Precursor ion scanning for detection and structural characterization of heterogeneous glycopeptide mixtures

AbstractThe structure of N-linked glycans is determined by a complex, anabolic, intracellular pathway but the exact role of individual glycans is not always clear. Characterization of carbohydrates attached to glycoproteins is essential to aid understanding of this complex area of biology. Specific mass spectral detection of glycopeptides from protein digests may be achieved by on-line HPLC-MS, with selected ion monitoring (SIM) for diagnostic product ions generated by cone voltage fragmentation, or by precursor ion scanning for terminal saccharide product ions, which can yield the same information more rapidly. When glycosylation is heterogeneous, however, these approaches can result in spectra that are complex and poorly resolved. We have developed methodology, based around precursor ion scanning for ions of high m/z, that allows site specific detection and structural characterization of glycans at high sensitivity and resolution. These methods have been developed using the standard glycoprotein, fetuin, and subsequently applied to the analysis of the N-linked glycans attached to the scrapie-associated prion protein, PrPSc. These glycans are highly heterogeneous and over 30 structures have been identified and characterized site specifically. Product ion spectra have been obtained on many glycopeptides confirming structure assignments. The glycans are highly fucosylated and carry Lewis X or sialyl Lewis X epitopes and the structures are in-line with previous results. [Abbreviations: Hex–Hexose, C6H12O6 carbohydrates, including mannnose and galactose; HexNAc—N-acetylhexosamine, C8H15NO6 carbohydrates, including N-acetylglucosamine and N-acetylgalactosamine; GlcNAc—N-acetylglucosamine; GalNAc—N-acetylgalactosamine; Fuc–Fucose; NeuAC—N-acetylneuraminic acid or sialic acid; TSE—Transmissible Spongiform Encephalopathy.

Giant Fluctuations of Coulomb Drag in a Bilayer System

We have observed reproducible fluctuations of the Coulomb drag, both as a function of magnetic field and electron concentration, which are a manifestation of quantum interference of electrons in the layers. At low temperatures the fluctuations exceed the average drag, giving rise to random changes of the sign of the drag. The fluctuations are found to be much larger than previously expected, and we propose a model which explains their enhancement by considering fluctuations of local electron properties.Comment: 10 pages, 4 figure

Some Empirical Criteria for Attributing Creativity to a Computer Program

Peer reviewedPostprin

The role of institutional and family embeddedness in the failure of Sub-Saharan African migrant family businesses

There is considerable interest among European politicians and policymakers in how to integrate migrants in the local and national economy. Drawing on in-depth qualitative interviews with 20 owners of Sub-Saharan African migrant family businesses (SSAMBs) in the United Kingdom, this article critically examines why SSAMBs fail or underperform. This investigation draws upon three streams of literature – notably migrant business failure, institutional theory and family embeddedness. The findings highlight the challenges of doing business and the reasons for business failure among this group. These are different from other small businesses and include culture, family interference and ethnicity. The main contribution of the article lies in the development of a conceptual model that highlights the relationships between institutional contexts and migrant family business outcomes. The model proposes that institution and family embeddedness results in the enactment of ethnic behaviours that drive migrant businesses into cultural markets leading to business underperformance or failure

Charge and spin state readout of a double quantum dot coupled to a resonator

State readout is a key requirement for a quantum computer. For semiconductor-based qubit devices it is usually accomplished using a separate mesoscopic electrometer. Here we demonstrate a simple detection scheme in which a radio-frequency resonant circuit coupled to a semiconductor double quantum dot is used to probe its charge and spin states. These results demonstrate a new non-invasive technique for measuring charge and spin states in quantum dot systems without requiring a separate mesoscopic detector