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排序方式: 共有252条查询结果,搜索用时 15 毫秒
1.
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
2.
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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M Bangerter F Moog I Buchmann J Kotzerke M Griesshammer M Hafner K Elsner N Frickhofen SN Reske L Bergmann 《Canadian Metallurgical Quarterly》1998,9(10):1117-1122
BACKGROUND: Staging of Hodgkin's disease (HD) is accomplished by a variety of invasive and non-invasive modalities. This prospective study was undertaken to investigate the value of whole-body positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) in defining regions involved by lymphoma compared with conventional staging methods in patients with HD. PATIENTS AND METHODS: Fourty-four newly diagnosed patients with HD underwent FDG-PET as part of their initial staging work-up. PET findings were correlated with findings of conventional staging including computed tomography, ultrasound, bone scanning, bone marrow biopsy, liver biopsy and laparotomy. When results of FDG-PET differed to those obtained by conventional methods reevaluation was performed by biopsy, if possible, or magnetic resonance imaging. RESULTS: The results of FDG-PET were compared with three hundred twenty-one conventional staging procedures performed in 44 patients. FDG-PET was positive in 38 of 44 (86%) patients at sites of documented disease. PET detected additional lesions in five cases previously not identified by conventional staging methods. In another case a nodal lesion suspect on CT was negative at FDG-PET and was settled as true negative by biopsy. As a consequence of PET findings five patients had to be upstaged and one patient had to be downstaged, resulting in changes in treatment strategy in all six cases (14%). FDG-PET failed to visualize sites of HD in four patients. In two of our patients a false positive PET result was obtained. CONCLUSIONS: Our data indicate that FDG-PET provides an imaging technique that appears to visualize involved lesions in most patients with HD and is useful in the management of these patients. 相似文献
6.
Laura Nicolle Jens Casper Melanie Willimann Cline M. A. Journot Pascal Detampel Toma Einfalt Hiu Man Grisch-Chan Beat Thny Sandrine Gerber-Lemaire Jrg Huwyler 《International journal of molecular sciences》2021,22(8)
There is an increasing interest in cationic polymers as important constituents of non-viral gene delivery vectors. In the present study, we developed a versatile synthetic route for the production of covalent polymeric conjugates consisting of water-soluble depolymerized chitosan (dCS; MW 6–9 kDa) and low molecular weight polyethylenimine (PEI; 2.5 kDa linear, 1.8 kDa branched). dCS-PEI derivatives were evaluated based on their physicochemical properties, including purity, covalent bonding, solubility in aqueous media, ability for DNA condensation, and colloidal stability of the resulting polyplexes. They were complexed with non-integrating DNA vectors coding for reporter genes by simple admixing and assessed in vitro using liver-derived HuH-7 cells for their transfection efficiency and cytotoxicity. Using a rational screening cascade, a lead compound was selected (dCS-Suc-LPEI-14) displaying the best balance of biocompatibility, cytotoxicity, and transfection efficiency. Scale-up and in vivo evaluation in wild-type mice allowed for a direct comparison with a commercially available non-viral delivery vector (in vivo-jetPEI). Hepatic expression of the reporter gene luciferase resulted in liver-specific bioluminescence, upon intrabiliary infusion of the chitosan-based polyplexes, which exceeded the signal of the in vivo jetPEI reference formulation by a factor of 10. We conclude that the novel chitosan-derivative dCS-Suc-LPEI-14 shows promise and potential as an efficient polymeric conjugate for non-viral in vivo gene therapy. 相似文献
7.
Rabbits were fed diets enriched with cholestanol or cholestereol (3.5 g/wk) for 4–12 weeks. During cholestanol feeding, the
concentration of cholestanol in blood serum, liver, heart and aorta increased 15–30 times. In serum and liver, the concentration
of cholesterol also increased. Cholestanol-fed rabbits developed inflammatory changes in the liver, with proliferation of
small bile ducts. Liver tests were only slightly abnormal. Morphological atherosclerosis of the aorta was only occasionally
seen in rabbits receiving cholestanol for eight weeks or less.
During cholesterol feeding, the amounts of cholesterol in different tissues increased dramatically, most in the aorta. Morphological
atherosclerosis in the aorta was found in all rabbits fed cholesterol-enriched diets for more than four weeks. Brain cholestanol
was doubled in rabbits fed cholestanol for eight weeks, whereas brain sterols did not change significantly during cholesterol
feeding. After an additional regression period with cholestyramine for eight weeks, the increased content of cholestanol in
the brain was unchanged in cholestanol-fed rabbits. These observations are discussed in relation to the cholestanolosis of
the brain that develops in the rare inherited human disease cerebrotendinous xanthomatosis. 相似文献
8.
Influence of compaction on the interfacial transition zone and the permeability of concrete 总被引:2,自引:0,他引:2
Andreas Leemann Beat Münch Philippe Gasser Lorenz Holzer 《Cement and Concrete Research》2006,36(8):1425-1433
The interfacial transition zone (ITZ) is regarded as a key feature for the transport properties and the durability of concrete. In this study one self-compacting concrete (SCC) mixture and two conventionally vibrated concrete (CVC) mixtures are studied in order to determine the influence of compaction on the porosity of the ITZ. Additionally oxygen permeability and water conductivity were measured in vertical and horizontal direction. The quantitative analysis of images made with an optical microscope and an environmental scanning electron microscope shows a significantly increased porosity and width of the ITZ in CVC compared to SCC. At the same time oxygen permeability and water conductivity of CVC are increased in comparison to SCC. Moreover, considerable differences in the porosity of the lower, lateral and upper ITZ are observed in both types of concrete. The anisotropic distribution of pores in the ITZ does not necessarily cause anisotropy in oxygen permeability and water conductivity though. 相似文献
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We present an approach to model-driven software product line engineering which is based on feature models and domain models. A feature model describes both common and varying properties of the instances of a software product line. The domain model is composed of a structural model (package and class diagrams) and a behavioral model (story diagrams). Features are mapped onto the domain model by annotating elements of the domain model with features. An element of a domain model is specific to the features included in its feature annotation. An instance of the product line is defined by a set of selected features (a feature configuration). A configuration of the domain model is built by excluding all elements whose feature set is not included in the feature configuration. To ensure consistency of the configured domain model, we define constraints on the annotations of inter-dependent domain model elements. These constraints guarantee that a model element may be selected only when the model elements are also included on which it depends. Violations of dependency constraints may be removed automatically with the help of an error repair tool which propagates features to dependent model elements. 相似文献