Unique pathogen peptidomes facilitate pathogen-specific selection and specialization of MHC alleles

A key component of pathogen-specific adaptive immunity in vertebrates is the presentation of pathogen-derived antigenic peptides by major histocompatibility complex (MHC) molecules. The excessive polymorphism observed at MHC genes is widely presumed to result from the need to recognize diverse pathogens, a process called pathogen-driven balancing selection. This process assumes that pathogens differ in their peptidomes—the pool of short peptides derived from the pathogen’s proteome—so that different pathogens select for different MHC variants with distinct peptide-binding properties. Here, we tested this assumption in a comprehensive data set of 51.9 Mio peptides, derived from the peptidomes of 36 representative human pathogens. Strikingly, we found that 39.7\% of the 630 pairwise comparisons among pathogens yielded not a single shared peptide and only 1.8\% of pathogen pairs shared more than 1\% of their peptides. Indeed, 98.8\% of all peptides were unique to a single pathogen species. Using computational binding prediction to characterize the binding specificities of 321 common human MHC class-I variants, we investigated quantitative differences among MHC variants with regard to binding peptides from distinct pathogens. Our analysis showed signatures of specialization toward specific pathogens especially by MHC variants with narrow peptide-binding repertoires. This supports the hypothesis that such fastidious MHC variants might be maintained in the population because they provide an advantage against particular pathogens. Overall, our results establish a key selection factor for the excessive allelic diversity at MHC genes observed in natural populations and illuminate the evolution of variable peptide-binding repertoires among MHC variants

Implications of CP violating 2HDM in B physics

The charged fermion mass matrices are invariant under $U(1)^3$ symmetry linked to the fermion number transformation. Under the condition that the definition of this symmetry in arbitrary weak basis does not depend upon Higgs parameters such as ratio of vacuum expectation values, a class of two Higgs doublet models (2HDM) can be identified in which tree level flavor changing neutral currents normally present in 2HDM are absent. However unlike the type I or type II Higgs doublet models, the charged Higgs couplings in these models contain additional flavor dependent CP violating phases. These phases can account for the recent hints of the beyond standard model CP violation in the $B_d$ and $B_s$ mixing. In particular, there is a range of parameters in which new phases do not contribute to the $K$ meson CP violation but give identical new physics phases in the $B_d$ and $B_s$ meson mixing.Comment: 7 pages, 1 figure, Talk given by Bhavik P. Kodrani at 16th International Symposium on Particles, Strings and Cosmology, July 19th - 23rd, 2010, Valencia, Spai

Center Vortices, Instantons, and Confinement

We study the relation between center vortices and instantons in lattice QCD.Comment: 3 pages, 1 color figure, LaTeX209 using BoxedEPS and esprc2.sty (provided); talk presented by J.W. Negele to be published in Lattice99 (Topology); email to [email protected]

The Path Integral for 1+1-dimensional QCD

We derive a path integral expression for the transition amplitude in 1+1-dimensional QCD starting from canonically quantized QCD. Gauge fixing after quantization leads to a formulation in terms of gauge invariant but curvilinear variables. Remainders of the curved space are Jacobians, an effective potential, and sign factors just as for the problem of a particle in a box. Based on this result we derive a Faddeev-Popov like expression for the transition amplitude avoiding standard infinities that are caused by integrations over gauge equivalent configurations.Comment: 16 pages, LaTeX, 3 PostScript figures, uses epsf.st

The optimal P3M algorithm for computing electrostatic energies in periodic systems

We optimize Hockney and Eastwood's Particle-Particle Particle-Mesh (P3M) algorithm to achieve maximal accuracy in the electrostatic energies (instead of forces) in 3D periodic charged systems. To this end we construct an optimal influence function that minimizes the RMS errors in the energies. As a by-product we derive a new real-space cut-off correction term, give a transparent derivation of the systematic errors in terms of Madelung energies, and provide an accurate analytical estimate for the RMS error of the energies. This error estimate is a useful indicator of the accuracy of the computed energies, and allows an easy and precise determination of the optimal values of the various parameters in the algorithm (Ewald splitting parameter, mesh size and charge assignment order).Comment: 31 pages, 3 figure

Constructing a Stochastic Model of Bumblebee Flights from Experimental Data

PMCID: PMC3592844This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Transverse QCD Dynamics Near the Light Cone

Starting from the QCD Hamiltonian in near-light cone coordinates, we study the dynamics of the gluonic zero modes. Euclidean 2+1 dimensional lattice simulations show that the gap at strong coupling vanishes at intermediate coupling. This result opens the possibility to synchronize the continuum limit with the approach to the light cone.Comment: 15 pages, LaTeX, 3 figures (7 PS files

A Double-Mode RR Lyrae Star with a Strong Fundamental Mode Component

NSVS 5222076, a thirteenth magnitude star in the Northern Sky Variability Survey, was identified by Oaster as a possible new double-mode RR Lyrae star. We confirm the double-mode nature of NSVS 5222076, supplementing the survey data with new V band photometry. NSVS 5222076 has a fundamental mode period of 0.4940 day and a first overtone period of 0.3668 day. Its fundamental mode light curve has an amplitude twice as large as that of the first overtone mode, a ratio very rarely seen. Data from the literature are used to discuss the location in the Petersen diagram of double-mode RR Lyrae stars having strong fundamental mode pulsation. Such stars tend to occur toward the short period end of the Petersen diagram, and NSVS 5222976 is no exception to this rule.Comment: 14 pages, 4 figures, To be published in the March, 2006, issue of PAS