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.     

Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5

This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC₅₀=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma.     

Controllability of One Spin and Two Interacting Spins

Mathematics of Control, Signals, and Systems - ?We consider the problem of steering control for the systems of one spin ½ particle and two interacting spin ½ particles in an...     

A Neural Network Model of Caenorhabditis Elegans: The Circuit of Touch Sensitivity

The paper presents a neural network model of the touch sensitivity circuit of the nematode Caenorhabditis elegans. We describe a serie of simulations in which neural networks are trained, using a genetic algorithm, to reproduce the habituation of the nematode's touch sensitive behavior. A lesion study of the network allows to make a direct comparison between the fine functioning of the model and the data collected in real organisms. The model accords well with the known neurobiological data and it suggests some hypotheses about the functioning of the neural circuit and of single neurons.     

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.     

Convolution profiles for right inversion of multivariable non-minimum phase discrete-time systems

The problem of the non-causal inversion of linear multivariable discrete-time systems is analyzed in the geometric approach framework and is solved through the computation of convolution profiles which guarantee perfect tracking under the assumption of infinite-length preaction and postaction time intervals. It is shown how the shape of the convolution profiles is related to both the relative degree and the invariant zeros of the plant. A computational setting for the convolution profiles is derived by means of the standard geometric approach tools. Feasibility constraints are also taken into account. A possible implementation scheme, based on a finite impulse response system acting on a stabilized control loop, is provided.