41 research outputs found

    FOXA1 repression is associated with loss of BRCA1 and increased promoter methylation and chromatin silencing in breast cancer

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    FOXA1 expression correlates with the breast cancer luminal subtype and patient survival. RNA and protein analysis of a panel of breast cancer cell lines revealed that BRCA1 deficiency is associated with the downregulation of FOXA1 expression. Knockdown of BRCA1 resulted in the downregulation of FOXA1 expression and enhancement of FOXA1 promoter methylation in MCF-7 breast cancer cells, whereas the reconstitution of BRCA1 in Brca1-deficent mouse mammary epithelial cells (MMECs) promoted Foxa1 expression and methylation. These data suggest that BRCA1 suppresses FOXA1 hypermethylation and silencing. Consistently, the treatment of MMECs with the DNA methylation inhibitor 5-aza-2'-deoxycitydine induced Foxa1 mRNA expression. Furthermore, treatment with GSK126, an inhibitor of EZH2 methyltransferase activity, induced FOXA1 expression in BRCA1-deficient but not in BRCA1-reconstituted MMECs. Likewise, the depletion of EZH2 by small interfering RNA enhanced FOXA1 mRNA expression. Chromatin immunoprecipitation (ChIP) analysis demonstrated that BRCA1, EZH2, DNA methyltransferases (DNMT)1/3a/3b and H3K27me3 are recruited to the endogenous FOXA1 promoter, further supporting the hypothesis that these proteins interact to modulate FOXA1 methylation and repression. Further co-immunoprecipitation and ChIP analysis showed that both BRCA1 and DNMT3b form complexes with EZH2 but not with each other, consistent with the notion that BRCA1 binds to EZH2 and negatively regulates its methyltransferase activity. We also found that EZH2 promotes and BRCA1 impairs the deposit of the gene silencing histone mark H3K27me3 on the FOXA1 promoter. These associations were validated in a familial breast cancer patient cohort. Integrated analysis of the global gene methylation and expression profiles of a set of 33 familial breast tumours revealed that FOXA1 promoter methylation is inversely correlated with the transcriptional expression of FOXA1 and that BRCA1 mutation breast cancer is significantly associated with FOXA1 methylation and downregulation of FOXA1 expression, providing physiological evidence to our findings that FOXA1 expression is regulated by methylation and chromatin silencing and that BRCA1 maintains FOXA1 expression through suppressing FOXA1 gene methylation in breast cancer.Oncogene advance online publication, 22 December 2014; doi:10.1038/onc.2014.421.published_or_final_versio

    Local spectrum of truncations of Kronecker products of Haar distributed unitary matrices

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    Sharp Rosenthal-type inequalities for mixtures and log-concave variables

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    Funder: Trinity College, CambridgeWe obtain Rosenthal‐type inequalities with sharp constants for moments of sums of independent random variables which are mixtures of a fixed distribution. We also identify extremizers in log‐concave settings when the moments of summands are individually constrained

    The unconditional case of the complex S-inequality

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    Molding properties of blast furnace slag cements with addition of granular blast furnace slag with different glassy phase content

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    W artykule przedstawiono wyniki badań właściwości cementów żużlowych wykonanych z granulowanego żużla wielkopiecowego o różnej zawartości fazy szklistej. Program badań obejmował próbki żużla o wyraźnie zróżnicowanej zawartości fazy szklistej od 58 do 99% masy. Przygotowano cementy CEM II/A-S, CEM II/B-S i hutniczy CEM III/A, zawierające odpowiednio 15, 30 i 60% masy żużla. Badano podstawowe właściwości cementów, będące przedmiotem wymagań i oceny zgodności norm PN-EN 197-1 i PN-EN 15167-1. Na podstawie uzyskanych wyników badań potwierdzono, że największy wpływ na aktywność hydrauliczną żużla ma zawartość fazy szklistej. Drugim ważnym parametrem oceny aktywności żużla jest jego współczynnik aktywności (CaO + MgO/SiO2). Przy tej samej zawartości fazy szklistej, im większy współczynnik aktywności, tym żużel wykazuje większą aktywność hydrauliczną. Wyniki badań cementów żużlowych potwierdzają te zależności. Spośród badanego żużla krajowego i zagranicznego, największe wskaźniki aktywności hydraulicznej wykazał żużel z Huty Katowice i Huty Sendzimira, zawierający odpowiednio 99 i 88% fazy szklistej; miały one zdecydowanie lepsze właściwości w porównaniu do żużla sprowadzanego w ostatnich latach w dużych ilościach z importu.Test results of properties of slag cements made of granulated blast furnace slag of different glassy phase content are presented in the paper. Research covered samples of blast furnace slags of significantly diverse glassy phase content, from 58% up to 99% by mass. Cements CEM II/A-S, CEM II/B-S and CEM III/A containing 15%, 30% and 60% of slag respectively have been prepared. Basic properties of cements, being a subject of requirements and conformity assessment of standard PN-EN 197-1 and PN-EN 15167-1, have been tested. On the basis of obtained test results it has been confirmed that the glassy phase content has the highest impact on the hydraulic activity of blast furnace slag. The oxides ratio (CaO + MgO/SiO2) of blast furnace slag is the second important parameter of its evaluation. With the same glassy phase content the higher is the oxides ratio the higher hydraulic activity of blast furnace slag is indicated. Test results of slag cements confirm these relationships. Among examined of domestic and foreign blast furnace slags the highest hydraulic activity indexes have been indicated by slags from Huta Katowice and Huta Sendzimir containing 99% and 98% of glassy phase respectively; they have had definitely better properties comparing to foreign blast furnace slags imported in high amounts during recent years

    Możliwość wykorzystania surowców wtórnych przemysłu energetycznego i hutniczego do wytwarzania szkła-ceramiki

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    An effective way to glass strengthening is controlled crystallization, which results in obtaining the material with very favourable mechanical properties compared to parent glass. Crystallization process is conducted between glass transformation temperature and liquidus temperature. Information concerning the production of glass-ceramics material, as well as materials, which are the most commonly used in its production, were analyzed in this paper.Skutecznym sposobem wzmocnienia szkła jest kontrolowana krystalizacja, co skutkuje otrzymaniem materiału o bardzo dobrych właściwościach mechanicznych w porównaniu do szkła macierzystego. Proces krystalizacji prowadzony jest pomiędzy temperaturą transformacji szkła a temperaturą likwidusu. W artykule przenalizowano informacje dotyczące otrzymywania tworzywa szkło-ceramiki, jak również materiałów najczęściej wykorzystywanych podczas produkcji tego materiału

    Dual rolls equal channel extrusion as unconventional SPD process of the ultralow-carbon steel: finite element simulation, experimental investigations and microstructural analysis

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    The paper presents results of FEM modelling as well as properties and microstructure of the ultralow-carbon ferritic steel after the unconventional SPD process-DRECE (dual rolls equal channel extrusion). Based on the conducted numerical simulation information about the deformation behaviour of a steel strip during the DRECE process was obtained. The simulation results were experimentally verified. The influence of DRECE process on hardness distribution, fracture behaviour and microstructure evolution of the investigated steel was analysed. The increase of steel strength properties after subsequent deformation passes was confirmed. The microstructural investigations revealed that the processed strips exhibit the dislocation cell microstructure and subgrains with mostly low-angle grain boundaries. The grains after processing had relatively high dislocation density and intense microband formation was observed. It was also proved that this unconventional SPD method fosters high grain refinement.Web of Science211art. no. 2
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