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.     

Formulation and in vitro Evaluation of pH-Sensitive Cross-linked Xanthan Gum-Grafted Acrylic Acid Copolymer for Controlled Delivery of Perindopril Erbumine (PE)

A novel xanthan gum-co-acrylic acid superabsorbent hydrogel composite was formulated by free radical polymerization reaction of acrylic acid on xanthan gum. Effect of variables like dynamic swelling ratio, equilibrium swelling ratio, drug loading and drug release was investigated. Swelling ratio increases with decrease in crosslinker concentration. Drug release studies were conducted in pH 7.4 and 0.1N HCl. In acidic environment, drug release was low whereas it was sustained release in alkaline. XG4 showed significant swelling and drug release up to 24?hr. Physicochemical evaluation also confirmed it was optimized formulation. Hence XG4-co-AA was optimized for once daily dose of Perindopril Erbumine.     

GABA and glutamate levels in the substantia nigra reticulata following repetitive cerebral ischemia in gerbils

Repetitive cerebral ischemia produces more severe damage than a similar single duration insult. We have previously shown that, in gerbils, damage in the substantia nigra reticulata (SNr) is seen with repetitive insults rather than a single insult. We have also shown that there is a progressive decrease in the extracellular GABA in the striatum in the days preceding such damage, speculating that a loss of GABA may be in part responsible for this damage. This study evaluates the GABA levels in the SNr in animals exposed to repetitive ischemic insults. Each animal received a total of three ischemic insults of 3-min duration at hourly intervals. In vivo microdialysis was carried out to analyze the GABA and glutamate dialysate levels on Days 1, 3, 5, 7, and 14 following the ischemic insult. In the control and treated (ischemic) animals, there was a significant increase in the GABA levels with the introduction of nipecotic acid on Days 1, 3, 5, and 14. However, on Day 7 there was a significant attenuation in the GABA response to nipecotic acid in the treated animals in comparison to the controls. The glutamate levels in the treated animals were similar to the control animals on Days 1, 3, 5, and 7. However, on Day 14 the glutamate levels were significantly lower than on previous days. Our experiments for the first time measure extracellular glutamate and GABA responses in the SNr in animals exposed to repetitive ischemic insults. Our experiments show that there is a significant decrease in the GABA concentrations at a time when ischemic damage is developing in this region. This confirms our hypothesis that a decrease in GABA may be one factor contributing to neuronal damage during the period following repetitive ischemic insults. Further, the rebound increase in GABA levels on Day 14 with a concomitant fall in glutamate levels would indicate that reparative processes are still active in the 2 weeks following the insult.     

Synthesis and thermomechanical characterization of polyurethane elastomers extended with α,ω‐alkane diols

A series of polyurethane (PU) elastomers was prepared by the reaction of poly(?‐caprolactone) and 4,4′‐diphenylmethane diisocyanate, which was extended with a series of chain extenders (CEs) having 2–10 methylene units in their structure. The completion of the reaction was confirmed by Fourier transform infrared spectroscopy. The chemical structures of the synthesized PU samples were characterized with Fourier transform infrared, ¹H‐NMR, and ¹³C‐NMR spectroscopy, and the thermal properties were determined by thermogravimetric analysis, DSC, and dynamic mechanical thermal analysis techniques. The mechanical properties were also studied and are discussed. The thermogravimetric analysis and DSC analysis showed that CE length had a considerable effect on the thermal properties of the prepared samples. The dynamic mechanical thermal analysis and damping peaks were also affected by the number of methylene units in the CE length. The elastomer extended with 1,2‐ethane diol exhibited optimum thermal properties, whereas the elastomer based on 1,10‐decane diol displayed the worst thermal properties. Tensile strength and elongation at break decreased with increasing CE length, whereas hardness showed the opposite trend. The glass‐transition temperature moved toward lower temperatures with increasing CE length. The decrease in the glass‐transition temperature and tensile properties were interpreted in terms of decreasing hard segments and increasing chain flexibility. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

A hybrid model for spelling error detection and correction for Urdu language

Neural Computing and Applications - Detecting and correcting misspelled words in a written text are of great importance in many natural language processing applications. Errors can be broadly...     

Design,Facile Synthesis and Characterization of Porphyrin-Zirconium-Ferrite@SiO2 Core-Shell and Catalytic Application in Cyclohexane Oxidation

Silicon - In this study, a new magnetic ZrFe2O4@SiO2-TCPP nanocatalyst with high efficiency was used for the oxidation of cyclohexane to cyclohexanone (Ke) and cyclohexanol (Al). The mesoporous...     

Light weight model for intra mode selection in HEVC

Multimedia Tools and Applications - The High Efficiency Video Coding (HEVC) efficiently reduces the size of the multimedia contents, but at the cost of high computation complexity. In order to make...     

A comprehensive decision making structure for partitioning of make-to-order, make-to-stock and hybrid products

Manufacturing systems produce their products by making use of three main strategies: make-to-order, make-to-stock and hybrid (combination of MTO and MTS strategies) systems. Hence, several products must be considered and partitioned in terms of many different conflicting criteria, leading to a large set of subjective or ambiguous data. Thus, an effective evaluation approach is essential to improve decision quality. In this paper a comprehensive decision, making structure is proposed to choose the proper strategy for producing the products. It consists of a novel hybrid methodology, which combines analytical hierarchy process (AHP) and technique for order performance by similarity to ideal solution (TOPSIS) for partitioning of products. In this study, the rating of each alternative regarding different criteria (throughout the TOPSIS technique) is described by means of linguistic variables. Furthermore, fuzzy AHP methodology is applied to determine the weights of evaluation criteria. At the end, the effectiveness of the proposed model is demonstrated through a case study.     

Determination of number of kanbans in a supply chain system via Memetic algorithm

In this research multi-stage supply chain system which is controlled by kanban system, is evaluated. In kanban system, decision making is based on determination of the number of kanbans as well as batch sizes. This paper attempts to model supply chain system with regard to costs under just-in-time (JIT) production philosophy. Since adopted model is of mixed integer non-linear programming (MINLP) type and solving it by exact algorithm such as branch and bound (B&B) takes a lot of time, a heuristic method via Memetic algorithm (MA) is presented. Some problems are solved by our proposed MA to illustrate its performance.