How to increase cross border transmission capacity? A case study: Belgium.

Cross border capacity allows electric energy to be traded internationally. The electricity sector used to be vertically integrated and often state-owned. High voltage grids were generally developed within the borders of a country. Connecting different national high voltage grids was done to improve the security of the system and to accomodate for a few historical long term contracts. By doing so, the different systems could share their reserve generation capacity. Since the liberalization of the electricity sector, cross border capacity has gained a renewed interest as this can increase the competition in the market. This paper aims to give an overview of recent and planned investments which increase the cross border capacity of Belgium. Also we give an insight into the different technologies which can be used and their advantages and drawbacks are discussed.

Impact of material properties and process parameters on tablet quality in a continuous direct compression line

The current paper shows how excipient properties impact the process parameters and the final tablet properties in a fully integrated continuous direct compression line. Blend properties of low-dose (1% w/w) and high-dose (40% w/w) paracetamol formulations were evaluated and linked to the blending and tableting performance via multivariate models (Partial Least Squares analysis, PLS). Feeding behavior was analyzed separately, as the amount of active pharmaceutical ingredient (API) that ended into tablets was driven by random fluctuations in the API feeding behavior. The developed PLS models elucidated that formulation behavior was mainly driven by the concentration of the active pharmaceutical ingredient (API), explained by the distinct API properties. Excipient properties also had a substantial impact on formulation behavior. Generally, formulations with microcrystalline cellulose as a filler showed better compactability, lower hold-up mass, lower flowability and higher cohesion than formulations with different lactose grades. The relative performance of a formulation with different fillers differed for 1% w/w and 40% w/w drug loading. Granular and spray dried lactose grades increased in compactability ranking compared to anhydrous lactose when evaluating higher drug loading, due to the difference in morphology. It was shown that besides understanding the impact of excipients on the formulation performance, processability of ingredients is crucial for formulation design.</p

Practical Tools to Implement Massive Parallel Pyrosequencing of PCR Products in Next Generation Molecular Diagnostics

Despite improvements in terms of sequence quality and price per basepair, Sanger sequencing remains restricted to screening of individual disease genes. The development of massively parallel sequencing (MPS) technologies heralded an era in which molecular diagnostics for multigenic disorders becomes reality. Here, we outline different PCR amplification based strategies for the screening of a multitude of genes in a patient cohort. We performed a thorough evaluation in terms of set-up, coverage and sequencing variants on the data of 10 GS-FLX experiments (over 200 patients). Crucially, we determined the actual coverage that is required for reliable diagnostic results using MPS, and provide a tool to calculate the number of patients that can be screened in a single run. Finally, we provide an overview of factors contributing to false negative or false positive mutation calls and suggest ways to maximize sensitivity and specificity, both important in a routine setting. By describing practical strategies for screening of multigenic disorders in a multitude of samples and providing answers to questions about minimum required coverage, the number of patients that can be screened in a single run and the factors that may affect sensitivity and specificity we hope to facilitate the implementation of MPS technology in molecular diagnostics

Global Integration of Central and Eastern European Financial Markets: The Role of Economic Sentiments

This paper examines the importance of different economic sentiments, e.g. consumer moods, for the Central and Eastern European countries (CEECs) during the transition process. We first analyze the importance of economic confidence with respect to the CEEC's financial markets. Since the integration of formerly strongly regulated markets into global markets can also lead to an increase of the dependence of the CEECs' domestic market performance from global sentiments, we also investigate the relationship between global economic sentiments and domestic income and share prices. Finally, we test whether the impact of global sentiments and stock prices on domestic variables increases proportionally with the degree of integration. For these purposes, we apply a structural cointegrating VAR (CVAR) framework based upon a restricted autoregressive model which allows us to distinguish between the long-run and the short-run dynamics. For the long run we find evidence supporting relationships between sentiments, income and share prices in case of the Czech Republic. Our results for the short run suggest that economic sentiments in general are strongly influenced by share prices and income but also offer some predictive power with respect to the latter. What is more, global sentiments play an important role in particular for the CEECs' share prices and income. The significance of this link increases with economic integration

RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition

High-risk neuroblastoma, a pediatric tumor originating from the sympathetic nervous system, has a low mutation load but highly recurrent somatic DNA copy number variants. Previously, segmental gains and/or amplifications allowed identification of drivers for neuroblastoma development. Using this approach, combined with gene dosage impact on expression and survival, we identified ribonucleotide reductase subunit M2 (RRM2) as a candidate dependency factor further supported by growth inhibition upon in vitro knockdown and accelerated tumor formation in a neuroblastoma zebrafish model coexpressing human RRM2 with MYCN. Forced RRM2 induction alleviates excessive replicative stress induced by CHK1 inhibition, while high RRM2 expression in human neuroblastomas correlates with high CHK1 activity. MYCN-driven zebrafish tumors with RRM2 co-overexpression exhibit differentially expressed DNA repair genes in keeping with enhanced ATR-CHK1 signaling activity. In vitro, RRM2 inhibition enhances intrinsic replication stress checkpoint addiction. Last, combinatorial RRM2-CHK1 inhibition acts synergistic in high-risk neuroblastoma cell lines and patient-derived xenograft models, illustrating the therapeutic potential

Nutri-Epigenomic Investigation Into the Effect of Selenium on Prostate Cancer.

Selenium (Se) is an essential trace element that has a role in cancer chemoprevention. DNA methylation is an important factor in carcinogenesis and one-carbon metabolism may influence this by providing methyl groups for DNA methylation. In previous studies Se was shown to be inversely correlated with homocysteine (Hcy), a product of one-carbon metabolism, in humans but it is unclear whether Se has a direct effect on DNA methylation. The relationship between Se and one-carbon metabolism was therefore investigated on two levels: (i) an investigation into the effect of Se supplementation on nutritional factors involved in one-carbon metabolism and (ii) an integrative epigenomic analysis using prostate cell lines and tissues to determine the effect of Se supplementation on DNA methylation. The interaction between Se, tHcy and B vitamins was investigated in a double-blind, placebo-controlled trial where 501 healthy UK elderly volunteers received 100, 200, or 300 mug Se/day as high-Se-yeast, or placebo-yeast for 6 months. Plasma Se, tHcy, folate, vitamin B-12, pyridoxal-5'-phosphate and its catabolite, 4-pyridoxic acid, were measured. At baseline, Se was inversely correlated with tHcy in males (p<0. 05). Before supplementation, tHcy concentration was significantly lower in the highest compared to the lowest Se tertile in males (p<0.05), and in females when folate concentrations were also in the top tertile (p<0.05). After 6 months of Se supplementation, only Se concentration had changed significantly. A genome-wide experimental design combining demethylation with 5-aza-2'-deoxycitidine (5-AZA) and subsequent gene re-expression, with methylome mapping via methylated DNA immunoprecipitation (MeDIP), investigated the global effect of Se supplementation on prostate cell lines RWPE-1, DU145, LnCAP and PC-3 and tissues. Se supplementation increased expression of hypermethylated genes and, in combination with 5-AZA, reduced global methylation levels in the PC-3 prostate cancer cell line (P<0.05). Se and 5-AZA individually activated anti-carcinogenic pathways while Se also inhibited cellular proliferation pathways. Genes that were Se-responsive after demethylation were involved in DNA repair, cell motility, the JAK/STAT pathway and stress-mediated translational regulation. MeDIP identified genes involved in vesicle-mediated transport, in all prostate cancer cell lines. Novel hypermethylated genes included GPx2, an anti-inflammatory and anti-carcinogenic selenoprotein. GPx3, known to be hypermethylated in prostate cancer, was shown to be re-expressed with 5-AZA and had a further increase in gene expression with Se supplementation. Clusters of hypermethylated genes were identified on almost all chromosomes. In conclusion, supplementation with Se does not affect tHcy concentration in the UK elderly population whereas in vitro Se supplementation of prostate cancer cells causes an increase in gene expression of hypermethylated genes. Hypermethylated Se-responsive genes are involved in anti-carcinogenic pathways and can be targeted for cancer therapy by demethylation and Se supplementation

Nieuwe technieken in de forensische genetica

Book chapter on novel techniques in forensic genetics.edition: 3rdstatus: publishe

Nutri-epigenomic investigation into the effect of selenium on prostate cancer

Selenium (Se) is an essential trace element that has a role in cancer chemoprevention. DNA methylation is an important factor in carcinogenesis and one-carbon metabolism may influence this by providing methyl groups for DNA methylation. In previous studies Se was shown to be inversely correlated with homocysteine (Hcy), a product of one-carbon metabolism, in humans but it is unclear whether Se has a direct effect on DNA methylation. The relationship between Se and one-carbon metabolism was therefore investigated on two levels: (i) an investigation into the effect of Se supplementation on nutritional factors involved in one-carbon metabolism and (ii) an integrative epigenomic analysis using prostate cell lines and tissues to determine the effect of Se supplementation on DNA methylation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo