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.     

Performance comparison of space-time block coded and cyclic delay diversity MC-CDMA systems

Spatial diversity is a widely applied technique for enhancing wireless system performance since it greatly reduces the detrimental effects of multipath fading. Space-time block codes have been considered the best choice for transmit diversity in narrowband environments, but their use in broadband channels is questionable due to their inability to pick up multipath diversity. However, when used in conjunction with an MC-CDMA system, they achieve not only full spatial but also variable multipath diversity depending on the employed spreading. In comparison, cyclic delay diversity is an attractive approach to achieve spatial and multipath diversity. Its simplicity and conformability with current standards makes it desirable for multicarrier systems. Previous studies suggest that CDD is only advantageous with an outer channel code for OFDM systems. In this article, we compare STBCs and CDD applied to an MC-CDMA system in terms of complexity and performance. It is shown that for an MC-CDMA system, CDD benefits from spreading and channel coding that makes it very competitive with STBCs, particularly since it is applicable to any number of transmit antennas with no loss in rate.     

Circuit analysis of an ultrafast junction mixing scanning tunnelingmicroscope

A lumped element circuit model for the operation of a junction mixing scanning tunneling microscope (JM-STM) is presented. Fits from this model show excellent agreement with experimental results in the picosecond time regime. The tip sample capacitance employed in the model was calculated to be 33 fF, using the method of images. By varying the capacitance, various tip/sample geometries can be investigated. Testing the response of the model tunnel junction, for faster electrical pulses, suggests how the JM-STM can be pushed into the femtosecond time regime     

An image multiresolution representation for lossless and lossycompression

We propose a new image multiresolution transform that is suited for both lossless (reversible) and lossy compression. The new transformation is similar to the subband decomposition, but can be computed with only integer addition and bit-shift operations. During its calculation, the number of bits required to represent the transformed image is kept small through careful scaling and truncations. Numerical results show that the entropy obtained with the new transform is smaller than that obtained with predictive coding of similar complexity. In addition, we propose entropy-coding methods that exploit the multiresolution structure, and can efficiently compress the transformed image for progressive transmission (up to exact recovery). The lossless compression ratios are among the best in the literature, and simultaneously the rate versus distortion performance is comparable to those of the most efficient lossy compression methods.     

Some Physical Properties of Pure and Doped Polyvinyl Alcohol under Applied Stress

Thick films of polyvinyl alcohol (PVA) containing very finemetallic powder, copper (Cu), iron (Fe) and aluminum (Al) 2.5% by weight,were prepared by the casting method. The temperature dependence of Young'smodulus at constant stress, the stress dependence of Young's modulus(Y), the stress dependence of dielectric constant (ε) and stressdependence of phonon velocity, were studied. It was found that Young'smodulus (Y) of the pure sample has the lowest value and that of PVA + Alhas the highest value. This can be explained on the basis that Ydepends on the ratio between the energy of molecular interactions andthe energy of thermal motion of the sample units. We also found that thedielectric constant increases with the addition of metallic powder, andwith an increasing applied stress. The phonon velocity increased withincreasing stress. The increase of stress decreases imperfectionsleading to the increased phonon velocity. The electronic absorptionspectra of PVA is not affected by doping Al and Fe, whereas the PVA dopedwith Cu shows a shift of the absorption maxima toward a longer wavelength.The instantaneous elastic behavior may be observed only at lowtemperatures and very short creep times.     

Cost estimation of structural skeleton using an interactive automation algorithm: A conceptual approach

This paper addresses a new concept for generating bills of quantities (B.o.Qs) using AutoCAD drawings for a building project, which demonstrates the application of Industry Foundation Class (IFC), developed by International Alliance for Interoperability (IAI). The procedure considers types of materials and the structural shapes of the AutoCAD drawings to compute the cost of the structural skeleton elements using interactive automation. The main concept focuses on using layer computation of the AutoCAD drawing after converting it into a drawing inter-exchangeable file format (DXF). Once the coordinates are detected, it is easier to determine the area and volume for any structural shape, including circles and polygons. The extracting method is a new technique for structural engineers and quantity surveyors to estimate required material for beam, columns, slabs and foundations. The algorithm extracts and recognizes the layers and objects from a two dimensional DXF drawing along with the coordinates information. The results obtained using this technique are more accurate and reliable than manual procedures or any other traditional techniques. In this paper, an automated and interactive procedure for B.o.Q computation is demonstrated. The process involves a user-friendly interface, dynamic linking to the structural drawings and tracking of B.o.Q modifications at the same time.     

