On the break in the single-particle energy dispersions and the `universal' nodal Fermi velocity in the high-temperature copper-oxide superconductors

Recent data from angle-resolved photoemission experiments published by Zhou et al. [Nature, Vol. 423, 398 (2003)] concerning a number of hole-doped copper-oxide-based high-temperature superconductors reveal that in the nodal directions of the underlying square Brillouin zones (i.e. the directions along which the d-wave superconducting gap is vanishing) the Fermi velocities for some finite range of k inside the Fermi sea and away from the nodal Fermi wavevector k_F are to within an experimental uncertainty of approximately 20% the same both in all the compounds investigated and over a wide range of doping concentrations and that, in line with earlier experimental observations, at some characteristic wavevector k_* away from k_F the Fermi velocities undergo a sudden change, with this change (roughly speaking, a finite discontinuity) being the greatest (smallest) in the case of underdoped (overdoped) compounds. In this paper we present a rigorous analysis concerning the implications of these observations. [Short abstract]Comment: 29 pages, 4 postscript figures. Brought into conformity with the published versio

Towards Universal Structure-Based Prediction of Class II MHC Epitopes for Diverse Allotypes

The binding of peptide fragments of antigens to class II MHC proteins is a crucial step in initiating a helper T cell immune response. The discovery of these peptide epitopes is important for understanding the normal immune response and its misregulation in autoimmunity and allergies and also for vaccine design. In spite of their biomedical importance, the high diversity of class II MHC proteins combined with the large number of possible peptide sequences make comprehensive experimental determination of epitopes for all MHC allotypes infeasible. Computational methods can address this need by predicting epitopes for a particular MHC allotype. We present a structure-based method for predicting class II epitopes that combines molecular mechanics docking of a fully flexible peptide into the MHC binding cleft followed by binding affinity prediction using a machine learning classifier trained on interaction energy components calculated from the docking solution. Although the primary advantage of structure-based prediction methods over the commonly employed sequence-based methods is their applicability to essentially any MHC allotype, this has not yet been convincingly demonstrated. In order to test the transferability of the prediction method to different MHC proteins, we trained the scoring method on binding data for DRB1*0101 and used it to make predictions for multiple MHC allotypes with distinct peptide binding specificities including representatives from the other human class II MHC loci, HLA-DP and HLA-DQ, as well as for two murine allotypes. The results showed that the prediction method was able to achieve significant discrimination between epitope and non-epitope peptides for all MHC allotypes examined, based on AUC values in the range 0.632–0.821. We also discuss how accounting for peptide binding in multiple registers to class II MHC largely explains the systematically worse performance of prediction methods for class II MHC compared with those for class I MHC based on quantitative prediction performance estimates for peptide binding to class II MHC in a fixed register