LINKING URBAN (STREET CANYON) MODELS WITH REGIONAL AIR QUALITY MODELS THROUGH URBAN BOUNDARY CONDITIONS

This contribution addresses the question of how detailed information from the urban canopy can be assimilated into regional models. This detailed information concerns, among others, road transport emissions, specific exchange and turbulence patterns in the built up canopy, and effects of roads and roughness elements on wind direction and wind speed. This information is typically obtained from detailed street canyon models in combination with traffic emission models. In order to integrate the dynamics of the urban canopy into regional air quality models, we propose the formulation of urban boundary conditions. The formulation has been tested and compared with measurements for benzene and NOx in the city of Antwerp, Belgium

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

LINKING URBAN (STREET CANYON) MODELS WITH REGIONAL AIR QUALITY MODELS THROUGH URBAN BOUNDARY CONDITIONS

This contribution addresses the question of how detailed information from the urban canopy can be assimilated into regional models. This detailed information concerns, among others, road transport emissions, specific exchange and turbulence patterns in the built up canopy, and effects of roads and roughness elements on wind direction and wind speed. This information is typically obtained from detailed street canyon models in combination with traffic emission models. In order to integrate the dynamics of the urban canopy into regional air quality models, we propose the formulation of urban boundary conditions. The formulation has been tested and compared with measurements for benzene and NOx in the city of Antwerp, Belgium

Fine structure in the alpha decay of Po-188,Po-192

The alpha decay of Po-188,Po-192 has been reexamined in order to probe the 0(+) states in the daughter nuclei Pb-184,Pb-188 that can be associated with coexisting spherical, oblate, and/or prolate configurations. Improved values were measured for the excitation energy and the feeding alpha -decay intensity of the 0(2)(+) state in Pb-184,Pb-188 and conflicting results on the 0(3)(+) state in Pb-188 were clarified. All known cases of fine structure in the alpha decay of the even-even Po nuclei are reviewed. The reduced alpha-decay width systematics combined with potential-energy-surface calculations confirm the onset of deformation in the ground state of the polonium nuclei around the neutron midshell. An isomeric state with a half-life of 580(100)ns has been identified in Po-192 .status: publishe

Charge radii and magnetic moments of odd-A 183-189Pb isotopes

Isotope shifts and hyperfine splitting parameters have been measured for the neutron-deficient odd-mass lead isotopes 183–189Pb. The measurement was performed at the ISOLDE (CERN) online mass separator using the in-source resonance ionization spectroscopy technique. The nuclear root mean square charge radii and the electromagnetic moments μ and Q_S have been deduced. They follow the smooth trend of the heavier isotopes and indicate the absence of deformation.status: publishe

Modulation of chromatin writer-reader-eraser enzymes by WA in MDA-MB-231 and MCF-7 cells.

<p><b>(A)</b> The heatmap represents gene expressions of 84 known or predicted genes coding for chromatin-modifying enzymes and two housekeeping genes (<i>ACTB, HPRT</i>) for control and WA-treated MDA-MB-231 and MCF-7 cells. Mean 2^−ΔCt values are compared pair-wise to MDA-MB-231 solvent control sample. The data represent values from at least two independent experiments. Color key legend above the heatmap represents 2^−ΔCt normalized expression values ranging from green (low expression) to red (high expression). <b>(B)</b> Bar graphs representing mean 2^−ΔCt normalized expression values of genes encoding for histone demethyltransferases from at least two independent experiments. Fold changes between control (DMSO) and 700 nM WA-treated samples are indicated above the corresponding bars. Significantly upregulated genes are marked with asterisks. <b>(C)</b> The scatter plot of the mean 2^−ΔCt normalized expression values of each gene in the control sample (MDA-MB-231 DMSO) versus the test sample (MCF-7 DMSO). The most differentially expressed genes are labeled next to the corresponding dot. WA-regulated genes are underlined. The black line indicates fold change 2^−ΔΔCt of 1. The dashed, gray lines indicate desired fold-change in gene expression threshold, here defined as 2.</p

Biological processes affected by WA treatment in MDA-MB-231 and MCF-7 cells.

<p><b>(A)</b> The heatmap represents gene expressions for control and WA 700 nM treated MDA-MB-231 and MCF-7 cells. Only genes that have a log₂ fold change (FC)≥1 or ≤1 between control and WA-treated samples and have a p-value<0.001 are plotted. Genes that are upregulated in treated samples are plotted above the dashed line (FC≥1), those that are downregulated in treated samples are plotted below (FC≤1). Genes that belong to a specific IPA biological process are clustered and represented by a colored square next to the heatmap. Color key legend represents log₂ normalized expression values ranging from green (low expression) to red (high expression). <b>(B)</b> Venn diagram represents common and cell line-specific IPA biological processes with predicted activation state (Red arrow represents increase of a biological process- Activation Z-score≥2; Green arrow represents decrease of a biological process- Activation Z-score≤-2).</p