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.     

Fatigue Behavior of a Pavement Foundation with Recycled Aggregate and Waste HDPE Strips

A laboratory investigation was conducted to evaluate the fatigue behavior of an alternative pavement foundation material containing cement stabilized reclaimed crushed aggregate. Class C fly ash, and waste-plastic strip [high density polyethylene (HDPE)] reinforcement. The primary motivation for this research was to evaluate a composite that contained more than 90% recycled materials for use as an alternative foundation layer underneath conventional flexible or rigid pavement. The specific objectives of this study were (1) to evaluate the flexural fatigue behavior of the new composite, and (2) to evaluate the accumulation of fatigue damage in the material. The results indicate that the fatigue resistance of this material is similar to other traditional stabilized pavement materials. It was found that the dynamic elastic modulus remained approximately constant (degraded slowly) for most specimens up to the end of fatigue life. Fatigue damage computed using a dissipated energy approach showed that the damage accumulation in this material approximately follows Miner's rule for cumulative damage, which is often used in pavement engineering.     

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.     

An investigation of pore cracking in titanium welds

Two welded Ti-6A1-4V pressure vessels leaked prematurely in service. The leaks were caused by cracks emanating from weld porosity. The cracks originated during fabrication, with subsequent growth in service leading to the formation of the leak paths. Pore cracking is thought to be caused by a mechanism that involves both sustained-load and cyclic contributions, with the former being the more prominent. It is shown that the tendency for cracking is influenced by pore position and that pore size is not a deciding factor in that regard. The factors that govern pore cracking are discussed, and the possible role of interstitial embrittlement is assessed.     

50-nm Self-Aligned and “Standard” T-gate InP pHEMT Comparison: The Influence of Parasitics on Performance at the 50-nm Node

Continued research into the development of III-V high-electron mobility transistors (HEMTs), specifically the minimization of the device gate length, has yielded the fastest performance reported for any three terminal devices to date. In addition, more recent research has begun to focus on reducing the parasitic device elements such as access resistance and gate fringing capacitance, which become crucial for short gate length device performance maximization. Adopting a self-aligned T-gate architecture is one method used to reduce parasitic device access resistance, but at the cost of increasing parasitic gate fringing capacitances. As the device gate length is then reduced, the benefits of the self-aligned gate process come into question, as at these ultrashort-gate dimensions, the magnitude of the static fringing capacitances will have a greater impact on performance. To better understand the influence of these issues on the dc and RF performance of short gate length InP pHEMTs, the authors present a comparison between In_0.7Ga_0.3As channel 50-nm self-aligned and "standard" T-gate devices. Figures of merit for these devices include transconductance greater than 1.9 S/mm, drive current in the range 1.4 A/mm, and fT up to 490 GHz. Simulation of the parasitic capacitances associated with the self-aligned gate structure then leads a discussion concerning the realistic benefits of incorporating the self-aligned gate process into a sub-50-nm HEMT system     

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.     

A Simple Quasi-2D Numerical Model of a Thermogage Furnace

A simple quasi-2D model for the temperature distribution in a graphite tube furnace is presented. The model is used to estimate the temperature gradients in the furnace at temperatures above which contact sensors can be used, and to assist in the redesign of the furnace heater element to improve the temperature gradients. The Thermogage graphite tube furnace is commonly used in many NMIs as a blackbody source for radiation thermometer calibration and as a spectral irradiance standard. Although the design is robust, easy to operate and can change temperature rapidly, it is limited by its effective emissivity of typically 99.5–99.8%. At NMIA, the temperature gradient along the tube is assessed using thermocouples up to about 1,500°C, and the blackbody emissivity is calculated from this. However, at higher operating temperatures (up to 2,900°C), it is impractical to measure the gradient, and we propose to numerically model the temperature distributions used to calculate emissivity. In another paper at this conference, the model is used to design an optimized heater tube with improved temperature gradients. In the model presented here, the 2-D temperature distribution is simplified to separate the axial and radial temperature distributions within the heater tube and the surrounding insulation. Literature data for the temperature dependence of the electrical and thermal conductivities of the graphite tube were coupled to models for the thermal conductivity of the felt insulation, particularly including the effects of allowing for a gas mixture in the insulation. Experimental measurements of the temperature profile up to 1,500°C and radial heat fluxes up to 2,200°C were compared to the theoretical predictions of the model and good agreement was obtained.     

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.     

Fabrication of an optically driven pH gradient generator based on self-assembled proton pumps

Optically manipulating the local pH of a target solution in a microchannel, or reservoir, provides a mechanism for activating and controlling a variety of biological and chemical processes on Lab-on-a-Chip (LOC) devices and micro-total analysis systems (μ-TAS). A microscale pH gradient generator that exploits the light-activated molecular proton pumps found in the purple membranes (PM) of bacteriorhodopsin is described in this paper. The photo-electro-chemical transducer is an ultrathin layer (~13?nm) of oriented PM patches self-assembled on an Au-coated porous substrate. A biotin labeling and streptavidin molecular recognition technique is used to ensure that the extracellular side of all PM patches is attached to the porous substrate enabling unidirectional and efficient transport of ions across the transducer surface. The photo-induced proton pumps generate a flow of ions that produce a measurable change in pH between the separated solutions. The self-assembly procedure is experimentally quantified based on the capacitance characteristics of the bR membranes. The investigation confirms that the transducer is covered with the bR proton pumps at a mass density of 2.33?ng/cm². Experimental tests also show that the proposed transducer can repeatedly generate pH gradients as high as 0.42 and absolute voltage differences as high as 25?mV when illuminated by an 18?mW, 568?nm light source. Furthermore, the ΔpH is observed to be nonlinear with respect to light intensity and exposure time. The ΔpH of the target solution is sufficient to cause a phenolphthalein indicator dye to change color or an ionic hydrogel micro-valve to expand.