Concentration profiles of cocaine, pyrolytic methyl ecgonidine and thirteen metabolites in human blood and urine: determination by gas chromatography-mass spectrometry

When cocaine is smoked, a pyrolytic product, methyl ecgonidine (anhydroecgonine methyl ester), is also consumed with the cocaine. The amount of methyl ecgonidine formed depends on the pyrolytic conditions and composition of the illicit cocaine. This procedure describes detection of cocaine and 10 metabolites--cocaethylene, nor-cocaine, nor-cocaethylene, methyl ecgonine, ethyl ecgonine, benzoylecgonine, nor-benzoylecgonine, m-hydroxybenzoylecgonine, p-hydroxybenzoylecgonine and ecgonine--in blood and urine. In addition, the detection of pyrolytic methyl ecgonidine and three metabolites--ecgonidine (anhydroecgonine), ethyl ecgonidine (anhydroecgonine ethyl ester) and nor-ecgonidine (nor-anhydroecgonine)--are included. The newly described metabolites, ethyl ecgonidine and nor-ecgonidine, were synthesized and characterized by gas chromatography-mass spectrometry (GC-MS). All 15 compounds were extracted from 3 mL of blood or urine by solid-phase extraction and identified by a GC-MS method. The overall recoveries were 49% for methyl ecgonine, 35% for ethyl ecgonine, 29% for ecgonine and more than 83% for all other drugs. The limits of detection were between 0.5 and 4.0 ng/mL except for ecgonine, which was 16 ng/mL. Linearity for each analyte was established and in all cases correlation coefficients were 0.9985-1.0000. The procedure was applied to examine the concentration profiles of analytes of interest in post-mortem (PM) blood and urine, and in urine collected from living individuals (LV). These specimens previously were shown to be positive for the cocaine metabolite, benzoylecgonine. Ecgonidine, the major metabolite of methyl ecgonidine, was present in 77% of PM and 88% of the LV specimens, indicating smoking as the major route of cocaine administration. The new pyrolytic metabolites, ethyl ecgonidine and nor-ecgonidine, were present in smaller amounts. The urine concentrations of nor-ecgonidine were 0-163 ng/mL in LV and 0-75 ng/mL in PM specimens. Ethyl ecgonidine was found only in PM urine at concentrations 0-39 ng/mL. Ethanol-related cocaine metabolites, ethyl ecgonine or cocaethylene, were present in 69% of PM and 53% of cocaine-positive LV specimens, implying alcohol consumption with cocaine use. The four major metabolites of cocaine--benzoylecgonine, ecgonine, nor-benzoylecgonine and methyl ecgonine--constituted approximately 88 and 97% of all metabolites in PM and LV specimens, respectively. The concentrations of nor-cocaine and nor-cocaethylene were consistently the lowest of all cocaine metabolites. At benzoylecgonine concentrations below 100 ng/mL, ecgonine was present at the highest concentrations. In 20 urine specimens, benzoylecgonine and ecgonine median concentrations (range) were 54 (0-47) and 418 ng/mL (95-684), respectively. Therefore, detection of ecgonine is advantageous when benzoylecgonine concentrations are below 100 ng/mL.     

UV-induced Coulomb crystallization of dust grains in high-pressuregas

A scheme for forming a Coulomb lattice of positively charged dust grains in a high-pressure (P>torr) gas is discussed theoretically. The grains are charged positively by photoemission in the presence of a flux of ultraviolet (UV) photons with energy larger than the work function of the grains, but lower than the ionization potential of the background gas. Methods for levitating and containing the dust using photophoretic forces (both UV and non-UV), gas drag, and electrostatic forces are considered     

Second-harmonic generation induced by electric currents in GaAs

We demonstrate a new, nonlinear optical effect of electric currents. First, a steady current is generated by applying a voltage on a doped GaAs crystal. We demonstrate that this current induces second-harmonic generation of a probe laser pulse. Second, we optically inject a transient current in an undoped GaAs crystal by using a pair of ultrafast laser pulses and demonstrate that it induces the same second-harmonic generation. In both cases, the induced second-order nonlinear susceptibility is proportional to the current density. This effect can be used for nondestructive, noninvasive, and ultrafast imaging of currents. These advantages are illustrated by the real-time observations of a coherent plasma oscillation and spatial resolution of current distribution in a device. This new effect also provides a mechanism for electrical control of the optical response of materials.     

Coherent Generation and Detection of Continuous Terahertz Waves Using Two Photomixers Driven by Laser Diodes

We report on a completely coherent, tunable, continuous-wave THz system where, for the first-time, both the transmitter and receiver are log-periodic-antenna coupled LTG-GaAs based finger-photomixers. This compact room-temperature system exhibits signal-to-noise ratios (> 10³) comparable to or better than what is reported in the literature, and has potential applications in high-resolution spectroscopy and imaging. For the purpose of demonstration, we also present results of spectroscopy measurements carried out on fused silica, which are in agreement with previously published THz-TDS measurements.     

