Equilibrium polymerization of cyclic carbonate oligomers. II. Role of multiple active sites

Ring opening polymerization of bisphenol A polycarbonate is studied by Monte Carlo simulations of a model comprising a fixed number of Lennard-Jones particles and harmonic bonds [J. Chem. Phys. 115, 3895 (2001)]. Bond interchanges produced by a low concentration (0.10%less than or equal toc(a)less than or equal to0.36%) of chemically active particles lead to equilibrium polymerization. There is a continuous transition in both 2D and 3D from unpolymerized cyclic oligomers at low density to a system of linear chains at high density, and the polymeric phase is much more stable in three dimensions than in two. The steepness of the polymerization transition increases rapidly as c(a) decreases, suggesting that it is discontinuous in the limit c(a)-->0. The transition is entropy driven, since the average potential energy increases systematically upon polymerization, and there is a steady decline in the degree of polymerization as the temperature is lowered. The mass distribution functions for open chains and for rings are unimodal, with exponentially decaying tails that can be fitted by Zimm-Schulz functions and simpler exponential forms. (C) 2002 American Institute of Physics.

A new lead for nonpeptidic active-site-directed inhibitors of the severe acute respiratory syndrome coronavirus main protease discovered by a combination of screening and docking methods.

The coronavirus main protease, Mpro, is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential Mpro inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed Mpro inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a Ki value of 35.3 M. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.

Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor.

The coronavirus main protease, Mpro, is considered a major target for drugs suitable to combat coronavirus infections including the severe acute respiratory syndrome (SARS). In this study, comprehensive HPLC- and FRET-substrate-based screenings of various electrophilic compounds were performed to identify potential Mpro inhibitors. The data revealed that the coronaviral main protease is inhibited by aziridine- and oxirane-2-carboxylates. Among the trans-configured aziridine-2,3-dicarboxylates the Gly-Gly-containing peptide 2c was found to be the most potent inhibitor.

Mutational analysis of the active centre of coronavirus 3C-like proteases.

Formation of the coronavirus replication-transcription complex involves the synthesis of large polyprotein precursors that are extensively processed by virus-encoded cysteine proteases. In this study, the coding sequence of the feline infectious peritonitis virus (FIPV) main protease, 3CL(pro), was determined. Comparative sequence analyses revealed that FIPV 3CL(pro) and other coronavirus main proteases are related most closely to the 3C-like proteases of potyviruses. The predicted active centre of the coronavirus enzymes has accepted unique replacements that were probed by extensive mutational analysis. The wild-type FIPV 3CL(pro) domain and 25 mutants were expressed in Escherichia coli and tested for proteolytic activity in a peptide-based assay. The data strongly suggest that, first, the FIPV 3CL(pro) catalytic system employs His(41) and Cys(144) as the principal catalytic residues. Second, the amino acids Tyr(160) and His(162), which are part of the conserved sequence signature Tyr(160)-Met(161)-His(162) and are believed to be involved in substrate recognition, were found to be indispensable for proteolytic activity. Third, replacements of Gly(83) and Asn(64), which were candidates to occupy the position spatially equivalent to that of the catalytic Asp residue of chymotrypsin-like proteases, resulted in proteolytically active proteins. Surprisingly, some of the Asn(64) mutants even exhibited strongly increased activities. Similar results were obtained for human coronavirus (HCoV) 3CL(pro) mutants in which the equivalent Asn residue (HCoV 3CL(pro) Asn(64)) was substituted. These data lead us to conclude that both the catalytic systems and substrate-binding pockets of coronavirus main proteases differ from those of other RNA virus 3C and 3C-like proteases.

Ultrafast coherent control and quantum encoding of molecular vibrations in D2+ using intense laser pulses

Intense, few-femtosecond pulse technology has enabled studies of the fastest vibrational relaxation processes. The hydrogen group vibrations can be imaged and manipulated using intense infrared pulses. Through numerical simulation, we demonstrate an example of ultrafast coherent control that could be effected with current experimental facilities, and observed using high-resolution time-of-flight spectroscopy. The proposal is a pump-probe-type technique to manipulate the D2+ ion with ultrashort pulse sequences. The simulations presented show that vibrational selection can be achieved through pulse delay. We find that the vibrational system can be purified to a two-level system thus realizing a vibrational qubit. A novel scheme for the selective transfer of population between these two levels, based on a Raman process and conditioned upon the delay time of a second control-pulse is outlined, and may enable quantum encoding with this system.

Imaging quantum vibrations on an ultrashort timescale: the deuterium molecular ion

The vibrational wavepacket revival of a basic quantum system is demonstrated experimentally. Using few-cycle laser pulse technology, pump and probe imaging of the vibrational motion of D+2 molecules is conducted, and together with a quantum-mechanical simulation of the excited wavepacket motion, the vibrational revival phenomenon has been characterised. The simulation shows good correlation with the temporal motion and structural features obtained from the data, relaying fundamental information on this diatomic system.

Neural network controlled three-phase four-wire shunt active powerfilter

A three-phase four-wire shunt active power filter for harmonic mitigation and reactive power compensation in power systems supplying nonlinear loads is presented. Three adaptive linear neurons are used to tackle the desired three-phase filter current templates. Another feedforward three-layer neural network is adopted to control the output filter compensating currents online. This is accomplished by producing the appropriate switching patterns of the converter's legs IGBTs. Adequate tracking of the filter current references is obtained by this method. The active filter injects the current required to compensate for the harmonic and reactive components of the line currents, Simulation results of the proposed active filter indicate a remarkable improvement in the source current waveforms. This is reflected in the enhancement of the unified power quality index defined. Also, the filter has exhibited quite a high dynamic response for step variations in the load current, assuring its potential for real-time applications

Nonlinear excitations in electron-positron-ion plasmas in accretion disks of active galactic nuclei

The propagation of acoustic nonlinear excitations in an electron-positron-ion (e-p-i) plasma composed of warm electrons and positrons, as well as hot ions, has been investigated by adopting a two-dimensional cylindrical geometry. The electrons and positrons are modeled by hydrodynamic fluid equations, while the ions are assumed to follow a temperature-parametrized Boltzmann distribution (the fixed ion model is recovered in the appropriate limit). This situation applies in the accretion disk near a black hole in active galactic nuclei, where the ion temperature may be as high as 3 to 300 times that of the electrons. Using a reductive perturbation technique, a cylindrical Kadomtsev-Petviashvili equation is derived and its exact soliton solutions are presented. Furthermore, real situations in which the strength of the nonlinearity may be weak are considered, so that higher-order nonlinearity plays an important role. Accordingly, an extended cylindrical Kadomtsev-Petviashvili equation is derived, which admits both soliton and double-layer solutions. The characteristics of the nonlinear excitations obtained are investigated in detail

High-frequency oscillations in a solar active region observed with the RAPID DUAL IMAGER

High-cadence, synchronized, multiwavelength optical observations of a solar active region (NOAA 10794) are presented. The data were obtained with the Dunn Solar Telescope at the National Solar Observatory/Sacramento Peak using a newly developed camera system: the rapid dual imager. Wavelet analysis is undertaken to search for intensity related oscillatory signatures, and periodicities ranging from 20 to 370 s are found with significance levels exceeding 95%. Observations in the H-α blue wing show more penumbral oscillatory phenomena when compared to simultaneous G-band observations. The H-α oscillations are interpreted as the signatures of plasma motions with a mean velocity of 20 km s-1. The strong oscillatory power over H-α blue-wing and G-band penumbral bright grains is an indication of the Evershed flow with frequencies higher than previously reported.