108 research outputs found

    The effect of the histone deacetylase inhibitor M344 on BRCA1 expression in breast and ovarian cancer cells

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    <p>Abstract</p> <p>Background</p> <p>The inhibition of Breast Cancer 1 (BRCA1) expression sensitizes breast and ovarian cancer cells to platinum chemotherapy. However, therapeutically relevant agents that target BRCA1 expression have not been identified. Our recent report suggested the potential of the histone deacetylase (HDAC) inhibitor, M344, to inhibit BRCA1 expression. In this study, we further evaluated the effect of M344 on BRCA1 mRNA and protein expression, as well as its effect on cisplatin-induced cytotoxicity in various breast (MCF7, T-47D and HCC1937) and ovarian (A2780s, A2780cp and OVCAR-4) cancer cell lines.</p> <p>Results</p> <p>With the addition of M344, the platinum-sensitive breast and ovarian cancer cell lines that displayed relatively high BRCA1 protein levels demonstrated significant potentiation of cisplatin cytotoxicity in association with a reduction of BRCA1 protein. The cisplatin-resistant cell lines, T-47D and A2780s, elicited increased cytotoxicity of cisplatin with M344 and down regulation of BRCA1 protein levels. A2780s cells subjected to combination platinum and M344 treatment, demonstrated increased DNA damage as assessed by the presence of phosphorylated H2A.X foci in comparison to either treatment alone. Using Chromatin Immunoprecipitation, A2780s and MCF7 cells exposed to M344 alone and in combination with cisplatin, did not demonstrate enhanced acetylated Histone 4 at the <it>BRCA1 </it>promoter, suggesting an indirect effect on this promoter.</p> <p>Conclusions</p> <p>The enhanced sensitivity of HDAC inhibition to platinum may be mediated through a BRCA1-dependent mechanism in breast and ovarian cancer cells. The findings of this study may be important in the future design of clinical trials involving HDAC inhibitors using BRCA1 as a tumour biomarker.</p

    On de-bunking “Fake News” in the post-truth era : how to reduce statistical error in research

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    The authors note with alarm that statistical noise caused by statistical incompetence is beginning to creep into research on cost overrun in public investment projects, contaminating research with work that does not meet basic standards of validity and reliability. The paper gives examples of such work and proposes three heuristics to root out the problem. First, researchers who are not statisticians, or do not have a strong background in statistics, should abstain from doing statistical analysis, and instead rely on more experienced colleagues, preferably professional statisticians. Second, journal referees should clearly state their level of statistical proficiency to journal editors, so these can set the right referee team. Finally, journal editors should make sure that at least one referee is capable of reviewing the statistical and methodological aspects of a paper. The work under review would have benefitted from observing these simple heuristics, as would any work based on statistical analysis.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Transport and Logistic

    Placement depth of seed corn in the region of Campos Gerais, Paraná, Brazil

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    No Tillage system is fully incorporated to farming in the region of Campos Gerais, state of Paraná. Accuracy and precision in the planting process are items of great importance for the success of this system. In order to evaluate the planting process, thirty eight farms were selected as sites for analysis of the placement depth of seeds. The research area was 4 or 5 planting rows, evaluating 10 plantlets per row. The average seed depth was around 46 mm, and significant differences between rows were observed in 21 areas. The average coefficient of variation was around 20%, the statistical limit between medium and high. Analyses of other parameters show that those coefficients may represent different errors in the process. The planting process in Campos Gerais can be considered efficient regarding to the average seed depth. However, the analysis of variability implies de need of actions concerning to anthropic and machinery factors.O sistema plantio direto encontra-se hoje plenamente incorporado à região dos Campos Gerais no Paraná. A acurácia e a precisão no processo de semeadura são itens de grande importância para que tal sistema alcance sucesso. Sendo assim, foram selecionadas 50 propriedades e, em 38, determinou-se a profundidade de deposição da semente de milho. A área experimental era formada por quatro ou cinco linhas de semeadura, onde se avaliaram dez plântulas por linha. A profundidade ficou em torno de 46 mm, observando-se diferenças significativas entre as linhas, em 21 áreas. O coeficiente de variação médio ficou em torno de 20%, limite estatístico entre médio e alto. Conforme análise de outros parâmetros, tais coeficientes podem representar diferentes tipos de erro no processo. Pode-se considerar o processo de semeadura da região como eficiente quando considerada a média da profundidade. Entretanto, a análise da variabilidade demonstra necessidade de ações junto a fatores antrópicos e de máquina.78278

    Quasiparticle interfacial level alignment of highly hybridized frontier levels: H2_2O on TiO2_2(110)

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    Knowledge of the frontier levels' alignment prior to photo-irradiation is necessary to achieve a complete quantitative description of H2_2O photocatalysis on TiO2_2(110). Although H2_2O on rutile TiO2_2(110) has been thoroughly studied both experimentally and theoretically, a quantitative value for the energy of the highest H2_2O occupied levels is still lacking. For experiment, this is due to the H2_2O levels being obscured by hybridization with TiO2_2(110) levels in the difference spectra obtained via ultraviolet photoemission spectroscopy (UPS). For theory, this is due to inherent difficulties in properly describing many-body effects at the H2_2O-TiO2_2(110) interface. Using the projected density of states (DOS) from state-of-the-art quasiparticle (QP) G0W0G_0W_0, we disentangle the adsorbate and surface contributions to the complex UPS spectra of H2_2O on TiO2_2(110). We perform this separation as a function of H2_2O coverage and dissociation on stoichiometric and reduced surfaces. Due to hybridization with the TiO2_2(110) surface, the H2_2O 3a1_1 and 1b1_1 levels are broadened into several peaks between 5 and 1 eV below the TiO2_2(110) valence band maximum (VBM). These peaks have both intermolecular and interfacial bonding and antibonding character. We find the highest occupied levels of H2_2O adsorbed intact and dissociated on stoichiometric TiO2_2(110) are 1.1 and 0.9 eV below the VBM. We also find a similar energy of 1.1 eV for the highest occupied levels of H2_2O when adsorbed dissociatively on a bridging O vacancy of the reduced surface. In both cases, these energies are significantly higher (by 0.6 to 2.6 eV) than those estimated from UPS difference spectra, which are inconclusive in this energy region. Finally, we apply self-consistent QPGWGW (scQPGWGW1) to obtain the ionization potential of the H2_2O-TiO2_2(110) interface.Comment: 12 pages, 12 figures, 1 tabl

    Impact of amendments on the physical properties of soil under tropical long-term no till conditions

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    Tropical regions have been considered the world's primary agricultural frontier; however, some physico-chemical deficiencies, such as low soil organic matter content, poor soil structure, high erodibility, soil acidity, and aluminum toxicity, have affected their productive capacity. Lime and gypsum are commonly used to improve soil chemical fertility, but no information exists about the long-term effects of these products on the physical attributes and C protection mechanisms of highly weathered Oxisols. A field trial was conducted in a sandy clay loam (kaolinitic, thermic Typic Haplorthox) under a no-tillage system for 12 years. The trial consisted of four treatments: a control with no soil amendment application, the application of 2.1 Mg ha-1 phosphogypsum, the application of 2.0 Mg ha-1 lime, and the application of lime + phosphogypsum (2.0 + 2.1 Mg ha-1, respectively). Since the experiment was established in 2002, the rates have been applied three times (2002, 2004, and 2010). Surface liming effectively increased water-stable aggregates > 2.0 mm at a depth of up to 0.2 m; however, the association with phosphogypsum was considered a good strategy to improve the macroaggregate stability in subsoil layers (0.20 to 0.40 m). Consequently, both soil amendments applied together increased the mean weight diameter (MWD) and geometric mean diameter (GMD) in all soil layers, with increases of up to 118 and 89%, respectively, according to the soil layer. The formation and stabilization of larger aggregates contributed to a higher accumulation of total organic carbon (TOC) on these structures. In addition to TOC, the MWD and aggregate stability index were positively correlated with Ca2+ and Mg2+ levels and base saturation. Consequently, the increase observed in the aggregate size class resulted in a better organization of soil particles, increasing the macroporosity and reducing the soil bulk density and penetration resistance. Therefore, adequate soil chemical management plays a fundamental role in improving the soil's physical attributes in tropical areas under conservative management and highly affected by compaction caused by intensive farming
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