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.     

La0.6Sr0.4Co0.2Fe0.8O3-δ nanofiber cathode for intermediate-temperature solid oxide fuel cells by water-based sol-gel electrospinning: Synthesis and electrochemical behaviour

Water-based sol-gel electrospinning is employed to manufacture perovskite oxide La_0.6Sr_0.4Co_0.2Fe_0.8O_3-δ (LSCF) nanofiber cathodes for intermediate-temperature solid oxide fuel cells. LSCF fibrous scaffolds are synthesized through electrospinning of a sol-gel solution employing water as the only solvent. Morphological characterizations demonstrate that the LSCF fibers have highly crystalline structure with uniform elemental distribution. After heat treatment, the average fiber diameter is 250 nm and the porosity of the nanofiber tissue is 37.5 %. The heat treated LSCF nanofibers are applied directly onto a Ce_0.9Gd_0.1O_1.95 (CGO) electrolyte disk to form a symmetrical cell. Electrochemical characterization is carried out through electrochemical impedance spectroscopy (EIS) in the temperature range 550?°C–950?°C, and reproducibility of the electrochemical performance for a series of cells is demonstrated. At 650?°C, the average measured polarization resistance R_p is 1.0 Ω cm². Measured performance decay is 1 % during the first 33?h of operation at 750?°C, followed by an additional 0.7 % over the subsequent 70?h.     

A note on the variance of rank-based selection strategies for genetic algorithms and genetic programming

This paper evaluates different forms of rank-based selection that are used with genetic algorithms and genetic programming. Many types of rank based selection have exactly the same expected value in terms of the sampling rate allocated to each member of the population. However, the variance associated with that sampling rate can vary depending on how selection is implemented. We examine two forms of tournament selection and compare these to linear rank-based selection using an explicit formula. Because selective pressure has a direct impact on population diversity, we also examine the interaction between selective pressure and different mutation strategies.     

Hypercoagulability and chronic atrial fibrillation: the role of markers of thrombin generation

BACKGROUND: We have studied 64 patients with congestive heart failure, half of them also with chronic nonvalvular atrial fibrillation (AF). Patients were also stratified according to a history of prior stroke. METHODS: The generation of thrombin was investigated by means of the molecular markers prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin III complex (TAT), because AF patients may have a hypercoagulable state. There was only a trend toward higher values of TAT and F1 + 2 for AF patients, while subjects with previous stroke (irrespective of AF) had increased levels of the markers of thrombin generation (TAT stroke+ 18.95 +/- 5.15 vs TAT stroke- 8.34 +/- 2.41; F1 + 2 stroke+ 2.22 +/- 0.29 vs F1 + 2 stroke- 1.32 +/- 0.12). The presence of spontaneous echo contrast (SEC) within left atrium was also investigated in 32 AF patients by transesophageal echocardiography. RESULTS: TAT were significantly higher in subjects (n = 11) with SEC (TAT sec+ 37.5 +/- 13.41 vs TAT sec- 8.7 +/- 2.51, p = 0.008). CONCLUSIONS: Finally, when we grouped into 1) those with both AF and stroke, 2) AF alone, 3) stroke alone and 4) sinus rhythm without stroke, levels of F1 + 2 were higher (and marginally higher TAT) in patients with AF and stroke than in those without stroke, revealing that there is a true clotting activation state in these subjects.     

User modeling in an OAM support system

This paper outlines studies relative to a research project on the development of a system that permits different people of an enterprise, with different roles and experience, to gain an adequate and personalized vision of the real status of the network and managed systems. What has been achieved is an easy to handle system, which permits quick and simple queries without utilizing complex man machine languages, and tailors personalized answers on the basis of the characteristics of the user. To achieve these results, User Modeling aspects have been considered and pursued.     

A rate adaptive bit-loading algorithm for in-building power-line communications based on DMT-modulated systems

This paper deals with a variable rate discrete multitone modulation system for broadband power-line communications, based on the bit-loading algorithm proposed by Leke and Cioffi. In the proposed system a suitable least mean square channel estimator is considered, which is based on the insertion of a training sequence (TS). The proposed approach will be compared with the ideal channel estimates, showing its effectiveness. Moreover, different TS lengths will be compared. The system performance, expressed in terms of bit rate and bit-error rate, is derived by simulation with and without estimation errors. The propagation environment has been assumed as a frequency-selective multipath fading channel with additive colored Gaussian noise, according to the in-building networks model.