223 research outputs found

    Expression of the Gi-coupled RASSL Ro1 in GFAP-positive cells: a novel model of hydrocephalus

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    Hydrocephalus is a disorder of cerebrospinal fluid dynamics within the central nervous system. Although symptoms of hydrocephalus are often relieved by shunt implantation, complications are common and underlying pathology remains. Understanding the molecular mechanisms of hydrocephalus is critical for development of new therapeutics; however few experimental models allow early events to be studied. Originally designed to study astrocytic Gi signaling, we developed a transgenic mouse line expressing the Gi-coupled RASSL (receptor activated solely by synthetic ligand) Ro1 in GFAP-positive cells by crossing the hGFAP-tTA (tet transactivator behind the human glial fibrillary acidic protein promoter) mouse line with the tetO-Ro1/tetO-LacZ mouse line. Surprisingly, we found that all double-transgenic mice developed hydrocephalus by postnatal day 15, while single-transgenic littermate controls appeared normal. Hydrocephalic Ro1 mice had enlarged lateral and third ventricles, thinned cortex, partial denudation of the ependymal cell layer, abnormal subcommissural organ, and obliteration of the cerebral aqueduct. Severely affected mice had increased phosphoErk and GFAP expression. Giving breeding pairs doxycycline prevented the expression of Ro1 and onset of hydrocephalus in double-transgenic offspring. Double transgenic mice taken off dox at weaning developed enlarged ventricles within 7 weeks, indicating that Ro1 expression also induces hydrocephalus in adults. Double-transgenic mice injected with a Ro1 inverse agonist when taken off dox did not develop enlarged ventricles or have ependymal detachment, demonstrating that signaling through Ro1 is required for hydrocephalus. We have discovered a new model that allows onset of hydrocephalus to be controlled, providing the unique ability to study the earliest events in juvenile and adult-onset hydrocephalus. Ependymal denudation is a common feature of hydrocephalus that appears to occur early in the disease. Positive GFAP and Ro1 staining was detected in a subset of ependymal cells from double transgenic mice off dox. Timed studies showed that Ro1 expression began within three days of dox removal and ependymal denudation began within ten days. Affymetrix gene arrays were utilized to screen for changes in ependymal gene expression at five and nine days after dox removal. No differentially expressed genes were detected between double-transgenic mice and controls at either timepoint; RT-PCR also failed to detect significant changes

    Backward-Angle (uu-channel) Production at an Electron-Ion Collider

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    In backward photoproduction of mesons, γpMp\gamma p\rightarrow M p, the target proton takes most of the photon momentum, while the produced meson recoils in the direction from which the photon came. Thus the Mandelstam uu is small, while the squared momentum transfer tt is typically large, near the kinematic limit. In a collider geometry, backward production transfers the struck baryon by many units of rapidity, in a striking similarity to baryon stopping. We explore this similarity, and point out the similarities between the Regge theories used to model baryon stopping with those that are used for backward production. We then explore how backward production can be explored at higher energies than are available at fixed target experiments, by studying production at an electron-ion collider. We calculate the expected epep cross sections and rates, finding that the rate for backward ω\omega production is about 1/300 that of forward ω\omegas. We discuss the kinematics of backward production and consider the detector requirements for experimental study.Comment: 11 pages, 8 figure

    Experimental investigation of cavitation signatures in an automotive torque converter using a microwave telemetry technique

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    A unique experimental investigation of cavitation signatures in an automotive torque converter under stall conditions is reported. A quantitative criterion is proposed for predicting early and advanced cavitation in terms of suitable nondimensional pump speeds. The dimensionless pump speed that marks early cavitation is obtained by relating this parameter to the appearance of charge-pressure–dependent pressure fluctuations in the differential pressure transducer readings. The differential pressure transducers were mounted at well-defined locations in the pump passage of a torque converter. The data were transmitted by a wireless telemetry system mounted on the pump housing. Data were received and processed by a ground-based data acquisition system. Automatic transmission fluid exhibited cavitation for charge pressures of 70–130 psi and pump speeds of 1000– 2250 rpm. Advanced cavitation was marked by operating conditions that exhibited a 2% or more torque degradation from the converter\u27s noncavitating performance. For a given family of torque-converter designs and a given transmission fluid, the proposed nondimensional pumpspeed criteria are capable of marking early and advanced stages of cavitation for a range of torque-converter sizes and a range of charge pressures in the torque converter

    Experimental investigation of cavitation signatures in an automotive torque converter using a microwave telemetry technique

