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排序方式: 共有111条查询结果,搜索用时 15 毫秒
1.
Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
2.
Daun Marian Brings Jennifer Krajinski Lisa Stenkova Viktoria Bandyszak Torsten 《Requirements Engineering》2021,26(3):325-370
Requirements Engineering - Collaborative cyber-physical systems are capable of forming networks at runtime to achieve goals that are unachievable for individual systems. They do so by connecting to... 相似文献
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Marie Ebeyer-Masotta Tanja Eichhorn Ren Weiss Vladislav Semak Lucia Laukov Michael B. Fischer Viktoria Weber 《International journal of molecular sciences》2022,23(3)
Inflammation and thrombosis are closely intertwined in numerous disorders, including ischemic events and sepsis, as well as coronavirus disease 2019 (COVID-19). Thrombotic complications are markers of disease severity in both sepsis and COVID-19 and are associated with multiorgan failure and increased mortality. Immunothrombosis is driven by the complement/tissue factor/neutrophil axis, as well as by activated platelets, which can trigger the release of neutrophil extracellular traps (NETs) and release further effectors of immunothrombosis, including platelet factor 4 (PF4/CXCL4) and high-mobility box 1 protein (HMGB1). Many of the central effectors of deregulated immunothrombosis, including activated platelets and platelet-derived extracellular vesicles (pEVs) expressing PF4, soluble PF4, HMGB1, histones, as well as histone-decorated NETs, are positively charged and thus bind to heparin. Here, we provide evidence that adsorbents functionalized with endpoint-attached heparin efficiently deplete activated platelets, pEVs, PF4, HMGB1 and histones/nucleosomes. We propose that this elimination of central effectors of immunothrombosis, rather than direct binding of pathogens, could be of clinical relevance for mitigating thrombotic complications in sepsis or COVID-19 using heparin-functionalized adsorbents. 相似文献
5.
Olena V. Moshynets Taras P. Baranovskyi Olga S. Iungin Nadiia P. Kysil Larysa O. Metelytsia Ianina Pokholenko Viktoria V. Potochilova Geert Potters Kateryna L. Rudnieva Svitlana Y. Rymar Ivan V. Semenyuta Andrew J. Spiers Oksana P. Tarasyuk Sergiy P. Rogalsky 《International journal of molecular sciences》2022,23(2)
The choice of effective biocides used for routine hospital practice should consider the role of disinfectants in the maintenance and development of local resistome and how they might affect antibiotic resistance gene transfer within the hospital microbial population. Currently, there is little understanding of how different biocides contribute to eDNA release that may contribute to gene transfer and subsequent environmental retention. Here, we investigated how different biocides affect the release of eDNA from mature biofilms of two opportunistic model strains Pseudomonas aeruginosa ATCC 27853 (PA) and Staphylococcus aureus ATCC 25923 (SA) and contribute to the hospital resistome in the form of surface and water contaminants and dust particles. The effect of four groups of biocides, alcohols, hydrogen peroxide, quaternary ammonium compounds, and the polymeric biocide polyhexamethylene guanidine hydrochloride (PHMG-Cl), was evaluated using PA and SA biofilms. Most biocides, except for PHMG-Cl and 70% ethanol, caused substantial eDNA release, and PHMG-Cl was found to block biofilm development when used at concentrations of 0.5% and 0.1%. This might be associated with the formation of DNA–PHMG-Cl complexes as PHMG-Cl is predicted to bind to AT base pairs by molecular docking assays. PHMG-Cl was found to bind high-molecular DNA and plasmid DNA and continued to inactivate DNA on surfaces even after 4 weeks. PHMG-Cl also effectively inactivated biofilm-associated antibiotic resistance gene eDNA released by a pan-drug-resistant Klebsiella strain, which demonstrates the potential of a polymeric biocide as a new surface-active agent to combat the spread of antibiotic resistance in hospital settings. 相似文献
6.
