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.     

Analysis and Modelling of the LPC VD Annular Reactor

This paper presents the results of our work on a new type of CVD reactor, annular reactor. This equipment is able to deposit pure silicon and also in-situ phosphorus doped silicon on a large number of substrates     

Properties of cast austenitic materials for light water reactors

Primary piping elbows of ligh water reactors are made of cast austeno-ferritic materials (grade CF8 or CF8M) which are susceptible to embrittlement by thermal ageing in service. Ageing kinetics depends on chromium content and on the temperature. The effect of ageing on mechanical properties is determined by the decreasing of Charpy-U energy. It is shown that the rupture of such aged material comes from a combination of cleavage of the ferrite and shearing or ductile tearing of austenite ligaments. The fracture toughness is determined by J-R curves, which exhibit a large scatter related to the solidification macrostructure of the steel. It is shown that J-R curves are independent of the geometry of the specimens.     

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.     

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     

Nondestructive evaluation of corrosion by fractal geometry

Fractal geometry is finding its application in the nondestructive evaluation (NDE) of corrosion by characterizing the corrosion surface with fractal dimensions. It was found that corrosion surfaces can be well described by multifractals. Two algorithms were used to obtain the fractal dimensions of a corroded aluminum alloy surface, one being box-counting and another being coherent light scattering. Fractal dimensions were related with the damage caused by corrosion and fatigue.     

A comparative thermodynamic study of sorption systems: second law analysis

As a consequence of the phasing out of CFCs, sorption systems appear to be potential candidates to replace vapour compression systems. Amongst sorption systems there exists a choice between several systems, such as liquid absorption, solid adsorption and chemical reaction heat pumps. Nevertheless, few comparative studies between these systems have been undertaken so far. It is the aim of this paper to present such a study based on combined first and second law thermodynamical analysis of the different cycles. Simple entropy generation processes explain why the basic cycles for these systems yield performances much lower than the Carnot efficiency. The possibility of operating regenerative cycles with internal heat recovery and higher efficiencies has also been considered for typical common base conditions. Different entropy generation considerations have been visualised, such as thermal coupling (external/internal), non-uniform temperature component entropy production and other irreversible processes for the COP degradation in these systems. It is found that thermal coupling irreversibilities in solid sorption systems and other internal irreversibilities in liquid sorption systems with solution heat exchanger are dominant in the actual COP degradation with respect to the reversible Carnot COP.