    Get PDF
    A unique experimental investigation of cavitation signatures in an automotive torque converter under stall conditions is reported. A quantitative criterion is proposed for predicting early and advanced cavitation in terms of suitable nondimensional pump speeds. The dimensionless pump speed that marks early cavitation is obtained by relating this parameter to the appearance of charge-pressure–dependent pressure fluctuations in the differential pressure transducer readings. The differential pressure transducers were mounted at well-defined locations in the pump passage of a torque converter. The data were transmitted by a wireless telemetry system mounted on the pump housing. Data were received and processed by a ground-based data acquisition system. Automatic transmission fluid exhibited cavitation for charge pressures of 70–130 psi and pump speeds of 1000– 2250 rpm. Advanced cavitation was marked by operating conditions that exhibited a 2% or more torque degradation from the converter\u27s noncavitating performance. For a given family of torque-converter designs and a given transmission fluid, the proposed nondimensional pumpspeed criteria are capable of marking early and advanced stages of cavitation for a range of torque-converter sizes and a range of charge pressures in the torque converter

    Modeling Backward-Angle (uu-channel) Virtual Compton Scattering at an Electron-Ion Collider

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    High-energy backward (uu-channel) reactions can involve very large momentum transfers to the target baryons, shifting them by many units of rapidity. These reactions are difficult to understand in conventional models in which baryon number is carried by the valence quarks. Backward Compton scattering is an especially attractive experimental target, because of its simple final state. There is currently limited data on this process, and that data is at low center-of-mass energies. In this paper, we examine the prospects for studying backward Compton scattering at the future Electron-Ion Collider (EIC). We model the cross-section and kinematics using the limited data on backward Compton scattering and backward meson production, and then simulate Compton scattering at EIC energies, in a simple model of the ePIC detector. Generally, the proton is scattered toward mid-rapidity, while the produced photon is in the far-forward region, visible in a Zero Degree Calorimeter (ZDC). We show that the background from backward π0\pi^0 production can be rejected using a high-resolution, well-segmented ZDC.Comment: 12 pages, 9 figure

    Low Energy Light Yield of Fast Plastic Scintillators

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    Compact neutron imagers using double-scatter kinematic reconstruction are being designed for localization and characterization of special nuclear material. These neutron imaging systems rely on scintillators with a rapid prompt temporal response as the detection medium. As n-p elastic scattering is the primary mechanism for light generation by fast neutron interactions in organic scintillators, proton light yield data are needed for accurate assessment of scintillator performance. The proton light yield of a series of commercial fast plastic organic scintillators---EJ-200, EJ-204, and EJ-208---was measured via a double time-of-flight technique at the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory. Using a tunable deuteron breakup neutron source, target scintillators housed in a dual photomultiplier tube configuration, and an array of pulse-shape-discriminating observation scintillators, the fast plastic scintillator light yield was measured over a broad and continuous energy range down to proton recoil energies of approximately 50 keV. This work provides key input to event reconstruction algorithms required for utilization of these materials in emerging neutron imaging modalities.Comment: 15 pages, 6 figure

    Gs G Protein–Coupled Receptor Signaling in Osteoblasts Elicits Age-Dependent Effects on Bone Formation

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    Age-dependent changes in skeletal growth are important for regulating skeletal expansion and determining peak bone mass. However, how G protein–coupled receptors (GPCRs) regulate these changes is poorly understood. Previously, we described a mouse model expressing Rs1, an engineered receptor with high basal Gs activity. Rs1 expression in osteoblasts induced a dramatic age-dependent increase in trabecular bone with features resembling fibrous dysplasia. To further investigate how activation of the Gs-GPCR pathway affects bone formation at different ages, we used the tetracycline-inducible system in the ColI(2.3)+/Rs1+ mouse model to control the timing of Rs1 expression. We found that the Rs1 phenotype developed rapidly between postnatal days 4 and 6, that delayed Rs1 expression resulted in attenuation of the Rs1 phenotype, and that the Rs1-induced bone growth and deformities were markedly reversed when Rs1 expression was suppressed in adult mice. These findings suggest a distinct window of increased osteoblast responsiveness to Gs signaling during the early postnatal period. In addition, adult bones encode information about their normal shape and structure independently from mechanisms regulating bone expansion. Finally, our model provides a powerful tool for investigating the effects of continuous Gs-GPCR signaling on dynamic bone growth and remodeling. © 2010 American Society for Bone and Mineral Research

    What Is the Role of Astrocyte Calcium in Neurophysiology?

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    Astrocytes comprise approximately half of the volume of the adult mammalian brain and are the primary neuronal structural and trophic supportive elements. Astrocytes are organized into distinct nonoverlapping domains and extend elaborate and dense fine processes that interact intimately with synapses and cerebrovasculature. The recognition in the mid 1990s that astrocytes undergo elevations in intracellular calcium concentration following activation of G protein-coupled receptors by synaptically released neurotransmitters demonstrated not only that astrocytes display a form of excitability but also that astrocytes may be active participants in brain information processing. The roles that astrocytic calcium elevations play in neurophysiology and especially in modulation of neuronal activity have been intensely researched in recent years. This review will summarize the current understanding of the function of astrocytic calcium signaling in neurophysiological processes and discuss areas where the role of astrocytes remains controversial and will therefore benefit from further study
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