A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

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 Lewis^x 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 Lewis^x 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.     

Novel strategy for encapsulation and targeted delivery of poorly water-soluble active substances

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.     

Photo-Chemically-Deposited and Industrial Cu/ZnO/Al2O3 Catalyst Material Surface Structures During CO2 Hydrogenation to Methanol: EXAFS,XANES and XPS Analyses of Phases After Oxidation,Reduction, and Reaction

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...     

How Cancer Cells Invade Bladder Epithelium and Form Tumors: The Mouse Bladder Tumor Model as a Model of Tumor Recurrence in Patients

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.     

Online learning and fusion of orientation appearance models for robust rigid object tracking

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.     

Dissecting the protocol and network traffic of the OnLive cloud gaming platform

Cloud gaming is a new paradigm that is envisaged to play a pivotal role in the video game industry in forthcoming years. Cloud gaming, or gaming on demand, is a type of online gaming that allows on-demand streaming of game content onto non-specialised devices (e.g. PC, smart TV, etc.). This approach requires no downloads or game installation because the actual game is executed on the game company’s server and is streamed directly to the client. Nonetheless, this revolutionary approach significantly affects the network load generated by online games. As cloud gaming presents new challenges for both network engineers and the research community, both groups need to be fully conversant with these new cloud gaming platforms. The purpose of this paper is to investigate OnLive, one of the most popular cloud gaming platforms. Our key contributions are: (a) a review of the state-of-the-art of cloud gaming; (b) reverse engineering of the OnLive protocol; and (c) a synthetic traffic model for OnLive.