Chemistry of Lipid A: At the Heart of Innate Immunity

In many Gram‐negative bacteria, lipopolysaccharide (LPS) and its lipid A moiety are pivotal for bacterial survival. Depending on its structure, lipid A carries the toxic properties of the LPS and acts as a potent elicitor of the host innate immune system via the Toll‐like receptor 4/myeloid differentiation factor 2 (TLR4/MD‐2) receptor complex. It often causes a wide variety of biological effects ranging from a remarkable enhancement of the resistance to the infection to an uncontrolled and massive immune response resulting in sepsis and septic shock. Since the bioactivity of lipid A is strongly influenced by its primary structure, a broad range of chemical syntheses of lipid A derivatives have made an enormous contribution to the characterization of lipid A bioactivity, providing novel pharmacological targets for the development of new biomedical therapies. Here, we describe and discuss the chemical aspects regarding lipid A and its role in innate immunity, from the (bio)synthesis, isolation and characterization to the molecular recognition at the atomic level.     

Static and dynamic response of a multiplexed-array piezoresistive contact sensor

Multiplexed piezoresistive sensor arrays hold great potential for measuring contact stress distributions for orthopedic research applications. However, their acceptance has been handicapped by output drift and the fact that their dynamic response has not been well characterized. In this report, the static and dynamic responses of one device of this class (the K-Scan piezoresistive contact stress sensor) are formally characterized using a specially made pressure vessel that provides spatially homogeneous contact stress. Drift was predominant early in static loading, reaching relationtive errors of approximately 30 percent over a 10-min period. During loading, first-order dynamic analysis showed that the time constant (and time lag) was nearly zero and there was little attenuation of the output up to 20 Hz. A deconvolution algorithm proved capable of compensating for the great majority of static drift.     

Rheo NMR and shear banding

The phenomenon of shear banding in complex fluids has been investigated using NMR velocimetry and NMR spectroscopy, mostly in wormlike micelle systems, but more recently in colloidal systems and multilayer vesicles. A particular advantage of NMR is the ability to simultaneously investigate structural ordering and to compare such ordering with local strain rates. In this paper, we describe the basics of Rheo-NMR and summarise its recent application to the study of shear banding.     

Anomalous shear banding: multidimensional dynamics under fluctuating slip conditions

The strain-controlled flow of a wormlike micellar solution in cylindrical Couette geometries with smooth and rough glass inner walls is investigated using 2D ¹H NMR velocimetry. We find anomalous shear banding in which fluctuating slip dynamics in combination with surfactant properties lead to a non-lever rule behaviour where the interface position remains constant while the high and low shear rates change. Velocities in the flow direction are imaged in the flow-gradient/vorticity plane. The spatiotemporal resolution achieved reveals fluctuations in flow structure along the vorticity axis and instability of the high shear band.     

Time-dependent velocities in porous media dispersive flow.

Pulsed Gradient Spin Echo (PGSE) NMR methods may be used to measure the asymptotic dispersion coefficient as well as the velocity autocorrelation function (VACF) in porous media flow. The VACF can be measured in the frequency domain using repetitive gradient pulse trains, and in the time domain using double PGSE encoding. The one dimensional double PGSE method, and the two dimensional velocity exchange experiment (VEXSY) are briefly outlined and their application to flow in monodisperse 0.5 mm diameter beads packs described, both axial and transverse VACFs being examined. The measured correlation times are shown to agree well with calculated values. The asymptotic dispersion coefficients agree with literature values in the case of transverse flow while in axial flow it is shown that asymptotic conditions are not achieved, even for observation times longer than the correlation time for flow around a bead.     

A Stochastic Model for Wound Healing

We present a discrete stochastic model which represents many of the salient features of the biological process of wound healing. The model describes fronts of cells invading a wound. We have numerical results in one and two dimensions. In one dimension we can give analytic results for the front speed as a power series expansion in a parameter, p, that gives the relative size of proliferation and diffusion processes for the invading cells. In two dimensions the model becomes the Eden model for p ≈ 1. In both one and two dimensions for small p, front propagation for this model should approach that of the Fisher-Kolmogorov equation. However, as in other cases, this discrete model approaches Fisher-Kolmogorov behavior slowly.     

NMR velocimetry and spectroscopy at microscopic resolution in small rheometric devices

We describe several different rheometric devices for use within the nuclear-magnetic-resonance probe of a standard widebore microimaging system. These include both vertical and horizontal Couette cells and the cone- and -plate cell, which produce shearing flows, and the four-roll mill and the opposed-jet (cross-flow junction) cells which produce extensional flow. We demonstrate that velocity images can be obtained for each and that detailed information about local shear and extension rates can be extracted. These systems have considerable potential for use in the study of non-Newtonian viscosity, and of molecular ordering under shear or extension.