Crystal Structure and Size-Dependent Neutralization Properties of HK20, a Human Monoclonal Antibody Binding to the Highly Conserved Heptad Repeat 1 of gp41

The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 Å resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool

Magnetic particle biosensors

Abstract With the recent technological advances in the synthesis and characterization of nano- and microparticles, there has been a growing interest in applying this technology to different areas, such as diagnosis of diseases and detection of pollutants. The use of magnetic particles as biosensors is favored due to the mobility of magnetic particles under magnetic fields and the low magnetic background observed in most biological samples. This chapter briefly discusses the basic ways to modify the surface of magnetic particles to enhance interaction with biological targets, and thoroughly reviews the different applications of magnetic particles as biosensors. The use of magnetic particles is divided into three categories by the functionality of the magnetic particles in these biosensors, namely magnetic particles as carriers for signal intensification, magnetic particles as labels to detect magnetic contents, and bio-sensing based on the dynamics of magnetic particles. The strategy and theory of different magnetic particle biosensors are elucidated in details and illustrated through examples

TABLE S1 - Supplemental material for Colchicine for Erythema Nodosum: A Retrospective Case Series

Supplemental material, TABLE S1, for Colchicine for Erythema Nodosum: A Retrospective Case Series by Matthew L. Hrin, Palak V. Patel, Joseph L. Jorizzo, Steven R. Feldman and William W. Huang in Journal of Cutaneous Medicine and Surgery</p

An integrated approach to measuring the whole journey traveller experience

Transport authorities and providers use various standardized indicators in order to evaluate the system performance. The main objective of this study is to identify the most significant variables that describe travellers' satisfaction. An original survey and stakeholder consultation were conducted across Europe. The relations between overall satisfaction and travel experience variables, subjective well-being indices, travel-related attitudes as well as individual- and trip-specific attributes were investigated for individual trip stages as well as the whole journey experience. The segmentation of the population into distinguished travellers' groups revealed distinctively different sets of main determinants of their satisfaction with various trip stages. The results of this survey will facilitate the development of a traveller satisfaction measurement too

An integrated approach to measuring the whole journey traveller experience

Transport authorities and providers use various standardized indicators in order to evaluate the system performance. The main objective of this study is to identify the most significant variables that describe travellers’ satisfaction. An original survey and stakeholder consultation were conducted across Europe. The relations between overall satisfaction and travel experience variables, subjective well-being indices, travel-related attitudes as well as individual- and trip-specific attributes were investigated for individual trip stages as well as the whole journey experience. The segmentation of the population into distinguished travellers’ groups revealed distinctively different sets of main determinants of their satisfaction with various trip stages. The results of this survey will facilitate the development of a traveller satisfaction measurement tool