A new formulation for web crippling strength of cold-formed steel sheeting using genetic programming

This study presents Genetic programming (GP) as a new tool for the formulation of web crippling strength of cold-formed steel decks for various loading cases. There is no well established analytical solution of the problem due to complex plastic behaviour. The objective of this study is to provide an alternative robust formulation to related design codes and to verify the robustness of GP for the formulation of such structural engineering problems. The training and testing patterns of the proposed GP formulation are based on well established experimental results from the literature. The GP based formulation results are compared with experimental results and current design codes and found to be more accurate.     

Synergistic decrease of clonal proliferation, induction of differentiation, and apoptosis of acute promyelocytic leukemia cells after combined treatment with novel 20-epi vitamin D3 analogs and 9-cis retinoic acid

Patients with acute promyelocytic leukemia (APL) usually relapse after all-trans retinoic acid (RA) treatment because this therapy fails to eradicate the malignant clone. Our data showed that KH 1060 and other 20-epi vitamin D3 analogs alone were potent inhibitors of clonal growth of NB4 cells, an APL cell line (ED50, approximately 5 x 10(-11) M). The combination of KH 1060 and 9-cis-RA synergistically and irreversibly enhanced this effect. Neither KH 1060 nor 9-cis-RA (10(-6) M, 3 d) were strong inducers of differentiation of NB4 cells. However, 98% of the cells underwent differentiation to a mature phenotype with features of both granulocytes and monocytes after exposure to a combination of both compounds. Apoptosis only increased after incubation of NB4 cells with 9-cis-RA alone (28%) or with a combination of 9-cis-RA plus KH1060 (32%). Immunohistochemistry showed that the bcl-2 protein decreased from nearly 100% of the wild-type NB4 cells to 2% after incubation with a combination of KH 1060 and 9-cis-RA, and the bax protein increased from 50% of wild-type NB4 cells to 92% after culture with both analogs (5 x 10(-7) M, 3 d). Western blot analysis paralleled these results. Studies of APL cells from one untreated individual paralleled our results with NB4 cells. Taken together, the data demonstrated that nearly all of the NB4 cells can be irreversibly induced to differentiate terminally when exposed to the combination of KH 1060 and 9-cis-RA.     

Application of a hybrid finite element method to determine stress intensity factors in unidirectional composites

In this paper a hybrid finite element method is applied in evaluation of the stress intensity factors K _I and K _II of unidirectional fiber reinforced composites. In order to satisfy the stress singularity at the crack tip a singular super-element based on a modified complementary energy principle is developed. The stress and displacement fields in the super-element are expressed in terms of polynomials of two complex variables ₁ and ₂ in the transformed -plane. The stiffness matrix of the super-element was determined by using a line integral along the boundary of the super-element. The displacement vector was expressed in terms of the element nodal displacement vector {q} and a properly selected shape function defined along the element boundary.Numerical results for K _I and K _II of glass-epoxy and graphite-epoxy unidirectional composites with cracks along the diameter of a circular cut out as well as elliptical cut outs were evaluated

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Résumé On applique, dans la présente étude, une méthode d'éléments finis hybrides à l'évaluation des facteurs d'intensité de contrainte K_I et K_II pour des composites renforcés de fibres unidirectionnelles. Pour tenir compte de la singularité de la contrainte à l'extrémité de la fissure, on développe un super élément singulier en se basant sur un principe modifié d'énergie complémentaire. Les champs de contraintes et de déplacements dans le super-élément sont exprimés sous forme polynormale de deux variables complexes ₁, et ₂ dans le plan de la transformée. La matrice de rigidité du super élément est, quant à elle, définie en utilisant une intégrale linéaire le long du contour de l'élément. Le vecteur de déplacement est exprimé par un vecteur (9) de déplacement nodal de l'élément, et par une fonction de forme appropriée, définie le long du contour de l'élément.On évalue les résultats numériques pour K_I et K_II, correspondant à des composites à fibres unidirection-nelles de types verre-epoxy et graphite-epoxy, oú des fissures se situeraient sur le diamètre de découpes circulaires et elliptiques

     

Eco-friendly Geopolymer Composite Based on Non-heat-treated Phosphate Sludge Reinforced With Polypropylene Fibers

Silicon - Geopolymers produced with metakaolin (MK) and thermally untreated phosphate sludge (PS) are beneficial and environmentally advantageous materials, but their fragility limits its...