Fault tree analysis for system modeling in case of intentional EMI

The complexity of modern systems on the one hand and the rising threat of intentional electromagnetic interference (IEMI) on the other hand increase the necessity for systematical risk analysis. Most of the problems can not be treated deterministically since slight changes in the configuration (source, position, polarization, ...) can dramatically change the outcome of an event. For that purpose, methods known from probabilistic risk analysis can be applied. One of the most common approaches is the fault tree analysis (FTA). The FTA is used to determine the system failure probability and also the main contributors to its failure. In this paper the fault tree analysis is introduced and a possible application of that method is shown using a small computer network as an example. The constraints of this methods are explained and conclusions for further research are drawn

Expression of interleukin 10 in human melanoma.

The expression of interleukin 10 (IL-10) mRNA in human malignant melanoma was investigated by reverse transcriptase polymerase chain reaction analysis. Selective expression of IL-10 mRNA in tissues of primary melanomas and melanoma metastases was found in comparison with normal skin. In addition, strong expression of IL-10 mRNA and of biologically active IL-10 was detected in 3 out of 13 melanoma cell lines. Normal melanocytes consistently expressed low levels of IL-10 mRNA but did not produce detectable IL-10 protein, nor did keratinocytes or fibroblasts. The production of biologically active IL-10 by melanoma cell lines suggests that IL-10 mRNA in melanoma lesions may derive at least in part from the tumour cells themselves. Tumour-infiltrating cells, however, could also be a source of IL-10 in melanoma tissues. The presence of IL-10 in melanoma lesions may contribute to the postulated 'paralysis' of an anti-melanoma immune response

A strategy for tissue self-organization that is robust to cellular heterogeneity and plasticity

Developing tissues contain motile populations of cells that can self-organize into spatially ordered tissues based on differences in their interfacial surface energies. However, it is unclear how self-organization by this mechanism remains robust when interfacial energies become heterogeneous in either time or space. The ducts and acini of the human mammary gland are prototypical heterogeneous and dynamic tissues comprising two concentrically arranged cell types. To investigate the consequences of cellular heterogeneity and plasticity on cell positioning in the mammary gland, we reconstituted its self-organization from aggregates of primary cells in vitro. We find that self-organization is dominated by the interfacial energy of the tissue–ECM boundary, rather than by differential homo- and heterotypic energies of cell–cell interaction. Surprisingly, interactions with the tissue–ECM boundary are binary, in that only one cell type interacts appreciably with the boundary. Using mathematical modeling and cell-type-specific knockdown of key regulators of cell–cell cohesion, we show that this strategy of self-organization is robust to severe perturbations affecting cell–cell contact formation. We also find that this mechanism of self-organization is conserved in the human prostate. Therefore, a binary interfacial interaction with the tissue boundary provides a flexible and generalizable strategy for forming and maintaining the structure of two-component tissues that exhibit abundant heterogeneity and plasticity. Our model also predicts that mutations affecting binary cell–ECM interactions are catastrophic and could contribute to loss of tissue architecture in diseases such as breast cancer

Role for DNA Methylation in the Regulation of miR-200c and miR-141 Expression in Normal and Cancer Cells

The microRNA-200 family participates in the maintenance of an epithelial phenotype and loss of its expression can result in epithelial to mesenchymal transition (EMT). Furthermore, the loss of expression of miR-200 family members is linked to an aggressive cancer phenotype. Regulation of the miR-200 family expression in normal and cancer cells is not fully understood.Epigenetic mechanisms participate in the control of miR-200c and miR-141 expression in both normal and cancer cells. A CpG island near the predicted mir-200c/mir-141 transcription start site shows a striking correlation between miR-200c and miR-141 expression and DNA methylation in both normal and cancer cells, as determined by MassARRAY technology. The CpG island is unmethylated in human miR-200/miR-141 expressing epithelial cells and in miR-200c/miR-141 positive tumor cells. The CpG island is heavily methylated in human miR-200c/miR-141 negative fibroblasts and miR-200c/miR-141 negative tumor cells. Mouse cells show a similar inverse correlation between DNA methylation and miR-200c expression. Enrichment of permissive histone modifications, H3 acetylation and H3K4 trimethylation, is seen in normal miR-200c/miR-141-positive epithelial cells, as determined by chromatin immunoprecipitation coupled to real-time PCR. In contrast, repressive H3K9 dimethylation marks are present in normal miR-200c/miR-141-negative fibroblasts and miR-200c/miR-141 negative cancer cells and the permissive histone modifications are absent. The epigenetic modifier drug, 5-aza-2′-deoxycytidine, reactivates miR-200c/miR-141 expression showing that epigenetic mechanisms play a functional role in their transcriptional control.We report that DNA methylation plays a role in the normal cell type-specific expression of miR-200c and miR-141 and this role appears evolutionarily conserved, since similar results were obtained in mouse. Aberrant DNA methylation of the miR-200c/141 CpG island is closely linked to their inappropriate silencing in cancer cells. Since the miR-200c cluster plays a significant role in EMT, our results suggest an important role for DNA methylation in the control of phenotypic conversions in normal cells

Background paper to the recommendation for routine rotavirus vaccination of infants in Germany

Two rotavirus (RV) vaccines were introduced to the European market in 2006. To support the decision-making process of the German Standing Committee on Vaccination ("Ständige Impfkommission", STIKO) regarding adoption of routine RV vaccination into the national vaccination schedule in Germany relevant scientific background was reviewed. According to STIKO’s Standard Operating Procedures for the development of evidence-based vaccination recommendations, a set of key questions was addressed and systematic reviews were performed with a focus on the efficacy, effectiveness, impact and safety of RV vaccines. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of available evidence. Data from 5 randomized controlled trials demonstrated a high efficacy of RV vaccines in preventing severe RV-associated gastroenteritis (91%) and hospitalization (92%) in settings comparable to Germany. Post-marketing observational studies confirmed these findings. In several countries, impact studies suggest that age groups not eligible for vaccination might also benefit from herd effects and demonstrated a decrease in the number of nosocomial RV infections after RV vaccine introduction. The vaccines were considered safe, except for a slightly increased risk of intussusception shortly after the first dose, corresponding to 1-2 additional cases per 100,000 infants vaccinated (relative risk =1.21, 95% confidence interval [CI] 0.68-2.14). RV case-fatality is extremely low in Germany. However, RV incidence among children age

Oncogenic GNAQ mutations are not correlated with disease-free survival in uveal melanoma

BackgroundRecently, oncogenic G protein alpha subunit q (GNAQ) mutations have been described in about 50% of uveal melanomas and in the blue nevi of the skin.MethodsGNAQ exon 5 was amplified from 75 ciliary body and choroidal melanoma DNAs and sequenced directly. GNAQ mutation status was correlated with disease-free survival (DFS), as well as other clinical and histopathological factors, and with chromosomal variations detected by FISH and CGH.ResultsOf the 75 tumour DNA samples analysed, 40 (53.3%) harboured oncogenic mutations in GNAQ codon 209. Univariate and multivariate analysis showed that GNAQ mutation status was not significantly correlated with DFS.ConclusionThe GNAQ mutation status is not suitable to predict DFS. However, the high frequency of GNAQ mutations may render it a promising target for therapeutic intervention