpha10 integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential.

Mesenchymal stem cells (MSCs) are multipotent cells that have the capacity to differentiate into various different cell lineages and can generate bone, cartilage and adipose tissue. MSCs are presently characterized using a broad range of different cell-surface markers that are not exclusive to MSCs and not sensitive to culture conditions or differentiation capacity. We show that the integrin subunits alpha10 and alpha11 of the collagen binding integrins alpha10beta1 and alpha11beta1 are expressed by human MSCs in monolayer cultures. We also demonstrate that the expression of alpha10 increases, while alpha1 and alpha11 decrease, during aggregate culture of MSCs in chondrogenic medium. Alpha10beta1 is expressed by chondrocytes in cartilage, whereas alpha11beta1 integrins are predominantly expressed by subsets of the fibroblastic lineage. In extensive monolayer cultures of MSCs, alpha10 expression is down-regulated. We show that this down-regulation is reversed by fibroblast growth factor-2 (FGF-2) treatment. Addition of FGF-2 to MSCs not only results in increased alpha10 expression, but also in decreased alpha11 expression. FGF-2 treatment of MSCs has been shown to keep the cells more multipotent and also induces cell proliferation and Sox-9 up-regulation. We demonstrate improved chondrogenecity as well as increased collagen-dependant migratory potential of FGF-2-treated MSCs having a high alpha10 expression. We also demonstrate expression of alpha10 and alpha11 integrin subunits in the endosteum and periosteum of mice, but very low or not detectable expression levels in freshly aspired human or mouse BM. We show that MSCs with high chondrogenic differentiation potential are highly alpha10 positive and propose alpha10 as a potential marker to predict the differentiation state of MSCs

Pharmacokinetics of IdeS in serum.

<p>IdeS concentrations in serum samples from study subjects were determined by selected reaction monitoring mass spectrometry targeting four IdeS specific tryptic peptides. A) Comparison of serum IdeS concentration one minute before end of infusion versus dose levels of IdeS (0.01, 0.04, 0.12, and 0.24 mg/kg BW). Individual mean of two to four peptides. B) Comparison of serum concentration of mean values of two to four peptides versus time profiles up to 24 hours after infusion of 0.12 or 0.24 mg/kg BW IdeS (<i>n</i> = 8). Mean ± SEM.</p

Pharmacodynamics of antigen-specific IgG following IdeS treatment.

<p>Human serum samples from the 0.24 mg/kg BW group (<i>n</i> = 4) were addressed for presence of specific IgG against a vaccine mixture of antigens (diphtheria, pertussis, tetanus, polio and <i>Haemophilus influenzae</i> type b). The results are given as percent remaining IgG on the y-axis compared to the start value for each subject. To be able to follow both early, rapid degradation as well as recovery of IgG, graph A shows data up to 48 hours after dosing (x-axis in hours) and graph B shows data until last visit (x-axis in days).</p

Anti-IdeS antibodies were followed before and throughout the study.

<p>Human serum samples were analyzed using the IdeS-ImmunoCAP (Thermo Fisher Scientific) on a Phadia 250 instrument. The cut off (LLOQ) for IgG was 2 mg/L. A) Samples from 130 human donors (reference) were compared to the 78 healthy human male subjects screened in this study (screening). The lines show median for the reference group (6.1 mg/L) and the screening group (10.6 mg/L). B) Kinetics of the anti-IdeS IgG levels shown as a mean for the 0.12 and 0.24 mg/kg BW groups (<i>n</i> = 8; mean ± SEM). No increase in anti-IdeS IgG is seen in any of the subjects prior to day 14. C) Anti-IdeS IgG levels shown for the separate groups at day 14 (<i>n</i>_Placebo = 9, <i>n</i>_0.01 = 8, <i>n</i>_0.04 = 4, <i>n</i>_0.12 = 4 and <i>n</i>_0.24 = 4), and D) at day 182 (<i>n</i>_Placebo = 5, <i>n</i>_0.01 = 7, <i>n</i>_0.04 = 4, <i>n</i>_0.12 = 2 and <i>n</i>_0.24 = 4). The subjects were asked to come back for an outside the study protocol sample on day 182. 17 out of 20 on active and 5 out of 9 on placebo volunteered. The lines show median level for each group. In C and D the groups were compared using Kruskal-Wallis, One-Way ANOVA, P = 0.0003 and P = 0.0082 respectively. The P-values shown in the graph represent comparisons of the mean rank of each dose-group with the placebo group using Dunn’s Multiple Comparison. The placebo group contains all subjects from all dose-groups treated with placebo.</p

Schematic representation of IgG cleavage by IdeS.

<p>Intact human IgG, regardless of isotype, is cleaved by IdeS in two steps. The first step generates a single-cleaved IgG molecule (scIgG) with one intact heavy chain. The second step generates one F(ab’)₂ fragment and one homo-dimeric Fc fragment held together by non-covalent interactions.</p

Quantitative pharmacodynamics analysis by ELISA showed rapid degradation of IgG.

<p>Serum IgG levels from all four individual subjects dosed with 0.12 mg/kg BW IdeS (A and B) and all four individual subjects dosed with 0.24 mg/kg BW IdeS (C and D) determined using a validated ELISA method performed by Covance Laboratories Ltd, UK. To be able to follow both early, rapid degradation as well as recovery of IgG, graphs A and C show data up to 48 hours after dosing (x-axis in hours) and graphs B and D show data until last visit (x-axis in days).</p

Pharmacokinetics of IdeS in serum.

<p>IdeS concentrations in serum samples from study subjects were determined by selected reaction monitoring mass spectrometry targeting four IdeS specific tryptic peptides. A) Comparison of serum IdeS concentration one minute before end of infusion versus dose levels of IdeS (0.01, 0.04, 0.12, and 0.24 mg/kg BW). Individual mean of two to four peptides. B) Comparison of serum concentration of mean values of two to four peptides versus time profiles up to 24 hours after infusion of 0.12 or 0.24 mg/kg BW IdeS (<i>n</i> = 8). Mean ± SEM.</p