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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
3.
Maja D. Markovic Vesna V. Panic Sanja I. Seslija Ana D. Milivojevic Pavle M. Spasojevic Nevenka M. Boskovic-Vragolovic Rada V. Pjanovic 《Polymer Engineering and Science》2020,60(8):2008-2022
Carriers for targeted delivery and controlled release of poorly water-soluble active substances (PWSAS) are facing three challenges: (a) the encapsulation issues, (b) limitations of PWSAS water solubility, and (c) burst drug release which can be pharmacologically dangerous and economically inefficient. The present study brings a novel strategy for encapsulation and controlled release of PWSAS—caffeine in concentrations which are higher than its maximal water solubility without the possibility of burst effect. The modification of hydrophilic carrier based on poly(methacylic acid) was done using casein and liposomes. To further increase the maximal caffeine loading inside the carrier nicotinamide was used. The release study of the encapsulated PWSAS was elaborated with respect to morphology of the carriers and interactions that could be established between its structural components. The carriers swelling and the release of caffeine and nicotinamide were also investigated depending on caffeine concentration, the presence of different liposomal formulations and the volume ratio of liposomal formulation, in three media with different pH simulating the path of the carrier through the human gastrointestinal tract. The synthesized carriers are promising candidates for encapsulation of PWSAS in concentrations which are higher than its maximal water solubility and for the targeted delivery of those dosages. 相似文献
4.
Andrew Klapper 《Journal of Cryptology》1994,7(1):33-51
A new method of cryptologic attack on binary sequences is given, using their linear complexities relative to odd prime numbers. We show that, relative to a particular prime number p, the linear complexity of a binary geometric sequence is low. It is also shown that the prime p can be determined with high probability by a randomized algorithm if a number of bits much smaller than the linear complexity is known. This determination is made by exploiting the imbalance in the number of zeros and ones in the sequences in question, and uses a new statistical measure, the partial imbalance.This project was sponsored by the National Security Agency under Grant No. MDA904-91-H-0012. The United States Government is authorized to reproduce and distribute reprints notwithstanding any copyright notation hereon. 相似文献
5.
Pori Maja Arčon Iztok Dasireddy Venkata D. B. C. Likozar Blaž Orel Zorica Crnjak Marinšek Marjan 《Catalysis Letters》2021,151(11):3114-3134
Catalysis Letters - Industrial Cu/ZnO/Al2O3 or novel rate catalysts, prepared with a photochemical deposition method, were studied under functional CH3OH synthesis conditions at the set temperature... 相似文献
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Andreja Erman Urka Kamenek Urka Dragin Jerman Mojca Pavlin Maja emaar Peter Verani
Rok Romih 《International journal of molecular sciences》2021,22(12)
Non-muscle-invasive bladder cancer is the most common form of bladder cancer. The main problem in managing bladder tumors is the high recurrence after the transurethral resection of bladder tumors (TURBT). Our study aimed to examine the fate of intravesically applied cancer cells as the implantation of cancer cells after TURBT is thought to be a cause of tumor recurrence. We established an orthotopic mouse bladder tumor model with MB49-GFP cancer cells and traced them during the first three days to define their location and contacts with normal urothelial cells. Data were obtained by Western blot, immunolabeling, and light and electron microscopy. We showed that within the first two hours, applied cancer cells adhered to the traumatized epithelium by cell projections containing α3β1 integrin on their tips. Cancer cells then migrated through the epithelium and on day 3, they reached the basal lamina or even penetrated it. In established bladder tumors, E-cadherin and desmoplakin 1/2 were shown as feasible immunohistochemical markers of tumor margins based on the immunolabeling of various junctional proteins. Altogether, these results for the first time illustrate cancer cell implantation in vivo mimicking cellular events of tumor recurrence in bladder cancer patients. 相似文献
8.
Ioannis Marras Georgios Tzimiropoulos Stefanos Zafeiriou Maja Pantic 《Image and vision computing》2014
We introduce a robust framework for learning and fusing of orientation appearance models based on both texture and depth information for rigid object tracking. Our framework fuses data obtained from a standard visual camera and dense depth maps obtained by low-cost consumer depth cameras such as the Kinect. To combine these two completely different modalities, we propose to use features that do not depend on the data representation: angles. More specifically, our framework combines image gradient orientations as extracted from intensity images with the directions of surface normals computed from dense depth fields. We propose to capture the correlations between the obtained orientation appearance models using a fusion approach motivated by the original Active Appearance Models (AAMs). To incorporate these features in a learning framework, we use a robust kernel based on the Euler representation of angles which does not require off-line training, and can be efficiently implemented online. The robustness of learning from orientation appearance models is presented both theoretically and experimentally in this work. This kernel enables us to cope with gross measurement errors, missing data as well as other typical problems such as illumination changes and occlusions. By combining the proposed models with a particle filter, the proposed framework was used for performing 2D plus 3D rigid object tracking, achieving robust performance in very difficult tracking scenarios including extreme pose variations. 相似文献
9.
Summary Novel organic nanoparticles functionalized with nucleophilic polypropyleneoxide (PPO) chains on their surfaces for supporting metallocene catalysts in heterogeneous olefin polymerization are presented. The nanoparticles (60–100 nm) were obtained by miniemulsion polymerization of styrene, divinylbenzene and PPO functionalized styrene. It is demonstrated that Me2Si(2MeBenzlnd)2ZrCl2/MAO supported on these nanoparticles is suitable for the homopolymerization of ethylene, resulting in excellent product morphologies and high activities. lt is shown that by varying the MAO/Zr ratios and Zr concentrations the activities and productivities of the catalysts as well as the qualities of the polyethylene products can be tuned. These new supported catalysts are also suitable for the copolymerization of ethylene with several comonomers (1-hexene, 1-octene, 1-decene or norbornene). As the obtained product properties like crystallinity, melting temperature or bulk density match the results of silica supported systems, these organic nanoparticles can be considered as alternative carriers in comparison to the established inorganic ones. 相似文献
10.
Summary The synthesis of in-situ hydrophobic functionalized ZnO nanoparticles via an emulsion process is systematically investigated.
Different parameters are varied, such as precursor salt concentration and ultrasonification, to optimize the size and the
size distribution of the ZnO particles. Particles with a size below 25 nm and surrounded by a hydrophobic polymer shell can
be easily obtained. The influence of the polymeric shell on the compatibility with different polymeric matrices is described.
Due to the small size of the inorganic particles and the excellent hydrophobization, highly transparent inorganic/organic
nanocomposites can be obtained by spin-coating and extrusion. 相似文献