1,078 research outputs found

    Novel mGluR- and CB1R-Independent Suppression of GABA Release Caused by a Contaminant of the Group I Metabotropic Glutamate Receptor Agonist, DHPG

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    Metabotropic glutamate receptors (mGluRs) are ubiquitous throughout the body, especially in brain, where they mediate numerous effects. MGluRs are classified into groups of which group I, comprising mGluRs 1 and 5, is especially important in neuronal communication. Group I actions are often investigated with the selective agonist, S-3,5-dihydroxyphenylglycine (DHPG). Despite the selectivity of DHPG, its use has often led to contradictory findings. We now report that a particular commercial preparation of DHPG can produce mGluR-independent effects. These findings may help reconcile some discrepant reports.We carried out electrophysiological recordings in the rat in vitro hippocampal slice preparation, focusing mainly on pharmacologically isolated GABA(A)-receptor-mediated synaptic currents.While preparations of DHPG from three companies suppressed GABAergic transmission in an mGluR-dependent way, one batch had an additional, unusual effect. Even in the presence of antagonists of mGluRs, it caused a reversible, profound suppression of inhibitory transmission. This mGluR-independent action was not due to a higher potency of the compound, or its ability to cause endocannabinoid-dependent responses. Field potential recordings revealed that glutamatergic transmission was not affected, and quantal analysis of GABA transmission confirmed the unusual effect was on GABA release, and not GABA(A) receptors. We have not identified the responsible factor in the DHPG preparation, but the samples were 99% pure as determined by HPLC and NMR analyses.In certain respects our observations with the anomalous batch strikingly resemble some published reports of unusual DHPG effects. The present findings could therefore contribute to explaining discrepancies in the literature. DHPG is widely employed to study mGluRs in different systems, hence rigorous controls should be performed before conclusions based on its use are drawn

    Peer Evaluation of Teaching in an Online Information Literacy Course

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    This paper reports on the development and implementation of a process of peer evaluation of teaching to assess librarian instruction in a high-enrollment online information literacy course for undergraduates. This paper also traces a shift within libraries from peer coaching to peer evaluation models. One common model for peer evaluation, using pre- and post-observation meetings between instructor and evaluator, as well as a formal summative report, has been adapted to focus attention on key aspects of online teaching. The paper also discusses the need for evaluating librarians’ online teaching performance, as distinct from online course design

    Advanced information processing system: The Army fault tolerant architecture conceptual study. Volume 1: Army fault tolerant architecture overview

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    Digital computing systems needed for Army programs such as the Computer-Aided Low Altitude Helicopter Flight Program and the Armored Systems Modernization (ASM) vehicles may be characterized by high computational throughput and input/output bandwidth, hard real-time response, high reliability and availability, and maintainability, testability, and producibility requirements. In addition, such a system should be affordable to produce, procure, maintain, and upgrade. To address these needs, the Army Fault Tolerant Architecture (AFTA) is being designed and constructed under a three-year program comprised of a conceptual study, detailed design and fabrication, and demonstration and validation phases. Described here are the results of the conceptual study phase of the AFTA development. Given here is an introduction to the AFTA program, its objectives, and key elements of its technical approach. A format is designed for representing mission requirements in a manner suitable for first order AFTA sizing and analysis, followed by a discussion of the current state of mission requirements acquisition for the targeted Army missions. An overview is given of AFTA's architectural theory of operation

    Advanced information processing system: The Army fault tolerant architecture conceptual study. Volume 2: Army fault tolerant architecture design and analysis

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    Described here is the Army Fault Tolerant Architecture (AFTA) hardware architecture and components and the operating system. The architectural and operational theory of the AFTA Fault Tolerant Data Bus is discussed. The test and maintenance strategy developed for use in fielded AFTA installations is presented. An approach to be used in reducing the probability of AFTA failure due to common mode faults is described. Analytical models for AFTA performance, reliability, availability, life cycle cost, weight, power, and volume are developed. An approach is presented for using VHSIC Hardware Description Language (VHDL) to describe and design AFTA's developmental hardware. A plan is described for verifying and validating key AFTA concepts during the Dem/Val phase. Analytical models and partial mission requirements are used to generate AFTA configurations for the TF/TA/NOE and Ground Vehicle missions

    Individual tree biomass equations or biomass expansion factors for assessment of carbon stock changes in living biomass - A comparative study

