Exposure to secondhand smoke in Germany: air contamination due to smoking in German restaurants, bars, and other venues.

This study quantified exposure to secondhand smoke in German restaurants, bars, and entertainment venues by determining the concentration of respirable suspended particles measuring 2.5 microm or less (PM2.5) in indoor air. The measurements were taken using an inconspicuous device placed on the investigator's table in the venue. The concentration of particulate matter in the indoor air was measured for a minimum of 30 min. A total of 39 restaurants, 20 coffee bars, 12 bars, 9 discothèques, and 20 restaurant cars in trains were visited throughout Germany from September 30 to October 31, 2005. The readings disclosed a median PM2.5 of 260 microg/m3 and an arithmetic mean PM2.5 of 333 microg/m3. Median values were 378 microg/m3 in bars, 131 microg/m3 in cafes, and 173 microg/m3 in restaurants. The highest medians were measured in discothèques and restaurant cars, with values averaging 432 microg/m3 and 525 microg/m3 PM2.5, respectively. This study was the first to show the magnitude and extent of exposure to secondhand smoke on such an extensive scale in Germany. The contaminated air due to smoking is a human carcinogenic and major health hazard, which would be prevented most effectively and completely by implementing a ban on smoking. This study is important for the ongoing national debate in Germany as well as for debates in all countries without smoke-free air legislation, which includes most countries around the world.     

Differential In Vitro Effects of SGLT2 Inhibitors on Mitochondrial Oxidative Phosphorylation,Glucose Uptake and Cell Metabolism

(1) The cardio-reno-metabolic benefits of the SGLT2 inhibitors canagliflozin (cana), dapagliflozin (dapa), ertugliflozin (ertu), and empagliflozin (empa) have been demonstrated, but it remains unclear whether they exert different off-target effects influencing clinical profiles. (2) We aimed to investigate the effects of SGLT2 inhibitors on mitochondrial function, cellular glucose-uptake (GU), and metabolic pathways in human-umbilical-vein endothelial cells (HUVECs). (3) At 100 µM (supra-pharmacological concentration), cana decreased ECAR by 45% and inhibited GU (IC5o: 14 µM). At 100 µM and 10 µM (pharmacological concentration), cana increased the ADP/ATP ratio, whereas dapa and ertu (3, 10 µM, about 10× the pharmacological concentration) showed no effect. Cana (100 µM) decreased the oxygen consumption rate (OCR) by 60%, while dapa decreased it by 7%, and ertu and empa (all 100 µM) had no significant effect. Cana (100 µM) inhibited GLUT1, but did not significantly affect GLUTs’ expression levels. Cana (100 µM) treatment reduced glycolysis, elevated the amino acids supplying the tricarboxylic-acid cycle, and significantly increased purine/pyrimidine-pathway metabolites, in contrast to dapa (3 µM) and ertu (10 µM). (4) The results confirmed cana´s inhibition of mitochondrial activity and GU at supra-pharmacological and pharmacological concentrations, whereas the dapa, ertu, and empa did not show effects even at supra-pharmacological concentrations. At supra-pharmacological concentrations, cana (but not dapa or ertu) affected multiple cellular pathways and inhibited GLUT1.     

Computational Light Painting Using a Virtual Exposure

Light painting is an artform where a light source is moved during a long‐exposure shot, creating trails resembling a stroke on a canvas. It is very difficult to perform because the light source needs to be moved at the intended speed and along a precise trajectory. Additionally, images can be corrupted by the person moving the light. We propose computational light painting, which avoids such artifacts and is easy to use. Taking a video of the moving light as input, a virtual exposure allows us to draw the intended light positions in a post‐process. We support animation, as well as 3D light sculpting, with high‐quality results.     

Quad‐Based Fourier Transform for Efficient Diffraction Synthesis

Far‐field diffraction can be evaluated using the Discrete Fourier Transform (DFT) in image space but it is costly due to its dense sampling. We propose a technique based on a closed‐form solution of the continuous Fourier transform for simple vector primitives (quads) and propose a hierarchical and progressive evaluation to achieve real‐time performance. Our method is able to simulate diffraction effects in optical systems and can handle varying visibility due to dynamic light sources. Furthermore, it seamlessly extends to near‐field diffraction. We show the benefit of our solution in various applications, including realistic real‐time glare and bloom rendering.     

