890 research outputs found

    No-moving-part hybrid-synthetic jet actuator

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    In contrast to usual synthetic jets, the “hybrid-synthetic jets” of non-zero timemean nozzle mass flow rate are increasingly often considered for control of flow separation and/or transition to turbulence as well as heat and mass transfer. The paper describes tests of a scaled-up laboratory model of a new actuator version, generating the hybrid-synthetic jets without any moving components. Self-excited flow oscillation is produced by aerodynamic instability in fixed-wall cavities. The return flow in the exit nozzles is generated by jet-pumping effect. Elimination of the delicate and easily damaged moving parts in the actuator simplifies its manufacture and assembly. Operating frequency is adjusted by the length of feedback loop path. Laboratory investigations concentrated on the propagation processes taking place in the loop

    Tastes and technology in a two-country model of the business cycle: explaining international co-movements

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    The authors develop a two-country real business cycle model and examine its consistency with the behavior of relative prices, and the model's implications for economic aggregates at the sectoral level.Business cycles ; International finance

    Lupus nephritis management guidelines compared

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    In the past years, many (randomized) trials have been performed comparing the treatment strategies for lupus nephritis. In 2012, these data were incorporated in six different guidelines for treating lupus nephritis. These guidelines are European, American and internationally based, with one separate guideline for children. They offer information on different aspects of the management of lupus nephritis including induction and maintenance treatment of the different histological classes, adjunctive treatment, monitoring of the patient, definitions of response and relapse, indications for (repeat) renal biopsy, and additional challenges such as the presence of vascular complications, the pregnant SLE patient, treatment in children and adolescents and considerations about end-stage renal disease and transplantation. In this review, we summarize the guidelines, determine the common ground between them, highlight the differences and discuss recent literature

    The Chicken Yolk Sac IgY Receptor, a Mammalian Mannose Receptor Family Member, Transcytoses IgY across Polarized Epithelial Cells

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    In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds

    Advanced development for space robotics with emphasis on fault tolerance

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    This paper describes the ongoing work in fault tolerance at the University of Texas at Austin. The paper describes the technical goals the group is striving to achieve and includes a brief description of the individual projects focusing on fault tolerance. The ultimate goal is to develop and test technology applicable to all future missions of NASA (lunar base, Mars exploration, planetary surveillance, space station, etc.)

    Philosophy of education in a new key: A 'Covid Collective' of the Philosophy of Education Society of Great Britain (PESGB)

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    This article is a collective writing experiment undertaken by philosophers of education affiliated with the PESGB (Philosophy of Education Society of Great Britain). When asked to reflect on questions concerning the Philosophy of Education in a New Key in May 2020, it was unsurprising that the effects of the coronavirus pandemic on society and on education were foremost in our minds. We wanted to consider important philosophical and educational questions raised by the pandemic, while acknowledging that, first and foremost, it is a human tragedy. With nearly a million deaths reported worldwide to date, and with everyone effected in one way or another by Covid-19, there is a degree of discomfort, and a responsibility to be sensitive, in reflecting and writing about it academically. Members of this ‘Covid Collective’ come from various countries, with perspectives from Great Britain and Ireland well represented, and we see academic practice as a globally connected enterprise, especially since the digital revolution in academic publishing. The concerns raised in this article relate to but move beyond Covid-19, reflecting the impact of neoliberalism [and other political developments] on geopolitics with educational concerns as central to our focus

    Epigenomic Comparison Reveals Activation of “Seed” Enhancers during Transition from Naive to Primed Pluripotency

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    SummaryNaive mouse embryonic stem cells (mESCs) and primed epiblast stem cells (mEpiSCs) represent successive snapshots of pluripotency during embryogenesis. Using transcriptomic and epigenomic mapping we show that a small fraction of transcripts are differentially expressed between mESCs and mEpiSCs and that these genes show expected changes in chromatin at their promoters and enhancers. Unexpectedly, the cis-regulatory circuitry of genes that are expressed at identical levels between these cell states also differs dramatically. In mESCs, these genes are associated with dominant proximal enhancers and dormant distal enhancers, which we term seed enhancers. In mEpiSCs, the naive-dominant enhancers are lost, and the seed enhancers take up primary transcriptional control. Seed enhancers have increased sequence conservation and show preferential usage in downstream somatic tissues, often expanding into super enhancers. We propose that seed enhancers ensure proper enhancer utilization and transcriptional fidelity as mammalian cells transition from naive pluripotency to a somatic regulatory program

    Intracellular neutralization of viral infection in polarized epithelial cells by neonatal Fc receptor (FcRn)-mediated IgG transport

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    IgG was traditionally thought to neutralize virions by blocking their attachment to or penetration into mucosal epithelial cells, a common site of exposure to viruses. However, we describe an intracellular neutralizing action for an influenza hemagglutinin-specific monoclonal antibody, Y8-10C2 (Y8), which has neutralizing activity only at an acidic pH. When Y8 was applied to the basolateral surface of Madin–Darby canine kidney cells expressing the rat neonatal Fc receptor for IgG (FcRn), it significantly reduced viral replication following apical exposure of the cell monolayer to influenza virus. Virus neutralization by Y8 mAb was dependent on FcRn expression and its transport of IgG. As both FcRn and Y8 mAb bind their partners only at acidic pH, the Y8 mAb is proposed to carry out its antiviral activity intracellularly. Furthermore, the virus, Y8 mAb, and FcRn colocalized within endosomes, possibly inhibiting the fusion of viral envelopes with endosomal membranes during primary uncoating, and preventing the accumulation of the neutralized viral nucleoprotein antigen in the nucleus. Prophylactic administration of Y8 mAb before viral challenge in WT mice, but not FcRn-KO mice, conferred protection from lethality, prevented weight loss, resulted in a significant reduction in pulmonary virus titers, and largely reduced virus-induced lung pathology. Thus, this study reveals an intracellular mechanism for viral neutralization in polarized epithelial cells that is dependent on FcRn-mediated transport of neutralizing IgG

    NPTX1 Regulates Neural Lineage Specification from Human Pluripotent Stem Cells

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    SummaryNeural induction is the first fundamental step in nervous system formation. During development, a tightly regulated niche modulates transient extracellular signals to influence neural lineage commitment. To date, however, the cascade of molecular events that sustain these signals in humans is not well understood. Here we show that NPTX1, a secreted protein, is rapidly upregulated during neural induction from human pluripotent stem cells (hPSCs). By manipulating its expression, we were able to reduce or initiate neural lineage commitment. A time-course transcriptome analysis and functional assays show that NPTX1 acts in part by binding the Nodal receptor cofactor TDGF1, reducing both Nodal and BMP signaling. Our findings identify one of the earliest genes expressed upon neural induction and provide insight into human neural lineage specification
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