Solution structure of the superactive monomeric des-[Phe(B25)] human insulin mutant: elucidation of the structural basis for the monomerization of des-[Phe(B25)] insulin and the dimerization of native insulin

The three-dimensional solution structure of des-[Phe(B25)] human insulin has been determined by nuclear magnetic resonance spectroscopy and restrained molecular dynamics calculations. Thirty-five structures were calculated by distance geometry from 581 nuclear Overhauser enhancement-derived distance constraints, ten phi torsional angle restraints, the restraints from 16 helical hydrogen bonds, and three disulfide bridges. The distance geometry structures were optimized using simulated annealing and restrained energy minimization. The average root-mean-square (r.m.s.) deviation for the best 20 refined structures is 1.07 angstroms for the backbone and 1.92 angstroms for all atoms if the less well-defined N and C-terminal residues are excluded. The helical regions are more well defined, with r.m.s. deviations of 0.64 angstroms for the backbone and 1.51 angstroms for all atoms. It is found that the des-[Phe(B25)] insulin is a monomer under the applied conditions (4.6 to 4.7 mM, pH 3.0, 310 K), that the overall secondary and tertiary structures of the monomers in the 2Zn crystal hexamer of native insulin are preserved, and that the conformation-averaged NMR solution structure is close to the structure of molecule 1 in the hexamer. The structure reveals that the lost ability of des-[Phe(B25)] insulin to self-associate is caused by a conformational change of the C-terminal region of the B-chain, which results in an intra-molecular hydrophobic interaction between Pro(B28) and the hydrophobic region Leu(B11)-Leu(B15) of the B-chain alpha-helix. This interaction interferes with the inter-molecular hydrophobic interactions responsible for the dimerization of native insulin, depriving the mutant of the ability to dimerize. Further, the structure displays a series of features that may explain the high potency of the mutant on the basis of the current model for the insulin-receptor interaction. These features are: a change in conformation of the C-terminal region of the B-chain, the absence of strong hydrogen bonds between this region and the rest of the molecule, and a relatively easy accessibility to the Val(A3) residue.     

Room temperature characterization of Hg1-xCdxTe P-on-n heterostructure photodiodes

Measurements of 77K R_oA and 300K reverse bias dynamic impedance (R_dA) products at one volt reverse bias has been carried out to assess the degree of correlation of this figure of merit. Planar P-on-n heterostructures were grown on near lattice-matched CdZnTe substrates with Hg_1-xCd_xTe (0.20< x <0.30) by molecular beam epitaxy. These devices were passivated with CdTe and doped with indium and arsenic as n- and p-type dopants, respectively. Current-voltage characteristic of these devices exhibit thermally generated dark currents at small and modest reverse bias. We have observed that R_oA values of these long wavelength infrared P-on-n heterostructure photodiodes at 77K correlate with room temperature R_dA values. Diode arrays with high room temperature R_dA values at one volt reverse bias also have high R_oA values at 77K. Similarly, low R_dA values at room temperature indicate poor performance at 77K where deviation from diffusion current occurs at reverse bias of 0.2 to 1 volt at room temperature. The results presented here, for a small samples of devices, demonstrate that room temperature measurements of current-voltage characteristics to evaluate Hg_1-xCd_xTe (0.22< x <0.28) diode performance and array uniformity at lower temperatures can be used. This provides an acceptable criteria for further study at lower temperatures.     

Geochemical characteristics of the Yufuin outflow plume, Beppu hydrothermal system, Japan

