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.     

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...     

Exploring the Biomaterial-Induced Secretome: Physical Bone Substitute Characteristics Influence the Cytokine Expression of Macrophages

In addition to their chemical composition various physical properties of synthetic bone substitute materials have been shown to influence their regenerative potential and to influence the expression of cytokines produced by monocytes, the key cell-type responsible for tissue reaction to biomaterials in vivo. In the present study both the regenerative potential and the inflammatory response to five bone substitute materials all based on β-tricalcium phosphate (β-TCP), but which differed in their physical characteristics (i.e., granule size, granule shape and porosity) were analyzed for their effects on monocyte cytokine expression. To determine the effects of the physical characteristics of the different materials, the proliferation of primary human osteoblasts growing on the materials was analyzed. To determine the immunogenic effects of the different materials on human peripheral blood monocytes, cells cultured on the materials were evaluated for the expression of 14 pro- and anti-inflammatory cytokines, i.e., IL-6, IL-10, IL-1β, VEGF, RANTES, IL-12p40, I-CAM, IL-4, V-CAM, TNF-α, GM-CSF, MIP-1α, Il-8 and MCP-1 using a Bio-Plex^® Multiplex System. The granular shape of bone substitutes showed a significant influence on the osteoblast proliferation. Moreover, smaller pore sizes, round granular shape and larger granule size increased the expression of GM-CSF, RANTES, IL-10 and IL-12 by monocytes, while polygonal shape and the larger pore sizes increased the expression of V-CAM. The physical characteristics of a bone biomaterial can influence the proliferation rate of osteoblasts and has an influence on the cytokine gene expression of monocytes in vitro. These results indicate that the physical structure of a biomaterial has a significant effect of how cells interact with the material. Thus, specific characteristics of a material may strongly affect the regenerative potential in vivo.     

In Vivo Analysis of the Biocompatibility and Bone Healing Capacity of a Novel Bone Grafting Material Combined with Hyaluronic Acid

The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration.