298 research outputs found

    Patron for a Day (PFAD): A Space Assessment

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    A basic premise of User Experience (UX) is to empathize with your users. This assessment exercise encourages your staff to understand what users experience in your spaces and, as a bonus, identifes some immediate space usability issues as well

    Envisioning Reference at MIT

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    . In the past few years, the MIT Libraries has been focused on how to turn declining reference statistics, new modes of technology, users’ increasing needs and expectations, and constrained staff resources into a robust and valued reference service. A 5-year strategic plan written in 1999 spurred staff to develop a new service based on chat technology, but once the service was established, it was unclear how it fit into the future of reference at MIT. This article describes how library staff worked together to envision a future of reference at MIT that would incorporate the values of reference, the needs of the users, and the infrastructure of the Libraries. The final product was the Reference Vision, which now guides all of our new reference services

    Metrics with Meaning: How Can We Effect Change to Library Assessment Metrics used by Non-Library Organizations

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    Many library metrics and statistics that are gathered regularly by accreditation agencies, publishers, and other entities to inform stakeholders have stagnated and are no longer effective in illustrating library value. In this talk, we will highlight measures collected by accreditation agencies and publishers that are not effective, and then describe potential ways to have short-term and long-term impact on changing these national metrics so that they better represent libraries of the 21st century

    Metrics with Meaning: How Can We Effect Change to Library Assessment Metrics used by Non-Library Organizations

    Get PDF
    Many library metrics and statistics that are gathered regularly by accreditation agencies, publishers, and other entities to inform stakeholders have stagnated and are no longer effective in illustrating library value. In this talk, we will highlight measures collected by accreditation agencies and publishers that are not effective, and then describe potential ways to have short-term and long-term impact on changing these national metrics so that they better represent libraries of the 21st century

    Plasma oxylipins and unesterified precursor fatty acids are altered by DHA supplementation in pregnancy: Can they help predict risk of preterm birth?

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    Oxidized lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids, collectively known as oxylipins, are bioactive signaling molecules that play diverse roles in human health and disease. Supplementation with n-3 docosahexaenoic acid (DHA) during pregnancy has been reported to decrease the risk of preterm birth in singleton pregnancies, which may be due to effects of DHA supplementation on oxylipins or their precursor n-6 and n-3 fatty acids. There is only limited understanding of the levels and trajectory of changes in plasma oxylipins during pregnancy, effects of DHA supplementation on oxylipins and unesterified fatty acids, and whether and how oxylipins and their unesterified precursor fatty acids influence preterm birth. In the present study we used liquid chromatography-tandem mass spectrometry to profile oxylipins and their precursor fatty acids in the unesterified pool using plasma samples collected from a subset of pregnant Australian women who participated in the ORIP (Omega-3 fats to Reduce the Incidence of Prematurity) study. ORIP is a large randomized controlled trial testing whether daily supplementation with n-3 DHA can reduce the incidence of early preterm birth compared to control. Plasma was collected at study entry (≈pregnancy week 14) and again at ≈week 24, in a subgroup of 48 ORIP participants-12 cases with spontaneous preterm (<37 weeks) birth and 36 matched controls with spontaneous term (≥40 weeks) birth. In the combined preterm and term pregnancies, we observed that in the control group without DHA supplementation unesterified AA and AA-derived oxylipins 12-HETE, 15-HETE and TXB2 declined between weeks 14-24 of pregnancy. Compared to control, DHA supplementation increased unesterified DHA, EPA, and AA, DHA-derived 4-HDHA, 10-HDHA and 19,20-EpDPA, and AA-derived 12-HETE at 24 weeks. In exploratory analysis independent of DHA supplementation, participants with concentrations above the median for 5-lipoxygenase derivatives of AA (5-HETE, Odds Ratio (OR) 8.2; p = 0.014) or DHA (4-HDHA, OR 8.0; p = 0.015) at 14 weeks, or unesterified AA (OR 5.1; p = 0.038) at 24 weeks had higher risk of spontaneous preterm birth. The hypothesis that 5-lipoxygenase-derived oxylipins and unesterified AA could serve as mechanism-based biomarkers predicting spontaneous preterm birth should be evaluated in larger, adequately powered studies

    Regulation of KCNQ2/KCNQ3 Current by G Protein Cycling: The Kinetics of Receptor-mediated Signaling by Gq

