ω‐Phthalimidoalkyl Aryl Ureas as Potent and Selective Inhibitors of Cholesterol Esterase

Cholesterol esterase (CEase), a serine hydrolase thought to be involved in atherogenesis and thus coronary heart disease, is considered as a target for inhibitor development. We investigated recombinant human and murine CEases with a new fluorometric assay in a structure–activity relationship study of a small library of ω‐phthalimidoalkyl aryl ureas. The urea motif with an attached 3,5‐bis(trifluoromethyl)phenyl group and the aromatic character of the ω‐phthalimide residue were most important for inhibitory activity. In addition, an alkyl chain composed of three or four methylene groups, connecting the urea and phthalimide moieties, was found to be an optimal spacer for inhibitors. The so‐optimized compounds 2 [1‐(3,5‐bis(trifluoromethyl)phenyl)‐3‐(3‐(1,3‐dioxoisoindolin‐2‐yl)propyl)urea] and 21 [1‐(3,5‐bis(trifluoromethyl)phenyl)‐3‐(4‐(1,3‐dioxoisoindolin‐2‐yl)butyl)urea] exhibited dissociation constants (K_i) of 1–19 μm on the two CEases and showed either a competitive ( 2 on the human enzyme and 21 on the murine enzyme) or a noncompetitive mode of inhibition. Two related serine hydrolases—monoacylglycerol lipase and fatty acid amide hydrolase—were inhibited by ω‐phthalimidoalkyl aryl ureas to a lesser extent.     

Characterization of a new miniCAST with diffusion flame and premixed flame options: Generation of particles with high EC content in the size range 30 nm to 200 nm

Flame-generated soot from miniCAST burners is increasingly being used in academia and industry as engine exhaust soot surrogate for atmospheric studies and instrument calibration. Previous studies have found that elemental carbon (EC) content of miniCAST soot is proportional to the mean particle size. Here, the characterization of a prototype miniCAST generator (5201 Type BC), which was designed to decouple the soot composition from the particle size and produce soot particles with high EC and BC content in a large size range, is reported. This prototype may operate either in a diffusion-flame or a partially premixed-flame mode, an option that was not available in former models. It was confirmed that soot properties, such as EC content and Ångström absorption exponent (AAE), were linked to the overall flame composition. In particular, combustion under fuel-rich conditions provided particles with size coupled to the EC fraction and AAE, i.e. smaller particles exhibited a lower EC fraction and higher AAE. In contrast, with fuel-lean diffusion flames and especially with premixed flames under near overall stoichiometric conditions small particles (down to 30?nm) with high EC/TC ratios (>60%) and low AAE (≈1.4) could be generated even without any thermal after-treatment. This new source might thus serve in the future as a useful surrogate for engine exhaust emissions and help to improve calibration procedures of common aerosol instruments.

Copyright © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC     

Modulation of Induced Cytotoxicity of Doxorubicin by Using Apoferritin and Liposomal Cages

Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin (“Apodox” and “lip-8-dox”) and compared its toxicity with doxorubicin and Myocet on prostate cell lines. Three different prostatic cell lines PNT1A, 22Rv1, and LNCaP were chosen. The toxicity of the modified doxorubicin forms was compared to conventional doxorubicin using the MTT assay, real-time cell impedance-based cell growth method (RTCA), and flow cytometry. The efficiency of doxorubicin entrapment was 56% in apoferritin cages and 42% in the liposome carrier. The accuracy of the RTCA system was verified by flow-cytometric analysis of cell viability. The doxorubicin half maximal inhibition concentrations (IC₅₀) were determined as 170.5, 234.0, and 169.0 nM for PNT1A, 22Rv1, and LNCaP, respectively by RTCA. Lip8-dox is less toxic on the non-tumor cell line PNT1A compared to doxorubicin, while still maintaining the toxicity to tumorous cell lines similar to doxorubicin or epirubicin (IC₅₀ = 2076.7 nM for PNT1A vs. 935.3 and 729.0 nM for 22Rv1 and LNCaP). Apodox IC₅₀ was determined as follows: 603.1, 1344.2, and 931.2 nM for PNT1A, 22Rv1, and LNCaP.     