Thermal water at Yufuin (Kyushu Island, Japan) is tapped through about 820 shallow wells and used mainly for hot-spring bathing purposes. Chemical and isotopic data for fluids from wells and fumaroles in Yufuin and Beppu indicate that the thermal activity at Yufuin represents a dilute, westward-flowing hydrothermal outflow plume from the Beppu hydrothermal system. Two other (eastward-flowing) outflow plumes have long been recognized at Beppu, but the Yufuin outflow plume is first recognized here. The Yufuin outflow plume is apparently a mixture of two end-member fluids: (1) deep high-temperature (250–300°C) fluid from the Beppu system having high chloride concentration (1400–1600 mg/L) and a δ¹⁸O value near −6.0%, and (2) meteoric water having low chloride concentration (≤7 mg/L) and a δ¹⁸O value near −9.2%.A permeable conduit for the vertical and lateral transport of deep fluid from the Beppu system is provided by the Yufuin Fault zone, which extends westward from the southern flank of Mt. Tsurumi volcano to the town of Yufuin. Stable isotope ratios and chloride concentrations for shallow groundwaters near the eastern end of the fault, at an elevation near 700 m, are consistent with those required for the low-chloride meteoric end-member of the Yufuin thermal waters. Recharge of this meteoric water, as well as mixing with the Beppu deep fluid, may occur along the Yufuin Fault. Enthalpy-chloride relations indicate additional conductive heating of the Yufuin waters, in the amount of 350–500 kJ/kg beyond that which can be accounted for by mixing between Beppu deep fluid and meteoric water. This could be a result of conductive heating with convection to a depth of 1–2 km. Estimates of the magnitude of the heat source for the Beppu hydrothermal system should take into account the heat being discharged at Yufuin.     

AC measurements of the minimum longitudinal resistance of a QHEsample from 10 Hz to 10 kHz

AC measurements of the longitudinal resistance, R_xx, of a quantum Hall effect (QHE) sample have been made in a frequency range from 10 Hz to 10 kHz. The results show no frequency effect on the minimum value of R_xx corresponding to the quantum numbers i=2 and i=4, within the measurement resolution of 0.5 mΩ. Therefore, the influence of frequency on the value of the quantized Hall resistance, R_H, should not exceed a few parts in 10⁹ . Some unwanted effects detected during the development of the resistance bridge have been pointed out     

Coriolis effects in the dynamics of a rotating elastic structure

Summary Small oscillations of a rotating elasticum with a mass at the free end are investigated with Poincaré-Lindstedt series. It is shown that the mass moves on a figure-eight shaped curve in a direction determined by the sign of the angular velocity and hence that the Coriolis force influences the motion.     

Motion of a solid sphere in a general flow near a plane boundary at zero Reynolds number

It is demonstrated how the hydrodynamic force and moment of force acting on a solid sphere may be calculated when it is placed at rest at an arbitrary position in a two dimensional flow at zero Reynolds number in which the region of flow is bounded by either an undeformable planar free surface or by a plane solid wall. The results so obtained are used to calculate the motion of a freely moving solid sphere in an asymmetric vortex in the presence of an underformable free surface. It is seen that the sphere, depending on the direction of the undisturbed flow, will either spiral into or out of the vortex. This implies that when a dilute suspension of such spherical particles undergoes such a vortex motion in the presence of the free surface, the vortex will either fill up with particles from the surrounding flow or become devoid of particles.Deceased, July 31, 1995     

Pulsed phase-locked loop calibration over frequency

This paper presents a method of correcting for unwanted phase shifts introduced by interchanging ultrasonic transducers and other measurement system components when using the pulsed phase-locked loop (PPLL) ultrasonic system. Theory is derived mathematically separating phase errors into their constituents. The relationship to a previously derived method of determining the number of periods into the tone-burst, at which the system samples, is established, and a method of adjusting this number to be an integer is presented. Implementation of the technology on a computer is demonstrated through experimental results on transducers of differing frequencies and diameters. Sensitivity to path-length is tested. This work has resulted in a straightforward means of calibrating transducers in conjunction with PPLL measurements using a single, fixed reference block     

Propagation of a quasi-shear horizontal acoustic wave in Z-Xlithium niobate plates [and conductivity sensor application]

It is found that an acoustic wave which is nearly polarized in the shear horizontal (SH) direction can propagate along the X axis of a Z-cut lithium niobate plate if the ratio h/λ, where h=plate thickness and λ=acoustic wavelength, is less than about 0.5. Attractive properties of this quasi-SH wave include: (1) phase velocity nearly constant for all values of h/λ; (2) ability to propagate in contact with a liquid medium; and (3) electromechanical coupling coefficient as high as 0.15. These properties make the wave attractive for use in a variety of sensor and signal processing applications. An example of sensor applications is illustrated by using the wave to measure conductivity of liquids (aqueous KCl solution). The frequency of a 12-MHz quasi-SH mode oscillator fabricated on a 0.48 wavelength thick Z-X lithium niobate plate is found to vary by more than 80 kHz for variation in KCI concentration from 0 to 0.15%