Seksan Udomsri Chris BalesAndrew R. Martin Viktoria Martin 《Energy and Buildings》2011,43(12):3311-3321
This article presents the monitoring results of a thermally driven chiller (TDC) driven by district heat from a network supplied by a centralised combined heat and power (CHP) fired with municipal waste. The main objective of this article is to analyse the monitoring results obtained from the demonstration and calibrate a system model that is later used for parametric studies in order to find improved system design and control. The calibration of the system model was made in three stages and all the energy performance figures were within 4% of the measured values. Results show that the TDC system is capable of providing maximum thermal and electrical COP's of 0.50 and 4.6 respectively during the hottest period. For the complete monitoring period during the summer of 2008, the figures were 0.41 and 2.1. The lower figures were due to continuous pump operation inside the TDC even during periods of no cold production and a period when no cold was produced. However the internal pumps inside the TDC have been removed in the new version TDC to increase the electrical COP. System simulation and parametric studies will be employed to further determine how the electrical COP can be improved. 相似文献
7.
Dipl.-Ing. Gunter Gschwandtner Robert Galler Viktoria Wörgetter Franz Riepler Sylke Hilberg 《BHM Berg- und Hüttenm?nnische Monatshefte》2013,158(2):53-59
The assessment of the stability of underground structures is an interdisciplinary task which consists of geology, hydrogeology, surveying and geotechnical engineering. This paper gives an example of how these disciplines, their methods and the acquisition of data work together to create a complex three-dimensional computer-model of underground structures. It demonstrates, that especially the complex layout of old and “grown” underground structures cannot be represented accurately in two-dimensional analyses or models and provide no realistic results for stability investigations. Related to the stability of underground structures, a non-negligible factor is the influence of water, whether surface, rain or groundwater. The occurring leaching process of gypsum leads to a weakening of the surrounding rock which causes a strength reduction. This softening of the material must be considered in long-term simulations. The presented comprehensive approach tries to provide a possibility to predict the time-dependent occurrence of vulnerabilities in the rock mass and thus gives the possibility to install support measures in an early stage. 相似文献
8.
Water kefir is a home made fermented beverage based on a sucrose solution with fruit extracts. The inoculum of such fermentations consists of macroscopic granula containing lactic and acetic acid bacteria, and yeasts, which are embedded in an exopolysaccharide (EPS) matrix. In this work, a strain of Lactobacillus hilgardii producing large amounts of the granule-forming dextran could be isolated. The glycosyltransferans (Gtf) commonly called glucansucrase responsible for the production of this dextran was purified from L. hilgardii. Characteristic enzyme kinetic data were obtained. Optimum activity was observed between pH 4.3 and 4.6 and temperatures between 40 °C and 45 °C. A Michaelis–Menten kinetic could be fit to the experimental data and a KM of 0.0385 M was calculated. The corresponding gtf gene was identified and characterized. It encodes a 1448 amino acid protein with higher homologies to Gtfs of Lactobacillus parabuchneri, Lactobacillus sakei and Lactobacillus fermentum followed by lower homologies to Lactobacillus reuteri Gtfs. By knockout experiments the role of this gene in granule dextran production was demonstrated. 相似文献
9.
Renata Reisfeld Tsiala Saraidarov Gerard Panzer Viktoria Levchenko Michael Gaft 《Optical Materials》2011,34(2):351-354
In our search for efficient Luminescent Solar Concentrators (LSC) we have prepared polyvinyl pyrrolidone (PVP) films incorporated by ethylenediamine tetraacetic acid (EDTA) complex of europium and co-doped with silver nanoparticles (NPs). Steady state fluorescence was studied under weak and strong excitation. Dynamical study was performed by second harmonic of Nd laser. Under weak excitation the fluorescence of europium co-doped with silver plasmons increased by a factor of three and excited by continuous laser by a factor of 50. The lifetimes of films doped by the complex were 755 μs and co-doped with silver nanoparticles 946 μs. This is the first finding that the photon density accumulates the number of plasmons interacting with electronic states of europium increasing its transition probability resulting in the strong intensification of fluorescence. In dynamical measurements of lifetimes a single pulse does not provide enough energy to create such number of plasmons. 相似文献
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