Systems of Support: The Educators with Disabilities Caucus and Its Mentoring Program

In the field of education, critics have described the experiences of beginning teaching as “sink or swim, trial by fire, or boot camp experiences.

Thermal Instability and Current-Voltage Scaling in Superconducting Fault Current Limiters

We have developed a computer model for the simulation of resistive superconducting fault current limiters in three dimensions. The program calculates the electromagnetic and thermal response of a superconductor to a time-dependent overload voltage, with different possible cooling conditions for the surfaces, and locally variable superconducting and thermal properties. We find that the cryogen boil-off parameters critically influence the stability of a limiter. The recovery time after a fault increases strongly with thickness. Above a critical thickness, the temperature is unstable even for a small applied AC voltage. The maximum voltage and maximum current during a short fault are correlated by a simple exponential law.Comment: submitted to Superconductor Science and Technology (Dec 2003

Tests of the Equivalence Principle with Neutral Kaons

We test the Principle of Equivalence for particles and antiparticles, using CPLEAR data on tagged K0 and K0bar decays into pi^+ pi^-. For the first time, we search for possible annual, monthly and diurnal modulations of the observables |eta_{+-}| and phi_{+-}, that could be correlated with variations in astrophysical potentials. Within the accuracy of CPLEAR, the measured values of |eta_{+-}| and phi_{+-} are found not to be correlated with changes of the gravitational potential. We analyze data assuming effective scalar, vector and tensor interactions, and we conclude that the Principle of Equivalence between particles and antiparticles holds to a level of 6.5, 4.3 and 1.8 x 10^{-9}, respectively, for scalar, vector and tensor potentials originating from the Sun with a range much greater than the distance Earth-Sun. We also study energy-dependent effects that might arise from vector or tensor interactions. Finally, we compile upper limits on the gravitational coupling difference between K0 and K0bar as a function of the scalar, vector and tensor interaction range.Comment: 15 pages latex 2e, five figures, one style file (cernart.csl) incorporate

Test of CPT Symmetry and Quantum Mechanics with Experimental data from CPLEAR

We use fits to recent published CPLEAR data on neutral kaon decays to $\pi^+\pi^-$ and $\pi e\nu$ to constrain the CPT--violation parameters appearing in a formulation of the neutral kaon system as an open quantum-mechanical system. The obtained upper limits of the CPT--violation parameters are approaching the range suggested by certain ideas concerning quantum gravity.Comment: 9 pages of uuencoded postscript (includes 3 figures

In Vitro Evolution of Allergy Vaccine Candidates, with Maintained Structure, but Reduced B Cell and T Cell Activation Capacity

Allergy and asthma to cat (Felis domesticus) affects about 10% of the population in affluent countries. Immediate allergic symptoms are primarily mediated via IgE antibodies binding to B cell epitopes, whereas late phase inflammatory reactions are mediated via activated T cell recognition of allergen-specific T cell epitopes. Allergen-specific immunotherapy relieves symptoms and is the only treatment inducing a long-lasting protection by induction of protective immune responses. The aim of this study was to produce an allergy vaccine designed with the combined features of attenuated T cell activation, reduced anaphylactic properties, retained molecular integrity and induction of efficient IgE blocking IgG antibodies for safer and efficacious treatment of patients with allergy and asthma to cat. The template gene coding for rFel d 1 was used to introduce random mutations, which was subsequently expressed in large phage libraries. Despite accumulated mutations by up to 7 rounds of iterative error-prone PCR and biopanning, surface topology and structure was essentially maintained using IgE-antibodies from cat allergic patients for phage enrichment. Four candidates were isolated, displaying similar or lower IgE binding, reduced anaphylactic activity as measured by their capacity to induce basophil degranulation and, importantly, a significantly lower T cell reactivity in lymphoproliferative assays compared to the original rFel d 1. In addition, all mutants showed ability to induce blocking antibodies in immunized mice.The approach presented here provides a straightforward procedure to generate a novel type of allergy vaccines for safer and efficacious treatment of allergic patients

