44 research outputs found

    Searching for the Slater Transition in the Pyrochlore Cd2_{2}Os2_{2}O7_{7} with Infrared Spectroscopy

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    Infrared reflectance measurements were made on the single crystal pyrochlore Cd2_{2}Os2_{2}O7_{7} in order to examine the transformations of the electronic structure and crystal lattice across the boundary of the metal insulator transition at TMIT=226KT_{MIT}=226K. All predicted IR active phonons are observed in the conductivity over all temperatures and the oscillator strength is found to be temperature independent. These results indicate that charge ordering plays only a minor role in the MIT and that the transition is strictly electronic in nature. The conductivity shows the clear opening of a gap with 2Δ=5.2kBTMIT2\Delta=5.2k_{B}T_{MIT}. The gap opens continuously, with a temperature dependence similar to that of BCS superconductors, and the gap edge having a distinct σ(ω)ω1/2\sigma(\omega)\thicksim\omega^{1/2} dependence. All of these observables support the suggestion of a Slater transition in Cd2_{2}% Os2_{2}O7_{7}.Comment: 4 pages, 4 figure

    Local endothelial complement activation reverses endothelial quiescence, enabling t-cell homing, and tumor control during t-cell immunotherapy.

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    Cancer immunotherapy relies upon the ability of T cells to infiltrate tumors. The endothelium constitutes a barrier between the tumor and effector T cells, and the ability to manipulate local vascular permeability could be translated into effective immunotherapy. Here, we show that in the context of adoptive T cell therapy, antitumor T cells, delivered at high enough doses, can overcome the endothelial barrier and infiltrate tumors, a process that requires local production of C3, complement activation on tumor endothelium and release of C5a. C5a, in turn, acts on endothelial cells promoting the upregulation of adhesion molecules and T-cell homing. Genetic deletion of C3 or the C5a receptor 1 (C5aR1), and pharmacological blockade of C5aR1, impaired the ability of T cells to overcome the endothelial barrier, infiltrate tumors, and control tumor progression in vivo, while genetic chimera mice demonstrated that C3 and C5aR1 expression by tumor stroma, and not leukocytes, governs T cell homing, acting on the local endothelium. In vitro, endothelial C3 and C5a expressions were required for endothelial activation by type 1 cytokines. Our data indicate that effective immunotherapy is a consequence of successful homing of T cells in response to local complement activation, which disrupts the tumor endothelial barrier

    The ODD protocol for describing agent-based and other simulation models: A second update to improve clarity, replication, and structural realism

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    © 2020, University of Surrey. All rights reserved. The Overview, Design concepts and Details (ODD) protocol for describing Individual-and Agent-Based Models (ABMs) is now widely accepted and used to document such models in journal articles. As a standardized document for providing a consistent, logical and readable account of the structure and dynamics of ABMs, some research groups also find it useful as a workflow for model design. Even so, there are still limitations to ODD that obstruct its more widespread adoption. Such limitations are discussed and addressed in this paper: the limited availability of guidance on how to use ODD; the length of ODD documents; limitations of ODD for highly complex models; lack of sufficient details of many ODDs to enable reimplementation without access to the model code; and the lack of provision for sections in the document structure covering model design ratio-nale, the model’s underlying narrative, and the means by which the model’s fitness for purpose is evaluated. We document the steps we have taken to provide better guidance on: structuring complex ODDs and an ODD summary for inclusion in a journal article (with full details in supplementary material; Table 1); using ODD to point readers to relevant sections of the model code; update the document structure to include sections on model rationale and evaluation. We also further advocate the need for standard descriptions of simulation experiments and argue that ODD can in principle be used for any type of simulation model. Thereby ODD would provide a lingua franca for simulation modelling

    Complement deficiency promotes cutaneous wound healing in mice

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    Wound healing is a complex homeostatic response to injury that engages numerous cellular activities, processes, and cell-to-cell interactions. The complement system, an intricate network of proteins with important roles in immune surveillance and homeostasis, has been implicated in many physiological processes; however, its role in wound healing remains largely unexplored. In this study, we employ a murine model of excisional cutaneous wound healing and show that C3-/- mice exhibit accelerated early stages of wound healing. Reconstitution of C3-/- mice with serum from C3+/+ mice or purified human C3 abrogated the accelerated wound-healing phenotype. Wound histology of C3-/- mice revealed a reduction in inflammatory infiltrate compared with C3+/+ mice. C3 deficiency also resulted in increased accumulation of mast cells and advanced angiogenesis. We further show that mice deficient in the downstream complement effector C5 exhibit a similar wound-healing phenotype, which is recapitulated in C5aR1-/- mice, but not C3aR-/- or C5aR2-/- mice. Taken together, these data suggest that C5a signaling through C5aR may in part play a pivotal role in recruitment and activation of inflammatory cells to the wound environment, which in turn could delay the early stages of cutaneous wound healing. These findings also suggest a previously underappreciated role for complement in wound healing, and may have therapeutic implications for conditions of delayed wound healing. Copyright © 2015 by The American Association of Immunologists, Inc

    Self-Similarity and Scaling Behavior in Nuclear Collision

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    A simple model is used to explore issues related to self-similarity, intermittency and scaling behavior in nuclear collisions. Both scaled factorial moments and power moments are considered in the investigation of these features. The product mass yields are used to construct probability distributions and generalized Renyi entropies. The scaling properties of the resulting Renyi entropies are studied. Both exponential and power law behavior are found. A discussion of dimensions associated with these scaling properties is also given. An analysis of some experimental data is presented.Comment: 51 pages in LATEX, 14 figures (available form the authors), RU-92-07, to appear in Phys. Rev.

    Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens

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    Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably little is known at the molecular level. We describe the genome, secretory proteome, and expression of selected genes of Malassezia globosa. Further, we report a comparative survey of the genome and secretory proteome of Malassezia restricta, a close relative implicated in similar skin disorders. Adaptation to the skin environment and associated pathogenicity may be due to unique metabolic limitations and capabilities. For example, the lipid dependence of M. globosa can be explained by the apparent absence of a fatty acid synthase gene. The inability to synthesize fatty acids may be complemented by the presence of multiple secreted lipases to aid in harvesting host lipids. In addition, an abundance of genes encoding secreted hydrolases (e.g., lipases, phospholipases, aspartyl proteases, and acid sphingomyelinases) was found in the M. globosa genome. In contrast, the phylogenetically closely related plant pathogen Ustilago maydis encodes a different arsenal of extracellular hydrolases with more copies of glycosyl hydrolase genes. M. globosa shares a similar arsenal of extracellular hydrolases with the phylogenetically distant human pathogen, Candida albicans, which occupies a similar niche, indicating the importance of host-specific adaptation. The M. globosa genome sequence also revealed the presence of mating-type genes, providing an indication that Malassezia may be capable of sex.
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