254 research outputs found

    ACE/SWICS Observations of Heavy Ion Dropouts within the Solar Wind

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    We present the first in situ observations of heavy ion dropouts within the slow solar wind, observed for select elements ranging from helium to iron. For iron, these dropouts manifest themselves as depletions of the Fe/H ratio by factors up to ~25. The events often exhibit mass-dependent fractionation and are contained in slow, unsteady wind found within a few days from known stream interfaces. We propose that such dropouts are evidence of gravitational settling within large coronal loops, which later undergo interchange reconnection and become source regions of slow, unsteady wind. Previously, spectroscopic studies by Raymond et al. in 1997 (and later Feldman et al. in 1999) have yielded strong evidence for gravitational settling within these loops. However, their expected in situ signature plasma with heavy elements fractionated by mass was not observed prior to this study. Using data from the SWICS instrument on board the Advanced Composition Explorer ( ACE ), we investigate the composition of the solar wind within these dropouts and explore long term trends over most of a solar cycle.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98580/1/0004-637X_760_1_30.pd

    Ankle Brachial Index and Subsequent Cardiovascular Disease Risk in Patients With Chronic Kidney Disease

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/1/jah31554.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/2/jah31554_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139089/3/jah31554-sup-0001-TableS1.pd

    A Reappraisal of Children’s ‘Potential’

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    What does it mean for a child to fulfil his or her potential? This article explores the contexts and implications of the much-used concept of potential in educational discourses. We claim that many of the popular, political and educational uses of the term in relation to childhood have a problematic blind spot: interpersonality, and the necessary coexistence for the concept to be receivable of all children’s ‘potentials’. Rather than advocating abandoning the term—a futile gesture given its emotive force—we argue that the concept of children’s potential must be profoundly rethought to be workable as a philosophical notion in education. In an era marked by the unspoken assumption that ‘unlimited potential’ is always a good thing, we argue that it might be necessary to think about the limitations of the notion of individual potential; namely, the moment when it comes into contact with other people’s projects. We propose a conceptualisation of potential as the negotiated, situated, ever-changing creation of a group of individuals, in a process marked by conflict, and which remains essentially difficult.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s11217-016-9508-

    REST and neural gene network Dysregulation in iPSC models of Alzheimer’s disease

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    The molecular basis of the earliest neuronal changes that lead to Alzheimer’s disease (AD) is unclear. Here, we analyze neural cells derived from sporadic AD (SAD), APOE4 gene-edited and control induced pluripotent stem cells (iPSCs). We observe major differences in iPSC-derived neural progenitor (NP) cells and neurons in gene networks related to neuronal differentiation, neurogenesis, and synaptic transmission. The iPSC-derived neural cells from SAD patients exhibit accelerated neural differentiation and reduced progenitor cell renewal. Moreover, a similar phenotype appears in NP cells and cerebral organoids derived from APOE4 iPSCs. Impaired function of the transcriptional repressor REST is strongly implicated in the altered transcriptome and differentiation state. SAD and APOE4 expression result in reduced REST nuclear translocation and chromatin binding, and disruption of the nuclear lamina. Thus, dysregulation of neural gene networks may set in motion the pathologic cascade that leads to AD

    RENEWAL: REpurposing study to find NEW compounds with Activity for Lewy body dementia—an international Delphi consensus

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    Drug repositioning and repurposing has proved useful in identifying new treatments for many diseases, which can then rapidly be brought into clinical practice. Currently, there are few effective pharmacological treatments for Lewy body dementia (which includes both dementia with Lewy bodies and Parkinson’s disease dementia) apart from cholinesterase inhibitors. We reviewed several promising compounds that might potentially be disease-modifying agents for Lewy body dementia and then undertook an International Delphi consensus study to prioritise compounds. We identified ambroxol as the top ranked agent for repurposing and identified a further six agents from the classes of tyrosine kinase inhibitors, GLP-1 receptor agonists, and angiotensin receptor blockers that were rated by the majority of our expert panel as justifying a clinical trial. It would now be timely to take forward all these compounds to Phase II or III clinical trials in Lewy body dementia

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
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