The influence of doping with Ca and Mg in YBa2Cu3O7-δ ceramic

We have investigated the effect of partial substitution of Ca for Y and/or Mg for Cu on structural, compositional and magnetic properties in γBa 2 Cu 3 O 7-δ polycrystalline compounds. All prepared samples were found to be single phase with small fraction of Ba-secondary phases. Substitution by more than 2% of magnesium causes an increase of spurious phases. Energy Dispersive Spectroscopy (EDS) revealed that the distribution of Ca in the sample is quite homogenous. DC susceptibility measurements show that superconducting transition temperature Tc is reduced much more by Ca than Mg. Hysteresis loops reveal that magnetic irreversibility is decreased by Ca and Mg content. The deduced critical current density Jc does not follow the same variation. Ca alone reduces Jc for x=0.1 and x=0.2. Together with Ca, Mg compensates the reduction of Jc and increasing its content near the solubility limit gives higher Jc than in the undoped sample

GIMAP6 is required for T cell maintenance and efficient autophagy in mice

The GTPases of the immunity-associated proteins (GIMAP) GTPases are a family of proteins expressed strongly in the adaptive immune system. We have previously reported that in human cells one member of this family, GIMAP6, interacts with the ATG8 family member GABARAPL2, and is recruited to autophagosomes upon starvation, suggesting a role for GIMAP6 in the autophagic process. To study this possibility and the function of GIMAP6 in the immune system, we have established a mouse line in which the Gimap6 gene can be inactivated by Cre-mediated recombination. In mice bred to carry the CD2Cre transgene such that the Gimap6 gene was deleted within the T and B cell lineages there was a 50-70% reduction in peripheral CD4(+) and CD8(+) T cells. Analysis of splenocyte-derived proteins from these mice indicated increased levels of MAP1LC3B, particularly the lipidated LC3-II form, and S405-phosphorylation of SQSTM1. Electron microscopic measurements of Gimap6(-/-) CD4(+) T cells indicated an increased mitochondrial/cytoplasmic volume ratio and increased numbers of autophagosomes. These results are consistent with autophagic disruption in the cells. However, Gimap6(-/-) T cells were largely normal in character, could be effectively activated in vitro and supported T cell-dependent antibody production. Treatment in vitro of CD4(+) splenocytes from GIMAP6(fl/fl) ERT2Cre mice with 4-hydroxytamoxifen resulted in the disappearance of GIMAP6 within five days. In parallel, increased phosphorylation of SQSTM1 and TBK1 was observed. These results indicate a requirement for GIMAP6 in the maintenance of a normal peripheral adaptive immune system and a significant role for the protein in normal autophagic processes. Moreover, as GIMAP6 is expressed in a cell-selective manner, this indicates the potential existence of a cell-restricted mode of autophagic regulation.Peer reviewe

Ageing promotes early T follicular helper cell differentiation by modulating expression of RBPJ.

Ageing profoundly changes our immune system and is thought to be a driving factor in the morbidity and mortality associated with infectious disease in older people. We have previously shown that the impaired immunity to vaccination that occurs in aged individuals is partly attributed to the effect of age on T follicular helper (Tfh) cell formation. In this study, we examined how age intrinsically affects Tfh cell formation in both mice and humans. We show increased formation of Tfh precursors (pre-Tfh) but no associated increase in germinal centre (GC)-Tfh cells in aged mice, suggesting age-driven promotion of only early Tfh cell differentiation. Mechanistically, we show that ageing alters TCR signalling which drives expression of the Notch-associated transcription factor, RBPJ. Genetic or chemical modulation of RBPJ or Notch rescues this age-associated early Tfh cell differentiation, and increased intrinsic Notch activity recapitulates this phenomenon in younger mice. Our data offer mechanistic insight into the age-induced changes in T-cell activation that affects the differentiation and ultimately the function of effector T cells

Reliability assessment of automotive components under fatigue using numerical simulation and accelerated testing