Chemo-Enzymatic Fluorescence Labeling Of Genomic DNA For Simultaneous Detection Of Global 5-Methylcytosine And 5-Hydroxymethylcytosine**

5-Methylcytosine and 5-hydroxymethylcytosine are epigenetic modifications involved in gene regulation and cancer. We present a new, simple, and high-throughput platform for multi-color epigenetic analysis. The novelty of our approach is the ability to multiplex methylation and de-methylation signals in the same assay. We utilize an engineered methyltransferase enzyme that recognizes and labels all unmodified CpG sites with a fluorescent cofactor. In combination with the already established labeling of the de-methylation mark 5-hydroxymethylcytosine via enzymatic glycosylation, we obtained a robust platform for simultaneous epigenetic analysis of these marks. We assessed the global epigenetic levels in multiple samples of colorectal cancer and observed a 3.5-fold reduction in 5hmC levels but no change in DNA methylation levels between sick and healthy individuals. We also measured epigenetic modifications in chronic lymphocytic leukemia and observed a decrease in both modification levels (5-hydroxymethylcytosine: whole blood 30 %; peripheral blood mononuclear cells (PBMCs) 40 %. 5-methylcytosine: whole blood 53 %; PBMCs 48 %). Our findings propose using a simple blood test as a viable method for analysis, simplifying sample handling in diagnostics. Importantly, our results highlight the assay‘s potential for epigenetic evaluation of clinical samples, benefiting research and patient management.     

Innovation in the creative industries: Linking the founder's creative and business orientation to innovation outcomes

Creative industries contain paradoxes because conflicting tensions arise between the market and the arts. Entrepreneurs need to find and maintain a balance between those two sides to create innovation. This study tests the interaction between business and creative orientations of a founder in their influence on innovation in the context of creative entrepreneurial firms and provides recommendations for how creative agents can leverage and manage their innovations based on their creative visions. Determinants on the individual level, such as the founder's creative or business orientations, have a lasting impact on the practices and process of their venture. To trace the imprinting influence of the founder's orientation on innovation, the empirical setting is a time-lagged study of German firm owners in the cultural and creative industries surveyed 5 years apart. The results show a significant relationship between creative orientation and innovation, whereas business orientation does not significantly relate to innovation. However, creative and business orientations reveal a negative interaction effect. This study contributes empirical evidence to the paradox theory and the interaction between the opposite poles. Our findings provide valuable insights about the relevance of creative orientation and its visionary impact on the firms' innovation process. Furthermore, the results shed new light on the tension between art and the market, as different compositions of the two orientation poles seem to have a varying impact on the degree of innovation. Thus, the study reveals the complexity of creative entrepreneurship and provides managerial guidance for other knowledge-based industries.     

Discovery and Biosynthesis of Anthrochelin,a Growth-Promoting Metallophore of the Human Pathogen Luteibacter anthropi

Various human pathogens have emerged from environmental strains by adapting to higher growth temperatures and the ability to produce virulence factors. A remarkable example of a pathoadapted bacterium is found in the genus Luteibacter, which typically comprises harmless soil microbes, yet Luteibacter anthropi was isolated from the blood of a diseased child. Up until now, nothing has been known about the specialized metabolism of this pathogen. By comparative genome analyses we found that L. anthropi has a markedly higher biosynthetic potential than other bacteria of this genus and uniquely bears an NRPS gene locus tentatively coding for the biosynthesis of a metallophore. By metabolic profiling, stable isotope labeling, and NMR investigation of a gallium complex, we identified a new family of salicylate-derived nonribosomal peptides named anthrochelins A–D. Surprisingly, anthrochelins feature a C-terminal homocysteine tag, which might be introduced during peptide termination. Mutational analyses provided insight into the anthrochelin assembly and revealed the unexpected involvement of a cytochrome P450 monooxygenase in oxazole formation. Notably, this heterocycle plays a key role in the binding of metals, especially copper(II). Bioassays showed that anthrochelin significantly promotes the growth of L. anthropi in the presence of low and high copper concentrations, which occur during infections.     

Interactive Depixelization of Pixel Art through Spring Simulation

We introduce an approach for converting pixel art into high-quality vector images. While much progress has been made on automatic conversion, there is an inherent ambiguity in pixel art, which can lead to a mismatch with the artist's original intent. Further, there is room for incorporating aesthetic preferences during the conversion. In consequence, this work introduces an interactive framework to enable users to guide the conversion process towards high-quality vector illustrations. A key idea of the method is to cast the conversion process into a spring-system optimization that can be influenced by the user. Hereby, it is possible to resolve various ambiguities that cannot be handled by an automatic algorithm.