734 research outputs found

    Imagining a Future in PreK: How Professional Identity Shapes Notions of Early Mathematics

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110548/1/aeq12086.pd

    Imagining a Future in PreK: How Professional Identity Shapes Notions of Early Mathematics

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    This article describes how early childhood teachers engaged in a public preK professional development program. We examine how developing teacher identities mediated engagement with the discourses of developmentally appropriate practice, early mathematics, and funds of knowledge and how they connected present practice to an imagined future. We found that helping them to connect practice experience and new mathematical content knowledge through play allowed them to envision a meaningful place for math with young children

    Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy

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    In mammals, the master circadian clock synchronizes daily rhythms of physiology and behavior with the day-night cycle. Failure of synchrony, which increases the risk for numerous chronic diseases, can be treated by phase adjustment of the circadian clock pharmacologically, for example, with melatonin, or a CK1delta/epsilon inhibitor. Here, using in silico experiments with a systems pharmacology model describing molecular interactions, and pharmacokinetic and behavioral experiments in cynomolgus monkeys, we find that the circadian phase delay caused by CK1delta/epsilon inhibition is more strongly attenuated by light in diurnal monkeys and humans than in nocturnal mice, which are common preclinical models. Furthermore, the effect of CK1delta/epsilon inhibition strongly depends on endogenous PER2 protein levels, which differs depending on both the molecular cause of the circadian disruption and the patient\u27s lighting environment. To circumvent such large interindividual variations, we developed an adaptive chronotherapeutics to identify precise dosing regimens that could restore normal circadian phase under different conditions. Our results reveal the importance of photosensitivity in the clinical efficacy of clock-modulating drugs, and enable precision medicine for circadian disruption

    Modeling and Validating Chronic Pharmacological Manipulation of Circadian Rhythms

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110096/1/psp4201334-sup-0010.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110096/2/psp4201334-sup-0009.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110096/3/psp4201334-sup-0011.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110096/4/psp4201334-sup-0008.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110096/5/psp4201334-sup-0005.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110096/6/psp4201334-sup-0012.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110096/7/psp4201334-sup-0006.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110096/8/psp4201334-sup-0013.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110096/9/psp4201334.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110096/10/psp4201334-sup-0007.pd

    Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

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    The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery

    Destination-directed, packet-switched architecture for a geostationary communications satellite network

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    A major goal of the Digital Systems Technology Branch at the NASA Lewis Research Center is to identify and develop critical digital components and technologies that either enable new commercial missions or significantly enhance the performance, cost efficiency, and/or reliability of existing and planned space communications systems. NASA envisions a need for low-data-rate, interactive, direct-to-the-user communications services for data, voice, facsimile, and video conferencing. The network would provide enhanced very-small-aperture terminal (VSAT) communications services and be capable of handling data rates of 64 kbps through 2.048 Mbps in 64-kbps increments. Efforts have concentrated heavily on the space segment; however, the ground segment has been considered concurrently to ensure cost efficiency and realistic operational constraints. The focus of current space segment developments is a flexible, high-throughput, fault-tolerant onboard information-switching processor (ISP) for a geostationary satellite communications network. The Digital Systems Technology Branch is investigating both circuit and packet architectures for the ISP. Destination-directed, packet-switched architectures for geostationary communications satellites are addressed

    Site-specific Forest-assembly of Single-Wall Carbon Nanotubes on Electron-beam Patterned SiOx/Si Substrates

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    Based on electron-beam direct writing on the SiOx/Si substrates, favorable absorption sites for ferric cations (Fe3+ ions) were created on the surface oxide layer. This allowed Fe3+-assisted self-assembled arrays of single-wall carbon nanotube (SWNT) probes to be produced. Auger investigation indicated that the incident energetic electrons depleted oxygen, creating more dangling bonds around Si atoms at the surface of the SiOx layer. This resulted in a distinct difference in the friction forces from unexposed regions as measured by lateral force microscopy (LFM). Atomic force microscopy (AFM) affirmed that the irradiated domains absorbed considerably more Fe3+ ions upon immersion into pH 2.2 aqueous FeCl3 solution. This rendered a greater yield of FeO(OH)/FeOCl precipitates, primarily FeO(OH), upon subsequent washing with lightly basic dimethylformamide (DMF) solution. Such selective metalfunctionalization established the basis for the subsequent patterned forest-assembly of SWNTs as demonstrated by resonance Raman spectroscopy
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