Measurement of the Relaxation Rates ofH Longitudinal Modes

Accurate decay rate measurements for longitudinal modes are essential for many of the methods proposed for investigating molecular dynamics by NMR. However, the effects of cross relaxation often make it impossible to determine accurate values for these quantities. A method is presented that enables the effects of cross relaxation to be largely eliminated from such measurements. Its reliability is assessed by comparing the values for internuclear distances that can be determined from the resulting relaxation rates with values obtained using other methods. Other consequences of using this technique include an increased robustness of experiments to short (i.e., <5T₁) relaxation times and the ability to make multiple “selective” relaxation measurements simultaneously.     

DYNGA: a general purpose QM-MM-MD program. I. Application to water

We present a general purpose QM-MM-MD engine (DYNGA) designed to test alternative hybrid Hamiltonians geared towards the treatment of problems of interest in structural biology including the use of experimental data constraints. In this first presentation we use DYNGA to explore the behaviour of a traditional QM-MM approach in the treatment of the water—water interaction. We find the potential energy hypersurface for the water dimer computed with the HF 4–31G*/TIP3P hybrid Hamiltonian tends to be too flat. We also explore the effect of using traditional QM-MM techniques on proton wires and conclude there is a need for improvement, possibly addressed by using polarizable force fields.     

Application of continuous-flow liquid chromatography/fast-atom bombardment mass spectrometry to the analysis of diagnostic acylcarnitines in human urine

Acylcarnitine profiles of diagnostic value were generated from the equivalent of 0.1 microL of raw urine using the continuous-flow liquid chromatography/fast-atom bombardment mass spectrometry (LC/FAB-MS) interface for sample introduction. Further analysis was accomplished by gradient LC/MS using a commercially available packed fused-silica microbore column.     

In-phase selective excitation of overlapping multiplets

An editing experiment is presented that selects for a peak on the basis of its chemical shift and that of one of its scalar coupling partners. The selected multiplet is pure in-phase. The editing procedure can be used in conjunction with 1D TOCSY/HOHAHA and NOE measurements. The pulse sequence described is particularly suitable for small molecules; data is presented for Gramicidin S and dehydrotestosterone.     

Structure Elucidation of a Complex Faldaprevir‐(±)‐α‐Tocopherol Addition Product Reveals Reactivity of Common Excipient Vitamin E‐TPGS

Vitamin E‐TPGS (d ‐α‐tocopheryl polyethylene glycol succinate) is a common excipient used in drug formulations. This excipient is formed by esterification of Vitamin E succinate with polyethylene glycol. As part of an oral formulation for active pharmaceutical ingredient (API) Faldaprevir, Vitamin E‐TPGS was found to decompose under ambient conditions producing free (±)‐α‐Tocopherol which subsequently formed an adduct composed of α‐Tocopherol and the API. The addition product was isolated using liquid chromatography with collections onto solid‐phase extraction cartridges, and full structure elucidation was achieved using mass spectrometry and nuclear magnetic resonance spectroscopy. The results revealed a regioselective addition of α‐Tocopherol to the API that likely occurs through the formation of a stabilized ortho‐quinone methide intermediate. This finding demonstrates the propensity of the common excipient (Vitamin E‐TPGS) to generate chemically active intermediates that may react with formulation ingredients.     

ConFlo III - an interface for high precision delta(13)C and delta(15)N analysis with an extended dynamic range

A newly developed interface coupling a CHN combustion device (elemental analyser 'EA') to an isotope ratio mass spectrometer is described and evaluated. The purpose of the device is to extend the dynamic range of delta(13)C and delta(15)N analysis from less than 2 orders of magnitude to more than 3 orders of magnitude. Carbon isotope ratio measurements of atropine as a model compound have been performed analysing between 1 μg to 5 mg C with acceptable to excellent precision (0.6 to 0.06 per thousand, delta-notation). The correction due to the blank signal is critical for sample amounts smaller than 4 μg C. The maximum sample weight is determined by the combustion capacity of the EA. Larger sample amounts are measured using dilution of a small part of the EA effluent with helium. The dilution mechanism works virtually free of isotope fractionation. Copyright 1999 John Wiley & Sons, Ltd.     

PAST AND FUTURE MANAGEMENT OF A COLLAPSED FISHERY: THE BAY OF BISCAY ANCHOVY

Abstract We analyze the efficiency of the international management of the Bay of Biscay anchovy. While a sharing agreement between France and Spain has been in place since 1992, the fish stock collapsed in 2005 and the fishery closed from 2005 to spring 2010. We consider differences in production technologies between both countries and calibrate our model using data from 1987 to 2009. Our results suggest two sources of rent dissipation under the existing sharing agreement: inefficient quota allocation and production inefficiencies due to inflexible national regulations. We discuss several alternatives to improve management.     

Guest Commentary

Abstract

Clustering and Classification edited by P. Arabie, L. J. Hubert, and G. De Soete, River Edge, New Jersey: World Scientific, 1996, 490 pp., $109 hardcover, $61 paperback. Reviewed by Jon R. Kettenring

Statistics as Principled Argument by Robert P. Abelson, Hillsdale, New Jersey: Lawrence Erlbaum Associates, 1995, 221 pp. Reviewed by Edward J. Shoben     

An Improved Upper Bound for Leo Moser's Worm Problem

Abstract. A worm ω is a continuous rectifiable arc of unit length in the Cartesian plane. Let W denote the class of all worms. A planar region C is called a cover for W if it contains a copy of every worm in W . That is, C will cover or contain any member ω of W after an appropriate translation and/ or rotation of ω is completed (no reflections). The open problem of determining a cover C of smallest area is attributed to Leo Moser [7], [8]. This paper reduces the smallest known upper bound for this area from 0.275237 [10] to 0.260437.