2,157 research outputs found

    Ejector nozzle with massive blowing

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    Jet-flap, wing-blowing system for use in short takeoff and landing aircraft is described. System depends on ejector nozzle with large blowing capacity to direct ducted air against deflected flap. Operation of equipment during takeoff and cruise conditions is discussed. Diagrams of equipment are provided

    Heterologous prion-forming proteins interact to cross-seed aggregation in Saccharomyces cerevisiae

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    AbstractThe early stages of protein misfolding remain incompletely understood, as most mammalian proteinopathies are only detected after irreversible protein aggregates have formed. Cross-seeding, where one aggregated protein templates the misfolding of a heterologous protein, is one mechanism proposed to stimulate protein aggregation and facilitate disease pathogenesis. Here, we demonstrate the existence of cross-seeding as a crucial step in the formation of the yeast prion [PSI+], formed by the translation termination factor Sup35. We provide evidence for the genetic and physical interaction of the prion protein Rnq1 with Sup35 as a predominant mechanism leading to self-propagating Sup35 aggregation. We identify interacting sites within Rnq1 and Sup35 and determine the effects of breaking and restoring a crucial interaction. Altogether, our results demonstrate that single-residue disruption can drastically reduce the effects of cross-seeding, a finding that has important implications for human protein misfolding disorders.</jats:p

    The NCAA Celebration Rule: A First Amendment Analysis

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    Adverse events in veterans affairs inpatient psychiatric units: Staff perspectives on contributing and protective factors.

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    OBJECTIVES: This study sought to identify risk factors and protective factors in hospital-based mental health settings in the Veterans Health Administration (VHA), with the goal of informing interventions to improve care of persons with serious mental illness. METHODS: Twenty key informants from a stratified sample of 7 VHA inpatient psychiatric units were interviewed to gain their insights on causes of patient safety events and the factors that constrain or facilitate patient safety efforts. RESULTS: Respondents identified threats to patient safety at the system-, provider-, and patient-levels. Protective factors that, when in place, made patient safety events less likely to occur included: promoting a culture of safety; advocating for patient-centeredness; and engaging administrators and organizational leadership to champion these changes. CONCLUSIONS: Findings highlight the impact of systems-level policies and procedures on safety in inpatient mental health care. Engaging all stakeholders, including patients, in patient safety efforts and establishing a culture of safety will help improve the quality of inpatient psychiatric care. Successful implementation of changes require the knowledge of local experts most closely involved in patient care, as well as support and buy-in from organizational leadership

    When the UN Addresses the Conditions Conducive to Terrorism, What Happens to Human Rights?

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    Article published in the Michigan State Law Review

    Listening to Dissonance at the Intersections of International Human Rights Law

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    Within the United Nations (UN) human rights system, there are ten human rights treaties, each with its own treaty body or “Committee” that claims to offer the most authoritative interpretation of its corresponding treaty. Rather than resolving contests for primacy, this arrangement often generates conflicting interpretations of certain human rights. This Article is the first to shed light on conflicts between treaty bodies’ interpretations within the UN human rights system and to confront the question of how to resolve such conflicts at the intersections of international human rights law. The Article analyzes three case studies of such conflicts: 1) clashing interpretations relating to a child’s right to live with a family; 2) the right to life, reproductive access, and disability-selective abortion; 3) and involuntary detention and the right to liberty and security. These conflicts of interpretation matter to individuals seeking clarification of potential legal claims, as well as to legislators and regulators seeking to draft legislation to comply, or to evade compliance, with human rights standards. This Article then argues that secondary rules of interpretation are unlikely to resolve these conflicts, as they avoid necessary contests of meaning. Even with the uncertainties that enduring conflicts create, they are preferable to rules of resolution favoring uniformity and systemic integration, as the related risk is either the hegemonic elevation of majoritarian interests or the elevation of possibly biased perspectives. This Article thus proposes pragmatic institutional design tools to promote dialogue and engage each conflict in a context-specific fashion. Mitigating the conflicts between treaties in this way will help optimize the object of all international human rights law treaties

    The [RNQ+] prion: A model of both functional and pathological amyloid

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    The formation of fibrillar amyloid is most often associated with protein conformational disorders such as prion diseases, Alzheimer disease and Huntington disease. Interestingly, however, an increasing number of studies suggest that amyloid structures can sometimes play a functional role in normal biology. Several proteins form self-propagating amyloids called prions in the budding yeast Saccharomyces cerevisiae. These unique elements operate by creating a reversible, epigenetic change in phenotype. While the function of the non-prion conformation of the Rnq1 protein is unclear, the prion form, [RNQ(+)], acts to facilitate the de novo formation of other prions to influence cellular phenotypes. The [RNQ(+)] prion itself does not adversely affect the growth of yeast, but the overexpression of Rnq1p can form toxic aggregated structures that are not necessarily prions. The [RNQ(+)] prion is also involved in dictating the aggregation and toxicity of polyglutamine proteins ectopically expressed in yeast. Thus, the [RNQ(+)] prion provides a tractable model that has the potential to reveal significant insight into the factors that dictate how amyloid structures are initiated and propagated in both physiological and pathological contexts

    Extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions

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    Amyloidogenic proteins associated with a variety of unrelated diseases are typically capable of forming several distinct self-templating conformers. In prion diseases, these different structures, called prion strains (or variants), confer dramatic variation in disease pathology and transmission. Aggregate stability has been found to be a key determinant of the diverse pathological consequences of different prion strains. Yet, it remains largely unclear what other factors might account for the widespread phenotypic variation seen with aggregation-prone proteins. Here, we examined a set of yeast prion variants of the [RNQ+] prion that differ in their ability to induce the formation of another yeast prion called [PSI+]. Remarkably, we found that the [RNQ+] variants require different, non-contiguous regions of the Rnq1 protein for both prion propagation and [PSI+] induction. This included regions outside of the canonical prion-forming domain of Rnq1. Remarkably, such differences did not result in variation in aggregate stability. Our analysis also revealed a striking difference in the ability of these [RNQ+] variants to interact with the chaperone Sis1. Thus, our work shows that the differential influence of various amyloidogenic regions and interactions with host cofactors are critical determinants of the phenotypic consequences of distinct aggregate structures. This helps reveal the complex interdependent factors that influence how a particular amyloid structure may dictate disease pathology and progression
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