Room temperature and low-field resonant enhancement of spin Seebeck effect in partially compensated magnets

Resonant enhancement of spin Seebeck effect (SSE) due to phonons was recently discovered in Y3Fe5O12 (YIG). This effect is explained by hybridization between the magnon and phonon dispersions. However, this effect was observed at low temperatures and high magnetic fields, limiting the scope for applications. Here we report observation of phonon-resonant enhancement of SSE at room temperature and low magnetic field. We observed in Lu2BiFe4GaO12 and enhancement 700 % greater than that in a YIG film and at very low magnetic fields around 10-1 T, almost one order of magnitude lower than that of YIG. The result can be explained by the change in the magnon dispersion induced by magnetic compensation due to the presence of non-magnetic ion substitutions. Our study provides a way to tune the magnon response in a crystal by chemical doping with potential applications for spintronic devices.Comment: 17 pages, 4 figure

Protective Allele for Multiple Sclerosis HLA-DRB1*01:01 Provides Kinetic Discrimination of Myelin and Exogenous Antigenic Peptides.

Risk of the development of multiple sclerosis (MS) is known to be increased in individuals bearing distinct class II human leukocyte antigen (HLA) variants, whereas some of them may have a protective effect. Here we analyzed distribution of a highly polymorphous HLA-DRB1 locus in more than one thousand relapsing-remitting MS patients and healthy individuals of Russian ethnicity. Carriage of HLA-DRB1*15 and HLA-DRB1*03 alleles was associated with MS risk, whereas carriage of HLA-DRB1*01 and HLA-DRB1*11 was found to be protective. Analysis of genotypes revealed the compensatory effect of risk and resistance alleles in trans. We have identified previously unknown MBP153−161 peptide located at the C-terminus of MBP protein and MBP90−98 peptide that bound to recombinant HLA-DRB1*01:01 protein with affinity comparable to that of classical antigenic peptide 306-318 from the hemagglutinin (HA) of the influenza virus demonstrating the ability of HLA-DRB1*01:01 to present newly identified MBP153−161 and MBP90−98 peptides. Measurements of kinetic parameters of MBP and HA peptides binding to HLA-DRB1*01:01 catalyzed by HLA-DM revealed a significantly lower rate of CLIP exchange for MBP153−161 and MBP90−98 peptides as opposed to HA peptide. Analysis of the binding of chimeric MBP-HA peptides demonstrated that the observed difference between MBP153−161, MBP90−98, and HA peptide epitopes is caused by the lack of anchor residues in the C-terminal part of the MBP peptides resulting in a moderate occupation of P6/7 and P9 pockets of HLA-DRB1*01:01 by MBP153−161 and MBP90−98 peptides in contrast to HA308−316 peptide. This leads to the P1 and P4 docking failure and rapid peptide dissociation and release of empty HLA-DM–HLA-DR complex. We would like to propose that protective properties of the HLA-DRB1*01 allele could be directly linked to the ability of HLA-DRB1*01:01 to kinetically discriminate between antigenic exogenous peptides and endogenous MBP derived peptides

The impact of HLA-DM on peptide binding to MHC class II

Thesis (M.S.) University of Alaska Fairbanks, 2016Recognition of peptides bound to class II major histocompatibility complex (MHCII) molecules by T cell receptors of CD4+ T cells initiates an adaptive immune response. Analysis of the antigen presentation pathway indicates that elements of the epitope selection process are critical to generation of the peptide repertoire presented to T cells. Antigen presentation by dedicated cells (APCs) involves the intracellular fragmentation of protein antigens by cathepsins, binding of the derived peptide epitopes to MHCII with the participation of the peptide-editing molecule HLA-DM (DM), and subsequent transport to the surface for recognition. This thesis focuses on the energetics and structural flexibility of the peptide-MHCII complex, and their correlation with DM-susceptibility, to identify the criteria associated with the selection of peptides by APCs for subsequent presentation to T cells. Using the human MHCII HLA-DR (DR), and peptides derived from influenza H3 HA305-318 as test system, it was observed that, in the absence of DM, stable peptide binding is not reached through independent contributions of single-point interactions, but is a distributive process that involves the peptide-DR groove dyad in its entirety highlighting the inherent flexibility of the binding process. Here, DM mechanism is investigated in its ability to impact structural flexibility of the complex. Analysis of release from and binding to DR of a gamut of HA-derived peptides at two different levels of pH reveals that structural stability is reduced as a consequence of DM function. The results indicate that the outcome of DM activity is favoring the endurance of complexes with limited structural flexibility

Localization of adaptive variants in human genomes using averaged one-dependence estimation.

Statistical methods for identifying adaptive mutations from population genetic data face several obstacles: assessing the significance of genomic outliers, integrating correlated measures of selection into one analytic framework, and distinguishing adaptive variants from hitchhiking neutral variants. Here, we introduce SWIF(r), a probabilistic method that detects selective sweeps by learning the distributions of multiple selection statistics under different evolutionary scenarios and calculating the posterior probability of a sweep at each genomic site. SWIF(r) is trained using simulations from a user-specified demographic model and explicitly models the joint distributions of selection statistics, thereby increasing its power to both identify regions undergoing sweeps and localize adaptive mutations. Using array and exome data from 45 ‡Khomani San hunter-gatherers of southern Africa, we identify an enrichment of adaptive signals in genes associated with metabolism and obesity. SWIF(r) provides a transparent probabilistic framework for localizing beneficial mutations that is extensible to a variety of evolutionary scenarios

Using a CD45dim/CD123bright/HLA-DRneg phenotyping protocol to gate basophils in FC for airway allergy. CD123 does not decrease

  Physicians in the field of respiratory medicine are particularly concerned about the availability of a reliable diagnostic tool to investigate respiratory allergy. Usually, basophils are easy to obtain from peripheral blood and therefore they represent a reproducible model to assess allergy in individuals. Cell assays called basophil activation tests (BATs) are widespread tools for allergy diagnosis and are easily available in most of the medical labs. The strategy by which basophils are captured in a flow cytometry protocol has met many suggestions, recommendations and experimental novelties in recent years, yet the debate needs to be further expanded. Concerns still remain about the suitability of the many approaches to make the basophil activation test (BAT) an excellent and practical tool to diagnose allergy, while improving its analytical performance. This technical report describes the methodological aspects of the use of the protocol adopting the panel CD45dim/CD123bright/HLA-DRneg to gate basophils in flow cytometry, trying to highlight the main biases related to an incorrect use of this protocol.

The Route of HIV Escape from Immune Response Targeting Multiple Sites Is Determined by the Cost-Benefit Tradeoff of Escape Mutations

Cytotoxic T lymphocytes (CTL) are a major factor in the control of HIV replication. CTL arise in acute infection causing escape mutations to spread rapidly through the population of infected cells. As a result, the virus develops partial resistance to the immune response. The factors controlling the order of mutating epitope sites are currently unknown and would provide a valuable tool for predicting conserved epitopes. In this work, we adapt a well-established mathematical model of HIV evolution under dynamical selection pressure from multiple CTL clones to include partial impairment of CTL recognition, ∆r, as well as cost to viral replication, ∆f. The process of escape is described in terms of the cost-benefit tradeoff of escape mutations and predicts a trajectory in the cost-benefit plane connecting sequentially escaped sites, which moves from high recognition loss/low fitness cost to low recognition loss/high fitness cost and has a larger slope for early escapes than for late escapes. The slope of the trajectory offers an interpretation of positive correlation between fitness costs and HLA binding impairment to HLA-A molecules and a protective subset of HLA-B molecules that was observed for clinically relevant escape mutations in the Pol gene. We estimate the value of ∆r from published experimental studies to be in the range (0.01-0.86) and show that the assumption of complete recognition loss (∆r = 1) leads to an overestimate of mutation cost. Our analysis offers a consistent interpretation of the commonly observed pattern of escape, in which several escape mutations are observed transiently in an epitope. This non-nested pattern is a combined effect of temporal changes in selection pressure and partial recognition loss. We conclude that partial recognition loss is as important as fitness loss for predicting the order of escapes and, ultimately, for predicting conserved epitopes that can be targeted by vaccines.Other Research Uni

Multi-stakeholder Interactive Simulation for Federated Satellite Systems

Federated satellite systems (FSS) are a new class of space-based systems which emphasize a distributed architecture. New information exchanging functions among FSS members enable data transportation, storage, and processing as on-orbit services. As a system-of-systems, however there are significant technical and social barriers to designing a FSS. To mitigate these challenges, this paper develops a multi-stakeholder interactive simulation for use in future design activities. An FSS simulation interface is defined using the High Level Architecture to include orbital and surface assets and associated transmitters, receivers, and signals for communication. Sample simulators (federates) using World Wind and Orekit open source libraries are applied in a prototype simulation (federation). The application case studies a conceptual FSS using the International Space Station (ISS) as a service platform to serve Earth-observing customers in sun-synchronous orbits (SSO). Results identify emergent effects between FSS members including favorable ISS power conditions and potential service bottlenecks to serving SSO customers

Analysis domain model for shared virtual environments

The field of shared virtual environments, which also encompasses online games and social 3D environments, has a system landscape consisting of multiple solutions that share great functional overlap. However, there is little system interoperability between the different solutions. A shared virtual environment has an associated problem domain that is highly complex raising difficult challenges to the development process, starting with the architectural design of the underlying system. This paper has two main contributions. The first contribution is a broad domain analysis of shared virtual environments, which enables developers to have a better understanding of the whole rather than the part(s). The second contribution is a reference domain model for discussing and describing solutions - the Analysis Domain Model