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     

Application of evolutionary programming to transient andsubtransient parameter estimation

This paper presents an artificial intelligence approach of using evolutionary programming to estimate the transient and subtransient parameters of a generator under normal operation. The estimation using evolutionary programming is compared with that using a corrected extended Kalman filter. The comparisons with both simulation and micromachine test results show that evolutionary programming is robust to search the real values of parameters even when the data are highly contaminated by noise, while with the extended Kalman filter, the estimation tends to diverge with such data     

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     

Process optimization and related material properties of silicon films produced by laser-induced chemical vapour deposition from silane

Laser-induced chemical vapour deposition of silicon films on SiO₂/Si (1 0 0) and Si (1 0 0) substrates was studied using ArF laser irradiation of silane/argon gas mixture in parallel to the substrate. The optimal deposition conditions were specified by examination of film morphology at a wide range of irradiation and process parameters. At optimal conditions, specular films were obtained with no powder formation. The effect of deposition parameters, such as laser energy and repetition rate, on the deposition rate and the related film quality, was investigated.     

Melt-extracted oxide ceramic fibres — the fundamentals

A melt-extraction technique, using a sharpened molybdenum wheel, has been used to produce fine oxide ceramic fibres. Wetting of the molybdenum wheel by molten ceramic is a key parameter in the melt-extraction process. Two types of fibre are generally obtained, depending on the extraction speed. At very low wheel speed, fine and uniform fibres of high quality are produced. However, when the wheel speed exceeds a critical velocity, Rayleigh waves are formed on the free surface of the fibres. Moreover, the average fibre thickness first increases with the wheel velocity, then passes through a maximum, decreasing at high velocity. This thickness variation is discussed in terms of both surface tension and viscosity of the liquid ceramics.     

Using internal fibre geometry to improve the performance of pin-loaded holes in composite materials

The anisotropic nature of fibre reinforced composites leads to large stress concentrations around pin-loaded holes through standard weave cloths. Proper understanding of how this anisotropic nature affects the load distribution around holes can be utilised to reduce these concentrations if sufficient thought is given to the internal fibre geometry near to the hole. Such local reinforcements need not be highly complex and can be readily produced without excessive effort, producing significant improvements in performance.