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Dr. Christopher M. Schneider Dr. Wei Li Dr. Kriangsak Khownium Dr. Gerald H. Lushington Prof. Dr. Gunda I. Georg 《ChemMedChem》2016,11(15):1600-1616
Analogues of the anticancer natural product oximidine II were prepared and evaluated for cytotoxicity. One analogue of oximidine II that carries a C15 allylic amide side chain as well as two analogues with C15 vinyl sulfone side chains were found to lack cytotoxicity against the cancer cell line SK‐Mel‐5, thereby confirming the necessity of the C15 enamide side chain of oximidine II for cytotoxicity. Four analogues, designed by comparative molecular similarity index analysis (CoMSIA), that feature a less complex macrolactone scaffold were prepared and tested. The two analogues carrying a C15 vinyl sulfone group and the two analogues with a C15 oximidine II enamide side chain showed weak cytotoxicity against the SK‐Mel‐5 cell line and other cell lines, indicating that the designed simplified macrocycles cannot replace the oximidine II macrocycle. 相似文献
74.
Jonas Winkelbauer Georg Puchas Stefan Schafföner Walter Krenkel 《International Journal of Applied Ceramic Technology》2022,19(2):1136-1147
This paper presents a novel fiber spraying process for the manufacturing of short fiber bundle-reinforced Nextel™ 610/Al2O3-ZrO2 oxide fiber composites (SF-OFC) and its characterization. First, the influence of varying fiber lengths (7, 14, and 28 mm, continuous fibers) and fiber orientations (unidirectional 0°, quasi-isotropic, ±45°) was investigated using hand-laid SF-OFC. Due to the weak matrix, the hand-laid material exhibited a strongly fiber-dominated material behavior, that is, variations in fiber length and orientation had a strong influence on the material properties. Second, the automated sprayed SF-OFC, however, exhibited a random orientation of the fiber bundles, which resulted in in-plane isotropic material properties. Average bending strengths of up to 177 MPa, strains of .39%, and a quasi-ductile fracture behavior were achieved. The strain was, therefore, in the range of fabric-reinforced OFC. While the bending strength of the SF-OFC was somewhat lower than that of fabric-reinforced OFC with the fiber orientation parallel to the loading direction, it was more than two times higher than the strength in 45° direction relative to the fabric reinforcement. Combined with good drapability and lower material costs compared to fabric-reinforced OFC, SF-OFC is, therefore, a promising material for industrial applications. 相似文献
75.
M. Faber Frank Jst Reiner Manstetten Georg MüllerFürstenberger 《Advanced Synthesis \u0026amp; Catalysis》1996,338(1):497-505
Joint Production and Environmental Policy: A Case Study for the Chlorine and Sulphuric Acid Industry The chemical industry is a key sector of industrialised economy. Thus, environmental policy with a focus on the chemical industry is likely to affect the economy as a whole. In this article we show, that environmental regulation of the chemical industry has major consequences for other production sectors. Two major problem areas of the chemical industry are considered: the chlorine industry and the sulphur industry. While the chlorine industry can cope with environmental legislation by process and product innovation without a substantial impact on other sectors, this is not the case with the sulphur industry. The production of its key product, sulphuric acid, utilises joint products of other sectors as inputs. The chemical industry offers these sectors the possibility to dispose of their unwanted by-products. Environmental policy, directed towards a reduction of sulphuric acid is likely to cause a waste disposal problem in sectors which manufacture sulphur or sulphur dioxide as by-products. Solving environmental problems within the chemical industry therefore creates new problems in other sectors. 相似文献
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Cindy Bay Gzona Bajraktari-Sylejmani Walter E. Haefeli Jürgen Burhenne Johanna Weiss Max Sauter 《International journal of molecular sciences》2022,23(7)
The solute carrier L-type amino acid transporter 1 (LAT-1/SLC7A5) is a viable target for drug delivery to the central nervous system (CNS) and tumors due to its high abundance at the blood–brain barrier and in tumor tissue. LAT-1 is only localized on the cell surface as a heterodimer with CD98, which is not required for transporter function. To support future CNS drug-delivery development based on LAT-1 targeting, we established an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) assay for stable isotopically labeled leucine ([13C6, 15N]-L-leucine), with a dynamic range of 0.1–1000 ng/mL that can be applied for the functional testing of LAT-1 activity when combined with specific inhibitors and, consequently, the LAT-1 inhibition capacity of new compounds. The assay was established in a 96-well format, facilitating high-throughput experiments, and, hence, can support the screening for novel inhibitors. Applicable recommendations of the US Food and Drug Administration and European Medicines Agency for bioanalytical method validation were followed to validate the assay. The assay was applied to investigate the IC50 of two well-known LAT-1 inhibitors on hCMEC/D3 cells: the highly specific LAT-1 inhibitor JPH203, which was also used to demonstrate LAT-1 specific uptake, and the general system L inhibitor BCH. In addition, the [13C6, 15N]-L-leucine uptake was determined on two human brain capillary endothelial cell lines (NKIM-6 and hCMEC/D3), which were characterized for their expressional differences of LAT-1 at the protein and mRNA level and the surface amount of CD98. The IC50 values of the inhibitors were in concordance with previously reported values. Furthermore, the [13C6, 15N]-L-leucine uptake was significantly higher in hCMEC/D3 cells compared to NKIM-6 cells, which correlated with higher expression of LAT-1 and a higher surface amount of CD98. Therefore, the UPLC-MS/MS quantification of ([13C6, 15N]-L-leucine is a feasible strategy for the functional characterization of LAT-1 activity in cells or tissue. 相似文献
78.
