Multiple solution conformations of the integrin-binding cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-). Analysis of the (phi, psi) space available to cyclic pentapeptides

The aqueous solution structure of the cyclic pentapeptide cyclo(-Ser-D-Leu-Asp-Val-Pro-) has been determined by two-dimensional 1H-NMR spectroscopy, combined with a conformational search and distance-geometry calculations. As many as five conformers in slow exchange were observed, and the rate of interconversion between components was measured from the build-up rates of exchange peaks. NMR data allowed the structures of the two predominant conformers to be determined. The major component (66%) contained a cis-proline as part of a type-VIa2 beta-turn encompassing residues Asp-Val-cis-Pro-Ser. The second component (16%) contained only trans-amide bonds, and a type-VIII beta-turn formed by residues Val-Pro-Ser-D-Leu. These structures are discussed in relation to the (phi, psi), space available to the cyclic pentapeptide, determined by a conformational search, and in relation to previously published cyclic-pentapeptide structures. The molecule exhibits activity in a scintillation-proximity assay for the inhibition of the interaction between the integrin very-late antigen-4 (VLA-4; alpha 4 beta 1) and vascular-cell-adhesion molecule-1 (VCAM-1). The structure/activity relationship of the LDV sequence is discussed and related to the recently published X-ray structure of VCAM-1. The relevance of the work to the design of anti-inflammatory drugs is discussed.     

p-aminohippurate uptake by syncytial microvillous membrane vesicles of human term placenta

The mechanism of uptake of p-aminohippurate (PAH) by syncytial microvillous membrane vesicles of human term placenta was investigated. Initial PAH uptake and efflux were increased in the presence of a pH-gradient and a Cl(-)-gradient, respectively. Forced negative and positive membrane potentials did not influence the uptake, which indicated that the transport is not electrogenic. The pH-dependent increase is probably the result of a higher rate of diffusion due to a lower degree of dissociation of PAH. Because several organic anions failed to transstimulate PAH uptake and FCCP did not decrease the uptake in the presence of an inwardly directed H(+)-gradient, ruling out a PAH/OH- antiport, an anion exchange system does not appear to be present in these membranes. Since electrogenicity and anion exchange seem not to be involved in the Cl(-)-dependent increase, an allosteric effect of Cl- on the transporter might be possible. Various organic anions were able to inhibit pH-stimulated PAH uptake significantly. Kinetic analysis of the probenecid sensitive part of uptake provided further evidence for mediated transport of PAH (Km = 7.4 +/- 2.6 mM and Vmax = 2.0 +/- 0.4 nmol/mg/15 s). Non-inhibitable diffusion accounted for the main part of total transport. Concentration dependent inhibition of PAH transport by probenecid showed a Ki of 2.5 +/- 0.9 mM. It is concluded that human placental syncytial microvillous membrane vesicles possess a low affinity transport mechanism for PAH with low specificity. The importance of this system, for placental excretion of anionic drugs, will depend on the intrasyncytial concentration of these drugs, caused by the transport across the basal membrane.     

Involution of the bovine mammary gland: histological and ultrastructural changes

Bovine mammary tissue was collected by surgical biopsy at intervals during involution for histological and ultrastructural observation. In lactating tissue (d 0 of involution, collected 8 h after the final milking), alveolar epithelial cells had marked ultrastructural evidence of lactation, including protein-containing secretory vesicles, lipid droplets, extensive rough endoplasmic reticulum, and numerous mitochondria. By d 2 of involution, alveolar epithelial cells contained large vacuoles apparently formed by coalescing of protein-containing secretory vesicles and lipid droplets. Large vacuoles were observed in epithelial cells until about the 3rd wk of involution. By d 2 of involution, the Golgi apparatus generally was not apparent. Rough endoplasmic reticulum and mitochondria were observed throughout the period studied, although in reduced amounts compared with their presence in lactating tissue. A marked increase in lysosomal or cytosegresomal structures in epithelial cells was not observed. There was no evidence of extensive sloughing of epithelial cells from the basement membrane. There was a progressive increase in the interalveolar area and a concurrent decrease in the alveolar luminal area as involution progressed. Ultrastructural examination showed that alveolar epithelial cells at d 21 and 30 of involution appear to be functionally active but not secreting milk components.     

Nonlinear self-guiding and switching in an all-fiber device

We study the nonlinear propagation of light in optical fibers in the strong nonlinearity limit. In this limit, the transverse guiding properties are altered and cannot be decoupled from the longitudinal part of the wave equation. We consider a refractive index profile with no bound modes at low intensities and show that stable self-guiding occurs at a critical intensity. This critical intensity is a property of the guide and can be made much lower than the threshold for unstable self-focusing. We consider a particular design for which self-guiding occurs at three orders of magnitude lower than the self-focusing threshold.     

Evaluating non-business e-commerce adoption decision processes and gender roles

Non-business e-commerce adoption refers to the use of e-commerce by not-for profit organizations such as religious organizations, government agencies and academic institutions to reduce their expenses or to improve their operations and customer service. Being a new research niche in the field of e-commerce, non-business e-commerce has received very little or no research attention. This has resulted in a very poor understanding of this niche, especially with regards to its adoption facilitators and inhibitors. Based on this impetus, a field survey of Malaysian Universities was conducted to determine the key factors that facilitate non-business EC adoption as well as the role of gender differential. A comprehensive list of potential facilitators for the strategic use of information technology was derived from extant research reports and used to collect data from five public universities in Malaysia. The data were factor-analysed to determine the key underlying dimensions of facilitators. On the basis of the resulting five dimensions namely, relative advantage orientation, network orientation, information efficiency orientation, innovativeness orientation and competitiveness orientation, regression analysis was done to determine the impact of the five dimensions on adoption. Dummy variable was created for gender and applied in the regression analysis in order to estimate the moderation effect of sex typing on the relationship between the resulting dimensions and adoption. Implications of the findings are discussed.     

The tail of localized states in the band gap of the quantum well in the In0.2Ga0.8N/GaN system and its effect on the laser-excited photoluminescence spectrum

Semiconductors - It is established experimentally that the peak in the photoluminescence spectrum of the In0.2Ga0.8N/GaN heterostructure with a quantum well shifts by ～150 meV as the power...     

Wake and aerodynamics loads in multiple bodies—application to turbomachinery blade rows

Two-dimensional, unsteady flow around bodies of complex geometry (or multiple bodies) at high Reynolds number is simulated using the vortex method. This method is modified to take into account the sub-grid scale phenomena through a second order velocity structure function model adapted to the Lagrangian scheme. The dynamics of the body wake is computed using the convection-diffusion splitting algorithm; the convection process is carried out with a Lagrangian Adams-Bashforth time-marching scheme and the diffusion process is simulated using the random walk method. The pressure distribution is obtained using an integral equation derived from the pressure Poisson equation, which was first developed for a single body. Results for the numerical simulation around a linear cascade of airfoils are presented. As the flow is periodic in the y direction, the discrete vortex shedding need only be considered for a reference airfoil. The flow characteristics around the NACA 65-410 series airfoils are calculated and comparisons are made with results available in the literature.