33 research outputs found

    Defining imaging biomarker cut points for brain aging and Alzheimer's disease

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    AbstractIntroductionOur goal was to develop cut points for amyloid positron emission tomography (PET), tau PET, flouro-deoxyglucose (FDG) PET, and MRI cortical thickness.MethodsWe examined five methods for determining cut points.ResultsThe reliable worsening method produced a cut point only for amyloid PET. The specificity, sensitivity, and accuracy of cognitively impaired versus young clinically normal (CN) methods labeled the most people abnormal and all gave similar cut points for tau PET, FDG PET, and cortical thickness. Cut points defined using the accuracy of cognitively impaired versus age-matched CN method labeled fewer people abnormal.DiscussionIn the future, we will use a single cut point for amyloid PET (standardized uptake value ratio, 1.42; centiloid, 19) based on the reliable worsening cut point method. We will base lenient cut points for tau PET, FDG PET, and cortical thickness on the accuracy of cognitively impaired versus young CN method and base conservative cut points on the accuracy of cognitively impaired versus age-matched CN method

    Targets for high repetition rate laser facilities: Needs, challenges and perspectives

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    A number of laser facilities coming online all over the world promise the capability of high-power laser experiments with shot repetition rates between 1 and 10Ã\u82 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: Dynamic compression physics, electron transport and isochoric heating, and laser-driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities

    Developmental expression of orphan g protein-coupled receptor 50 in the mouse brain

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    [Image: see text] Mental disorders have a complex etiology resulting from interactions between multiple genetic risk factors and stressful life events. Orphan G protein-coupled receptor 50 (GPR50) has been identified as a genetic risk factor for bipolar disorder and major depression in women, and there is additional genetic and functional evidence linking GPR50 to neurite outgrowth, lipid metabolism, and adaptive thermogenesis and torpor. However, in the absence of a ligand, a specific function has not been identified. Adult GPR50 expression has previously been reported in brain regions controlling the HPA axis, but its developmental expression is unknown. In this study, we performed extensive expression analysis of GPR50 and three protein interactors using rt-PCR and immunohistochemistry in the developing and adult mouse brain. Gpr50 is expressed at embryonic day 13 (E13), peaks at E18, and is predominantly expressed by neurons. Additionally we identified novel regions of Gpr50 expression, including brain stem nuclei involved in neurotransmitter signaling: the locus coeruleus, substantia nigra, and raphe nuclei, as well as nuclei involved in metabolic homeostasis. Gpr50 colocalizes with yeast-two-hybrid interactors Nogo-A, Abca2, and Cdh8 in the hypothalamus, amygdala, cortex, and selected brain stem nuclei at E18 and in the adult. With this study, we identify a link between GPR50 and neurotransmitter signaling and strengthen a likely role in stress response and energy homeostasis

    Contributions of animal models to the study of mood disorders

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    Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4

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    BACKGROUND: Migrainous vertigo (MV) is increasingly recognized as a common cause of episodic vertigo. MV displays several clinical similarities with familial hemiplegic migraine (FHM) and episodic ataxia type 2 (EA-2), which have been linked to mutations in 3 genes, CACNA1A, encoding a neuronal calcium channel alpha subunit, ATP1A2, encoding a catalytic subunit of a Na(+)/K(+)-ATPase, and most recently the voltage-gated sodium channel SCN1A. The present study explored the hypothesis that mutations in CACNA1A, ATP1A2, SCN1A, and the calcium channel beta(4) subunit CACNB4 confer susceptibility to MV. METHODS: Mutation analysis of the coding exons and exon/intron junctions of CACNA1A, ATP1A2, SCN1A, and CACNB4 was performed in 14 unrelated MV patients by conformation sensitive gel electrophoresis and automated sequence analysis. RESULTS: Analysis of the 4 candidate genes in the 14 MV patients resulted in the identification of a total of 26 sequence variants. The silent substitution D29D in CACNB4 was observed in 2 MV patients and was not present in 46 ethnically matched control DNA samples. The remaining variants were also observed in control DNA samples and the allele frequencies of variants that resulted in amino acid substitutions were not significantly different between patients and controls. CONCLUSIONS: Based on this group of patients there is no evidence that the genes causing FHM and EA-2 represent major susceptibility loci for MV

    X-ray spectroscopy station for sample characterization at ELI Beamlines

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    X-ray spectroscopy is a demanded tool across multiple user communities. Here we report on a new station for X-ray emission spectroscopy at the Extreme Light Infrastructure Beamlines Facility. The instrument utilizes the von Hamos geometry and works with a number of different sample types, notably including liquid systems. We demonstrate a simple and reliable method for source position control using two cameras. This approach addresses energy calibration dependence on sample position, which is a characteristic source of measurement uncertainty for wavelength dispersive spectrometers in XES arrangement. We also present a straightforward procedure for energy calibration of liquid and powder samples to a thin film reference. The developed instrumentation enabled us to perform the first experimental determination of the K alpha lines of liquidized K3Fe(CN)6 as well as powdered and liquidized FeNH4(SO4)2. Finally, we report on proof-of-principle use of a colliding jet liquid sample delivery system in an XES experiment

    Improving robot manipulation with data-driven object-centric models of everyday forces

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    © The Author(s) 2013. This article is published with open access at Springerlink.comDOI: 10.1007/s10514-013-9344-1Based on a lifetime of experience, people anticipate the forces associated with performing a manipulation task. In contrast, most robots lack common sense about the forces involved in everyday manipulation tasks. In this paper, we present data-driven methods to inform robots about the forces that they are likely to encounter when performing specific tasks. In the context of door opening, we demonstrate that data-driven object-centric models can be used to haptically recognize specific doors, haptically recognize classes of door (e.g., refrigerator vs. kitchen cabinet), and haptically detect anomalous forces while opening a door, even when opening a specific door for the first time.We also demonstrate that two distinct robots can use forces captured from people opening doors to better detect anomalous forces. These results illustrate the potential for robots to use shared databases of forces to bettermanipulate theworld and attain common sense about everyday forces

    Manipulation of laser-accelerated proton beam profiles by nanostructured and microstructured targets

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    Nanostructured and microstructured thin foils have been fabricated and used experimentally as targets to manipulate the spatial profile of proton bunches accelerated through the interaction with high intensity laser pulses (6 x 1019 W/cm(2)). Monolayers of polystyrene nanospheres were placed on the rear surfaces of thin plastic targets to improve the spatial homogeneity of the accelerated proton beams. Moreover, thin targets with grating structures of various configurations on their rear sides were used tomodify the proton beam divergence. Experimental results are presented, discussed, and supported by 3D particle-in-cell numerical simulations
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