Polysiloxane‐Derived Ceramics Containing Nanowires with Catalytically Active Tips

By direct foaming of a Pt‐containing polysiloxane precursor, macroporous ceramics were generated by pyrolysis at 1400°C under nitrogen or argon. The growth of nanowires was induced via a vapor–liquid–solid mechanism in which the Pt particles acted as deposition site for the decomposition gases released upon pyrolyzing the preceramic polymer. SEM, HR‐SEM, TEM/EDX, and XRD investigations revealed that pyrolysis under argon atmosphere leads to short SiC nanowires of only a few micrometers length and under nitrogen atmosphere Si₃N₄ nanowires evolved, with length of several 10 μm. In both cases the tips of the nanowires mainly consisted of PtSi. In contrast to samples pyrolyzed at 600°C, the components after higher temperature pyrolysis showed moderate‐specific surface areas of 55–67 m²/g. In CO oxidation experiments, a good catalytic activity was found for the Pt silicide particles, suggesting that despite their relatively large size, their location at the tips of the nanowires affords them good reactivity.     

Erfassen von Ursache-Wirkungs-Beziehungen in Flusslandschaften: Vermittlung von Systemwissen in Schulen als Beitrag für ein nachhaltiges Flussgebietsmanagement

A scientific understanding of the processes at work in river landscapes represents an important basis for including the local populace in effective and sustainable river landscape management. By conveying system-based knowledge to students, these future inhabitants and users of river landscapes will be better able to recognize contexts and connections, understand project-related decisions and policies, and support sustainable planning efforts. As such, in October 2012 the Austrian Federal Ministry for Science and Research started the “FlussAu:WOW!” project, part of the “Sparkling Science” research program. In the project, scientists work together with the students from two upper-level high-school classes over a period of two years, investigating research questions on river landscape management. The scientific goal of the project is to create a set of indicators to represent the functionality of floodplains. In the first school year, the researchers worked on key questions together with the students in workshops, performed field surveys and analyzed the results of fieldwork. In the subsequent discussions, the researchers constantly pointed out the complex interrelations at work in river-floodplain systems. Students’ knowledge was evaluated in pre-project and post-project tests. The analysis of the pre-tests revealed major knowledge gaps on questions concerning river landscape management, e.g. on factors that place major pressures on these regions. A comparison between the pre- and post-tests confirmed a significant improvement in the students’ factual knowledge after the first year; however, the post-project tests only showed a coupling of that knowledge with a recognition of cause-and-effect relations in sporadic cases. Beyond factual knowledge, it is above all a grasp of the interconnections between individual system elements that serves as an essential basis of education. Interactive, modern approaches are critical to conveying interdisciplinary knowledge. As part of the “FlussAu:WOW!” project, in the second school year system-based learning is implemented with the help of innovative modeling and simulation software. In both the pre- and post-tests, questions on the students’ interests revealed a high level of motivation to join in the research, and considerable interest in questions concerning nature and the environment. As a result, by the end of the first school year the cooperation between researchers, educators and students had already made a valuable contribution to sustainable river landscape management.     

Chemical,technological, and nutritional characteristics of two lines of “farro” (Triticum turgidum ssp. dicoccum)

In recent years, the renewed interest for foods with a natural image has increased the demand for dry pasta produced from “hulled” wheat such as the Triticum turgidum ssp. dicoccum, also known as “farro”. In order to contribute to the general knowledge, two lines of farro were considered in this study. To have a comparison, an old cultivar of Triticum turgidum ssp. durum (Senatore Cappelli) in addition to a commercial semolina were also examined. All semolina samples were used to produce pasta samples. Results showed some differences among pasta samples that seem to be due not to the presence of specific protein subunits but especially to the quantitative ratio between the different subunits. Results also reconfirmed the role played by the drying technology that is able to affect the sensory characteristics of pasta products.     

Influence of non‐enzymatic glycosylation (glycation) of pea (Pisum sativum) albumins on their enzymatic hydrolysis

The aim of this study was to investigate the influence of non‐enzymatic glycosylation (glycation) on the susceptibility of pea albumins to pepsin hydrolysis. It was proved that the aqueous albumin extract is de facto a nucleo‐glyco‐metalloprotein complex. The non‐enzymatic glycosylation of pea albumins decreased the content of nucleic acids, hexoses and zinc, which bound to this protein. Glycated pea albumins were more susceptible to hydrolysis by pepsin than non‐glycated ones. Copyright © 2005 Society of Chemical Industry