The immunoglobulin MOPC167, which binds the transition state analog p-nitrophenylphosphorylcholine with high affinity, catalyzed the hydrolysis of the corresponding carbonate 1. MOPC167 catalysis displayed saturation kinetics with catalytic constant (kcat) = 0.4 min-1 and Michaelis constant (Km) = 208 microM, showed substrate specificity, and was inhibited by p-nitrophenylphosphorylcholine. The rate of the reaction was first order in hydroxide ion concentration between pH 6.0 and 8.0. The lower limit for the rate of acceleration of hydrolysis by the antibody above the uncatalyzed reaction was 770. This study begins to define the rules for the generation of catalytic antibodies.

Investigations of the Richtmyer–Meshkov instability carried out in shock tubes have traditionally used membranes to separate the two gases. The use of membranes, in addition to introducing other experimental difficulties, impedes the use of advanced visualization techniques such as planar laser-induced fluorescence (PLIF). Jones & Jacobs (1997) recently developed a new technique by which a perturbed, membrane-free gas–gas interface can be created in a shock tube. The gases enter the shock tube from opposite ends and exit through two small slots on opposite sides of the test section, forming a stagnation point flow at the interface location. A gentle rocking motion of the shock tube then provides the initial perturbation in the form of a standing wave. The original investigation using this technique utilized dense fog seeding for visualization, which allowed large-scale effects to be observed, but was incapable of resolving smaller-scale features. PLIF visualization is used in the present study to investigate the instability generated by two incident shock strengths (Ms = 1.11 and 1.21), yielding very clear digital images of the flow. Early-time growth rate measurements obtained from these experiments are found to be in excellent agreement with incompressible linear stability theory (appropriately adjusted for a diffuse interface). Very good agreement is also found between the late-time amplitude measurements and the nonlinear models of Zhang & Sohn (1997) and Sadot et al. (1998). Comparison of images from the Ms = 1.11 and 1.21 sequences reveals a significant increase in the amount of turbulent mixing in the higher-Mach-number experiments, suggesting that a mixing transition has occurred.

A highly efficient method has been developed for the solid-phase synthesis of an "unnatural biopolymer" consisting of chiral aminocarbonate monomers linked via a carbamate backbone. Oligocarbamates were synthesized from N-protected p-nitrophenyl carbonate monomers, substituted with a variety of side chains, with greater than 99 percent overall coupling efficiencies per step. A spatially defined library of oligocarbamates was generated by using photochemical methods and screened for binding affinity to a monoclonal antibody. A number of high-affinity ligands were then synthesized and analyzed in solution with respect to their inhibition concentration values, water/octanol partitioning coefficients, and proteolytic stability. These and other unnatural polymers may provide new frameworks for drug development and for testing theories of protein and peptide folding and structure.

The management of sodium intake is clinically important in many disease states including heart failure, kidney disease, and hypertension. Tenapanor is an inhibitor of the sodium-proton (Na(+)/H(+)) exchanger NHE3, which plays a prominent role in sodium handling in the gastrointestinal tract and kidney. When administered orally to rats, tenapanor acted exclusively in the gastrointestinal tract to inhibit sodium uptake. We showed that the systemic availability of tenapanor was negligible through plasma pharmacokinetic studies, as well as autoradiography and mass balance studies performed with (14)C-tenapanor. In humans, tenapanor reduced urinary sodium excretion by 20 to 50 mmol/day and led to an increase of similar magnitude in stool sodium. In salt-fed nephrectomized rats exhibiting hypervolemia, cardiac hypertrophy, and arterial stiffening, tenapanor reduced extracellular fluid volume, left ventricular hypertrophy, albuminuria, and blood pressure in a dose-dependent fashion. We observed these effects whether tenapanor was administered prophylactically or after disease was established. In addition, the combination of tenapanor and the blood pressure medication enalapril improved cardiac diastolic dysfunction and arterial pulse wave velocity relative to enalapril monotherapy in this animal model. Tenapanor prevented increases in glomerular area and urinary KIM-1, a marker of renal injury. The results suggest that therapeutic alteration of sodium transport in the gastrointestinal tract instead of the kidney--the target of current drugs--could lead to improved sodium management in renal disease.

The late-time development of Richtmyer–Meshkov instability is studied in shock tube experiments. This investigation makes use of the experimental apparatus and visualization methods utilized in the earlier study of Collins and Jacobs [J. Fluid Mech. 464, 113 (2002)] but employs stronger shocks and initial perturbations with shorter wavelengths to obtain much later-time (in the dimensionless sense) images of the single-mode instability. These modifications produce a very detailed look at the evolution of the late-time single-mode instability, revealing the transition and development of turbulence in the vortex cores that eventually results in the disintegration of the laminar vortex structures into small scale features. Amplitude measurements taken from these images are shown to be effectively collapsed when plotted in dimensionless variables defined using the wave number and the initial growth rate. The amplitude measurements are compared with several late-time nonlinear models and solutions. The best agreement is obtained with the model of Sadot et al. [Phys. Rev. Lett. 80, 1654 (1998)] which can be slightly improved by modifying the expression for the late-time asymptotic growth rate.

Richtmyer–Meshkov instability causes spatially periodic perturbations initially imposed on a shock-accelerated, thin gas layer to develop into one of three distinct flow patterns. Planar laser-induced fluorescence imaging of the evolving layer, produced by a perturbed SF6 planar jet in air, shows an apparent flow bifurcation that is observed as mushroom-shaped or sinuous-shaped interfacial patterns. Analysis of this nonlinear instability growth, accomplished by modelling the flow field as a row of line vortices, predicts that the layer thickness grows logarithmically at later times and compares well with our measurements. Because the row of vortices is unstable, the model also provides an explanation for the appearance of the three observed interfacial patterns.

The Richtmyer-Meshkov instability of a two-liquid system is investigated experimentally. These experiments utilize a novel technique that circumvents many of the experimental difficulties that have previously limited the study of Richtmyer-Meshkov instability. The instability is generated by vertically accelerating a tank containing two stratified liquids by bouncing it off of a fixed coil spring. A controlled two-dimensional sinusoidal initial shape is given to the interface by oscillating the container in the horizontal direction to produce standing waves. The motion of the interface is recorded during the experiments using standard video photography. Instability growth rates are measured and compared with existing linear theory. Disagreement between measured growth rates and the theory are accredited to the finite bounce length. When the linear stability theory is modified to account for an acceleration pulse of finite duration, much better agreement is attained. Late time growth curves of many different experiments seem to collapse to a single curve when correlated with the circulation deposited by the impulsive acceleration. A theory based on modeling the late time evolution of the instability using a row of vortices is developed. The growth curve given by this model has similar shape to those measured, but underestimates the late-time growth rate.

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