Nature of subpicosecond terahertz pulse propagation in practical dielectric-filled parallel-plate waveguides

It is analytically shown that the presence of submicrometer-sized air gaps between the dielectric and metal contact surfaces in a dielectric-filled metallic parallel-plate waveguide can have a dramatic effect on the guided-wave propagation of subpicosecond terahertz pulses. Through the use of metal-evaporated dielectric surfaces to overcome the imperfect contact problem, and a special air-dielectric-air cascaded waveguide geometry to avoid multimode excitation, undistorted subpicosecond terahertz pulse propagation via the single-TEM mode is demonstrated, for what is believed to be the first time, in a silicon-filled PPWG.     

WRAO and OWA learning using Levenberg–Marquardt and genetic algorithms

The generalized Weighted Relevance Aggregation Operator (WRAO) is a non-additive aggregation function. The Ordered Weighted Aggregation Operator (OWA) (or its generalized form: Generalized Ordered Weighted Aggregation Operator (GOWA)) is more restricted with the additivity constraint in its weights. In addition, it has an extra weights reordering step making it hard to learn automatically from data. Our intension here is to compare the efficiency (or effectiveness) of learning these two types of aggregation functions from empirical data. We employed two methods to learn WRAO and GOWA: Levenberg–Marquardt (LM) and a Genetic Algorithm (GA) based method. We use UCI (University of California Irvine) benchmark data to compare the aggregation performance of non-additive WRAO and additive GOWA. We found that the non-constrained aggregation function WRAO was learnt well automatically and produced consistent results, while GOWA was learnt less well and quite inconsistently.     

Secondary emission from small dust grains at high electron energies

A previous model for secondary electron emission from small grains is modified to calculate yields for micron sized grains, both spherical and cylindrical, when the primary electrons constitute a high energy parallel beam. It is found that, in general, the secondary electron yield is significantly higher than for the case of normal incidence. Moreover, the equilibrium potentials of the grain are always positive due to this enhanced secondary emission. These results are compared with experimental data recently available for micron sized glass particles, and equilibrium potentials, calculated based on the model presented here, and are found to be in reasonably good agreement with their measured potentials     

Latin Squares with a Unique Intercalate

Suppose that and . We construct a Latin square of order n with the following properties:

• has no proper subsquares of order 3 or more .
• has exactly one intercalate (subsquare of order 2) .
• When the intercalate is replaced by the other possible subsquare on the same symbols, the resulting Latin square is in the same species as .

Hence generalizes the square that Sade famously found to complete Norton's enumeration of Latin squares of order 7. In particular, is what is known as a self‐switching Latin square and possesses a near‐autoparatopism.     

Molecular Docking of SP40 Peptide towards Cellular Receptors for Enterovirus 71 (EV-A71)

Enterovirus 71 (EV-A71) is one of the predominant etiological agents of hand, foot and mouth disease (HMFD), which can cause severe central nervous system infections in young children. There is no clinically approved vaccine or antiviral agent against HFMD. The SP40 peptide, derived from the VP1 capsid of EV-A71, was reported to be a promising antiviral peptide that targeted the host receptor(s) involved in viral attachment or entry. So far, the mechanism of action of SP40 peptide is unknown. In this study, interactions between ten reported cell receptors of EV-A71 and the antiviral SP40 peptide were evaluated through molecular docking simulations, followed by in vitro receptor blocking with specific antibodies. The preferable binding region of each receptor to SP40 was predicted by global docking using HPEPDOCK and the cell receptor-SP40 peptide complexes were refined using FlexPepDock. Local molecular docking using GOLD (Genetic Optimization for Ligand Docking) showed that the SP40 peptide had the highest binding score to nucleolin followed by annexin A2, SCARB2 and human tryptophanyl-tRNA synthetase. The average GoldScore for 5 top-scoring models of human cyclophilin, fibronectin, human galectin, DC-SIGN and vimentin were almost similar. Analysis of the nucleolin-SP40 peptide complex showed that SP40 peptide binds to the RNA binding domains (RBDs) of nucleolin. Furthermore, receptor blocking by specific monoclonal antibody was performed for seven cell receptors of EV-A71 and the results showed that the blocking of nucleolin by anti-nucleolin alone conferred a 93% reduction in viral infectivity. Maximum viral inhibition (99.5%) occurred when SCARB2 was concurrently blocked with anti-SCARB2 and the SP40 peptide. This is the first report to reveal the mechanism of action of SP40 peptide in silico through molecular docking analysis. This study provides information on the possible binding site of SP40 peptide to EV-A71 cellular receptors. Such information could be useful to further validate the interaction of the SP40 peptide with nucleolin by site-directed mutagenesis of the nucleolin binding site.     

UV-induced Coulomb crystallization in a dusty gas

Conditions are investigated for forming a Coulomb lattice of dust grains which are charged positively by the ultraviolet induced photoemission of electrons