Cleaning the Clyde—a Century of Progress?

A Royal Commission report in 1872 revealed that the Clyde was one of the most heavily polluted rivers in Britain. Despite notable efforts to reduce pollution after the Rivers Pollution Prevention Act, 1876, little real improvement took place, and the quality of the river actually worsened during the first half of the present century. The Clyde River Purification Board, established in 1956, has taken almost 30 years to restore the river to its present state of health, with salmon once again returning to spawn after an absence of over 120 years. The author examines the reasons for this long delay and considers whether present controls are adequate to meet the needs of the future in the face of rapidly changing industrial effluents.     

Speckle reduction in optical coherence tomography images by use of a spatially adaptive wavelet filter

A spatially adaptive two-dimensional wavelet filter is used to reduce speckle noise in time-domain and Fourier-domain optical coherence tomography (OCT) images. Edges can be separated from discontinuities that are due to noise, and noise power can be attenuated in the wavelet domain without significantly compromising image sharpness. A single parameter controls the degree of noise reduction. When this filter is applied to ophthalmic OCT images, signal-to-noise ratio improvements of >7 dB are attained, with a sharpness reduction of <3%.     

Mode transformer for miniaturized optical circuits

A novel mode transformer was fabricated that transforms a modal area by a factor of 100. Using the mode transformer improves the efficiency of mode transformation by an order of magnitude compared with that when no mode transformer is used. With this mode transformer, input-output coupling of miniaturized, on-chip integrated optical circuits to external optical fibers is achieved with low loss. The mode transformer's design, fabricated in silicon, is scalable to virtually any waveguide size, facilitating continuous miniaturization in silicon optoelectronics.     

Measurement of single electrons and implications for charm production in Au+Au collisions at square root[s(NN)] = 130 GeV

Transverse momentum spectra of electrons from Au+Au collisions at square root[s(NN)] = 130 GeV have been measured at midrapidity by the PHENIX experiment at the Relativistic Heavy Ion Collider. The spectra show an excess above the background from photon conversions and light hadron decays. The electron signal is consistent with that expected from semileptonic decays of charm. The yield of the electron signal dN(e)/dy for p(T) > 0.8 GeV/c is 0.025+/-0.004(stat)+/-0.010(syst) in central collisions, and the corresponding charm cross section is 380+/-60(stat)+/-200(syst) microb per binary nucleon-nucleon collision.     

Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High pH Dynamic Kinetic Reduction

Described here is an efficient stereoselective synthesis of vibegron enabled by an enzymatic dynamic kinetic reduction that proceeds in a high‐pH environment. To overcome enzyme performance limitations under these conditions, a ketoreductase was evolved by a computationally and structurally aided strategy to increase cofactor stability through tighter binding.     

Determination of drug concentrations in plasma by a highly automated, generic and flexible protein precipitation and liquid chromatography/tandem mass spectrometry method applicable to the drug discovery environment

This report presents a highly automated procedure for the determination of drug concentrations in plasma samples. The method is generic, in that it has been applied without adaptation to many different drug candidate molecules, but is also flexible, in that variations in the nature and number of samples to be analyzed can be readily accommodated. The method includes preparation of dilutions of analyte stock solutions, spiking these into control plasma to generate analytical standards, and preparation of samples suitable for analysis by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) by precipitation of plasma proteins with acetonitrile, centrifugation, and dilution of the supernatants with HPLC buffer. All of these steps, apart from centrifugation, are performed without manual intervention on an automated liquid-handling workstation using 96-well plates. Analysis is by HPLC/MS/MS, using a generic HPLC gradient. Commercially available software was used for optimization of parameters for analysis by HPLC/MS/MS, integration of chromatographic peaks, and quantification of drug concentrations. The use of this methodology in our laboratory has greatly facilitated the analysis of small sample sets for a large number of analytes, a situation regularly encountered in an early drug discovery environment.     

Liquid chromatography/mass spectrometric bioanalysis of a modified gamma-cyclodextrin (Org 25969) and Rocuronium bromide (Org 9426) in guinea pig plasma and urine: its application to determine the plasma pharmacokinetics of Org 25969

A sensitive and specific liquid chromatography/mass spectrometry (LC/MS) method has been developed and validated for the quantification of the modified gamma-cyclodextrin Org 25969 and Rocuronium bromide (Roc or Org 9426) in the plasma and urine of guinea pigs. The assay was linear and reproducible over the range 25-10000 ng/mL for both compounds. The lowest limit of quantification (LLOQ) for both compounds in urine was 25 ng/mL. In plasma, the LLOQ was 25 ng/mL for Org 9426 and 50 ng/mL for Org 25969. The inter- and intra-day variation was lower than 20%. The physicochemical properties of both compounds imposed different modes of extraction from plasma. The modified gamma-cyclodextrin was extracted by trifluoroacetic acid (TFA) precipitation while Rocuronium was extracted by acetonitrile precipitation. Both compounds were quantified in urine by direct injection onto the column. The LC/MS analyses of Org 25969 and Org 9426 were performed using two different assay conditions. It was not possible to quantify the complex of cyclodextrin and Roc as it dissociated on the LC column. The use of LC/MS conferred great advantage to the quantification of both Org 25969 and Org 9426, as they were not chromogenic enough to afford the sensitivity and specificity required for the assay.