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- SourceAvailable from: Peter F Ambros[Show abstract] [Hide abstract]
ABSTRACT: Background: Metastases in the bone marrow (BM) in form of disseminated tumor cells (DTCs) are frequent events at diagnosis and also at relapse in high-risk neuroblastoma patients. The frequently highly diluted occurrence of DTCs requires adequate enrichment strategies to enable their detailed characterization. However, to avoid methodical artifacts we tested whether pre-analytical processing steps-including transport duration, temperature and, importantly, tumor cell enrichment techniques-are confounding factors for gene expression analysis in DTCs. Methods: LAN-1 neuroblastoma cells were spiked into tumor free BM and/or peripheral blood and: i) kept at room temperature or at 4°C for 24, 48 and 72 hours; ii) frozen down at -80°C and thawed; iii) enriched via magnetic beads. The effect on the gene expression signature of LAN-1 cells was analyzed by qPCR arrays and gene expression microarrays. Results: Neither storage at -80°C in DMSO and subsequent thawing nor enrichment of spiked-in neuroblastoma cells changed the expression of the analyzed genes significantly. Whereas storage at 4°C altered the expression of analyzed genes (14.3%) only at the 72h-timepoint in comparison to the 0h-timepoint, storage at room temperature had a much more profound effect on gene expression by affecting 20% at 24h, 26% at 48h and 43% at 72h of the analyzed genes. Conclusion: Using neuroblastoma as a model, we show that tumor cell enrichment by magnetic bead separation has virtually no effect on gene expression in DTCs. However, transport time and temperature can influence the expression profile remarkably. Thus, the expression profile of routinely collected BM samples can be analyzed without concern as long as the transport conditions are monitored.PLoS ONE 09/2015; 10(9):e0137995. DOI:10.1371/journal.pone.0137995
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ABSTRACT: This paper proposes a genetic algorithm-based method for sizing the energy storage system (ESS) in microgrids. The main goal of the proposed method is to find the energy and power capacities of the storage system that minimizes the operating cost of the microgrid. The energy management strategy (EMS) used in this paper is based on a fuzzy expert system which is responsible for setting the power output of the ESS. The design of the EMS is carried out by means of a genetic algorithm that is used to set the fuzzy rules and membership functions of the expert system. Given that the size of the storage system has a major influence on the energy management strategy, in this paper the EMS and ESS capacities are jointly optimized. In addition, the proposed method uses an aging model to predict the lifetime of the ESS. In this way it is possible to determine the cost associated with energy storage in a more precise manner. The unit commitment problem, which is crucial for the proper operation of the microgrid, has been also considered in the present work. The suggested sizing methodology has been validated in two case studies.Renewable Energy 05/2015; 77:539-549. DOI:10.1016/j.renene.2014.12.039
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ABSTRACT: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. While the pathways that are deregulated in MB remain to be fully characterized, amplification and/or overexpression of the MYCN gene, which is has a critical role in cerebellar development as a regulator of neural progenitor cell fate, has been identified in several MB subgroups. Phenotypically, aberrant expression of MYCN is associated with the large-cell/anaplastic MB variant, which accounts for 5-15% of cases and is associated with aggressive disease and poor clinical outcome. To better understand the role of MYCN in MB in vitro and in vivo and to aid the development of MYCN-targeted therapeutics we established tumor-derived neurosphere cell lines from the GTML (Glt1-tTA/TRE-MYCN-Luc) genetically engineered mouse model. A fraction of GTML neurospheres were found to be growth factor independent, expressed CD133 (a marker of neural stem cells), failed to differentiate upon MYCN withdrawal and were highly tumorigenic when orthotopically implanted into the cerebellum. Principal component analyzes using single cell RNA assay data suggested that the clinical candidate aurora-A kinase inhibitor MLN8237 converts GTML neurospheres to resemble non-MYCN expressors. Correlating with this, MLN8237 significantly extended the survival of mice bearing GTML MB allografts. In summary, our results demonstrate that MYCN plays a critical role in expansion and survival of aggressive MB-propagating cells, and establish GTML neurospheres as an important resource for the development of novel therapeutic strategies.PLoS ONE 03/2015; 10(3):e0119834. DOI:10.1371/journal.pone.0119834
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