High-entropy alloys (HEAs) can have either high strength or high ductility, and a simultaneous achievement of both still constitutes a tough challenge. The inferior castability and compositional segregation of HEAs are also obstacles for their technological applications. To tackle these problems, here we proposed a novel strategy to design HEAs using the eutectic alloy concept, i.e. to achieve a microstructure composed of alternating soft fcc and hard bcc phases. As a manifestation of this concept, an AlCoCrFeNi2.1 (atomic portion) eutectic high-entropy alloy (EHEA) was designed. The as-cast EHEA possessed a fine lamellar fcc/B2 microstructure, and showed an unprecedented combination of high tensile ductility and high fracture strength at room temperature. The excellent mechanical properties could be kept up to 700°C. This new alloy design strategy can be readily adapted to large-scale industrial production of HEAs with simultaneous high fracture strength and high ductility.
Upon invasion of the erythrocyte cell, the malaria parasite remodels its environment; in particular, it establishes a complex membrane network, which connects the parasitophorous vacuole to the host plasma membrane and is involved in protein transport and trafficking. We have identified a novel subtelomeric gene family in Plasmodium falciparum that encodes 11 transmembrane proteins localized to the Maurer's clefts. Using coimmunoprecipitation and shotgun proteomics, we were able to enrich specifically for these proteins and detect distinct peptides, allowing us to conclude that four to 10 products were present at a given time. Nearly all of the Pfmc-2tm genes are transcribed during the trophozoite stage; this narrow time frame of transcription overlaps with the specific stevor and rif genes that are differentially expressed during the erythrocyte cycle. The description of the structural properties of the proteins led us to manually reannotate published sequences, and to detect potentially homologous gene families in both P. falciparum and Plasmodium yoelii yoelii, where no orthologs were predicted uniquely based on sequence similarity. These basic proteins with two transmembrane domains belong to a larger superfamily, which includes STEVORs and RIFINs
Infections and TLR signals at the time of transplantation have been shown to prevent the induction of tolerance, but their effect on allografts after tolerance has been established is unclear. We here report that infection with Listeria monocytogenes precipitated the loss of tolerance and the MyD88- and T cell-dependent rejection of accepted cardiac allografts in mice. This loss of tolerance was associated with increases in the numbers of graft-infiltrating macrophages and dendritic cells, as well as CD4+FoxP3− and CD8+ T cells. Rejection was also associated with increased numbers of graft-infiltrating alloreactive as well as Listeria-reactive IFNγ-producing T cells. Rejection of the established grafts required both IL-6 and IFNβ, cytokines produced during acute Listeria infection. However, IL-6 and IFNβ alone, even when present at higher concentrations than during Listeria infection, were insufficient to break tolerance, while the combination of IL-6 and IFNβ was able to break tolerance. These and in vitro observations that IL-6 but not IFNβ enhanced T cell proliferation while IFNβ but not IL-6 enhanced IFNγ production support a hypothesis that these cytokines play non-redundant roles. In conclusion, these studies demonstrate that the pro-inflammatory effects of infections can induce the loss of tolerance and acute rejection of accepted allografts.
High entropy alloys (HEAs) usually possess weak liquidity and castability, and considerable compositional inhomogeneity, mainly because they contain multiple elements with high concentrations. As a result, large-scale production of HEAs by casting is limited. To address the issue, the concept of eutectic high entropy alloys (EHEAs) was proposed, which has led to some promise in achieving good quality industrial scale HEAs ingots, and more importantly also good mechanical properties. In the practical large-scale casting, the actual composition of designed EHEAs could potentially deviate from the eutectic composition. The influence of such deviation on mechanical properties of EHEAs is important for industrial production, which constitutes the topic of the current work. Here we prepared industrial-scale HEAs ingots near the eutectic composition: hypoeutectic alloy, eutectic alloy and hypereutectic alloy. Our results showed that the deviation from eutectic composition does not significantly affect the mechanical properties, castability and the good mechanical properties of EHEAs can be achieved in a
Exposure to certain viruses and parasites has been shown to prevent the induction of transplantation tolerance in mice via the generation of cross-reactive memory T cell responses or the induction of bystander activation. Bacterial infections are common in the perioperative period of solid organ allograft recipients in the clinic, and correlations between bacterial infections and acute allograft rejection have been reported. However, whether bacterial infections at the time of transplantation have any effect on the generation of transplantation tolerance remains to be established. We used the Gram-positive intracellular bacterium Listeria monocytogenes (LM) as a model pathogen because its effects on immune responses are well described. Perioperative LM infection prevented cardiac and skin allograft acceptance induced by anti-CD154 and donor-specific transfusion in mice. LM-mediated rejection was not due to the generation of cross-reactive T cells and was largely independent of signaling via MyD88, an adaptor for most TLRs, IL-1, and IL-18. Instead, transplant rejection following LM infection was dependent on the expression of the phagosome-lysing pore former listeriolysin O and on type I IFN receptor signaling. Our results indicate that bacterial exposure at the time of transplantation can antagonize tolerogenic regimens by enhancing alloantigen-specific immune responses independently of the generation of cross-reactive memory T cells.
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