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    AbstractSignatory countries to the United Nations Framework Convention on Climate Change (UNFCCC) and its supplementary Kyoto Protocol (KP) are obliged to report greenhouse gas emissions and removals. Changes in the carbon stock of living biomass should be reported using either the default or stock change methods of the Intergovernmental Panel on Climate Change (IPCC) under the Land Use, Land-Use Change and Forestry sector. Traditionally, volume estimates are used as a forestry measures. Changes in living biomass may be assessed by first estimating the change in the volume of stem wood and then converting this volume to whole tree biomass using biomass expansion factors (BEFs). However, this conversion is often non-trivial because the proportion of stem wood increases with tree size at the expense of branches, foliage, stump and roots. Therefore, BEFs typically vary over time and their use may result in biased estimates. The objective of this study was to evaluate differences between biomass estimates obtained using biomass equations and BEFs with particular focus on uncertainty analysis. Assuming that the development of tree fractions in different ways can be handled by individual biomass equations, BEFs for standing stock were shown to overestimate the biomass sink capacity (Sweden). Although estimates for BEFs derived for changes in stock were found to be unbiased, the estimated BEFs varied substantially over time (0.85–1.22ton CO2/m3). However, to some extent this variation may be due to random sampling errors rather than actual changes. The highest accuracy was obtained for estimates based on biomass equations for different tree fractions, applied to data from the Swedish National Forest Inventory using a permanent sample design (estimated change in stock 1990–2005: 420million tons CO2, with a standard error amounting to 26.7million tons CO2) Many countries have adopted such a design combined with the stock change method for reporting carbon stock changes under the UNFCCC/KP

    Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric autism spectrum disorder demonstrated by 1H MRS and 1H MRSI.

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    Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy ((1)H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging ((1)H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD

    Optogenetic Release of ACh Induces Rhythmic Bursts of Perisomatic IPSCs in Hippocampus

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    Acetylcholine (ACh) influences a vast array of phenomena in cortical systems. It alters many ionic conductances and neuronal firing behavior, often by regulating membrane potential oscillations in populations of cells. Synaptic inhibition has crucial roles in many forms of oscillation, and cholinergic mechanisms regulate both oscillations and synaptic inhibition. In vitro investigations using bath-application of cholinergic receptor agonists, or bulk tissue electrical stimulation to release endogenous ACh, have led to insights into cholinergic function, but questions remain because of the relative lack of selectivity of these forms of stimulation. To investigate the effects of selective release of ACh on interneurons and oscillations, we used an optogenetic approach in which the light-sensitive non-selective cation channel, Channelrhodopsin2 (ChR2), was virally delivered to cholinergic projection neurons in the medial septum/diagonal band of Broca (MS/DBB) of adult mice expressing Cre-recombinase under the control of the choline-acetyltransferase (ChAT) promoter. Acute hippocampal slices obtained from these animals weeks later revealed ChR2 expression in cholinergic axons. Brief trains of blue light pulses delivered to untreated slices initiated bursts of ACh-evoked, inhibitory post-synaptic currents (L-IPSCs) in CA1 pyramidal cells that lasted for 10's of seconds after the light stimulation ceased. L-IPSC occurred more reliably in slices treated with eserine and a very low concentration of 4-AP, which were therefore used in most experiments. The rhythmic, L-IPSCs were driven primarily by muscarinic ACh receptors (mAChRs), and could be suppressed by endocannabinoid release from pyramidal cells. Finally, low-frequency oscillations (LFOs) of local field potentials (LFPs) were significantly cross-correlated with the L-IPSCs, and reversal of the LFPs near s. pyramidale confirmed that the LFPs were driven by perisomatic inhibition. This optogenetic approach may be a useful complementary technique in future investigations of endogenous ACh effects

    Electron Magnetic Resonance: The Modified Bloch Equation

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    We find a modified Bloch equation for the electronic magnetic moment when the magnetic moment explicitly contains a diamagnetic contribution (a magnetic field induced magnetic moment arising from the electronic orbital angular momentum) in addition to the intrinsic magnetic moment of the electron. The modified Bloch is coupled to equations of motion for the position and momentum operators. In the presence of static and time varying magnetic field components, the magnetic moment oscillates out of phase with the magnetic field and power is absorbed by virtue of the magnetic field induced magnetic moment, even in the absence of coupling to the environment. We explicitly work out the spectrum and absorption for the case of a pp state electron
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