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    Receptor-mediated modulation of KCNQ channels regulates neuronal excitability. This study concerns the kinetics and mechanism of M1 muscarinic receptor–mediated regulation of the cloned neuronal M channel, KCNQ2/KCNQ3 (Kv7.2/Kv7.3). Receptors, channels, various mutated G-protein subunits, and an optical probe for phosphatidylinositol 4,5-bisphosphate (PIP2) were coexpressed by transfection in tsA-201 cells, and the cells were studied by whole-cell patch clamp and by confocal microscopy. Constitutively active forms of Gαq and Gα11, but not Gα13, caused a loss of the plasma membrane PIP2 and a total tonic inhibition of the KCNQ current. There were no further changes upon addition of the muscarinic agonist oxotremorine-M (oxo-M). Expression of the regulator of G-protein signaling, RGS2, blocked PIP2 hydrolysis and current suppression by muscarinic stimulation, confirming that the Gq family of G-proteins is necessary. Dialysis with the competitive inhibitor GDPβS (1 mM) lengthened the time constant of inhibition sixfold, decreased the suppression of current, and decreased agonist sensitivity. Removal of intracellular Mg2+ slowed both the development and the recovery from muscarinic suppression. When combined with GDPβS, low intracellular Mg2+ nearly eliminated muscarinic inhibition. With nonhydrolyzable GTP analogs, current suppression developed spontaneously and muscarinic inhibition was enhanced. Such spontaneous suppression was antagonized by GDPβS or GTP or by expression of RGS2. These observations were successfully described by a kinetic model representing biochemical steps of the signaling cascade using published rate constants where available. The model supports the following sequence of events for this Gq-coupled signaling: A classical G-protein cycle, including competition for nucleotide-free G-protein by all nucleotide forms and an activation step requiring Mg2+, followed by G-protein–stimulated phospholipase C and hydrolysis of PIP2, and finally PIP2 dissociation from binding sites for inositol lipid on the channels so that KCNQ current was suppressed. Further experiments will be needed to refine some untested assumptions

    Phospholipase C in Living Cells: Activation, Inhibition, Ca2+ Requirement, and Regulation of M Current

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    We have further tested the hypothesis that receptor-mediated modulation of KCNQ channels involves depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphoinositide-specific phospholipase C (PLC). We used four parallel assays to characterize the agonist-induced PLC response of cells (tsA or CHO cells) expressing M1 muscarinic receptors: translocation of two fluorescent probes for membrane lipids, release of calcium from intracellular stores, and chemical measurement of acidic lipids. Occupation of M1 receptors activates PLC and consumes cellular PIP2 in less than a minute and also partially depletes mono- and unphosphorylated phosphoinositides. KCNQ current is simultaneously suppressed. Two inhibitors of PLC, U73122 and edelfosine (ET-18-OCH3), can block the muscarinic actions completely, including suppression of KCNQ current. However, U73122 also had many side effects that were attributable to alkylation of various proteins. These were mimicked or occluded by prior reaction with the alkylating agent N-ethylmaleimide and included block of pertussis toxin–sensitive G proteins and effects that resembled a weak activation of PLC or an inhibition of lipid kinases. By our functional criteria, the putative PLC activator m-3M3FBS did stimulate PLC, but with a delay and an irregular time course. It also suppressed KCNQ current. The M1 receptor–mediated activation of PLC and suppression of KCNQ current were stopped by lowering intracellular calcium well below resting levels and were slowed by not allowing intracellular calcium to rise in response to PLC activation. Thus calcium release induced by PLC activation feeds back immediately on PLC, accelerating it during muscarinic stimulation in strong positive feedback. These experiments clarify important properties of receptor-coupled PLC responses and their inhibition in the context of the living cell. In each test, the suppression of KCNQ current closely paralleled the expected fall of PIP2. The results are described by a kinetic model

    Holographic Domains of Anti-de Sitter Space

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    An AdS_4 brane embedded in AdS_5 exhibits the novel feature that a four-dimensional graviton is localized near the brane, but the majority of the infinite bulk away from the brane where the warp factor diverges does not see four-dimensional gravity. A naive application of the holographic principle from the point of view of the four-dimensional observer would lead to a paradox; a global holographic mapping would require infinite entropy density. In this paper, we show that this paradox is resolved by the proper covariant formulation of the holographic principle. This is the first explicit example of a time-independent metric for which the spacelike formulation of the holographic principle is manifestly inadequate. Further confirmation of the correctness of this approach is that light-rays leaving the brane intersect at the location where we expect four-dimensional gravity to no longer dominate. We also present a simple method of locating CFT excitations dual to a particle in the bulk. We find that the holographic image on the brane moves off to infinity precisely when the particle exits the brane's holographic domain. Our analysis yields an improved understanding of the physics of the AdS_4/AdS_5 model.Comment: 29 pages, 6 figure
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