Reaching the global minimum in docking simulations: a Monte Carlo energy minimization approach using Bezier splines

The docking problem faces two major challenges: the global optimization of a multivariable function, such as the energy, and the ability to discriminate between true and false positive results, i.e., native from nonnative structures based on the input energy function. Among all energy evaluation tools, only a local energy-minimization method using an accurate enough potential function is able to discriminate between native and nonnative structures. To meet these requirements, a Monte Carlo with energy-minimization method has been incorporated into a new ECEPP/3 docking program. The efficiency of the simulation results from the use of an energy-grid technique based on Bezier splines and from a simplification of the receptor by switching on the energy of only important residues of the active site. Simulations of a thrombin-inhibitor complex show that the global minimum of the energy function was reached in every independent run within less than 3 min of time on an IBM RX 6000 computer. For comparison, 10 standard independent Monte Carlo simulations with 10(6) steps in each were carried out. Only three of them led to a conformation close to the x-ray structure. The latter simulations required an average of 24 min and about 10 hr with and without the grid, respectively. Another important result is that the Bezier spline technique not only speeds up the calculation by reducing the number of operations during the energy evaluation but also helps in reaching the global minimum by smoothing out the potential energy surface.     

Dynamic digital holographic wavelength filtering

This paper describes the theory and results of a new generic technology for use in optical telecommunications and wavelength division multiplexing (WDM): dynamic digital holographic wavelength filtering. The enabling component is a polarization-insensitive ferroelectric liquid crystal (FLC) spatial light modulator (SLM) in conjunction with a highly wavelength-dispersive fixed diffractive element. The technology has been used to perform demultiplexing of single or multiple WDM signals, dynamic erbium doped fiber amplifier (EDFA) gain equalization and channel management, and used to tune an erbium-doped fiber laser (EDFL) functioning as a high power, very narrow linewidth WDM source     

Tracking and motion analysis of the left ventricle with deformable superquadrics

We present a new approach to analyse the deformation of the left ventricle of the heart based on a parametric model that gives a compact representation of a set of points in a 3-D image. We present a strategy for tracking surfaces in a sequence of 3-D cardiac images. Following tracking, we then infer quantitative parameters which characterize: left ventricle motion, volume of left ventricle, ejection fraction, amplitude and twist component of cardiac motion. We explain the computation of these parameters using our model. Experimental results are shown in time sequences of two modalities of medical images, nuclear medicine and X-ray computed tomography (CT). Video sequences presenting these results are on the CD-ROM.     

A novel metal-insulator-metal structure for field-programmabledevices

A metal-insulator-metal (MIM) capacitor structure has been developed for use in field-programmable gate arrays (FPGAs) as a voltage-programmable link (VPL). The structure relies on a combination of a refractory metal and aluminum as the lower electrode, and either a similar combination or aluminum alone as the top electrode. The insulator is prepared by means of plasma-enhanced chemical vapor deposition (PECVD). It comprises a sandwich of nearly stoichiometric silicon dioxide interposed between two like layers of silicon-rich silicon nitride. The structure has displayed characteristics desirable for use in emerging FPGA technology, including high density, low on-resistance, reduced capacitance, and low programming voltage     

Discussion of “an interpretation of the carbon redistribution process during aging of high-carbon martensite”

Y. OHMORI and I. TAMURA:Metall. Trans. A, 1992, vol. 23A,     

Exceptional convergent evolution in a virus

Replicate lineages of the bacteriophage phiX 174 adapted to growth at high temperature on either of two hosts exhibited high rates of identical, independent substitutions. Typically, a dozen or more substitutions accumulated in the 5.4-kilobase genome during propagation. Across the entire data set of nine lineages, 119 independent substitutions occurred at 68 nucleotide sites. Over half of these substitutions, accounting for one third of the sites, were identical with substitutions in other lineages. Some convergent substitutions were specific to the host used for phage propagation, but others occurred across both hosts. Continued adaptation of an evolved phage at high temperature, but on the other host, led to additional changes that included reversions of previous substitutions. Phylogenetic reconstruction using the complete genome sequence not only failed to recover the correct evolutionary history because of these convergent changes, but the true history was rejected as being a significantly inferior fit to the data. Replicate lineages subjected to similar environmental challenges showed similar rates of substitution and similar rates of fitness improvement across corresponding times of adaptation. Substitution rates and fitness improvements were higher during the initial period of adaptation than during a later period, except when the host was changed.     

Limited influence of the mesothelium on the influx of monocytes into the peritoneal cavity

Exposure of Farage, a human B-cell line, to interleukin 4 (IL4) reduced the amount of CD38 antigen on the surface of the cells and in cell lysates. No evidence was obtained for accelerated breakdown, shedding, or internalization of CD38 molecules following IL4 treatment, nor the accumulation of CD38 molecules in the cell interior. The inhibition of protein synthesis with cycloheximide (CXM) diminished the down-regulation of CD38 induced by IL4. CXM decreased the expression of CD38 in Farage cells with arrested mitosis, and IL4 failed to further reduce CD38 expression. Staurosporine, an inhibitor of serine/threonine protein kinases, and H7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine), a preferential inhibitor of protein kinase C (PKC), abrogated the effect of IL4 on CD38, while inhibitors of other serine protein kinases W7 (N-(aminohexyl)-5-chloro-1-naphthalenesulfoamide) and H8 (N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide) failed to interfere with the effect of IL4. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, resembled IL4 in decreasing the expression of CD38, and either staurosporine or H7 abolished this effect. Genistein, an inhibitor of tyrosine kinases, increased the expression of CD38, but failed to abrogate the inhibitory effect of IL4 on CD38. It is concluded that serine/threonine protein kinases mediated the IL4-induced down-regulation of the expression of CD38 molecules in B cells.