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Dr. Blijke S. Kroezen Gabriele Conti Benedetta Girardi Dr. Jonathan Cramer Dr. Xiaohua Jiang Dr. Said Rabbani Jennifer Müller Maja Kokot Enrico Luisoni Prof. Daniel Ricklin Dr. Oliver Schwardt Prof. Beat Ernst 《ChemMedChem》2020,15(18):1706-1719
Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewisx has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewisx and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved. 相似文献
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High‐intensity sweeteners in espresso coffee: ideal and equivalent sweetness and time–intensity analysis
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Bruna M. Azevedo Flávio L. Schmidt Helena M. A. Bolini 《International Journal of Food Science & Technology》2015,50(6):1374-1381
The efficient substitution of sucrose by a sweetener in beverages requires the application of some sensory techniques. First, one must determine the concentrations of the sweeteners under study, equivalent in sweetness to the ideal sucrose concentration. In addition, it is fundamental to determine which is most similar to sucrose. The objectives of this study were to determine the ideal sweetness for espresso coffee and the equivalent concentrations in sweetness of different sweeteners, as well as characterise the time–intensity profile of each sweetener in relation to sweetness. The sweeteners evaluated were sucralose, aspartame, neotame, a cyclamate/saccharin mixture (2:1) and stevia. The sucrose concentration considered ideal by consumers was 12.5% (w/v), and the equivalent concentrations of the sweeteners were 0.0159% for sucralose, 0.0549% for aspartame, 0.0016% for neotame, 0.0359% for the cyclamate/saccharin mixture and 0.0998% for stevia. The time–intensity analysis indicated that possibly the sweeteners neotame, aspartame and sucralose would be the best substitutes for sucrose. 相似文献
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Dr. Vlastimil Jirasko Dr. Nils-Alexander Lakomek Dr. Susanne Penzel Dr. Marie-Laure Fogeron Prof. Dr. Ralf Bartenschlager Prof. Dr. Beat H. Meier Dr. Anja Böckmann 《Chembiochem : a European journal of chemical biology》2020,21(10):1453-1460
Proton-detected 100 kHz magic-angle-spinning (MAS) solid-state NMR is an emerging analysis method for proteins with only hundreds of microgram quantities, and thus allows structural investigation of eukaryotic membrane proteins. This is the case for the cell-free synthesized hepatitis C virus (HCV) nonstructural membrane protein 4B (NS4B). We demonstrate NS4B sample optimization using fast reconstitution schemes that enable lipid-environment screening directly by NMR. 2D spectra and relaxation properties guide the choice of the best sample preparation to record 2D 1H-detected 1H,15N and 3D 1H,13C,15N correlation experiments with linewidths and sensitivity suitable to initiate sequential assignments. Amino-acid-selectively labeled NS4B can be readily obtained using cell-free synthesis, opening the door to combinatorial labeling approaches which should enable structural studies. 相似文献
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A theoretical model is presented by which a true expression of pregnancy rate resulting from stimulated cycles can be calculated. This includes the transfer of both fresh and cryopreserved embryos. It is concluded that the total reproductive potential of a single cycle of stimulation can only be evaluated by including pregnancies arising from all fresh and frozen embryo transfers resulting from that cycle. 相似文献
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Flávio A. Pavan Sidinei A. Gobbi Celso C. Moro Tania M.H. Costa Edilson V. Benvenutti 《Journal of Porous Materials》2002,9(4):307-311
Anilinepropylsilica hybrid powder was synthesized by a sol-gel route in basic medium using HF as catalyst. The effect of the amount of HF catalyst on the morphologies and on organic content was studied. The xerogels were characterized using FTIR, SEM and N2 adsorption-desorption isotherms. The increase in the HF quantity results in an slight increase in organic content and changes in the particle size, surface area and pore structure. 相似文献
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VA Fl?renes N Bhattacharya MR Bani Y Ben-David RS Kerbel JM Slingerland 《Canadian Metallurgical Quarterly》1996,13(11):2447-2457
We have studied TGF-beta mediated G1 arrest in WM35, an early stage human melanoma cell line. These cells have lost p15INK4B expression through loss of one chromosome 9 and rearrangement of the other. In asynchronously growing WM35, TGF-beta caused reductions in cyclin D1, cyclin A and cdk4 proteins and their associated kinase activities and an increase in both p21Cip1/WAF1 and p27Kip1. These findings were confirmed in cells released from quiescence in the presence of TGF-beta, in which TGF-beta inhibited or delayed the reduction in the cdk inhibitors that normally occurs in late G1. In contrast to observations in other cell types, there was an increased association of both p21Cip1/WAF1 and p27Kip1 with cyclin D1/cdk4 and with cyclin E/cdk2 during TGF-beta mediated arrest of asynchronously growing cells. Upregulation of p21Cip1/WAF1 preceded that of p27Kip1. Furthermore, p21Cip1/WAF1 and p27Kip1 were not present in the same cdk complexes but bound distinct populations of target cdk molecules. Both p21Cip1/WAF1 and p27Kip1 immunoprecipitates from asynchronously growing cells contained active kinase complexes. These KIP-associated kinase activities were reduced in TGF-beta arrested cells. It has been proposed that in TGF-beta arrested epithelial cells, up-regulation of p15INK4B and of p15INK4B binding to cdk4 serves to destabilize the association of p27Kip1 with cyclin D1/cdk4, promoting p27Kip1 binding and inhibition of cyclin E/cdk2. Our findings demonstrate that this is not a universal mechanism of G1 arrest by TGF-beta. In TGF-beta arrested WM35, which lack p15INK4B, the increased p21Cip1/WAF1 may serve a similar function to that of p15INK4B: initiating kinase inhibition and providing an additional mechanism to supplement the effect of p27Kip1 on G1 cyclin/cdks. 相似文献
9.
Karin Metz Stephanie Fl?ter Christoph Kr?ger Carolin Donath Daniela Piontek Sabine Gradl 《Nicotine & tobacco research》2007,9(8):853-863
Smokers with smoking-related diseases who are hospitalized in rehabilitation centers should be offered smoking cessation. This is the first study evaluating whether telephone booster sessions after intensive inpatient treatment are an effective strategy. The present study was conducted in 13 rehabilitation centers for somatic disorders as a prospective multicenter study with a randomized treatment-control group design. We compared abstinence rates after hospital discharge from treatment that included a group smoking cessation program with (treatment group) and without telephone booster sessions (control group). Data from 290 smokers were analyzed. After 6 and 12 months the treatment group achieved abstinence rates twice as high as those of the control group. Men profited more from telephone booster sessions than did women. Results indicated that telephone booster sessions were highly effective (even) after an inherently intensive group program during a hospital stay. Further research should focus on the special needs of women receiving telephone counseling. 相似文献
10.
Two different generators for ozone were tested, a traditional electrical discharge generator and a generator based upon UV–irradiation of air at 150–180 nm. It was demonstrated that the traditional generator gave slightly higher reductions in levels of color for equivalent ozone dosages. Both gases affected the molecular weight distribution in the way that the bigger molecules were broken down to smaller ones. No significant difference between the molecular weight reduction efficiency of the gases was found. 相似文献