In this paper, a Stochastic Response Surface (SRS) approach based on Polynomial Chaos Expansion (PCE) is used to conduct reliability analysis of automotive components subjected to fatigue loading. The PCE coefficients have been computed by regression analysis based on a quasi-random experimental design. In addition, an efficient truncation technique, namely low-rank index sets, has been used to reduce the number of unknown coefficients to be estimated, and consequently to reduce the number of finite element model calls required for the construction of the PCE. Once the PCE is obtained, the probability of failure for a target fatigue life is estimated by applying Monte-Carlo simulations. At the same time, fatigue accelerated testing are conducted on full scale automotive component to obtain experimental predictions of the structural reliability. The estimates of the probability of failure are in good agreement with those obtained by numerical computations based on PCE and Monte-Carlo simulations

Peptide-MHC Class I Tetramers Can Fail To Detect Relevant Functional T Cell Clonotypes and Underestimate Antigen-Reactive T Cell Populations.

Peptide-MHC (pMHC) multimers, usually used as streptavidin-based tetramers, have transformed the study of Ag-specific T cells by allowing direct detection, phenotyping, and enumeration within polyclonal T cell populations. These reagents are now a standard part of the immunology toolkit and have been used in many thousands of published studies. Unfortunately, the TCR-affinity threshold required for staining with standard pMHC multimer protocols is higher than that required for efficient T cell activation. This discrepancy makes it possible for pMHC multimer staining to miss fully functional T cells, especially where low-affinity TCRs predominate, such as in MHC class II-restricted responses or those directed against self-antigens. Several recent, somewhat alarming, reports indicate that pMHC staining might fail to detect the majority of functional T cells and have prompted suggestions that T cell immunology has become biased toward the type of cells amenable to detection with multimeric pMHC. We use several viral- and tumor-specific pMHC reagents to compare populations of human T cells stained by standard pMHC protocols and optimized protocols that we have developed. Our results confirm that optimized protocols recover greater populations of T cells that include fully functional T cell clonotypes that cannot be stained by regular pMHC-staining protocols. These results highlight the importance of using optimized procedures that include the use of protein kinase inhibitor and Ab cross-linking during staining to maximize the recovery of Ag-specific T cells and serve to further highlight that many previous quantifications of T cell responses with pMHC reagents are likely to have considerably underestimated the size of the relevant populations

VDJdb in 2019: database extension, new analysis infrastructure and a T-cell receptor motif compendium

Here, we report an update of the VDJdb database with a substantial increase in the number of T-cell receptor (TCR) sequences and their cognate antigens. The update further provides a new database infrastructure featuring two additional analysis modes that facilitate database querying and real-world data analysis. The increased yield of TCR specificity identification methods and the overall increase in the number of studies in the field has allowed us to expand the database more than 5-fold. Furthermore, several new analysis methods are included. For example, batch annotation of TCR repertoire sequencing samples allows for annotating large datasets on-line. Using recently developed bioinformatic methods for TCR motif mining, we have built a reduced set of high-quality TCR motifs that can be used for both training TCR specificity predictors and matching against TCRs of interest. These additions enhance the versatility of the VDJdb in the task of exploring T-cell antigen specificities. The database is available at https://vdjdb.cdr3.net

ZnO thin films deposition by spray pyrolysis: Influence of precursor solution properties

International audienceZinc oxide (ZnO) thin films were deposited by spray pyrolysis technique using different precursors. Three starting solutions salts namely: zinc acetate, zinc chloride and zinc nitrate were used. The properties of these solutions and their influence upon ZnO films growth rate are investigated. The obtained results indicate that the dissociation energy of the starting solution plays an important role on films growth rate. A linear relationship between the solution dissociation energy and the growth rate activation energy was found. However, the surface tension of the used solution controls the droplet shape impact. Both solution surface tension and dissociation enthalpy alter the microstructure of the formed film. Films deposited with zinc acetate are characterized by a smooth surface, dense network and high transparency, while films deposited with zinc chloride have a better crystallinity and low optical transmittance