MultiRTA: A simple yet reliable method for predicting peptide binding affinities for multiple class II MHC allotypes

abstract: Background The binding of peptide fragments of antigens to class II MHC is a crucial step in initiating a helper T cell immune response. The identification of such peptide epitopes has potential applications in vaccine design and in better understanding autoimmune diseases and allergies. However, comprehensive experimental determination of peptide-MHC binding affinities is infeasible due to MHC diversity and the large number of possible peptide sequences. Computational methods trained on the limited experimental binding data can address this challenge. We present the MultiRTA method, an extension of our previous single-type RTA prediction method, which allows the prediction of peptide binding affinities for multiple MHC allotypes not used to train the model. Thus predictions can be made for many MHC allotypes for which experimental binding data is unavailable. Results We fit MultiRTA models for both HLA-DR and HLA-DP using large experimental binding data sets. The performance in predicting binding affinities for novel MHC allotypes, not in the training set, was tested in two different ways. First, we performed leave-one-allele-out cross-validation, in which predictions are made for one allotype using a model fit to binding data for the remaining MHC allotypes. Comparison of the HLA-DR results with those of two other prediction methods applied to the same data sets showed that MultiRTA achieved performance comparable to NetMHCIIpan and better than the earlier TEPITOPE method. We also directly tested model transferability by making leave-one-allele-out predictions for additional experimentally characterized sets of overlapping peptide epitopes binding to multiple MHC allotypes. In addition, we determined the applicability of prediction methods like MultiRTA to other MHC allotypes by examining the degree of MHC variation accounted for in the training set. An examination of predictions for the promiscuous binding CLIP peptide revealed variations in binding affinity among alleles as well as potentially distinct binding registers for HLA-DR and HLA-DP. Finally, we analyzed the optimal MultiRTA parameters to discover the most important peptide residues for promiscuous and allele-specific binding to HLA-DR and HLA-DP allotypes. Conclusions The MultiRTA method yields competitive performance but with a significantly simpler and physically interpretable model compared with previous prediction methods. A MultiRTA prediction webserver is available at http://bordnerlab.org/MultiRTA.The electronic version of this article is the complete one and can be found online at: http://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-11-48

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

Determination of the T- and CPT-violation parameters in the neutral-kaon system using the Bell-Steinberger relation and data from CPLEAR

Data from the CPLEAR experiment, together with the most recent world averages for some of the neutral-kaon parameters, were constrained with the Bell--Steinberger (or unitarity) relation, allowing the T-violation parameter \ree and the CPT-violation parameter \imd of the neutral-kaon mixing matrix to be determined with an increased accuracy: \ree = (164.9 \pm 2.5)\times 10^{-5}, \imd = ( 2.4 \pm 5.0)\times 10^{-5}. Moreover, the constraint allows the CPT-violation parameter for the neutral-kaon semileptonic decays, \rey, to be determined for the first time. The $\Delta S \neq \Delta Q$ parameters \rexm and \imxp are given with an increased accuracy. The quantity $\mathrm{Re}(y~+~x_-)$, which enters the T-violation CPLEAR asymmetry previously published, is determined to be $(0.2 \pm 0.3)\times 10^{-3}$. The value obtained for \red is in agreement with the one resulting from a previous unconstrained fit and has a slightly smaller error

The neutral kaon decays to π+π−π0\pi^+ \pi^- \pi^0: a detailed analysis of the CPLEAR data

A detailed analysis of neutral kaons decaying to \Pgpp \Pgpm \Pgpz\ is presented based on the complete data set containing half a million events. Time-dependent decay rate asymmetries are measured between initially tagged \PKz\ and \PaKz\ and for different regions of the phase space. These asymmetries, resulting from the interference between the CP-conserving decay amplitude of \PKzL\ and the decay amplitude of \PKzS\ -- either CP-violating or CP-conserving -- allow the determinationof the \PKzS\ parameters \etapmz\ (CP-violating) and \lampmz\ (CP-conserving), and also of the main i sospin components of the \PKzS\ decay amplitude. The branching ratio of \PKzS\ $\rightarrow$ \Pgpp \Pgpm \Pgpz\ (CP-conserving) is deduced directly from \lampmz . In addition, we extract the slope parameters describing the energy dependence of the \PKzL \rightarrow \Pgpp \Pgpm \Pgpz Dalitz plot. The whole set of our results fits well within the current phenomenological picture of the neut ral-kaon system including CP violation and Chiral Perturbation Theory (ChPT)