Prof. Dr. Manfred Grote Dipl. Chem.-Ing. Didem Hanim Meriç Dr. Georg Langenkämper Dr. Heiko Hayen Dr. Thomas Betsche Prof. Dr. Mechthild Freitag 《Journal für Verbraucherschutz und Lebensmittelsicherheit》2009,4(3-4):287-304
Investigation on the transfer of pharmacologically active substances used in animal husbandry into leek and cabbage. The potential of leek and cabbage for uptake of highly prescribed veterinary drugs (antibiotics) was tested in hydroponically grown plants. For this purpose the antibiotics sulfadiazine (SFD), enrofloxacine (ENR), tetracycline (TC), chlortetracycline (CTC) and monensine (MON) were chosen. A further aim was to gain data on the situation of vegetables grown in agricultural practise with regard to antibiotic residues. The evident effects of the antibiotics on plants grown hydroponically (each antibiotic was administered at 5 μmol/l nutrient solution) were greatly different: With regard to leek there were no visible effects (MON, SFD), a weak bleaching of the younger leaf sections (CTC), and strong effects of ENR. The (phytotoxic) effects of antibiotics on cabbage were much more distinct. CTC caused a yellowing of the plant vasculature in cabbage. MON induced lesions on some leaves and finally led to leaf wilting. With administration of ENR a nearly complete bleaching of young leaves was observed. Using LC-MS/MS-methods (low-resolution and high-resolution MS) the administered antibiotics, as well as conversion products and metabolites, were separately identified and quantified in various organs of leek (roots, young and old sections of leaves) and cabbage (roots, stalks, young and old leaves). Depending on the type of antibiotic, vegetable species, and plant organ, the detected concentrations of antibiotic residues comprised several orders of magnitude ranging from μg/kg to mg/kg of fresh weight (fw). The highest concentrations of antibiotics were found in roots of both vegetable species: CTC and TC were detected at approximately 10 mg/kg fw in cabbage roots and at approximately 20 mg/kg fw in leek roots and ENR was determined at approximately 12 mg/kg fw in cabbage roots. Low amounts of ENR were metabolised to ciprofloxacine (CIP). ENR occurred at similar concentrations of approximately 7 mg/kg fw in roots and old leaves of cabbage, indicating a high transport rate of this antibiotic in the cabbage plant. In stalks, young and old leaves of cabbage and in young and old leaf sections of leek all administered antibiotics were detected. Within these antibiotics, ENR and CTC and their conversion products, e. g. demeclocycline (DMC) and TC, occurred at the highest concentrations. SFD and MON were found in considerably lower concentrations (<100 μg/kg fw). The results of our experiments in hydroponic cultures, using defined concentrations of antibiotics in the nutrient solution, evidently demonstrate that cabbage and leek have a very high potential for uptake of a number of veterinary antibiotic drugs, especially for tetracycline and ENR. 相似文献
79.
Thomsen C Knutsen HK Liane VH Frøshaug M Kvalem HE Haugen M Meltzer HM Alexander J Becher G 《Molecular nutrition & food research》2008,52(2):228-237
Very high concentrations of polybrominated diphenyl ethers (PBDE) have been reported in fish from Lake Mj?sa in Norway. This study was performed to examine the serum concentrations of PBDE and hexabromocyclododecane (HBCD) in consumers of fish from this lake and to investigate possible relationships between serum concentrations, self-reported fish intake and calculated total dietary PBDE exposure. Serum concentrations of the sum of the seven PBDE (BDE-28, 47, 99, 100, 153, 154 and 183) were significantly higher than those of a reference group of Norwegians eating only food with background levels of contamination (medians: 18 ng/g lipids men, 8.4 ng/g lipids women). The median dietary intake of Sum 7 PBDE was 2549 ng/day (30 ng/kg body weight/day), the highest dietary intake of PBDE reported. The contribution from fish caught from the contaminated lake comprised 98.7% of the total dietary exposure. For men, serum levels of PBDE were strongly correlated with the calculated dietary exposure, except for BDE-209. This suggests that sources other than the diet are important for human BDE-209 exposure. The median serum HBCD concentration was 4.1 and 2.6 ng/g lipids for men and women, respectively, and was also found to be associated with consumption of fish from Lake Mj?sa. 相似文献
80.
Staphylococcus aureus remains a leading cause of food-poisoning with substantial impact on public health. Using a multiplex polymerase chain reaction-DNA enzyme immunoassay (PCR-DEIA), we studied the presence of genes encoding staphylococcal enterotoxin-like (SEl) superantigens sem, sen, and seo, associated with the enterotoxin gene cluster (egc), in 429 clinical Staphylococcus aureus isolates. 294 (68.5%) isolates tested positive for at least one of the three SEl genes. In contrast to the fixed gene combination seg/sei also located on egc, a substantial number of isolates (n = 108) were found to bear only one or two of the genes encoding SElM, SElN, and SElO. Regarding the origin of the S. aureus isolates, a significant difference (P = 0.022) was found for the possession of seo (61.2% of blood isolates versus 42.9% of nasal strains). Also sem (not significantly) was found more common in blood isolates (52.1% versus 40.5%). The survey of the newly described SEl genes sem-seo supports the concept that most clinical S. aureus isolates harbor subsets of pyrogenic toxin superantigens. The potential contribution of seo and sem to the pathogenic potential of S. aureus has to be further evaluated. 相似文献